News Archive
2021
We Might Not Know Half of What's in Our Cells, New AI Technique Reveals
11/24/2021
Dr. Eugene Yeo and collaborating group has been working on tracing the multiple facets of the cell. In order to do so, Multi-Scale Integrated Cell (MuSIC) technique was utilized to figure the components of a human kidney cell line. The Yeo team discovered an unfamiliar group of proteins that are suggested to be involved with splicing, an important cellular process. Although considered a pilot study, the MuSIC strategy has open doors to the possiblities of further understanding the differences between healthy and diseased cells.
Full UCSD Press Release article
Refining the toolkit for sugar analysis
11/1/2021
Sialic acids, which cap glycan branches, are a topic of complexity to glycobiologists. This unique class of sugars is manipulated by microbes to detrimentally affect the human body.
Dr. Adjit Varki has used these microbes to his advantage, using them as a source of sialic-acid affinity reagents. His team assembled a panel of nine reagents along with a general detector for mammalian sialic acid. Dr. Adjit Varki states, "We are like kids in a candy shop," says Ajit Varki. "The bad part is, there aren't many kids in the shop." The new reagents should make it easier for other biologists to get a taste.
Stem cell agency gives out $2 million a minute
9/29/2021
The directors of the California stem cell agency provided $2 million in funding to Alysson Muorti, Ph.D. , a professor in the Departments of Pediatrics and Cellular & Molecular Medicine at the University of California, San Diego.
His proposed training program received high marks from anonymous reviewers, with a key comment stating "The program director and co-director have excellent track records leading the stem cell training program at the institution. Their respective experience in modeling human developmental disorders in human stem cell-based systems, and in clinical research is nicely complementary and gives the program overall a good balance between basic and more applied stem cell science."
Full article on Capitol Weekly
$6M NIH Grant Launches UC San Diego Consortium to Study Insulin-Producing Cells
9/9/2021
The NIH launched a new program, Impact of Genomic Variation on Function Consortium, which provided a team of UC San Diego School of Medicine researchers, including UC San Diego School of Medicine's Bing Ren, Ph.D., $6.4 million in grant funding to study how external signals and genetic variations influence the behavior of one cell type in particular: insulin-producing beta cells in the pancreas.
With this funding, the team will use their beta cell models to detail how external signals determine insulin output. They'll look at 10 different stimuli known to modify insulin secretion, including sugar, other nutrients and food-dependent hormones, and determine how the beta cell genome and insulin release change in response to those stimuli over various lengths of time.
Full UCSD Press Release article
Human Mini-Lungs Grown in Lab Dishes are Closest Yet to Real Thing
8/31/2021
To address whether adult lung organoid models are propagable, personalized, and complete with both proximal airway and distal alveolar cell types against existing models that are incomplete, Pradipta Ghosh, M.D., and Soumita Das, Ph.D., led a study to assess and cross-validate the adult lung organoid model against COVID-19 patient-derived respiratory samples.
"This human disease model will now allow us to test drug efficacy and toxicity, and reject ineffective compounds early in the process, at 'Phase 0,' before human clinical trials begin," said Pradipta Ghosh, M.D. . This development of lung organoids will enable the advancement of lung disease models beyond COVID-19. The HUMANOID CoRE lung organoids are being implemented in academic and industry already, transforming our understanding of lung disease.
Brain Organoids Mimic Head Size Changes Associated with Type of Autism
8/25/2021
A study was led by Lilia Iakoucheva, Ph.D. and Alysson Muorti, M.D. to study variations in the 16p11.2 region of the genome, which are associated with autism spectrum disorder. The team used brain organoids — tiny, 3D cellular models generated in the lab from people with 16p11.2 variations.
These organoids revealed new information about the molecular mechanisms that malfunction when the 16p11.2 region of the genome is disrupted. RhoA — a protein that plays a big part in many basic cellular functions, such as development and movement — was found to be more active in both 16p11.2-deleted and 16p11.2-duplicated organoids than it is in organoids without these variations. Interestingly, inhibiting this protein in autism-like organoids, caused the neuronal migration to be restored to levels seen in the control organoids. "Our work opens the possibility to therapeutically manipulate the RhoA pathway, which can potentially help millions of patients," said Alysson Muorti, M.D. .
Life’s Edge by Carl Zimmer review – what does it mean to be alive?
8/21/2021
At a medical research laboratory in California, Alysson Muotri, Ph.D. has used chemistry to change skin cells into neurons, which have multiplied to form “organoids” – globes of interconnected brain cells. The organoids can expand to hundreds of thousands of cells, live for years, and even produce detectable patterns of brain waves, like those of premature babies. “The most incredible thing is that they build themselves,” says Muotri. He even wonders whether they could one day become conscious.
Girdin One’s Loins
8/19/2021
A research team, led by senior author Pradipta Ghosh, M.D., professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, found that GIV — a member of the G protein family that serve as molecular switches inside cells, transmitting and fine-tuning signals — regulates the activity of enzymes that turn on and turn off the processes of capacitation and AR in mammalian reproduction.
“The findings demonstrate how GIV orchestrates distinct signaling programs in sperm that separated by space and time, effectively supporting capacitation while inhibiting premature AR,” said Ghosh. “As a result, GIV plays an essential role in male fertility.”
Full UCSD Press Release article
Unchanging Rules of Gene Expression Could Improve Drug Approval Odds
8/13/2021
Network theory holds that everything is connected, including people (e.g., Facebook), but few will have many connections, and most will have few. The same rule applies if the “nodes” happen to be human cells, genomes, proteomes, or transcriptomes, says Pradipta Ghosh, M.D., professor in the departments of medicine and cellular and molecular medicine at the University of California San Diego (UCSD) School of Medicine as well as cofounder of the Institute for Network Medicine (iNetMed) endeavoring to chart the most powerful connections.
AI Helps Predict Winners and Losers in Clinical Trials
8/3/2021
Somewhere between assessing safety in healthy volunteers and testing effectiveness in hundreds to thousands of patients, most drugs in clinical trials fail. Pradipta Ghosh, M.D., and her colleagues at the University of California, San Diego (UCSD) School of Medicine have developed a blueprint that they hope will end this disheartening phenomenon.
Ghosh and her team used artificial intelligence (AI) to discern patterns in gene expression datasets that apply to all patients with inflammatory bowel disease (IBD) and to identify clinically actionable drug targets. After testing drug candidates in mouse models, typically the final step before clinical trials, the researchers conducted a “Phase 0” clinical trial. Using patient-derived organoid models, they determined whether any observed therapeutic effect resulted from the candidate drug or confounding variables.
Artificial Intelligence Could Be New Blueprint for Precision Drug Discovery
7/12/2021
Writing in the July 12, 2021 online issue of Nature Communications, researchers at University of California San Diego School of Medicine describe a new approach that uses machine learning to hunt for disease targets and then predicts whether a drug is likely to receive FDA approval.
The study's findings could measurably change how researchers sift through big data to find meaningful information with significant benefit to patients, the pharmaceutical industry and the nation’s health care systems.
“Academic labs and pharmaceutical and biotech companies have access to unlimited amounts of ‘big data’ and better tools than ever to analyze such data. However, despite these incredible advances in technology, the success rates in drug discovery are lower today than in the 1970s,” said Pradipta Ghosh, M.D., senior author of the study and professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine.
Full UCSD Press Release article
Potential Drug Target for Difficult-To-Treat Breast Cancer: RNA-Binding Proteins
7/2/2021
In their latest study, published July 2, 2021 in Molecular Cell , the UC San Diego School of Medicine team discovered in human cells and mouse models that RNA-binding proteins represent a new class of drug targets for cancers, including triple-negative breast cancer, a particularly difficult-to-treat cancer because it lacks most other molecular drug targets.
One RNA-binding protein in particular stood out: YTHDF2. When the researchers genetically removed YTHDF2 from human triple-negative breast tumors transplanted into mice, the tumors shrank approximately 10-fold in volume.
“We’re excited that RNA-binding proteins look like they could be new class of drug targets for cancer,” said senior author Gene Yeo, Ph.D., professor of cellular and molecular medicine at UC San Diego School of Medicine. “We’re not yet sure how easily druggable they are in this context, but we’ve built a solid framework to begin exploring them.”
Full UCSD Press Release article
How Cells 'Read' Artificial Ingredients Tossed into Genetic Recipe
6/17/2021
In a study published June 17, 2021 in Nature Chemical Biology , a team led by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego helped address these hurdles revealed that yeast cell machinery seamlessly “reads” unnatural X and Y ingredients introduced into the genetic code of living bacteria, the way it would A, C, T and G, and translates them into RNA, which could eventually be translated into proteins, the basis for just about every part of a cell. Unlike bacteria, yeast are eukaryotes, part of the same multicellular class of life as animals, plants and fungi. (A note about safety: These synthetic cells can’t survive without special liquid food provided in the lab.)
“Now we can see exactly how eukaryotic cell machinery interacts with unnatural base pairs, but it’s not perfect, there’s room to improve in terms of selectivity and efficiency,” said senior author Dong Wang, Ph.D., professor in the Skaggs School of Pharmacy. “It’s our hope that this finding will have a profound impact in the field by enabling the design of more effective, next-generation unnatural base pairs.”
Full UCSD Press Release article
AI Predicts How Patients with Viral Infections, Including COVID-19, Will Fare
6/11/2021
Researchers at University of California San Diego School of Medicine used an artificial intelligence (AI) algorithm to sift through terabytes of gene expression data — which genes are “on” or “off” during infection — to look for shared patterns in patients with past pandemic viral infections, including SARS, MERS and swine flu.
Two telltale signatures emerged from the study, published June 11, 2021 in eBiomedicine.
One, a set of 166 genes, reveals how the human immune system responds to viral infections. A second set of 20 signature genes predicts the severity of a patient’s disease. For example, the need to hospitalize or use a mechanical ventilator. The algorithm’s utility was validated using lung tissues collected at autopsies from deceased patients with COVID-19 and animal models of the infection.
“These viral pandemic-associated signatures tell us how a person’s immune system responds to a viral infection and how severe it might get, and that gives us a map for this and future pandemics,” said Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center.
Full UCSD Press Release article
GWAS and Single-Cell Epigenomics Provide Insights Into Type 1 Diabetes
5/21/2021
Researchers have combined two approaches—genome-wide association studies (GWAS) and single-cell epigenomics—to map the genetic underpinnings of type 1 diabetes (T1D), a condition that affects more than 1.6 million Americans. In doing so, they have made two significant contributions: 1) identified a predictive causal role for specific cell types in type 1 diabetes by supporting a role for the exocrine pancreas in the pathogenesis of T1D and 2) highlight the power of large-scale genome-wide association studies and single-cell epigenomics for understanding the cellular origins of complex disease.
This work is published in Nature, in the article, “Interpreting type 1 diabetes risk with genetics and single-cell epigenomics.”
“The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis,” noted co-author Maike Sander, M.D., professor in the departments of pediatrics and cellular and molecular medicine at UCSD School of Medicine and director of the Pediatric Diabetes Research Center. Sander added that the findings represent a major leap in understanding the causes of T1D and describes the work as “a landmark study.”
COVID-19 Could Increase Dementia, Other Brain Disorders for Decades to Come
2/10/2021
Scientists have recently found another reason to fear the brain effects of COVID-19. Although it was originally thought to be primarily a respiratory disease, it's now known to share some similarities with cancer in that it has the ability to metastisize, says Dr. Carlos Cordon-Cardo, director of the department of pathology at Mount Sinai Health System in New York City. It uses its famous spike-like proteins like grappling hooks to glom onto ACE2 receptors that are present in many types of human cells.
"The virus, even though it enters through the nose, can reach the lungs, the kidney, the liver, and now the brain because it goes into the blood vessels, it circulates, it travels into these tunnels," says Cordon-Cardo. "And then it can meet in a specific site to produce an extent of organ damage."
One alarming illustration of the potential destruction this might cause comes from the lab of Akiko Iwasaki, an immunobiologist at Yale. She and her collaborators created tiny colonies of stem-cell-derived neurons and the cells that support them, then exposed these "organoids" to the COVID-19 virus. It quickly infected some of the neurons, which then went into metabolic overdrive, and commandeered the cellular machinery to churn out copies of itself. In this frenzy of viral reproduction, the infected cells "sucked out all the oxygen" in the area, slowly starving the surrounding neurons of essential nutrients and sending them into a death spiral.
This "bystander" effect was also observed in experiments in brain organoids conducted by Alysson Muotri, Ph.D., a professor of pediatrics and cellular and molecular medicine at the University of California, San Diego. When he exposed his colonies of organoids to SARS-CoV-2, he found that the virus infected only a handful of neurons but had a dramatic impact. Within 48 hours, it had killed off 50 percent of the synaptic connections between various cells, which could wreak havoc in a living brain.
Recipient of $22 million from stem cell agency named to its board
1/12/2021
Larry Goldstein, Ph.D., a well-known stem cell researcher at the University of California, San Diego who has received nearly $22 million in awards from the California stem cell agency, today was named to its governing board.
It was the first time in the history of the 16-year-old agency that a scientist who has received agency awards has been appointed to the board of the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is officially known.
Full article on Capitol Weekly
Study: E-Cigarettes Trigger Inflammation in the Gut
1/7/2021
Touted by makers as a “healthy” alternative to traditional nicotine cigarettes, new research indicates the chemicals found in e-cigarettes disrupt the gut barrier and trigger inflammation in the body, potentially leading to a variety of health concerns.
In the study, published Jan. 5, 2021 in the journal iScience , Soumita Das, PhD, associate professor of pathology, and Pradipta Ghosh, M.D., professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center at UC San Diego School of Medicine, with colleagues, found that chronic use of nicotine-free e-cigarettes led to a “leaky gut,” in which microbes and other molecules seep out of the intestines, resulting in chronic inflammation. Such inflammation can contribute to a variety of diseases and conditions, including inflammatory bowel disease, dementia, certain cancers, atherosclerosis, liver fibrosis, diabetes and arthritis.
Full UCSD Press Release article
Brain Organoids Mimic Head Size Changes Associated with Type of Autism
8/25/2021
A study was led by Lilia Iakoucheva, PhD and Alysson Muorti, MD to study variations in the 16p11.2 region of the genome, which are associated with autism spectrum disorder. The team used brain organoids — tiny, 3D cellular models generated in the lab from people with 16p11.2 variations.
These organoids revealed new information about the molecular mechanisms that malfunction when the 16p11.2 region of the genome is disrupted. RhoA — a protein that plays a big part in many basic cellular functions, such as development and movement — was found to be more active in both 16p11.2-deleted and 16p11.2-duplicated organoids than it is in organoids without these variations. Interestingly, inhibiting this protein in autism-like organoids, caused the neuronal migration to be restored to levels seen in the control organoids. "Our work opens the possibility to therapeutically manipulate the RhoA pathway, which can potentially help millions of patients," said Alysson Muorti, MD .
These organoids revealed new information about the molecular mechanisms that malfunction when the 16p11.2 region of the genome is disrupted. RhoA — a protein that plays a big part in many basic cellular functions, such as development and movement — was found to be more active in both 16p11.2-deleted and 16p11.2-duplicated organoids than it is in organoids without these variations. Interestingly, inhibiting this protein in autism-like organoids, caused the neuronal migration to be restored to levels seen in the control organoids. "Our work opens the possibility to therapeutically manipulate the RhoA pathway, which can potentially help millions of patients," said Alysson Muorti, MD .
Life’s Edge by Carl Zimmer review – what does it mean to be alive?
8/21/2021
At a medical research laboratory in California, Alysson Muotri, PhD has used chemistry to change skin cells into neurons, which have multiplied to form “organoids” – globes of interconnected brain cells. The organoids can expand to hundreds of thousands of cells, live for years, and even produce detectable patterns of brain waves, like those of premature babies. “The most incredible thing is that they build themselves,” says Muotri. He even wonders whether they could one day become conscious.
8/19/2021
A research team, led by senior author Pradipta Ghosh, MD, professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, found that GIV — a member of the G protein family that serve as molecular switches inside cells, transmitting and fine-tuning signals — regulates the activity of enzymes that turn on and turn off the processes of capacitation and AR in mammalian reproduction.
“The findings demonstrate how GIV orchestrates distinct signaling programs in sperm that separated by space and time, effectively supporting capacitation while inhibiting premature AR,” said Ghosh. “As a result, GIV plays an essential role in male fertility.”
“The findings demonstrate how GIV orchestrates distinct signaling programs in sperm that separated by space and time, effectively supporting capacitation while inhibiting premature AR,” said Ghosh. “As a result, GIV plays an essential role in male fertility.”
Unchanging Rules of Gene Expression Could Improve Drug Approval Odds
8/13/2021
Network theory holds that everything is connected, including people (e.g., Facebook), but few will have many connections, and most will have few. The same rule applies if the “nodes” happen to be human cells, genomes, proteomes, or transcriptomes, says Pradipta Ghosh, MD, professor in the departments of medicine and cellular and molecular medicine at the University of California San Diego (UCSD) School of Medicine as well as cofounder of the Institute for Network Medicine (iNetMed) endeavoring to chart the most powerful connections.
AI Helps Predict Winners and Losers in Clinical Trials
8/3/2021
Somewhere between assessing safety in healthy volunteers and testing effectiveness in hundreds to thousands of patients, most drugs in clinical trials fail. Pradipta Ghosh, MD, and her colleagues at the University of California, San Diego (UCSD) School of Medicine have developed a blueprint that they hope will end this disheartening phenomenon.
Ghosh and her team used artificial intelligence (AI) to discern patterns in gene expression datasets that apply to all patients with inflammatory bowel disease (IBD) and to identify clinically actionable drug targets. After testing drug candidates in mouse models, typically the final step before clinical trials, the researchers conducted a “Phase 0” clinical trial. Using patient-derived organoid models, they determined whether any observed therapeutic effect resulted from the candidate drug or confounding variables.
Ghosh and her team used artificial intelligence (AI) to discern patterns in gene expression datasets that apply to all patients with inflammatory bowel disease (IBD) and to identify clinically actionable drug targets. After testing drug candidates in mouse models, typically the final step before clinical trials, the researchers conducted a “Phase 0” clinical trial. Using patient-derived organoid models, they determined whether any observed therapeutic effect resulted from the candidate drug or confounding variables.
Artificial Intelligence Could Be New Blueprint for Precision Drug Discovery
7/12/2021
Writing in the July 12, 2021 online issue of Nature Communications , researchers at University of California San Diego School of Medicine describe a new approach that uses machine learning to hunt for disease targets and then predicts whether a drug is likely to receive FDA approval.
The study's findings could measurably change how researchers sift through big data to find meaningful information with significant benefit to patients, the pharmaceutical industry and the nation’s health care systems.
“Academic labs and pharmaceutical and biotech companies have access to unlimited amounts of ‘big data’ and better tools than ever to analyze such data. However, despite these incredible advances in technology, the success rates in drug discovery are lower today than in the 1970s,” said Pradipta Ghosh, MD, senior author of the study and professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine.
The study's findings could measurably change how researchers sift through big data to find meaningful information with significant benefit to patients, the pharmaceutical industry and the nation’s health care systems.
“Academic labs and pharmaceutical and biotech companies have access to unlimited amounts of ‘big data’ and better tools than ever to analyze such data. However, despite these incredible advances in technology, the success rates in drug discovery are lower today than in the 1970s,” said Pradipta Ghosh, MD, senior author of the study and professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine.
Potential Drug Target for Difficult-To-Treat Breast Cancer: RNA-Binding Proteins
7/2/2021
In their latest study, published July 2, 2021 in Molecular Cell , the UC San Diego School of Medicine team discovered in human cells and mouse models that RNA-binding proteins represent a new class of drug targets for cancers, including triple-negative breast cancer, a particularly difficult-to-treat cancer because it lacks most other molecular drug targets.
One RNA-binding protein in particular stood out: YTHDF2. When the researchers genetically removed YTHDF2 from human triple-negative breast tumors transplanted into mice, the tumors shrank approximately 10-fold in volume.
“We’re excited that RNA-binding proteins look like they could be new class of drug targets for cancer,” said senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine. “We’re not yet sure how easily druggable they are in this context, but we’ve built a solid framework to begin exploring them.”
One RNA-binding protein in particular stood out: YTHDF2. When the researchers genetically removed YTHDF2 from human triple-negative breast tumors transplanted into mice, the tumors shrank approximately 10-fold in volume.
“We’re excited that RNA-binding proteins look like they could be new class of drug targets for cancer,” said senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine. “We’re not yet sure how easily druggable they are in this context, but we’ve built a solid framework to begin exploring them.”
How Cells 'Read' Artificial Ingredients Tossed into Genetic Recipe
6/17/2021
In a study published June 17, 2021 in Nature Chemical Biology , a team led by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego helped address these hurdles revealed that yeast cell machinery seamlessly “reads” unnatural X and Y ingredients introduced into the genetic code of living bacteria, the way it would A, C, T and G, and translates them into RNA, which could eventually be translated into proteins, the basis for just about every part of a cell. Unlike bacteria, yeast are eukaryotes, part of the same multicellular class of life as animals, plants and fungi. (A note about safety: These synthetic cells can’t survive without special liquid food provided in the lab.)
“Now we can see exactly how eukaryotic cell machinery interacts with unnatural base pairs, but it’s not perfect, there’s room to improve in terms of selectivity and efficiency,” said senior author Dong Wang, PhD, professor in the Skaggs School of Pharmacy. “It’s our hope that this finding will have a profound impact in the field by enabling the design of more effective, next-generation unnatural base pairs.”
“Now we can see exactly how eukaryotic cell machinery interacts with unnatural base pairs, but it’s not perfect, there’s room to improve in terms of selectivity and efficiency,” said senior author Dong Wang, PhD, professor in the Skaggs School of Pharmacy. “It’s our hope that this finding will have a profound impact in the field by enabling the design of more effective, next-generation unnatural base pairs.”
AI Predicts How Patients with Viral Infections, Including COVID-19, Will Fare
6/11/2021
Researchers at University of California San Diego School of Medicine used an artificial intelligence (AI) algorithm to sift through terabytes of gene expression data — which genes are “on” or “off” during infection — to look for shared patterns in patients with past pandemic viral infections, including SARS, MERS and swine flu.
Two telltale signatures emerged from the study, published June 11, 2021 in eBiomedicine .
One, a set of 166 genes, reveals how the human immune system responds to viral infections. A second set of 20 signature genes predicts the severity of a patient’s disease. For example, the need to hospitalize or use a mechanical ventilator. The algorithm’s utility was validated using lung tissues collected at autopsies from deceased patients with COVID-19 and animal models of the infection.
“These viral pandemic-associated signatures tell us how a person’s immune system responds to a viral infection and how severe it might get, and that gives us a map for this and future pandemics,” said Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center.
Two telltale signatures emerged from the study, published June 11, 2021 in eBiomedicine .
One, a set of 166 genes, reveals how the human immune system responds to viral infections. A second set of 20 signature genes predicts the severity of a patient’s disease. For example, the need to hospitalize or use a mechanical ventilator. The algorithm’s utility was validated using lung tissues collected at autopsies from deceased patients with COVID-19 and animal models of the infection.
“These viral pandemic-associated signatures tell us how a person’s immune system responds to a viral infection and how severe it might get, and that gives us a map for this and future pandemics,” said Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center.
GWAS and Single-Cell Epigenomics Provide Insights Into Type 1 Diabetes
5/21/2021
Researchers have combined two approaches—genome-wide association studies (GWAS) and single-cell epigenomics—to map the genetic underpinnings of type 1 diabetes (T1D), a condition that affects more than 1.6 million Americans. In doing so, they have made two significant contributions: 1) identified a predictive causal role for specific cell types in type 1 diabetes by supporting a role for the exocrine pancreas in the pathogenesis of T1D and 2) highlight the power of large-scale genome-wide association studies and single-cell epigenomics for understanding the cellular origins of complex disease.
This work is published in Nature, in the article, “Interpreting type 1 diabetes risk with genetics and single-cell epigenomics.”
“The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis,” noted co-author Maike Sander, MD, professor in the departments of pediatrics and cellular and molecular medicine at UCSD School of Medicine and director of the Pediatric Diabetes Research Center. Sander added that the findings represent a major leap in understanding the causes of T1D and describes the work as “a landmark study.”
This work is published in Nature, in the article, “Interpreting type 1 diabetes risk with genetics and single-cell epigenomics.”
“The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis,” noted co-author Maike Sander, MD, professor in the departments of pediatrics and cellular and molecular medicine at UCSD School of Medicine and director of the Pediatric Diabetes Research Center. Sander added that the findings represent a major leap in understanding the causes of T1D and describes the work as “a landmark study.”
Genetic Tools Help Identify a Cellular Culprit for Type 1 Diabetes
5/19/2021
By mapping its genetic underpinnings, researchers at University of California San Diego School of Medicine have identified a predictive causal role for specific cell types in type 1 diabetes, a condition that affects more than 1.6 million Americans.
The findings are published in the May 19, 2021 online issue of Nature .
Co-author Maike Sander, MD, professor in the departments of Pediatrics and Cellular and Molecular Medicine at UC San Diego School of Medicine and director of the Pediatric Diabetes Research Center, said the findings represent a major leap in understanding the causes of type 1 diabetes. She described the work as “a landmark study.”
“The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis.”
The findings are published in the May 19, 2021 online issue of Nature .
Co-author Maike Sander, MD, professor in the departments of Pediatrics and Cellular and Molecular Medicine at UC San Diego School of Medicine and director of the Pediatric Diabetes Research Center, said the findings represent a major leap in understanding the causes of type 1 diabetes. She described the work as “a landmark study.”
“The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis.”
Do other animals get heart attacks?
5/9/2021
Every 40 seconds, someone in the U.S. has a heart attack, which amounts to about 805,000 heart attacks every year. Of course, this statistic applies only to humans. But what about other animals — do they also experience this debilitating and potentially deadly condition?
Not even chimpanzees in captivity, which are not only closely related to humans but also share similar risk factors for heart disease, such as physical inactivity and high cholesterol levels, have heart attacks, as UCSD husband and wife duo Dr. Nissi Varki and Dr. Ajit Varki, MD, PhD pointed out in a 2009 paper in the journal Evolutionary Applications.
Rather than asking why other animals don't get heart attacks, it might make more sense to ask why humans do.
Not even chimpanzees in captivity, which are not only closely related to humans but also share similar risk factors for heart disease, such as physical inactivity and high cholesterol levels, have heart attacks, as UCSD husband and wife duo Dr. Nissi Varki and Dr. Ajit Varki, MD, PhD pointed out in a 2009 paper in the journal Evolutionary Applications.
Rather than asking why other animals don't get heart attacks, it might make more sense to ask why humans do.
Failure of Genetic Therapies for Huntington’s Devastates Community
5/7/2021
Two pharmaceutical companies have halted clinical trials of gene-targeting therapies for Huntington’s disease (HD), following the drugs’ disappointing performance.
Researchers had hoped that the treatments—known as antisense oligonucleotides (ASOs)—would be a game changer for HD, an incurable genetic condition that affects cognition, behaviour and movement. But back-to-back announcements from Roche, headquartered in Basel, Switzerland, and Wave Life Sciences, in Cambridge, Massachusetts, have dealt a crushing blow to those affected by the disease.
Although hopes for a genetic therapy for Huntington’s have been dashed—at least temporarily—researchers are eagerly awaiting the results of a large phase III trial of an ASO for motor neuron disease (amyotrophic lateral sclerosis, or ALS). What happened with tominersen is not a cause for concern for this trial, says Don Cleveland, PhD, a neuroscientist at the University of California, San Diego, and consultant for Ionis Pharmaceuticals in Carlsbad, California, which developed both this drug and tominersen. This is because, unlike in the early trials for tominersen, the phase I/II trial of the ALS drug did show signs of slowing the disease’s progression in those with a rapidly advancing form of ALS.
“I think we have reason for guarded optimism,” Cleveland says.
Researchers had hoped that the treatments—known as antisense oligonucleotides (ASOs)—would be a game changer for HD, an incurable genetic condition that affects cognition, behaviour and movement. But back-to-back announcements from Roche, headquartered in Basel, Switzerland, and Wave Life Sciences, in Cambridge, Massachusetts, have dealt a crushing blow to those affected by the disease.
Although hopes for a genetic therapy for Huntington’s have been dashed—at least temporarily—researchers are eagerly awaiting the results of a large phase III trial of an ASO for motor neuron disease (amyotrophic lateral sclerosis, or ALS). What happened with tominersen is not a cause for concern for this trial, says Don Cleveland, PhD, a neuroscientist at the University of California, San Diego, and consultant for Ionis Pharmaceuticals in Carlsbad, California, which developed both this drug and tominersen. This is because, unlike in the early trials for tominersen, the phase I/II trial of the ALS drug did show signs of slowing the disease’s progression in those with a rapidly advancing form of ALS.
“I think we have reason for guarded optimism,” Cleveland says.
Researchers Read the Sugary ‘Language’ on Cell Surfaces
5/3/2021
Scientists may be verging on a breakthrough in the understanding of glycans and glycobiology. After analyzing a comprehensive data set of glycan structures and their known interactions, researchers at Harvard University and the Massachusetts Institute of Technology found a shared structural “language” that all organisms use when making glycans, like a municipal building code that ensures consistent, compatible architecture. The researchers have released a set of online tools that anyone can use to analyze glycan structures and functions.
To Ajit Varki, MD, PhD, glycans are still one of the greatest enigmas of the biological universe. They’re “actually so prominent, they’re a major component of biomass on the planet.” In fact, glycans make up most of the organic matter by mass: Cellulose and chitin, the major building material of arthropod exoskeletons and fungal cell walls, are nature’s two most abundant organic polymers. And yet in contrast with the overabundance of glycans, “this whole field has been left behind,” Varki said.
To Ajit Varki, MD, PhD, glycans are still one of the greatest enigmas of the biological universe. They’re “actually so prominent, they’re a major component of biomass on the planet.” In fact, glycans make up most of the organic matter by mass: Cellulose and chitin, the major building material of arthropod exoskeletons and fungal cell walls, are nature’s two most abundant organic polymers. And yet in contrast with the overabundance of glycans, “this whole field has been left behind,” Varki said.
Who is Making Asian American Pacific Islander History in 2021: The GMA Inspiration List
5/1/2021
Asian American and Pacific Islander Heritage Month celebrates the contributions of one of the fastest-growing groups of people living in the United States. Asian Americans and Pacific Islanders contain multitudes. They are a global community with a homegrown and unique perspective on America.
As a scientist, technologist and entrepreneur who masterfully bridges disciplines to accelerate progress in science and medicine, Dr. Gene Yeo, PhD is exactly the type of outside-the-box thinker Mark [Zuckerberg] and I hoped we’d have the chance to work with through our philanthropic organization, the Chan Zuckerberg Initiative (CZI). Dr. Yeo, a professor of cellular and molecular Medicine at the University of California, San Diego, is an integral part of CZI’s Neurodegeneration Challenge Network, where he collaborates with a diverse group of scientists, clinicians and engineers to understand disorders like ALS and how technology could help answer the most challenging questions. Dr. Yeo is also someone who stays close to the work in service of his local community. In the early days of the pandemic, Dr. Yeo founded the San Diego COVID-19 Research Enterprise Network (SCREEN), a community-focused effort that set up testing sites across the city and galvanized early research coordination. SCREEN has since grown to more than 800 local researchers. He later helped found the San Diego Epidemiology and Research for COVID Health, which conducted a 12,000-person scientific study to learn more about transmission of the virus and better protect his neighbors. I also love that Dr. Yeo -- himself a fast-rising star in science -- is at the forefront of training and mentoring the next generation of scientists. He is a faculty founder of the Diversity and Science Lecture series at UCSD, centering and elevating the experience of graduate students and postdocs of color, while also celebrating their scientific achievements.
As a scientist, technologist and entrepreneur who masterfully bridges disciplines to accelerate progress in science and medicine, Dr. Gene Yeo, PhD is exactly the type of outside-the-box thinker Mark [Zuckerberg] and I hoped we’d have the chance to work with through our philanthropic organization, the Chan Zuckerberg Initiative (CZI). Dr. Yeo, a professor of cellular and molecular Medicine at the University of California, San Diego, is an integral part of CZI’s Neurodegeneration Challenge Network, where he collaborates with a diverse group of scientists, clinicians and engineers to understand disorders like ALS and how technology could help answer the most challenging questions. Dr. Yeo is also someone who stays close to the work in service of his local community. In the early days of the pandemic, Dr. Yeo founded the San Diego COVID-19 Research Enterprise Network (SCREEN), a community-focused effort that set up testing sites across the city and galvanized early research coordination. SCREEN has since grown to more than 800 local researchers. He later helped found the San Diego Epidemiology and Research for COVID Health, which conducted a 12,000-person scientific study to learn more about transmission of the virus and better protect his neighbors. I also love that Dr. Yeo -- himself a fast-rising star in science -- is at the forefront of training and mentoring the next generation of scientists. He is a faculty founder of the Diversity and Science Lecture series at UCSD, centering and elevating the experience of graduate students and postdocs of color, while also celebrating their scientific achievements.
COVID-19 Could Increase Dementia, Other Brain Disorders for Decades to Come
2/10/2021
Scientists have recently found another reason to fear the brain effects of COVID-19. Although it was originally thought to be primarily a respiratory disease, it's now known to share some similarities with cancer in that it has the ability to metastisize, says Dr. Carlos Cordon-Cardo, director of the department of pathology at Mount Sinai Health System in New York City. It uses its famous spike-like proteins like grappling hooks to glom onto ACE2 receptors that are present in many types of human cells.
"The virus, even though it enters through the nose, can reach the lungs, the kidney, the liver, and now the brain because it goes into the blood vessels, it circulates, it travels into these tunnels," says Cordon-Cardo. "And then it can meet in a specific site to produce an extent of organ damage."
One alarming illustration of the potential destruction this might cause comes from the lab of Akiko Iwasaki, an immunobiologist at Yale. She and her collaborators created tiny colonies of stem-cell-derived neurons and the cells that support them, then exposed these "organoids" to the COVID-19 virus. It quickly infected some of the neurons, which then went into metabolic overdrive, and commandeered the cellular machinery to churn out copies of itself. In this frenzy of viral reproduction, the infected cells "sucked out all the oxygen" in the area, slowly starving the surrounding neurons of essential nutrients and sending them into a death spiral.
This "bystander" effect was also observed in experiments in brain organoids conducted by Alysson Muotri, PhD, a professor of pediatrics and cellular and molecular medicine at the University of California, San Diego. When he exposed his colonies of organoids to SARS-CoV-2, he found that the virus infected only a handful of neurons but had a dramatic impact. Within 48 hours, it had killed off 50 percent of the synaptic connections between various cells, which could wreak havoc in a living brain.
"The virus, even though it enters through the nose, can reach the lungs, the kidney, the liver, and now the brain because it goes into the blood vessels, it circulates, it travels into these tunnels," says Cordon-Cardo. "And then it can meet in a specific site to produce an extent of organ damage."
One alarming illustration of the potential destruction this might cause comes from the lab of Akiko Iwasaki, an immunobiologist at Yale. She and her collaborators created tiny colonies of stem-cell-derived neurons and the cells that support them, then exposed these "organoids" to the COVID-19 virus. It quickly infected some of the neurons, which then went into metabolic overdrive, and commandeered the cellular machinery to churn out copies of itself. In this frenzy of viral reproduction, the infected cells "sucked out all the oxygen" in the area, slowly starving the surrounding neurons of essential nutrients and sending them into a death spiral.
This "bystander" effect was also observed in experiments in brain organoids conducted by Alysson Muotri, PhD, a professor of pediatrics and cellular and molecular medicine at the University of California, San Diego. When he exposed his colonies of organoids to SARS-CoV-2, he found that the virus infected only a handful of neurons but had a dramatic impact. Within 48 hours, it had killed off 50 percent of the synaptic connections between various cells, which could wreak havoc in a living brain.
Recipient of $22 million from stem cell agency named to its board
1/12/2021
Larry Goldstein, PhD, a well-known stem cell researcher at the University of California, San Diego who has received nearly $22 million in awards from the California stem cell agency, today was named to its governing board.
It was the first time in the history of the 16-year-old agency that a scientist who has received agency awards has been appointed to the board of the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is officially known.
It was the first time in the history of the 16-year-old agency that a scientist who has received agency awards has been appointed to the board of the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is officially known.
Study: E-Cigarettes Trigger Inflammation in the Gut
1/7/2021
Touted by makers as a “healthy” alternative to traditional nicotine cigarettes, new research indicates the chemicals found in e-cigarettes disrupt the gut barrier and trigger inflammation in the body, potentially leading to a variety of health concerns.
In the study, published Jan. 5, 2021 in the journal iScience , Soumita Das, PhD, associate professor of pathology, and Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center at UC San Diego School of Medicine, with colleagues, found that chronic use of nicotine-free e-cigarettes led to a “leaky gut,” in which microbes and other molecules seep out of the intestines, resulting in chronic inflammation. Such inflammation can contribute to a variety of diseases and conditions, including inflammatory bowel disease, dementia, certain cancers, atherosclerosis, liver fibrosis, diabetes and arthritis.
In the study, published Jan. 5, 2021 in the journal iScience , Soumita Das, PhD, associate professor of pathology, and Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center at UC San Diego School of Medicine, with colleagues, found that chronic use of nicotine-free e-cigarettes led to a “leaky gut,” in which microbes and other molecules seep out of the intestines, resulting in chronic inflammation. Such inflammation can contribute to a variety of diseases and conditions, including inflammatory bowel disease, dementia, certain cancers, atherosclerosis, liver fibrosis, diabetes and arthritis.
2020
Breaking Bad: How Shattered Chromosomes Make Cancer Cells Drug-Resistant
12/23/2020
Chromothripsis is a catastrophic mutational event in a cell’s history that involves massive rearrangement of its genome, as opposed to a gradual acquisition of rearrangements and mutations over time. Genomic rearrangement is a key characteristic of many cancers, allowing mutated cells to grow or grow faster, unaffected by anti-cancer therapies.
“These rearrangements can occur in a single step,” said first author Ofer Shoshani, PhD, a postdoctoral fellow in the lab of the paper’s co-senior author Don Cleveland, PhD, professor of medicine, neurosciences and cellular and molecular medicine at UC San Diego School of Medicine.
“These rearrangements can occur in a single step,” said first author Ofer Shoshani, PhD, a postdoctoral fellow in the lab of the paper’s co-senior author Don Cleveland, PhD, professor of medicine, neurosciences and cellular and molecular medicine at UC San Diego School of Medicine.
Human Evolution Could Be to Blame for Being Prone to Cancer, Study Says
12/15/2020
Recent research reveals that a human-specific evolutionary genetic alteration could be partially responsible for growing cancer cells.
Research performed by researchers at the University of California (UC), San Diego, School of Medicine and Moores Cancer Center helps understand why their report was published in FASEB BioAdvances.
Senior author Ajit Varki, MD, distinguished professor at the UC San Diego School of Medicine and Moores Cancer Center, said that the cancer cell SIGLEC12 gene creates a mutation that destroys the immune response the capacity to discriminate between 'self' and invading microbes.
Research performed by researchers at the University of California (UC), San Diego, School of Medicine and Moores Cancer Center helps understand why their report was published in FASEB BioAdvances.
Senior author Ajit Varki, MD, distinguished professor at the UC San Diego School of Medicine and Moores Cancer Center, said that the cancer cell SIGLEC12 gene creates a mutation that destroys the immune response the capacity to discriminate between 'self' and invading microbes.
Human Evolution Could Be to Blame for Being Prone to Cancer, Study Says
12/15/2020
Recent research reveals that a human-specific evolutionary genetic alteration could be partially responsible for growing cancer cells.
Research performed by researchers at the University of California (UC), San Diego, School of Medicine and Moores Cancer Center helps understand why their report was published in FASEB BioAdvances.
Senior author Ajit Varki, MD, distinguished professor at the UC San Diego School of Medicine and Moores Cancer Center, said that the cancer cell SIGLEC12 gene creates a mutation that destroys the immune response the capacity to discriminate between 'self' and invading microbes. The body wanted, then to get rid of it.
Research performed by researchers at the University of California (UC), San Diego, School of Medicine and Moores Cancer Center helps understand why their report was published in FASEB BioAdvances.
Senior author Ajit Varki, MD, distinguished professor at the UC San Diego School of Medicine and Moores Cancer Center, said that the cancer cell SIGLEC12 gene creates a mutation that destroys the immune response the capacity to discriminate between 'self' and invading microbes. The body wanted, then to get rid of it.
Lab-Grown Human Brain Organoids Mimic an Autism Spectrum Disorder, Help Test Treatments
12/8/2020
Researchers at University of California San Diego School of Medicine and Sanford Consortium for Regenerative Medicine recently used stem cell-derived brain organoids — also called “mini-brains” — that lack the functional MECP2 gene to better study Rett Syndrom, an autism disorder.
“The gene mutation that causes Rett syndrome was discovered decades ago, but progress on treating it has lagged, at least in part because mouse model studies haven’t translated to humans,” said senior author Alysson R. Muotri, PhD, professor of pediatrics and cellular and molecular medicine at UC San Diego School of Medicine. “This study was driven by the need for a model that better mimics the human brain.”
“The gene mutation that causes Rett syndrome was discovered decades ago, but progress on treating it has lagged, at least in part because mouse model studies haven’t translated to humans,” said senior author Alysson R. Muotri, PhD, professor of pediatrics and cellular and molecular medicine at UC San Diego School of Medicine. “This study was driven by the need for a model that better mimics the human brain.”
Evolution May Be to Blame for High Risk of Advanced Cancers in Humans
12/8/2020
A recent study led by researchers at University of California San Diego School of Medicine and Moores Cancer Center helps explain why umans are particularly prone to developing advanced carcinomas.
“At some point during human evolution, the SIGLEC12 gene — and more specifically, the Siglec-12 protein it produces as part of the immune system — suffered a mutation that eliminated its ability to distinguish between ‘self’ and invading microbes, so the body needed to get rid of it,” said senior author Ajit Varki, MD, Distinguished Professor at UC San Diego School of Medicine and Moores Cancer Center.
“At some point during human evolution, the SIGLEC12 gene — and more specifically, the Siglec-12 protein it produces as part of the immune system — suffered a mutation that eliminated its ability to distinguish between ‘self’ and invading microbes, so the body needed to get rid of it,” said senior author Ajit Varki, MD, Distinguished Professor at UC San Diego School of Medicine and Moores Cancer Center.
California Approves Billions for Stem-Cell Research
11/12/2020
California voters have granted the state's nearly broke first-of-its-kind stem-cell research program a desperately needed $5.5 billion cash infusion.
Supporters said new money was needed to keep running promising clinical trials involving the use of stem cells to treat cancer, Alzheimer’s disease, Parkinson’s disease, paralysis, autoimmune diseases and other conditions.
“Trials that use human embryonic-derived stem cells to treat diabetes, to treat blindness and to treat spinal cord injury, those trials are early but already showing signs of patient benefit. Losing those trials would be a terrible tragedy for those patients.” said Professor Larry Goldstein, Ph.D., director of the University of California, San Diego’s stem cell research program.
Supporters said new money was needed to keep running promising clinical trials involving the use of stem cells to treat cancer, Alzheimer’s disease, Parkinson’s disease, paralysis, autoimmune diseases and other conditions.
“Trials that use human embryonic-derived stem cells to treat diabetes, to treat blindness and to treat spinal cord injury, those trials are early but already showing signs of patient benefit. Losing those trials would be a terrible tragedy for those patients.” said Professor Larry Goldstein, Ph.D., director of the University of California, San Diego’s stem cell research program.
Measure for $5.5 Billion in Stem Cell Funding Leads Narrowly
11/4/2020
With about 11 million votes counted, approval for Proposition 14 was ahead 51% to 49% late Tuesday night.
If the proposition passes it would approve a bond sale that would bail out the California Institute for Regenerative Medicine, which was created by a similar $3 billion bond measure in 2014 but is now nearly broke. Millions more votes remained to be counted.
With dozens of clinical trials involving the use of stem cells to treat cancer, Alzheimer's disease, Parkinson's disease, paralysis, autoimmune diseases and other conditions underway at universities across California, supporters say it is crucial to keep that money flowing.
Professor Larry Goldstein, Ph.D., who directs the stem cell research program at the University of California, San Diego, called the early results “very encouraging.”
If the proposition passes it would approve a bond sale that would bail out the California Institute for Regenerative Medicine, which was created by a similar $3 billion bond measure in 2014 but is now nearly broke. Millions more votes remained to be counted.
With dozens of clinical trials involving the use of stem cells to treat cancer, Alzheimer's disease, Parkinson's disease, paralysis, autoimmune diseases and other conditions underway at universities across California, supporters say it is crucial to keep that money flowing.
Professor Larry Goldstein, Ph.D., who directs the stem cell research program at the University of California, San Diego, called the early results “very encouraging.”
Opinion: Proposition 14 Could Save the Life of Someone You Love
10/30/2020
A yes vote on Proposition 14 is crucial to continue the pace of medical research and our state’s journey to save lives. For millions of Californians who live with a chronic disease or condition, and who need new therapies, this may be their last hope. Advancing medical progress to fight devastating and life-threatening diseases and conditions is an urgent matter now.
Experts Fear Lab-Grown Brains Will Become Sentient, Which Is Upsetting
10/28/2020
A thought-provoking new article poses some hugely important scientific questions: Could brain cells initiated and grown in a lab become sentient? What would that look like, and how could scientists test for it? And would a sentient, lab-grown brain “organoid” have some kind of rights?
In Nature, reporter Sara Reardon explains a specific area where the debate over sentience gets very heated, very quickly. In August 2019, Alysson Muotri, Ph.D., a professor in the Departments of Pediatrics and Cellular & Molecular Medicine at the University of California, San Diego, published a paper with colleagues in Cell Stem Cell on the "creation of human brain organoids that produced coordinated waves of activity, resembling those seen in premature babies."
In Nature, reporter Sara Reardon explains a specific area where the debate over sentience gets very heated, very quickly. In August 2019, Alysson Muotri, Ph.D., a professor in the Departments of Pediatrics and Cellular & Molecular Medicine at the University of California, San Diego, published a paper with colleagues in Cell Stem Cell on the "creation of human brain organoids that produced coordinated waves of activity, resembling those seen in premature babies."
Confusion, stroke, memory loss: How coronavirus affects the brain
10/25/2020
CONFUSION, loss of smell, behavioural changes – these are some of the neurological symptoms of the novel coronavirus as witnessed in Covid-19 patients lately.
Some people, hospitalised with Covid-19, experience delirium – they are confused, disorientated and agitated. Stroke, brain haemorrhage and memory loss are some other serious impacts coronavirus has on few patients.
As Alysson Muotri, Ph.D., a neuroscientist at the University of California, San Diego, put it in science journal Nature, “The neurological symptoms are only becoming more and more scary”.
Some people, hospitalised with Covid-19, experience delirium – they are confused, disorientated and agitated. Stroke, brain haemorrhage and memory loss are some other serious impacts coronavirus has on few patients.
As Alysson Muotri, Ph.D., a neuroscientist at the University of California, San Diego, put it in science journal Nature, “The neurological symptoms are only becoming more and more scary”.
California Voters to Decide Future of Stem Cell Funding Agency
10/24/2020
Over the course of its 16-year existence, the California Institute for Regenerative Medicine in Oakland has helped transform its state into an innovation hub of stem cell science. But CIRM announced last year that its first $3 billion of funding has dried up, and now it’s up to voters to decide on November 3 whether to give the agency a second life.
Larry Goldstein, Ph.D., a stem cell scientist at the University of California, San Diego, says the agency has filled a critical funding gap by supporting the progression of interesting scientific discoveries to late-stage clinical trials. Using CIRM funding—Goldstein has received some $21 million as a principal investigator, according to the agency’s website—he’s created an in vitro model of hereditary forms of Alzheimer’s disease using iPS cells and used it to identify drug candidates that target pathological processes in the disease. He says the project was “too risky” to attract NIH funding, but CIRM funded “most of the work, up to getting it to the point where we can get it into trials.”
Larry Goldstein, Ph.D., a stem cell scientist at the University of California, San Diego, says the agency has filled a critical funding gap by supporting the progression of interesting scientific discoveries to late-stage clinical trials. Using CIRM funding—Goldstein has received some $21 million as a principal investigator, according to the agency’s website—he’s created an in vitro model of hereditary forms of Alzheimer’s disease using iPS cells and used it to identify drug candidates that target pathological processes in the disease. He says the project was “too risky” to attract NIH funding, but CIRM funded “most of the work, up to getting it to the point where we can get it into trials.”
Conservatives confront moral dilemma of vaccines and treatments derived from fetal tissue cells
10/18/2020
The race to develop vaccines and treatments for COVID-19 has newly highlighted a longstanding dilemma for religious conservatives: much of the cutting-edge research relies on the use of material derived from human fetal tissue -- something they have spent years fighting against.
"President Trump has been an outspoken opponent of fetal tissue research -- and he used it. I just think it's incredibly hypocritical across the board," Dr. Lawrence Goldstein, Ph.D., fetal tissue ethics board member and senior faculty member at the University of California at San Diego.
"President Trump has been an outspoken opponent of fetal tissue research -- and he used it. I just think it's incredibly hypocritical across the board," Dr. Lawrence Goldstein, Ph.D., fetal tissue ethics board member and senior faculty member at the University of California at San Diego.
Protein that Keeps Immune System from Freaking Out Could Form Basis for New Therapeutics
10/14/2020
The immune response to infections is a delicate balance. We need just enough action to clear away the offending bacteria or viruses, but not so much that our own bodies suffer collateral damage.
Macrophages are immune cells at the front line, detecting pathogens and kicking off an inflammatory response when needed. Understanding how macrophages determine when to go all-out and when to keep calm is key to finding new ways to strike the right balance — particularly in cases where inflammation goes too far, such as in sepsis, colitis and other autoimmune disorders.
“When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria,” said senior author Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center. “It’s similar to what we’re seeing now with dangerous ‘cytokine storms’ that can result from infection with the novel coronavirus SARS-CoV-2.
Macrophages are immune cells at the front line, detecting pathogens and kicking off an inflammatory response when needed. Understanding how macrophages determine when to go all-out and when to keep calm is key to finding new ways to strike the right balance — particularly in cases where inflammation goes too far, such as in sepsis, colitis and other autoimmune disorders.
“When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria,” said senior author Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center. “It’s similar to what we’re seeing now with dangerous ‘cytokine storms’ that can result from infection with the novel coronavirus SARS-CoV-2.
Prop. 14 Asks Voters To OK $5.5 Billion In Bonds For Additional Stem Cell Research
10/13/2020
roposition 14 asks California voters to issue $5.5 billion in bonds to continue financing the state’s stem cell research institute. Supporters want the money to continue the science, but critics say the science didn’t do enough the first time.
In 2004, under the Bush Administration, California voters decided to issue $3 billion in bonds so the state could create the California Institute for Regenerative Medicine, or CIRM. This was at a time when the federal government closed off funding for stem cell research for religious reasons.
Now that money for CIRM has dried up, and supporters such as UC San Diego Health neuroscientist Larry Goldstein, PhD, say voters should agree to provide more money.
In 2004, under the Bush Administration, California voters decided to issue $3 billion in bonds so the state could create the California Institute for Regenerative Medicine, or CIRM. This was at a time when the federal government closed off funding for stem cell research for religious reasons.
Now that money for CIRM has dried up, and supporters such as UC San Diego Health neuroscientist Larry Goldstein, PhD, say voters should agree to provide more money.
Prop. 14 Asks Voters To OK $5.5 Billion In Bonds For Additional Stem Cell Research
10/13/2020
Proposition 14 asks California voters to issue $5.5 billion in bonds to continue financing the state’s stem cell research institute. Supporters want the money to continue the science, but critics say the science didn’t do enough the first time.
In 2004, under the Bush Administration, California voters decided to issue $3 billion in bonds so the state could create the California Institute for Regenerative Medicine, or CIRM. This was at a time when the federal government closed off funding for stem cell research for religious reasons.
Now that money for CIRM has dried up, and supporters such as UC San Diego Health neuroscientist Larry Goldstein, Ph.D., say voters should agree to provide more money.
In 2004, under the Bush Administration, California voters decided to issue $3 billion in bonds so the state could create the California Institute for Regenerative Medicine, or CIRM. This was at a time when the federal government closed off funding for stem cell research for religious reasons.
Now that money for CIRM has dried up, and supporters such as UC San Diego Health neuroscientist Larry Goldstein, Ph.D., say voters should agree to provide more money.
9 Signs You've Already Had COVID in Your Brain
10/12/2020
Every day, more and more people are sharing stories about how COVID has changed their life for the worse—and there's a subset of people who may never be the same again. "I feel like I have dementia," one patient tells the New York Times, which chronicles patients suffering from neurological symptoms. As COVID-19 attacks your nervous system, it can impact your brain.
"The neurological symptoms are only becoming more and more scary," Alysson Muotri, Ph.D., a neuroscientist at the University of California, San Diego, in La Jolla, told the website.
"The neurological symptoms are only becoming more and more scary," Alysson Muotri, Ph.D., a neuroscientist at the University of California, San Diego, in La Jolla, told the website.
Trump’s Covid Treatments Were Tested in Cells Derived From Fetal Tissue
10/8/2020
When the Trump administration suspended federal funding in 2019 for most new scientific research projects involving fetal tissue derived from abortions, officials argued that whatever the scientific benefits, there was a pressing moral imperative to find alternative research methods.
“Promoting the dignity of human life from conception to natural death is one of the very top priorities of President Trump’s administration,” the Department of Health and Human Services said in a statement released at the time.
Yet the treatment for Covid-19 received by Mr. Trump — a cocktail of monoclonal antibodies he described as a “cure” in a celebratory video posted on Twitter — was developed using human cells derived from a fetus aborted decades ago.
Some scientists saw a double standard in the president’s endorsement. “Hypocrisy has never bothered the man, as near as I can tell,” Lawrence Goldstein, PhD, a neuroscientist at the University of California, San Diego, who has used fetal tissue in his research, said of Mr. Trump.
“Promoting the dignity of human life from conception to natural death is one of the very top priorities of President Trump’s administration,” the Department of Health and Human Services said in a statement released at the time.
Yet the treatment for Covid-19 received by Mr. Trump — a cocktail of monoclonal antibodies he described as a “cure” in a celebratory video posted on Twitter — was developed using human cells derived from a fetus aborted decades ago.
Some scientists saw a double standard in the president’s endorsement. “Hypocrisy has never bothered the man, as near as I can tell,” Lawrence Goldstein, PhD, a neuroscientist at the University of California, San Diego, who has used fetal tissue in his research, said of Mr. Trump.
UC San Diego research offers potential new treatments for COVID by revealing how virus enters cells
10/6/2020
The National Institutes of Health highlighted research Tuesday out of UC San Diego that could unlock a new way to treat COVID-19.
The research reveals new insight into how the coronavirus hijacks cells, and how doctors might be able to set traps or decoys to combat the virus. The findings were published in the journal Cell last month.
“It does open up another avenue for a potential treatment,” said UC San Diego distinguished professor Dr. Jeffrey Esko, PhD. “It’s not a cure. It would be something that would tamp down infection potentially.”
The research reveals new insight into how the coronavirus hijacks cells, and how doctors might be able to set traps or decoys to combat the virus. The findings were published in the journal Cell last month.
“It does open up another avenue for a potential treatment,” said UC San Diego distinguished professor Dr. Jeffrey Esko, PhD. “It’s not a cure. It would be something that would tamp down infection potentially.”
California's Stem-Cell Research Program Nearly Out of Money
10/2/2020
California's first-of-its-kind state program to fund stem-cell research is running out of money and supporters want voters to provide a $5.5 billion infusion.
The California Institute for Regenerative Medicine has doled out nearly $3 billion for research since the non-profit was created in a 2004 ballot question supported by 59% of voters. New stem-cell labs were created around the state and grants were awarded to Stanford University, the University of California, Berkeley, and other prominent institutions.
“I would be optimistic that having a medical emergency at the international level would hopefully drive people to realize that funding for medical research that leads to therapies and cures — including for COVID-19 where there are some interesting approaches underway that CIRM has funded — would persuade some people to vote yes,” said Larry Goldstein, PhD, director of the University of California, San Diego’s stem cell research program.
The California Institute for Regenerative Medicine has doled out nearly $3 billion for research since the non-profit was created in a 2004 ballot question supported by 59% of voters. New stem-cell labs were created around the state and grants were awarded to Stanford University, the University of California, Berkeley, and other prominent institutions.
“I would be optimistic that having a medical emergency at the international level would hopefully drive people to realize that funding for medical research that leads to therapies and cures — including for COVID-19 where there are some interesting approaches underway that CIRM has funded — would persuade some people to vote yes,” said Larry Goldstein, PhD, director of the University of California, San Diego’s stem cell research program.
Researchers describe details of protein linked to genetically inherited Parkinson's disease
9/18/2020
In August, a team of researchers at the University of California San Diego published groundbreaking back-to-back studies describing unprecedented details of a protein linked to genetically inherited Parkinson's disease.
The researchers produced the first visualizations of leucine-rich repeat kinase 2, or LRRK2, as seen within its natural environment inside the cell, as well as the first high-resolution blueprint of the protein.
"The goal of this project is to understand the basic cell biology and structure of this really fundamentally important LRRK2 molecule," said Samara Reck-Peterson, PhD, the lead principal investigator of the project, a professor at UC San Diego School of Medicine and Division of Biological Sciences and a Howard Hughes Medical Institute investigator.
"If we can find out why LRRK2--when it doesn't work--causes Parkinson's disease, that's really the ultimate goal. When you are thinking about designing a drug, you really need to understand all the details of the parts in order to engineer therapeutics."
Project co-principal investigator Andres Leschziner, PhD, and his colleagues have used the growing cryo-EM facility at UC San Diego to produce atomic-level visualizations of LRRK2 in the most detailed images of the protein to date. Leschziner plans to use cryo-EM to develop a full blueprint of LRRK2 in normal and mutant states.
The researchers produced the first visualizations of leucine-rich repeat kinase 2, or LRRK2, as seen within its natural environment inside the cell, as well as the first high-resolution blueprint of the protein.
"The goal of this project is to understand the basic cell biology and structure of this really fundamentally important LRRK2 molecule," said Samara Reck-Peterson, PhD, the lead principal investigator of the project, a professor at UC San Diego School of Medicine and Division of Biological Sciences and a Howard Hughes Medical Institute investigator.
"If we can find out why LRRK2--when it doesn't work--causes Parkinson's disease, that's really the ultimate goal. When you are thinking about designing a drug, you really need to understand all the details of the parts in order to engineer therapeutics."
Project co-principal investigator Andres Leschziner, PhD, and his colleagues have used the growing cryo-EM facility at UC San Diego to produce atomic-level visualizations of LRRK2 in the most detailed images of the protein to date. Leschziner plans to use cryo-EM to develop a full blueprint of LRRK2 in normal and mutant states.
UC San Diego Scientists to Explore New Frontiers in Parkinson’s Disease Research with $7.2M Grant
9/17/2020
In August, a team of researchers at the University of California San Diego published groundbreaking back-to-back studies describing unprecedented details of a protein linked to genetically inherited Parkinson’s disease. The researchers produced the first visualizations of leucine-rich repeat kinase 2, or LRRK2, as seen within its natural environment inside the cell, as well as the first high-resolution blueprint of the protein.
The Aligning Science Across Parkinson’s (ASAP) initiative has announced support for the next phase of the research as the scientists focus on understanding the basic mechanisms underlying Parkinson’s, a neurodegenerative disorder affecting millions. ASAP’s goal is to support research that will inform a path to a cure for Parkinson’s. The three-year, $7.2 million grant will fund research across three UC San Diego laboratories and two others based in Germany. The Michael J. Fox Foundation for Parkinson’s Research is the implementation partner for ASAP and issuer of the grant, which contributes to the Campaign for UC San Diego.
“The goal of this project is to understand the basic cell biology and structure of this really fundamentally important LRRK2 molecule,” said Samara Reck-Peterson, PhD, the lead principal investigator of the project and professor at UC San Diego School of Medicine and Division of Biological Sciences and a Howard Hughes Medical Institute investigator.
“LRRK2 is a complicated molecule with a lot of moving parts, and its dynamic behavior is very likely to play a role in both its normal function and Parkinson’s pathology. Understanding how the structure of LRRK2 changes in different states and with different disease mutations will be key to developing treatments. The equipment and expertise in cryo-EM here at UC San Diego put us in a great position to visualize all of this,” said Andres Leschziner, PhD, a professor at UC San Diego School of Medicine and Division of Biological Sciences.
The Aligning Science Across Parkinson’s (ASAP) initiative has announced support for the next phase of the research as the scientists focus on understanding the basic mechanisms underlying Parkinson’s, a neurodegenerative disorder affecting millions. ASAP’s goal is to support research that will inform a path to a cure for Parkinson’s. The three-year, $7.2 million grant will fund research across three UC San Diego laboratories and two others based in Germany. The Michael J. Fox Foundation for Parkinson’s Research is the implementation partner for ASAP and issuer of the grant, which contributes to the Campaign for UC San Diego.
“The goal of this project is to understand the basic cell biology and structure of this really fundamentally important LRRK2 molecule,” said Samara Reck-Peterson, PhD, the lead principal investigator of the project and professor at UC San Diego School of Medicine and Division of Biological Sciences and a Howard Hughes Medical Institute investigator.
“LRRK2 is a complicated molecule with a lot of moving parts, and its dynamic behavior is very likely to play a role in both its normal function and Parkinson’s pathology. Understanding how the structure of LRRK2 changes in different states and with different disease mutations will be key to developing treatments. The equipment and expertise in cryo-EM here at UC San Diego put us in a great position to visualize all of this,” said Andres Leschziner, PhD, a professor at UC San Diego School of Medicine and Division of Biological Sciences.
UCSD Researchers Discover Carbohydrate In Lungs That COVID-19 Uses To Infect
9/16/2020
UC San Diego School of Medicine researchers announced Tuesday they have discovered a carbohydrate that the SARS-CoV-2 virus uses to latch onto a cellular molecule in the lungs, which has potential implications for treatment of COVID-19 patients.
Since January, researchers have known that the novel coronavirus primarily uses a molecule known as ACE2 -- which sits like a doorknob on the outer surfaces of the cells that line the lungs -- to enter and infect those cells. Finding a way to lock out that interaction between virus and doorknob as a means to treat the infection has become the goal of many research studies.
"ACE2 is only part of the story," said Jeffrey Esko, PhD a professor of cellular and molecular medicine at UCSD and co-director of the Glycobiology Research and Training Center. "It isn't the whole picture."
Since January, researchers have known that the novel coronavirus primarily uses a molecule known as ACE2 -- which sits like a doorknob on the outer surfaces of the cells that line the lungs -- to enter and infect those cells. Finding a way to lock out that interaction between virus and doorknob as a means to treat the infection has become the goal of many research studies.
"ACE2 is only part of the story," said Jeffrey Esko, PhD a professor of cellular and molecular medicine at UCSD and co-director of the Glycobiology Research and Training Center. "It isn't the whole picture."
COVID-19 Virus Uses Heparan Sulfate to Get Inside Cells
9/15/2020
A molecule known as ACE2 sits like a doorknob on the outer surfaces of the cells that line the lungs. Since January 2020, researchers have known that SARS-CoV-2, the novel coronavirus that causes COVID-19, primarily uses ACE2 to enter these cells and establish respiratory infections. Finding a way to lock out that interaction between virus and doorknob, as a means to treat the infection, has become the goal of many research studies.
University of California San Diego School of Medicine researchers have discovered that SARS-CoV-2 can’t grab onto ACE2 without a carbohydrate called heparan sulfate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry.
“ACE2 is only part of the story,” said Jeffrey Esko, PhD, Distinguished Professor of Cellular and Molecular Medicine at UC San Diego School of Medicine and co-director of the Glycobiology Research and Training Center. “It isn’t the whole picture.”
University of California San Diego School of Medicine researchers have discovered that SARS-CoV-2 can’t grab onto ACE2 without a carbohydrate called heparan sulfate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry.
“ACE2 is only part of the story,” said Jeffrey Esko, PhD, Distinguished Professor of Cellular and Molecular Medicine at UC San Diego School of Medicine and co-director of the Glycobiology Research and Training Center. “It isn’t the whole picture.”
How COVID-19 can damage the brain
9/15/2020
In the early months of the COVID-19 pandemic, doctors struggled to keep patients breathing, and focused mainly on treating damage to the lungs and circulatory system. But even then, evidence for neurological effects was accumulating. Some people hospitalized with COVID-19 were experiencing delirium: they were confused, disorientated and agitated2. In April, a group in Japan published3 the first report of someone with COVID-19 who had swelling and inflammation in brain tissues. Another report4 described a patient with deterioration of myelin, a fatty coating that protects neurons and is irreversibly damaged in neurodegenerative diseases such as multiple sclerosis.
“The neurological symptoms are only becoming more and more scary,” says Alysson Muotri, PhD a neuroscientist at the University of California, San Diego, in La Jolla.
“The neurological symptoms are only becoming more and more scary,” says Alysson Muotri, PhD a neuroscientist at the University of California, San Diego, in La Jolla.
Twist on CRISPR Gene Editing Treats Adult-Onset Muscular Dystrophy in Mice
9/14/2020
CRISPR-Cas9 is a technique increasingly used in efforts to correct the genetic (DNA) defects that cause a variety of diseases. A few years ago, University of California San Diego School of Medicine researchers redirected the technique to instead modify RNA in a method they call RNA-targeting Cas9 (RCas9).
In a new study, publishing September 14, 2020 in Nature Biomedical Engineering , the team demonstrates that one dose of RCas9 gene therapy can chew up toxic RNA and almost completely reverse symptoms in a mouse model of myotonic dystrophy.
“Many other severe neuromuscular diseases, such as Huntington’s and ALS, are also caused by similar RNA buildup,” said senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine. “There are no cures for these diseases.” Yeo led the study with collaborators at Locanabio, Inc. and the University of Florida.
In a new study, publishing September 14, 2020 in Nature Biomedical Engineering , the team demonstrates that one dose of RCas9 gene therapy can chew up toxic RNA and almost completely reverse symptoms in a mouse model of myotonic dystrophy.
“Many other severe neuromuscular diseases, such as Huntington’s and ALS, are also caused by similar RNA buildup,” said senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine. “There are no cures for these diseases.” Yeo led the study with collaborators at Locanabio, Inc. and the University of Florida.
Cancers with High TRIM37 Enzyme Levels More Susceptible to Centrosome Blocker
9/9/2020
Several years ago, researchers at UC San Diego and Ludwig Institute for Cancer Research developed centrinone, a chemical inhibitor that blocks a cellular enzyme called PLK4, which is needed to make centrosomes. Treatment with centrinone, the only PLK4-specific inhibitor in existence, forces cells to divide without centrosomes.
More recently, the team determined that a second enzyme called TRIM37 affects how cells divide after centrinone treatment, revealing certain tumor types for which the inhibitor might work best.
The study, published September 9, 2020 in Nature, was led by Karen Oegema, PhD, and Arshad Desai, PhD, both professors at UC San Diego School of Medicine and members of the San Diego branch of the Ludwig Institute for Cancer Research. Oegema explains:
More recently, the team determined that a second enzyme called TRIM37 affects how cells divide after centrinone treatment, revealing certain tumor types for which the inhibitor might work best.
The study, published September 9, 2020 in Nature, was led by Karen Oegema, PhD, and Arshad Desai, PhD, both professors at UC San Diego School of Medicine and members of the San Diego branch of the Ludwig Institute for Cancer Research. Oegema explains:
How the Coronavirus Attacks the Brain
9/9/2020
A new study offers the first clear evidence that, in some people, the coronavirus invades brain cells, hijacking them to make copies of itself. The virus also seems to suck up all of the oxygen nearby, starving neighboring cells to death.
These findings are consistent with other observations in organoids infected with the coronavirus, said Alysson Muotri, PhD a neuroscientist at the University of California, San Diego, who has also studied the Zika virus.
These findings are consistent with other observations in organoids infected with the coronavirus, said Alysson Muotri, PhD a neuroscientist at the University of California, San Diego, who has also studied the Zika virus.
Inflammatory bowel disease linked to an overactive memory immune cell
8/31/2020
A new study has identified a link between IBD and the presence of a dysfunctional immune cell that continues to overreact for a long time.
The research, published in the journal Science Immunology, lays the groundwork for a better understanding of how and why IBD occurs and possible future therapies to treat the disease.
To understand what role the immune system plays in IBD, a team of scientists from across the world conducted an experiment to analyze in detail the immune cells present in rectal biopsies or blood of people with IBD.
Prof. Gene Yeo, PhD of the University of California San Diego School of Medicine and a co-author of the paper notes, “[w]e took advantage of a state-of-the-art approach allowing us to generate mRNA and antigen receptor sequencing data from the same single-cells and analyzed thousands of individual cells, which is quite exciting.”
The research, published in the journal Science Immunology, lays the groundwork for a better understanding of how and why IBD occurs and possible future therapies to treat the disease.
To understand what role the immune system plays in IBD, a team of scientists from across the world conducted an experiment to analyze in detail the immune cells present in rectal biopsies or blood of people with IBD.
Prof. Gene Yeo, PhD of the University of California San Diego School of Medicine and a co-author of the paper notes, “[w]e took advantage of a state-of-the-art approach allowing us to generate mRNA and antigen receptor sequencing data from the same single-cells and analyzed thousands of individual cells, which is quite exciting.”
Inflammatory Bowel Disease Linked to an Immune Cell Run Amok
8/24/2020
In a new study, published August 21, 2020 in Science Immunology , an international team of researchers, led by scientists at University of California San Diego School of Medicine, report that the lasting nature of IBD may be due to a type of long-lived immune cell that can provoke persistent, damaging inflammation in the intestinal tract.
Led by co-senior authors John T. Chang, MD, professor of medicine, and Gene W. Yeo, PhD, professor of cellular and molecular medicine, the research team performed mRNA and antigen receptor sequencing from immune cells isolated from samples taken from rectal biopsies or blood of IBD patients and healthy controls.
Led by co-senior authors John T. Chang, MD, professor of medicine, and Gene W. Yeo, PhD, professor of cellular and molecular medicine, the research team performed mRNA and antigen receptor sequencing from immune cells isolated from samples taken from rectal biopsies or blood of IBD patients and healthy controls.
Trump fetal tissue ethics board urges rejection of nearly all research proposals
8/18/2020
A new advisory board, created to review the ethics of proposed fetal tissue research grants, is urging the Trump administration to block government funding for nearly all of the applications — essentially seeking to ban support for most such scientific work.
The recommendation that the National Institutes of Health withhold funds from all but one of a slate of 14 research proposals means that Health and Human Services Secretary Alex Azar, who has the final say, would need to buck the will of a board he convened — and of social conservatives crucial to President Trump’s political base — for the projects to get federal support.
The one [...] member who has used fetal tissue in his own research, Lawrence Goldstein, PhD, a senior faculty member at the University of California at San Diego, denounced the process late Tuesday. “I think the whole thing is a travesty,” he said shortly after the report’s release. “They handpicked a board that wouldn’t approve very much, if anything. And they got the outcome that they wanted.”
Goldstein recalled that when the administration announced plans to create an ethics review board, he “went out of my way to defend” to skeptical colleagues that it could be fair. “I tried to keep an open mind, let’s see what we get. And this is what we get. I was clearly wrong to defend the administration.”
The recommendation that the National Institutes of Health withhold funds from all but one of a slate of 14 research proposals means that Health and Human Services Secretary Alex Azar, who has the final say, would need to buck the will of a board he convened — and of social conservatives crucial to President Trump’s political base — for the projects to get federal support.
The one [...] member who has used fetal tissue in his own research, Lawrence Goldstein, PhD, a senior faculty member at the University of California at San Diego, denounced the process late Tuesday. “I think the whole thing is a travesty,” he said shortly after the report’s release. “They handpicked a board that wouldn’t approve very much, if anything. And they got the outcome that they wanted.”
Goldstein recalled that when the administration announced plans to create an ethics review board, he “went out of my way to defend” to skeptical colleagues that it could be fair. “I tried to keep an open mind, let’s see what we get. And this is what we get. I was clearly wrong to defend the administration.”
Leading-edge Technology Unmasks Protein Linked to Parkinson’s Disease
8/16/2020
Researchers studying the primary causes of the disease have focused on mutations of the protein known as leucine-rich repeat kinase 2, or LRRK2. Understanding how LRRK2 disrupts normal functioning has been difficult due to a lack of information on the structure of the protein. Since LRRK2 is a major drug target, efforts to decipher LRRK2’s architecture have even included launching samples into space as a way of using microgravity conditions to help crystalize protein samples, but with no success.
Now, University of California San Diego scientists using leading-edge technologies have produced the first visualizations of LRRK2 inside its natural cellular environment and the first high-resolution blueprint of the protein. They leveraged these depictions to describe how LRRK2 binds to cellular tracks called microtubules and acts as a roadblock for motors that move along these tracks. The findings are described in two research papers published in the journals Cell and Nature .
In order to understand how LRRK2 works at a chemical level and to design therapeutics, an even higher resolution structure is required to reveal the position of atoms and how they interact with potential drugs. In the Nature study, co-senior authors Samara Reck-Peterson, PhD, and Andres Leschziner, PhD, took a deeper look at LRRK2’s structure and function and teamed up with Villa’s group to determine how LRRK2 interacts with microtubules.
Now, University of California San Diego scientists using leading-edge technologies have produced the first visualizations of LRRK2 inside its natural cellular environment and the first high-resolution blueprint of the protein. They leveraged these depictions to describe how LRRK2 binds to cellular tracks called microtubules and acts as a roadblock for motors that move along these tracks. The findings are described in two research papers published in the journals Cell and Nature .
In order to understand how LRRK2 works at a chemical level and to design therapeutics, an even higher resolution structure is required to reveal the position of atoms and how they interact with potential drugs. In the Nature study, co-senior authors Samara Reck-Peterson, PhD, and Andres Leschziner, PhD, took a deeper look at LRRK2’s structure and function and teamed up with Villa’s group to determine how LRRK2 interacts with microtubules.
Eclipse Cofounders Publish Foundational Dataset Revealing Extensive Hidden Signals in Human Genes
8/11/2020
Eclipse Bioinnovations, an RNA genomics company that helps scientists accelerate RNA research and medicines, celebrates the publication of the largest dataset of RNA-binding protein-interactomes, which provides a foundation for understanding human diseases caused by failed RNA processing. The study was published in Nature and led by UC San Diego scientists and Eclipse cofounders Gene Yeo, PhD, and Eric Van Nostrand, PhD, in collaboration with international researchers.
“Synthetic Lethality” – Exploiting Cancer-Specific Genetic Defects to Target Cancers
8/3/2020
With advances in genome sequencing, cancer treatments have increasingly sought to leverage the idea of “synthetic lethality,” exploiting cancer-specific genetic defects to identify targets that are uniquely essential to the survival of cancer cells. Synthetic lethality results when non-lethal mutations in different genes become deadly when combined in cells. In a new study led by senior study author Richard D. Kolodner, PhD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the Ludwig Institute for Cancer Research San Diego Branch, and published online July 27, 2020 in the Proceedings of the National Academy of Sciences (PNAS), researchers at the San Diego branch of Ludwig Institute for Cancer Research and University of California San Diego School of Medicine report that inhibiting a key enzyme caused human cancer cells associated with two major types of breast and ovarian cancer to die and in mouse studies reduced tumor growth.
Humans Might Be So Sickly Because We Evolved to Avoid a Single Devastating Disease
8/1/2020
New research has uncovered evidence that mutations arising between 600,000 and 2 million years ago were part of a complex of adaptations that may have inadvertently made us prone to inflammatory diseases and even other pathogens.
An international team of researchers compared around a thousand human genomes with a few from our extinct cousins, the Neanderthals and Denisovans, to fill in missing details on the evolution of a family of chemicals that coat the human body's cells.
Sialic acids are a diverse group of carbohydrates that blossom like leaves from the tips of proteins covering the surfaces of human cells.
This canopy of sugars is typically the first thing you'd bump into if you were the size of a virus or bacterium.
A wide variety of viruses and bacteria gain entry to our cells by grabbing onto the fuzz of sialic acid, many of which infect humans but not apes. Many, such as cholera, smallpox, influenza, and coronaviruses, are far from trivial.
"Most coronaviruses infect cells in two steps – first by recognising abundant sialic acids as binding sites to gain a foothold, and then seeking out the higher affinity protein receptors like ACE2," physician Ajit Varki, PhD told Science magazine's Ann Gibbons.
An international team of researchers compared around a thousand human genomes with a few from our extinct cousins, the Neanderthals and Denisovans, to fill in missing details on the evolution of a family of chemicals that coat the human body's cells.
Sialic acids are a diverse group of carbohydrates that blossom like leaves from the tips of proteins covering the surfaces of human cells.
This canopy of sugars is typically the first thing you'd bump into if you were the size of a virus or bacterium.
A wide variety of viruses and bacteria gain entry to our cells by grabbing onto the fuzz of sialic acid, many of which infect humans but not apes. Many, such as cholera, smallpox, influenza, and coronaviruses, are far from trivial.
"Most coronaviruses infect cells in two steps – first by recognising abundant sialic acids as binding sites to gain a foothold, and then seeking out the higher affinity protein receptors like ACE2," physician Ajit Varki, PhD told Science magazine's Ann Gibbons.
UC San Diego Scientists Part of Special Package of Studies Describing Human Genome
7/29/2020
Researchers at University of California San Diego School of Medicine are among the contributors to a package of 10 studies, published July 29, 2020 in the journal Nature, describing the latest results from the ongoing Encyclopedia of DNA Elements (ENCODE) project, a worldwide effort led by the National Institutes of Health (NIH) to understand how the human genome functions.
Research teams headed by Bing Ren, PhD, professor of cellular and molecular medicine, director of the Center for Epigenomics at UC San Diego School of Medicine and a member of the San Diego branch of the Ludwig Institute for Cancer Research, and Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine, each published a study in the latest issue of Nature.
Research teams headed by Bing Ren, PhD, professor of cellular and molecular medicine, director of the Center for Epigenomics at UC San Diego School of Medicine and a member of the San Diego branch of the Ludwig Institute for Cancer Research, and Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine, each published a study in the latest issue of Nature.
Ancient microbial arms race sharpened our immune system—but also left us vulnerable
7/24/2020
At a recent symposium on the evolution of infectious diseases, University of California, San Diego (UCSD), pathologist Nissi Varki noted that humans suffer from a long list of deadly diseases—including typhoid fever, cholera, mumps, whooping cough, and gonorrhea—that don’t afflict apes and most other mammals. All of those pathogens follow the same well-trodden pathway to break into our cells: They manipulate sugar molecules called sialic acids. Hundreds of millions of these sugars stud the outer surface of every cell in the human body—and the sialic acids in humans are different from those in apes.
Varki and an international team of researchers including UCSD Physician Scientist, Ajit Varki, PhD, have now traced how evolution may have scrambled to construct new defenses after that molecular vulnerability emerged in our distant ancestors.
Varki and an international team of researchers including UCSD Physician Scientist, Ajit Varki, PhD, have now traced how evolution may have scrambled to construct new defenses after that molecular vulnerability emerged in our distant ancestors.
Bringing a Child into the World, While the World Battles COVID-19
6/25/2020
It was Halloween 2019 when Gene Yeo, PhD, and Corina Antal learned they were going to have twin girls. “We were beyond excited,” said Antal.
But they also learned that day that their daughters were monoamniotic (MoMo) twins, which means the fetuses shared a single placenta and amniotic sac. It’s an extremely rare type of pregnancy, occurring in just 1 in 60,000 pregnancies.
Pregnancies with MoMo twins are considered very high risk because of heightened dangers of umbilical cord entanglement and compression. This meant Antal would be under close supervision by her medical team. “I had to go to the clinic for ultrasounds every two weeks and knew I would be hospitalized several weeks before delivery for fetal monitoring.”
Then, the COVID-19 pandemic hit.
Yeo is a professor in the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine, and Antal is a postdoctoral fellow at the Salk Institute for Biological Studies. “As scientists, we were not only reading all the studies we could find on MoMo twins, but we were now learning all we could about COVID-19,” said Yeo.
But they also learned that day that their daughters were monoamniotic (MoMo) twins, which means the fetuses shared a single placenta and amniotic sac. It’s an extremely rare type of pregnancy, occurring in just 1 in 60,000 pregnancies.
Pregnancies with MoMo twins are considered very high risk because of heightened dangers of umbilical cord entanglement and compression. This meant Antal would be under close supervision by her medical team. “I had to go to the clinic for ultrasounds every two weeks and knew I would be hospitalized several weeks before delivery for fetal monitoring.”
Then, the COVID-19 pandemic hit.
Yeo is a professor in the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine, and Antal is a postdoctoral fellow at the Salk Institute for Biological Studies. “As scientists, we were not only reading all the studies we could find on MoMo twins, but we were now learning all we could about COVID-19,” said Yeo.
One-Time Treatment Generates New Neurons, Eliminates Parkinson’s Disease in Mice
6/24/2020
Xiang-Dong Fu, PhD, has never been more excited about something in his entire career. He has long studied the basic biology of RNA, a genetic cousin of DNA, and the proteins that bind it. But a single discovery has launched Fu into a completely new field: neuroscience.
San Diego's scientific and medical institutes collaborate on large-scale research program to study spread of COVID-19
6/16/2020
A consortium that includes many of San Diego's top medical and scientific research institutes has launched a large-scale COVID-19 screening effort to better understand the spread and prevalence of the virus in the local community, with an initial focus on evaluating healthcare workers and first responders.
Known as the San Diego Epidemiology and Research for COVID Health (SEARCH) alliance, the cross-institutional collaboration is co-led by scientists and clinical researchers at Rady Children's Hospital-San Diego, Rady Children's Institute for Genomic Medicine, Scripps Research and University of California San Diego.
SEARCH's core research team consists of the following members of the San Diego scientific and medical communities:
Kristian Andersen, PhD, Professor of Immunology and Microbiology at Scripps Research
Lauge Farnaes, MD, PhD, Assistant Medical Director at Rady Children's Institute for Genomic Medicine
Rob Knight, PhD, Professor of Pediatrics, Bioengineering and Computer Science & Engineering, and Founding Director of the Center for Microbiome Innovation at UC San Diego
Louise Laurent, MD, PhD, Professor of Obstetrics, Gynecology, and Reproductive Sciences at UC San Diego School of Medicine
Gene Yeo, PhD, MBA, Professor of Cellular and Molecular Medicine and Co-Director Bioinformatics and Systems Biology Graduate Program.at UC San Diego School of Medicine
Known as the San Diego Epidemiology and Research for COVID Health (SEARCH) alliance, the cross-institutional collaboration is co-led by scientists and clinical researchers at Rady Children's Hospital-San Diego, Rady Children's Institute for Genomic Medicine, Scripps Research and University of California San Diego.
SEARCH's core research team consists of the following members of the San Diego scientific and medical communities:
Kristian Andersen, PhD, Professor of Immunology and Microbiology at Scripps Research
Lauge Farnaes, MD, PhD, Assistant Medical Director at Rady Children's Institute for Genomic Medicine
Rob Knight, PhD, Professor of Pediatrics, Bioengineering and Computer Science & Engineering, and Founding Director of the Center for Microbiome Innovation at UC San Diego
Louise Laurent, MD, PhD, Professor of Obstetrics, Gynecology, and Reproductive Sciences at UC San Diego School of Medicine
Gene Yeo, PhD, MBA, Professor of Cellular and Molecular Medicine and Co-Director Bioinformatics and Systems Biology Graduate Program.at UC San Diego School of Medicine
UC system awards $2M to CA COVID-19 researchers
6/8/2020
More than $2 million in emergency funding is being distributed to California researchers to mitigate the impacts of COVID-19 among vulnerable communities.
On Wednesday, the UC Office of the President, or UCOP, announced the recipients of its emergency research funding. UC San Diego researcher Pradipta Ghosh, MD, said she will use the UCOP money her center received to infect lab-grown human lungs with the COVID-19 virus to discover the potential causes of the virus’s fatality. “Growing stem cells out of tissues is not a trivial matter,” Ghosh said. “It costs a huge amount of money and we are happy UCOP gave us some money to do this research — $50,000 is a drop in the bucket and we have also reached out” to the National Institutes of Health.
On Wednesday, the UC Office of the President, or UCOP, announced the recipients of its emergency research funding. UC San Diego researcher Pradipta Ghosh, MD, said she will use the UCOP money her center received to infect lab-grown human lungs with the COVID-19 virus to discover the potential causes of the virus’s fatality. “Growing stem cells out of tissues is not a trivial matter,” Ghosh said. “It costs a huge amount of money and we are happy UCOP gave us some money to do this research — $50,000 is a drop in the bucket and we have also reached out” to the National Institutes of Health.
Helping San Diegans Return to Work
6/4/2020
UC San Diego donors Jean and Gary Shekhter are leading support for a collaborative COVID-19 screening effort by key research institutions in the region.
The Shekhters gave $350,000 to the UC San Diego COVID-19 Emergency Response Fund to help fund SEARCH—San Diego Epidemiology and Research for COVID-19 Health, a collaborative research study that aims to help local businesses and employees return to work safely by screening community members for presence of the coronavirus. The SEARCH alliance is co-led by UC San Diego, Scripps Research and Rady Children’s Hospital-San Diego. Other research partners include the Sanford Consortium for Regenerative Medicine, Salk Institute for Biological Studies and Biocom. At UC San Diego, SEARCH is led by researchers Gene Yeo, PhD, Rob Knight and Louise Laurent.
The Shekhters gave $350,000 to the UC San Diego COVID-19 Emergency Response Fund to help fund SEARCH—San Diego Epidemiology and Research for COVID-19 Health, a collaborative research study that aims to help local businesses and employees return to work safely by screening community members for presence of the coronavirus. The SEARCH alliance is co-led by UC San Diego, Scripps Research and Rady Children’s Hospital-San Diego. Other research partners include the Sanford Consortium for Regenerative Medicine, Salk Institute for Biological Studies and Biocom. At UC San Diego, SEARCH is led by researchers Gene Yeo, PhD, Rob Knight and Louise Laurent.
$350,000 Gift to UCSD to Create COVID-19 Epidemiological Tracking Study
6/4/2020
UC San Diego announced Thursday a $350,000 donation from Jean and Gary Shekhter, which will help fund San Diego Epidemiology and Research for COVID-19 Health, a collaborative research study aimed at helping local businesses and employees return to work safely by screening community members for presence of the coronavirus.
The research study is co-led by UC San Diego, Scripps Research and Rady Children’s Hospital-San Diego.
Other research partners include the Sanford Consortium for Regenerative Medicine, Salk Institute for Biological Studies and Biocom. At UC San Diego, SEARCH is led by researchers Gene Yeo, PhD, Rob Knight and Louise Laurent.
The research study is co-led by UC San Diego, Scripps Research and Rady Children’s Hospital-San Diego.
Other research partners include the Sanford Consortium for Regenerative Medicine, Salk Institute for Biological Studies and Biocom. At UC San Diego, SEARCH is led by researchers Gene Yeo, PhD, Rob Knight and Louise Laurent.
Local Couple Detail Experience of High-Risk Pregnancy During Pandemic
5/27/2020
A local couple is sharing their experience of undergoing a high-risk pregnancy that resulted in the birth of their healthy twin daughters amid the coronavirus pandemic.
Corina Antal and Gene Yeo, PhD, were ecstatic to learn they were expecting twin girls, but that excitement soon turned to concern upon learning their babies tested as Monoamniotic (MoMo). The rare condition means the fetuses shared one placenta and amniotic sac, which made for a high-risk pregnancy, according to UC San Diego Health.
The couple did everything they could to learn more about the condition. Antal is a postdoctoral fellow at the Salk Institute for Biological Studies while Yeo is a professor in the Department of Cellular and Molecular Medicine at the UC San Diego School of Medicine.
Corina Antal and Gene Yeo, PhD, were ecstatic to learn they were expecting twin girls, but that excitement soon turned to concern upon learning their babies tested as Monoamniotic (MoMo). The rare condition means the fetuses shared one placenta and amniotic sac, which made for a high-risk pregnancy, according to UC San Diego Health.
The couple did everything they could to learn more about the condition. Antal is a postdoctoral fellow at the Salk Institute for Biological Studies while Yeo is a professor in the Department of Cellular and Molecular Medicine at the UC San Diego School of Medicine.
Disease expert tells how we'll know we've peaked in the spread of the coronavirus
4/19/2020
A University of California professor says testing for antibodies is the key to tracking the curve of COVID-19's rate of spread.
UC San Diego Professor Stephen Hedrick, PhD has decades of experience in studying and writing about diseases.
"It would be great to be in the lab now and test some vaccines," he said.
Hedrick said creating a vaccine and testing people for antibodies to COVID-19 is essential, "if they just test for the virus that only tells us if you have an acute infection but if they test for antibodies that tells us whether you've ever had the disease."
UC San Diego Professor Stephen Hedrick, PhD has decades of experience in studying and writing about diseases.
"It would be great to be in the lab now and test some vaccines," he said.
Hedrick said creating a vaccine and testing people for antibodies to COVID-19 is essential, "if they just test for the virus that only tells us if you have an acute infection but if they test for antibodies that tells us whether you've ever had the disease."
Researchers Move Closer to Industrial Production of Heparin in Cell Culture
4/16/2020
Scientists at the University of California-San Diego say they have moved one step closer to the ability to make heparin in cultured cells. Heparin is a potent anti-coagulant and the most prescribed drug in hospitals, yet cell-culture-based production of heparin is currently not possible, according to the researchers who published their study, “ZNF263 is a transcriptional regulator of heparin and heparan sulfate biosynthesis” in PNAS.
“Heparin is the most widely prescribed biopharmaceutical in production globally. Its potent anticoagulant activity and safety makes it the drug of choice for preventing deep vein thrombosis and pulmonary embolism. In 2008, adulterated material was introduced into the heparin supply chain, resulting in several hundred deaths and demonstrating the need for alternate sources of heparin. Heparin is a fractionated form of heparan sulfate derived from animal sources, predominantly from connective tissue mast cells in pig mucosa. While the enzymes involved in heparin biosynthesis are identical to those for heparan sulfate, the factors regulating these enzymes are not understood,” write the investigators.
“Examination of the promoter regions of all genes involved in heparin/heparan sulfate assembly uncovered a transcription factor-binding motif for ZNF263, a C2H2 zinc finger protein. CRISPR-mediated targeting and siRNA knockdown of ZNF263 in mammalian cell lines and human primary cells led to dramatically increased expression levels of HS3ST1, a key enzyme involved in imparting anticoagulant activity to heparin, and HS3ST3A1, another glucosaminyl 3-O-sulfotransferase expressed in cells. Enhanced 3-O-sulfation increased binding to antithrombin, which enhanced Factor Xa inhibition, and binding of neuropilin-1. Analysis of transcriptomics data showed distinctively low expression of ZNF263 in mast cells compared with other (non–heparin-producing) immune cells. These findings demonstrate a novel regulatory factor in heparan sulfate modification that could further advance the possibility of bioengineering anticoagulant heparin in cultured cells.”
The UC San Diego scientists reasoned that heparin synthesis must be under the control of transcription factors, whose tissue-specific occurrence might give mast cells the unique ability to produce heparin. Since regulators for heparin were not known, a research team led by UC San Diego professors Jeffrey Esko, PhD, and Nathan Lewis, PhD, used bioinformatic software to scan the genes encoding enzymes involved in heparin production and specifically look for sequence elements that could represent binding sites for transcription factors.
“Heparin is the most widely prescribed biopharmaceutical in production globally. Its potent anticoagulant activity and safety makes it the drug of choice for preventing deep vein thrombosis and pulmonary embolism. In 2008, adulterated material was introduced into the heparin supply chain, resulting in several hundred deaths and demonstrating the need for alternate sources of heparin. Heparin is a fractionated form of heparan sulfate derived from animal sources, predominantly from connective tissue mast cells in pig mucosa. While the enzymes involved in heparin biosynthesis are identical to those for heparan sulfate, the factors regulating these enzymes are not understood,” write the investigators.
“Examination of the promoter regions of all genes involved in heparin/heparan sulfate assembly uncovered a transcription factor-binding motif for ZNF263, a C2H2 zinc finger protein. CRISPR-mediated targeting and siRNA knockdown of ZNF263 in mammalian cell lines and human primary cells led to dramatically increased expression levels of HS3ST1, a key enzyme involved in imparting anticoagulant activity to heparin, and HS3ST3A1, another glucosaminyl 3-O-sulfotransferase expressed in cells. Enhanced 3-O-sulfation increased binding to antithrombin, which enhanced Factor Xa inhibition, and binding of neuropilin-1. Analysis of transcriptomics data showed distinctively low expression of ZNF263 in mast cells compared with other (non–heparin-producing) immune cells. These findings demonstrate a novel regulatory factor in heparan sulfate modification that could further advance the possibility of bioengineering anticoagulant heparin in cultured cells.”
The UC San Diego scientists reasoned that heparin synthesis must be under the control of transcription factors, whose tissue-specific occurrence might give mast cells the unique ability to produce heparin. Since regulators for heparin were not known, a research team led by UC San Diego professors Jeffrey Esko, PhD, and Nathan Lewis, PhD, used bioinformatic software to scan the genes encoding enzymes involved in heparin production and specifically look for sequence elements that could represent binding sites for transcription factors.
Call for Citizen Scientists to Contribute to COVID-19 Studies
4/6/2020
The Microsetta Initiative, a crowdsourced research effort based at the University of California San Diego School of Medicine, has expanded its capabilities to now allow citizen-scientists around the world to help collect crucial information about SARS-CoV-2, the novel coronavirus causing a COVID-19 pandemic.
Microsetta’s ability to pivot to RNA collection was driven by collaboration with several other UC San Diego School of Medicine faculty members, including Karsten Zengler, Jack Gilbert, Gene Yeo, PhD,and Dr. Victor Nizet. Rapid collaboration among labs, departments and neighboring institutions has been enabled by a new group and Slack channel created by Yeo called San Diego COVID Research Enterprise Network (SCREEN), which now includes more than 800 San Diego researchers.
Microsetta’s ability to pivot to RNA collection was driven by collaboration with several other UC San Diego School of Medicine faculty members, including Karsten Zengler, Jack Gilbert, Gene Yeo, PhD,and Dr. Victor Nizet. Rapid collaboration among labs, departments and neighboring institutions has been enabled by a new group and Slack channel created by Yeo called San Diego COVID Research Enterprise Network (SCREEN), which now includes more than 800 San Diego researchers.
Retrospective: Marilyn Farquhar (1928 – 2019)
2/20/2020
The passing of Marilyn Farquhar on Nov. 23 brought to a close a long and inspiring career in cell biology. She rightly ranks among the pioneers in her field and especially as a role model for women in science.
Human Gut-in-a-Dish Model Helps Define ‘Leaky Gut,’ and Outline a Pathway to Treatment
2/10/2020
Once a vague scapegoat for a variety of ills, increasing evidence suggests a condition known as “leaky gut” — in which microbes and other molecules seep out of the intestines — may be more common, and more harmful, than previously thought.
University of California San Diego School of Medicine researchers are now able to simulate leaky gut conditions for the first time, using 3D models of human intestines generated from patient cells. These small organoids, or “mini-guts,” have revealed new biomarkers that help define what a leaky gut looks like — molecular signals that could one day help clinicians better diagnose the condition, track its progression and evaluate the success or failure of treatments.
The study, published February 10, 2020 in Life Science Alliance , was led by first author Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center, and senior author Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.
University of California San Diego School of Medicine researchers are now able to simulate leaky gut conditions for the first time, using 3D models of human intestines generated from patient cells. These small organoids, or “mini-guts,” have revealed new biomarkers that help define what a leaky gut looks like — molecular signals that could one day help clinicians better diagnose the condition, track its progression and evaluate the success or failure of treatments.
The study, published February 10, 2020 in Life Science Alliance , was led by first author Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center, and senior author Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.
Stem Cells, CRISPR and Gene Sequencing Technology are Basis of New Brain Cancer Model
1/28/2020
Using genetically engineered human pluripotent stem cells, University of California San Diego School of Medicine researchers created a new type of cancer model to study in vivo how glioblastoma, the most common and aggressive form of brain cancer, develops and changes over time.
Reporting in the January 28, 2020 issue of Nature Communications, researchers used CRISPR editing to make precise mutations in an otherwise “normal” genome to create the genetic conditions that enable tumor development. The resulting avatars are unique in that they behave like a grade 4 glioma — a fast-growing type of tumor that starts in the glial cells of the brain — in their level of pathology, transcriptome signatures, engineered genetic alterations and evolution of genetic mutations, such as the emergence of extrachromosomal DNA and chromosomal rearrangements.
“The addition of single-cell RNA sequencing and computational tools enabled efficient analysis of big data to truly evaluate the surprising intra-tumor heterogeneity present in our avatars which replicates what is seen in patients samples,” said co-senior author Gene W. Yeo, PhD, professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego and faculty member in the Sanford Consortium for Regenerative Medicine.
Reporting in the January 28, 2020 issue of Nature Communications, researchers used CRISPR editing to make precise mutations in an otherwise “normal” genome to create the genetic conditions that enable tumor development. The resulting avatars are unique in that they behave like a grade 4 glioma — a fast-growing type of tumor that starts in the glial cells of the brain — in their level of pathology, transcriptome signatures, engineered genetic alterations and evolution of genetic mutations, such as the emergence of extrachromosomal DNA and chromosomal rearrangements.
“The addition of single-cell RNA sequencing and computational tools enabled efficient analysis of big data to truly evaluate the surprising intra-tumor heterogeneity present in our avatars which replicates what is seen in patients samples,” said co-senior author Gene W. Yeo, PhD, professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego and faculty member in the Sanford Consortium for Regenerative Medicine.
How to Be Humane to a Lab-Grown Brain
1/26/2020
The study of brain organoids can be fraught with ethical dilemmas. “In order for it to be a good model, you want it to be as human as possible,” said Hank Greely, a law professor at Stanford University who specializes in ethical and legal issues in the biosciences. “But the more human it gets, the more you’re backing into the same sorts of ethics questions that are the reasons why you can’t just use living humans.”
Ethicists and scientists are now working together to figure out whether organoids warrant their own rules. The ethical discussions are progressing at a fast clip, well ahead of the science. The National Institutes of Health has sponsored meetings and workshops, and there’s been talk of creating another kind of oversight committee. Scientists have reached out privately to ethicists to discuss the particulars of their research, and Alysson Muotri, PhD, a biologist at UC San Diego, has organized conferences to connect ethicists with both stem cell biologists and consciousness researchers.
Ethicists and scientists are now working together to figure out whether organoids warrant their own rules. The ethical discussions are progressing at a fast clip, well ahead of the science. The National Institutes of Health has sponsored meetings and workshops, and there’s been talk of creating another kind of oversight committee. Scientists have reached out privately to ethicists to discuss the particulars of their research, and Alysson Muotri, PhD, a biologist at UC San Diego, has organized conferences to connect ethicists with both stem cell biologists and consciousness researchers.