Jan Nolta, Ph.D.
Stem Cell Program
Dr. Nolta is the Director of the Stem Cell Program at UC Davis School of Medicine, and directs the new Institute for Regenerative Cures. The UC Davis stem cell program has over 145 faculty members collaborating to work toward stem cell-related cures for a spectrum of diseases and injuries. The current research in Dr. Nolta’s laboratory is focused on developing therapies that will use mesenchymal stem cells (MSCs) to deliver factors for treating Huntington’s disease and other disorders and injuries. Her group focuses on “bench to the bedside” research, and she has been involved in numerous clinical trials of gene and cell therapy. She is scientific director of the new Good Manufacturing Practice clean room facility at UC Davis, where stem cells of different types are being isolated or expanded for clinical trials.
The basic research in the Nolta laboratory focuses on understanding the dynamics of stem cell migration and attraction to sites of injury. Following intravenous infusion, adult stem cells home to sites of tissue damage. Areas studied are cellular response to hypoxia and chemokines, cell motility, cell-to-cell interactions, and paracrine factors secreted by MSC at the site of injury.
David Segal, Ph.D.
Almost every disease has a genetic component. Often this information is used only to determine how condemned a person is to develop disease. We would like to use the genetic information to fix the disease. A guiding principle for our work has been to study how nature does what it does, then attempt to use that knowledge to make useful tools to improve public health, either through increased knowledge or therapeutic intervention. Specific research foci in the Segal Lab revolve around engineering zinc finger, TALE, and CRISPR/Cas nucleases and transcription factors.
- Manipulating epigenetic mechanisms in neurologic genetic diseases
Angelman syndromes is a rare neurogenetic disease that is the textbook examples of imprinting disorder. We are using artificial transcription factors to activate the epigenetically silenced gene in in the brain. This project is funded by the Foundation for Angelman Syndrome Therapeutics..
- Functional genomics of non-coding elements
In collaboration with Peggy Farnham and the ENCODE consortium, we are using targetable nucleases and transcription factors based on zinc fingers, Transcription Activator-like Effector (TALE), and Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein (CRISPR/Cas) to disrupt non-coding genetic elements in the human genome to better understand their function. Our most recent efforts focus on creating epigenomic editing tools that can precisely manipulate epigenetic information at specific loci. Such tools can be used for the long-term control of gene expression for both research and therapeutic applications.
- Genetic variation in health and disease
Several genetic variations (SNPs) have been associated with an increased risk of common complex disorders, such as colorectal cancer. In collaboration with Luis Carvajal-Carmona, we are using targetable nucleases identify causative SNPs and determine their mechanism of function. Our most recent efforts focus on creating tools that can precisely alter a single base pair at specific loci. Our approach overcomes the historic barrier of trying to study the affects of specific human mutations in a background of millions of other genetic differences between two individuals.
- High-throughput investigations of CRISPR-DNA interactions
We continue to develop new methodologies for genome editing, such as methods to study off-target activity of CRISPRs and factors for targeted epigenetic modification. We employ methods of directed evolution for protein engineering and ChIP-seq and RNA-seq to examine the effects of tools on a genome-wide scale.
Kyle Fink, Ph.D.
Neurology and Institute for Regenerative Cures
Dr. Fink received his Ph.D. in Neuroscience from Central Michigan University and the University of Nantes. He trained as a Postdoctoral Scholar on a Ruth L. Kirschstein NRSA Fellowship from NINDS with Jan Nolta at UC Davis. He became an Assistant Professor at UC Davis in the Department of Neurology in 2017. His lab focuses 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. The key focus of the lab in this field involves understanding the therapeutic benefit in human cellular models of disease, functional efficacy in transgenic rodent models, and optimization of delivery modalities in clinically-relevant models. The Fink lab is developing gene modifying therapies for HD, Angelman Syndrome, CDKL5 deficiency disorder, Rett Syndrome, and Jordan’s Syndrome. His lab focuses on translating novel gene modifying therapeutics using patient-derived human iPSC, transgenic rodents, and large animals to develop gene modifying and stem cell and therapies for clinical trials. His team builds on the existing strengths and expertise at UC Davis and utilizes the necessary resources to develop a therapeutic pipeline in which precision medicine can be used to identify novel disease-causing genetic variants to advance Precision Neurotherapeutics to clinical applications.
His current research focuses on two major goals 1) The therapeutic application of transcription activator-like effector (TALE) and clustered regularly interspaced short palindrome repeats (CRISPR) to modify gene expression in genetically-linked pediatric neurological diseases; and 2) the development of delivery systems that can safely and efficaciously target the central nervous system with our novel gene editing platforms. These goals specifically address: A) how to deliver these potent therapeutics to maximize the biodistribution in the central nervous system; B) how to increase the specificity of each construct to limiting off-target effects; and C) how to minimize the immune response to increase safety and the therapeutic potential of this approach. These platforms can turn on or enhance transcription of a gene, transcriptionally silence expression, cause permanent epigenetic changes, or remove a piece of DNA via targeted double stranded breaks essentially allowing for custom modifications to be made at the genomic level.
Randi Hagerman, M.D.
Medical Director, UC Davis MIND Institute, Distinguished Professor, Endowed Chair in Fragile X Research, Department of Pediatrics, UC Davis School of Medicine
Dr. Randi Hagerman is a developmental and behavioral pediatrician and the Medical Director of the MIND Institute at UC Davis. She is internationally recognized as both a clinician and researcher in the fragile X field. Dr. Hagerman received her M.D. from Stanford University where she also carried out her Pediatric residency. She completed a Fellowship in Learning and Disabilities and Ambulatory Pediatrics at UC San Diego and, subsequently, spent the next 20 years from 1980 to 2000 at the University of Colorado where she headed Developmental and Behavioral Pediatrics. She co-founded the National Fragile X Foundation in 1984 in Colorado and developed a world-renowned fragile X research and treatment center. In 2000, Professor Hagerman moved to UC Davis to be the Medical Director of the MIND Institute. Dr. Hagerman and her team discovered the Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) which is a neurological disorder that affects older male and rare female carriers of fragile X. Dr. Hagerman’s research involves genotype-phenotype correlations in fragile X and she carries out this research in collaboration with her husband, Paul Hagerman, M.D., Ph.D. Professor Randi Hagerman has written over 200 peer-reviewed articles and numerous book chapters on neurodevelopmental disorders. She has written several books on fragile X including a 3rd Edition of Fragile X Syndrome: Diagnosis, Treatment, and Research which was published in 2002 by Johns Hopkins University Press. Dr. Hagerman has received numerous awards for her research in fragile X syndrome including the Jerrett Cole Award from the National Fragile X Foundation for unselfish dedication to work with fragile X children and adults, the Bonfils-Stanton Foundation Award for Science including Medicine, the IASSID Distinguished Achievement Award for Scientific Literature, the 2005 Distinguished Scholarly Public Service Award from UC Davis, and the 2006 Dean’s Award for Outstanding Mentoring at UC Davis. In 2004, to honor both Randi and Paul Hagerman in recognition of their work in FXTAS, the National Fragile X Foundation established the Hagerman Award. This award recognizes research accomplishments in the field of FXTAS and is given at the bi-annual International Conference on Fragile X. In 2008, the National Fragile X Foundation again honored Dr. Hagerman with a Lifetime Achievement Award. Dr. Hagerman has worked internationally to establish fragile X clinical programs and research programs throughout the world. Dr Hagerman is currently carrying out multiple targeted treatment trials in FXS and in autism including a controlled trial of Arbaclofen, minocycline, ganaxolone, mGluR5 antagonists developed by Roche and another by Novartis, and sertraline. She is also the PI of a controlled trial of memantine in older fragile X premutation carriers with FXTAS.
Tata Monfared’s wide-ranging life and career activities have all been governed by an abiding passion to be a bridge-builder across boundaries of country, culture, politics and time. Toward that end, she has filled a number of roles that have now found common purpose and expression in the creation of Senses Cultural, an organization dedicated to raising awareness and research on autism and neurological disorders in Iran, the Middle East, Asia and in the Middle East and Asian communities in the United States.