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Our Researchers

Therapeutic Research

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K. Mukherjee, Ph.D

Assistant Professor at the Franlin Biomedical Research Instititue VTC

Dr K. Mukherjee obtained his MBBS degree from Indira Gandhi Medical College in Nagpur, India. Thereafter he switched his career to scientific biomedical research and pursued a Ph.D from National Institute of Immunology, New Delhi, India. The bulk of his postdoctoral work was done under the supervision of the Nobel laureate neuroscientist, Professor Thomas Sudhof at UT Southwestern Medical center at Dallas, USA and Stanford University School of Medicine, Palo Alto, USA. He also received training in the laboratories of prominent neuroscientists, Professor Reinhard Jahn at Max Planck Institute of Biophysical Chemistry, Gottingen, Germany and Professor Leslie Griffith at Brandeis University, Waltham, USA.
In his own laboratory at Fralin Biomedical Research Institute, Virginia Tech, Dr Mukherjee has combined his clinical and scientific background to develop a research program aimed at understanding the pathogenesis of CASK-linked disorder and then design interventional strategies.

Cure Cask Research

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Kyle Fink

Assistant Professor University of California Davis, Department of Neurology

Dr. Fink’s lab is focused on the therapeutic development of gene modifying modalities such as Zinc Fingers, Transcription Activator-like Effectors, and CRISPR/Cas9 to treat genetically-linked neurological disorders. Dr. Fink’s unique academic training and research experience have provided me with an excellent background in multiple biological disciplines including neuroscience, molecular biology, microbiology, chemistry, and genetics. As a graduate student with Dr. Gary Dunbar and Dr. Laurent Lescaudron, my research focused on therapeutic potential of genetically-engineered stem cells in animal models of Huntington’s disease. This work was performed under an international fellowship provided by the French Embassy of Science and Technology to work with a neuroimmunology group at an INSERM lab in France. During his undergraduate and graduate careers, he received several research awards, including the being named the top neuroscience predoctoral student in the state of Michigan. During my postdoctoral training, Dr. Fink was awarded a Ruth L. Kirschstein National Research Service Award from the NIH to develop novel gene therapies for Huntington’s Disease, with Dr. Jan Nolta, a world’s leader in regenerative medicine. Dr. Fink has also played an integral role in obtaining grant funding from NIH, CIRM, UPenn Orphan Disease Center, the Loulou Foundation and Rett Syndrome Trust to develop gene modifying therapies. His lab is focused on translating novel gene modifying therapeutics using patient-derived human iPSC, transgenic rodents, and large animals for translation.
Dr. Fink’s group focuses on assessments of cellular phenotypes in human models of disease, such as induced pluripotent stem cells, indictors of molecular efficacy in transgenic rodent models, and optimization of delivery modalities, such as viral vectors, liponanoparticles and hemapoetic blood and mesenchymal stem cells
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Jill Lynn Silverman, PH.D

Professor

The overarching Silverman laboratory goal is to apply her 20 years of experience with rodent model systems to design and implement effective translational science for neurodevelopmental disorders (NDDs) in four thematic areas. Her research uses multi-faceted approaches in order to: 1) define clinically relevant outcome measures and identify biological markers using next generation genetic models of intellectual disability (ID), autism spectrum disorders (ASD) and paediatric epilepsy with known genetic origins; 2) develop rigorous methods for phenotypic detection in rat models of NDDs and neurodegenerative disorders; 3) continue to evaluate the most prominent environmental contributors to risk of NDDs and neurodegenerative disorders; and 4) utilize innovative, non-behaviorally based phenotypes, such as ex and in vivo neuroimaging, and neurophysiology including EEG, sleep/circadian analysis and sleep spindle modulation, which are biomarkers and translationally relevant to the symptoms of multiple brain disorders.
A major goal of the Department of Psychiatry is fostering distinguished basic neuroscience research. Dr. Silverman’s translational research on the causes of, and development of treatments for, severe genetically based neurodevelopmental disorders (NDDs), is a timely and crucial component to the department. During this evaluation period, from 2017-2020, Dr. Silverman expanded her independent research program that uses novel preclinical rodent models and innovative assays for translational research to include several new techniques and to narrow down therapeutic discovery angles from the wide array of repurposed existing compounds to the development, validation, safety and efficacy testing of gene and stem cell based “curative, precision strategies,” for single gene caused NDDs, IDs and pediatric epilepsy. This shift from treatment screening to focused development of innovative cures occurred organically as the Silverman lab shifted from non-known causal or idiopathic ASDs to known genetic syndromic NDDs.
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David Segal, Ph.D

Professor

Research Interests

Zinc finger, TALE, CRISPR/Cas genome engineering and targeted gene regulation for applications in research and therapeutics, especially neurologic disorders.

Research Synopsis

  • Molecular therapy for neurologic genetic diseases
    Together with the labs of Kyle Fink and Jill Silverman, we are developing molecular therapies for neurologic disorders. We use programable DNA- or RNA-binding platforms (Zinc finger, TALE, CRISPR/Cas9, Cas12, Cas13) to cause long-term changes in the expression of disease genes. This approach avoids problematic double-strand breaks. We use a variety of delivery systems (protein, AAV, lipo-particles, stem cells) to treat the brain in animal models of disease, which are extensively characterized on a molecular and behavioral level. A flagship project is Angelman syndrome, for which the therapeutic strategy is to reactivate a silenced gene in the brain. We collaborate with groups around the world to de-risk genetic therapies for this and several other related disorders.
  • Epigenetics of non-genetic mental illness
    Fortunately, monogenic disorders are rare. However, adverse experiences/ exposures in early life (stress, impoverished conditions, abuse) and later life (PTSD) can lead to adverse mental health outcomes later in life. There is evidence that the experience cause long-term epigenetic changes that play a role in the long-term outcomes. Can we identify the causative changes? Can we reverse them with epigenetic editing?
  • Determinants of epigenetic persistence
    In a related effort, seek to understand how nature causes life-long changes in gene expression. Interestingly, we know a lot about active and inactive epigenetic states, but far less about how to transition from one state to another. Our most recent efforts focus on creating epigenomic editing tools that can precisely manipulate epigenetic information at specific loci. We employ methods of genome wide screens for regulatory elements and genes, as well as ChIP-seq and RNA-seq to examine effects on a genome-wide scale. Such tools can be used for the long-term control of gene expression for both research and therapeutic applications.

Addressing the challenges for gene editing in the clinic.
As part of the NIH Somatic Cell Genome Engineering consortium, we continue to develop new methodologies for genome editing and delivery in small and large animal models. Our work involves testing new viral vectors and a detailed analysis of on- and off-target editing in live animals. The SCGE consortium is composed of 40+ labs around the country. Through the Innovative Genomics Institute at UC Berkeley, we are creating new molecular tools for manipulating and studying the genome. We have recently developed molecular probes that can detect unique DNA sequences (such as a gene edit) in individual living cells. And that’s just the beginning.

Cure cask
Julian Halmai

Postdoctoral Scholar

As a postdoctoral scholar under the mentorship of Dr. Kyle Fink, Julian’s research focusses on epigenome editing strategies to specifically target epi-alleles of genes that are causative for disease utilizing the DNA binding platform CRISPR/dCas9 fused to transcriptional activators and epigenetic editors.

These DNA modifying modalities are engineered to alter gene-expression with the ultimate goal to permanently change aberrantly transcribed genes as a novel therapeutic approach.Julian’s work is focused on adapting CRISPR in a translational manner for genetically-linked neurodevelopmental disorders of the X chromosome, including CDKL5 deficiency (a rare intractable pediatric epilepsy) and Rett syndrome.

Julian been awarded a competitive CDKL5 junior fellowship award and his primary author manuscript has been cited in the top three “must read” publications from the CDKL5 forum. In his current research he is interested in altering the epigenetic landscape of the target gene by means of epigenetic effector domains and analysing its impact on gene reactivation. This includes the removal of repressive histone marks, and the addition of marks that are representative of active promoters and enhancer elements.

His recent work demonstrates that targeted X chromosome reactivation is feasible and can potentially be used as a therapeutic approach to those suffering from X-linked disorders, such as Rett syndrome. In addition he has also been instrumental in novel delivery methods of these epigenetic editors into the brain in a mouse model of Angelman syndrome.