My research is centered on the study of neuromuscular junctions and the pathological mechanisms that drive muscle denervation in ALS. My efforts are principally focused on the discovery of molecules that have the potential to induce muscle reinnervation.
Ph.D., University of Barcelona, Spain, 2013
M.S., University of Barcelona, Spain, 2009
B.S., Autonomous University of Barcelona, Spain, 2006
2019 Muscular Dystrophy Association (MDA) Development Grant
2016 The Milton Safenowitz Post Doctoral Fellowship for ALS Research
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
When healthy cells divide, they bequeath an equal complement of chromosomes to each of their daughter cells—a capability often compromised in cancer. To ensure this occurs without error, dividing cells assemble a mitotic checkpoint complex (MCC). This complex inhibits the protein engine that greenlights the parceling out of chromosomes. MCC is, however, also produced at low levels in the early stages of the mitotic process, when it is thought to prevent a premature mitotic exit—a key stage of the cell cycle that signals the official end of mitosis. In this regard, I am interested in function of the actions of two functionally distinct enzymes, TRIP13 or APC/C and possible cancer therapy.
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
For my thesis work I am primarily focused on the targeted correction of RNA processing defects in the neurodegenerative diseases ALS and FTD, on engineering systems to degrade specific proteins in a cell, and genome-scale screens to determine the underpinnings of non-canonical cell uptake.
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.
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
Sonia Vazquez-Sanchez, Postdoctoral Fellow
TDP-43 is an RNA-binding protein that undergo liquid-liquid phase separation, resembling oil droplets in vinegar. In many neurodegenerative diseases such as ALS, TDP-43 forms solid aggregates, which are the major hallmark of the disease. A potential pathway to TDP-43 aggregation might be driven by an initial event of phase separation followed by transition to solid state. My postdoctoral efforts are designed to identify basic mechanisms underlining TDP-43 phase separation and its contribution to aberrant TDP-43 aggregation.
Ph.D., Neuroscience at Vrije Universiteit Amsterdam (VU), Marie Curie ITN-Cognitionnet fellow, The Netherlands, 2019
M.S., Biochemistry and Molecular Biology at Universidad Complutense de Madrid (UCM), Spain, 2014
Melinda Beccari, Ph.D. Student
Stathmin-2 is a protein shown to be crucial for motor neuron regeneration, and is depleted in ALS patients who present a TDP-43 pathology (which represents ~95% of cases). For my thesis work, I am interested in understanding the biology of this protein. I am investigating what roles this protein plays in neuronal axons, how it is regulated, and how it is involved in tubulin biology using iPS-derived motor neurons as a cellular model.
Roy Maimon, Postdoctoral Fellow
During my PhD I have demonstrated that ALS-diseased muscles secrete toxic factors which facilitate motor neuron degeneration in early stages of ALS disease. Currently, as postdoc fellow, I test a new concept for treating neurodegeneration: ASO-dependent generation of new neurons by direct conversion from astrocytes in the adult nervous system. Ultimately this approach may open new era for treating neurodegenerative diseases.
Ph.D., Tel Aviv University
M.S., Tel Aviv University
B.S., Bar Ilan University