Assistant Professor at the Franlin Biomedical Research Instititue VTC
Cure Cask Research
Assistant Professor University of California Davis, Department of Neurology
Zinc finger, TALE, CRISPR/Cas genome engineering and targeted gene regulation for applications in research and therapeutics, especially neurologic disorders.
- 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.