I am interested in characterizing the nature of human CENP-A-containing chromatin. This includes characterization of possible cell-cycle dependent changes in the structure of the CENP-A nucleosome, as well as identifying the DNA sequences bound by the centromere components CENP-C, CENP-T, CENP-W and CENP-A and the affect that CENP-B binding might have on their positioning.
Ph.D., Hebrew University of Jerusalem, 2009
M.Sc. Hebrew University of Jerusalem, 2003
B.Sc.Med, Hebrew University of Jerusalem, 2001
2014 FISEB/ILANIT 2014 Congress travel stipend2010 The Lamas Fund Award for post-doctoral fellows, The Hebrew University of Jerusalem
Chromosome segregation during cell division is carefully regulated to ensure accurate partitioning of the replicated genome to daughter cells. Errors in such tightly controlled processes can trigger genomic instability, one of the central hallmarks of cancer. My research utilizes a spectrum of cell biological and molecular genetic approaches to decode how errors in mitosis can directly shape the frequently chaotic landscape of cancer genomes.
Ph.D., University of Texas Southwestern Medical Center, 2012
B.A., Baylor University, 2008
My research is centered in the study of neuromuscular junctions and the pathological mechanisms that drive muscle denervation in ALS. My efforts are principally focused in the discovery of molecules that induce muscle reinnervation.
Ph.D., University of Barcelona, Spain, 2013
M.S., University of Barcelona, Spain, 2009
Awards: 2016 The Milton Safenowitz Post Doctoral Fellowship for ALS Research
My research focuses on understanding pathogenic mechanisms and therapy development of GGGGCC repeat expansions in the C9orf72 gene leading to Amyotrophic lateral sclerosis and Frontotemporal Dementia.
Ph.D., University of Pittsburgh, 2011
My research focuses on determining how a GGGGCC hexanucleotide expansion in the C9ORF72 gene leads to neurodegeneration in ALS and Frontal Temporal Dementia (FTD). I am using gene targeting and transgenic tools to establish novel mouse and cellular models by either disrupting endogenous C9ORF72 gene or expressing human C9ORF72 with different hexanucleotide repeat expansions. These genetically modified models will enable us to define pathogenic mechanisms including loss of C9ORF72 function and/or gain of repeat-mediated toxicity. Furthermore, I am especially excited to examine the efficacy of antisense oligonucleotides that mediate degradation of C9ORF72 RNAs carrying repeat expansions as a therapeutic approach in these transgenic mice and cell lines. My hope is that these efforts will provide a greater understanding of disease mechanism and provide the rationale and basis for therapy development in ALS patients carrying C9ORF72 mutation.
Ph.D., University of Louisville, 2011
2017 The ALSA Investigator Initiated Starter Grant
2013 The Milton Safenowitz Post Doctoral Fellowship for ALS Research
2010 National Society for Neuroscience Graduate Student Chapter Travel Award
I am part of the Huntington's disease effort. We are currently working to characterize a gene silencing therapy for the treatment of HD.
Education:B.S., UC San Diego, 2006
I am a research project specialist providing consultation, training & surgical expertise for those who have transgenic experiments as well as manage and coordinate all animal studies on-going in the lab. My primary research focus is Antisense Oligonucleotide Therapy for Familial ALS and Huntington's Disease Models and most recently discovered C9orf72 disease models. I also serve as part of a collaborative disease research team funded by CIRM focused on the therapeutic potential of spinal grafting of neuronal precursors (NPSC’s) and stem cell-derived astrocyte precursor transplants in ALS.
B.S., Pennsylvania State University, University Park, 1999
M.S., Johns Hopkins University, 2002Surgical Research Specialist (certified), Academy of Surgical Research, 2005
In my Ph.D.work, I demonstrated that even bacteria can acquire, propagate, and maintain prions, self templating proteins that can induce misfolding of even normal proteins. My main effort as a postdoc is to elucidate the mechanism by ALS pathogenic proteins (SOD1, TDP43) are accumulated in neuron cells and are able to spread their aberrant conformation in the nervous system.
Ph.D., Centro de Investigaciones Biológicas - Consejo Superior de Investigaciones Cientificas, Spain 2012B.S., University Complutense, Madrid, Spain 2005
During early mitosis, the spindle assembly checkpoint act to maintain genome stability by delaying cell division until accurate chromosome segregation can be guaranteed. I am interested in catalysis of Cdc20 by conformational changes of Mad2 during spindle assembly checkpoint.
I am part of the Neuro Group, assisting mainly the project that
the lab is performing to find a therapy for Huntington's disease.
I am part of the Neuro Group, assisting mainly the project that the lab is performing to find a therapy for Huntington's disease.
B.S. in Research's Laboratory, Universidad Auntónoma de Madrid, 2005
Chromosome instability and chromosome rearrangements are both known to be involved in cancer. In my work, I study the effect chromosome instability has on cancer formation and progression by utilizing a mouse model in which I can induce chromosome miss-segregation. I am also interested in the evolution of chromosome rearrangements in cancer cells, and use a unique cell model to follow such changes in culture.
Ph.D., Weizmann Institute of Science, 2012
M.Sc., Tel-Aviv University, 2006B.Sc., Tel-Aviv University, 2004
The discovery of ALS-causing mutations in several genes encoding proteins with fundamental roles in RNA processing pathways highlights dysfunction in RNA metabolism as an emerging, pivotal mechanism underlying ALS pathogenesis. It remains a mystery, however, how mutations in number of genes are unified by the common devastating phenotype of progressive, adult-onset, motor neuron degeneration, and death within 2-5 years. My goal is to uncover the aberrant RNA metabolism and its potential contribution to toxicity in ALS pathogenesis, using neurons “trans-differentiated” from ALS patient fibroblasts with mutations in RNA-binding proteins (RBPs). Aggregates containing misfolded RBPs are key features of ALS pathology in both familial and sporadic ALS cases, thus my study has the potential to discover and characterize unknown mechanisms through which RNA processing abnormalities provoke ALS pathogenesis.
Ph.D., Tel Aviv University, 2014
EMBO Long-Term Fellowship 2014
Human Frontiers (HSFP) Long-Term Fellowship 2015
Abnormal protein aggregation and trans-cellular transmission of pathogenic protein are hallmarks of neurodegenerative diseases. However, whether TDP43, the main component of ubiquitinated protein aggregates found in most ALS patients, can spread cell-to-cell and further cause degeneration in motor system is unknown. My research focuses on understanding the mechanism underlying spreading of TDP43 pathology, and its causal function in ALS. I am also interested in mechanism of the liquid-liquid phase separation of RNA-binding proteins, like TDP-43, and the physiological function and/or the pathological roles of the TDP-43-riched membrane-less organelles in mammalian cells.
Ph.D., Zhejiang University, 2015
M.S., Zhejiang University, 2010
M.S., Zhejiang University, 2010
B.S., Zhejiang University, 2007
To date, five separate neurodegeneration therapy approaches utilizing modified
Antisense Oligonucleotide (ASO) drugs have transitioned from the benches of the Cleveland Laboratory to clinical trials in humans.
These drugs are proving to be very powerful tools for combating previously incurable diseases of the central nervous system and may
represent an upcoming revolution in neurology. All of these ASO drugs rely upon a virtually unknown mechanism of cellular uptake to
reach the RNA molecules they are designed to target. My work in the Cleveland Laboratory is applying cutting-edge genome-wide CRISPR-Cas9
based screening technology to identify the genetic basis of productive ASO uptake in cells and modulate these genes and pathways to
increase drug efficacy and enable more advanced targeting of these important compounds in complex tissue environments.
To date, five separate neurodegeneration therapy approaches utilizing modified Antisense Oligonucleotide (ASO) drugs have transitioned from the benches of the Cleveland Laboratory to clinical trials in humans. These drugs are proving to be very powerful tools for combating previously incurable diseases of the central nervous system and may represent an upcoming revolution in neurology. All of these ASO drugs rely upon a virtually unknown mechanism of cellular uptake to reach the RNA molecules they are designed to target. My work in the Cleveland Laboratory is applying cutting-edge genome-wide CRISPR-Cas9 based screening technology to identify the genetic basis of productive ASO uptake in cells and modulate these genes and pathways to increase drug efficacy and enable more advanced targeting of these important compounds in complex tissue environments.
B.S.Cellular,Molecular,and Developmental Biology University of Washington, Seattle. 2010
I am interested in the contribution of kinases and innate immune signaling in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Recently, TBK1 loss-of-function mutations are identified in both familial and sporadic ALS. TBK1 is a kinase that involves in innate immune signaling to phosphorylate and activate IRF3/7 transcription factors. It also regulates autophagy by phosphorylating autophagy receptors OPTN and p62, which are also mutated in ALS. I am using cellular and mouse model approaches to study how TBK1 loss-of-function causes ALS.
Ph.D. Washington University in St. Louis, 2015
B.S. Nankai University, 2008
2018 NIH F32 postdoctoral fellowship
I am interested in studying the mechanism of muscle denervation in ALS using Mass Spectrometry. My research interest mainly focused on characterizing the disease-specific changes of whole proteome and local translated proteins at the axons of motor neurons.
Ph. D., National Institute of Biological Sciences, Beijing, 2015
B.S., Nankai University, 2009
Nuclear integrity is crucial for proper cell function. I am interested in understanding the mechanisms underlying genome rearrangements observed upon nuclear envelope rupture. I am also focused on identifying the role of factors controlling mitotic progression in chromosome instability and cancer, using a combination of cellular and animal models.
Ph.D., University of Strasbourg (France), 2014
M.S., Lomonosov Moscow State University (Russia), 2008
My research focuses on unraveling the pathways of cellular uptake of Antisense Oligonucleotides (ASOs), a promising therapy for several neurodegenerative diseases including Huntington’s Disease, Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. I am further interested in understanding mechanisms underlying defective nucleocytoplasmic compartmentalization and genome instability in aging and disease.
Ph.D. (Dr. Sc.), ETH Zurich (Switzerland), 2014
M.S., St. Petersburg State University (Russia), 2008
B.S., St. Petersburg State University (Russia), 2006