Sharan Srinivasan, M.D., Ph.D.
Biography: Dr. Srinivasan’s research interests focus on developing targeted therapeutics for neurodegenerative disease. He completed his undergraduate degrees in both Biochemistry and Molecular Biology at Northwestern University. Following this, he enrolled in the Medical Scientist Training Program at the University of Michigan Medical School, earning an M.D./Ph.D. upon completion. During his graduate thesis work, Dr. Srinivasan worked on developing small molecular inhibitors of heat shock proteins towards destabilizing the proteome as a targeted anti-cancer therapeutic. His work helped uncover a novel cell death pathway that may be hijacked by both scientists and clinicians to help therapeutics avoid resistance. Currently, he is completing his neurology residency training and plans to specialize with a fellowship in Movement Disorders.
Project Title: Increasing BK Channel Activity towards Treatment of Spinocerebellar Ataxia.
Project description: Spinocerebellar Ataxia is characterized by absent spontaneous firing of purkinje cells in the cerebellum. These deficits in potassium channel activity lead not only to disease symptoms, but also eventual cerebellar atrophy. Using a combination of site-directed mutagenesis, targeted drug design, and high-throughput screening, Dr. Srinivasan will work towards identifying compounds that improve BK channel activity leading to both symptomatic relief and disease modifying therapies for these devastating diseases.
Project mentors: Vikram Shakkottai, M.D., Ph.D.; Vince Groppi, Ph.D.
Jason Chua, M.D., Ph.D.
Biography: Dr. Chua's primary research interest is in neurodegenerative disease, with a special focus on pathways of protein quality control and their impact on disease pathogenesis. After completing his undergraduate degree in Biology and Classical Studies at Brown University, Dr. Chua earned his M.D. and Ph.D. through the Medical Scientist Training Program at the University of Michigan Medical School. His thesis work investigated the influence of SUMOylation and macroautophagy on disease pathogenesis in spinobulbar muscular atrophy, or Kennedy's disease. His work was supported by the F31 Ruth L. Kirschstein National Research Service Award through the National Institute of Neurologic Disorders and Stroke. He is currently undergoing residency training in neurology at Michigan Medicine and plans to specialize in Movement Disorders.
Project Title: Characterizing the molecular and cell-specific determinants of neuronal autophagy.
Project description: Using an induced pluripotent stem cell (iPSC) model system derived from fibroblasts of amyotrophic lateral sclerosis (ALS) patients, Dr. Chua will determine the specific RNA and protein effectors that differentially regulate neuronal autophagy compared to non-neuronal cell types. These studies will provide crucial information for targeting neuronal autophagy in a novel, highly specific fashion for therapy development in ALS and other neurodegenerative diseases.
Project mentors: Sami Barmada, M.D., Ph.D.; Lois Weisman, Ph.D.
Kevin Chen, M.D.
Biography: Dr. Chen is primarily interested in cell based therapies for neurologic diseases. Dr. Chen completed his undergraduate education at Johns Hopkins University, where he worked extensively with Prof. Lee Martin on Motor Neuron Disease. He received his M.D. from Duke University, and entered the Neurosurgery Residency at the University of Michigan. Dr. Chen was supported by the UMCNTP for 2 years during his residency to pursue research on cell based therapies. He is presently a Fellow in Functional Neurosurgery at Stanford University.
Project Title: Inhibitory synapse formation and reversal of excitotoxicity in amyotrophic lateral sclerosis (ALS): a potential mechanism for human spinal cord stem cell transplantation.
Project Description: Dr. Chen developed methods to differentiate human embryonic stem cells into inhibitory neurons. The ability of these cells and other human embryonic stem cells to modify neurodegeneration in models of ALS was evaluated. Dr. Chen assessed whether the effects of human embryonic stem cell transplantation are mediated by modulation by excitotoxic injury.
Project Mentor: Eva L. Feldman, M.D., Ph.D.
Andrew Sas, M.D., Ph.D.
Biography: Dr. Sas is interested in mechanisms of injury and repair in traumatic brain injury, particularly closed head injury. He received his undergraduate education at Dickinson College. He earned his M.D. and Ph.D. degrees at the Medical University of South Carolina with his dissertation work on HIV encephalopathy. He entered the UMCNTP during his Neurology residency at Michigan. He was supported by the UMCNTP during and after residency, concurrently pursuing a fellowship in Sports Neurology. He was appointed to the Neurology faculty at Michigan in 2018 and is the recipient of a K08 award from the National Eye Institute.
Project Title: Immune-driven repair pathways following traumatic injury to the central nervous system.
Project Description: Dr. Sas studied axonal regeneration in an optic nerve crush model of traumatic injury. Intraocular inflammation enhances axonal outgrowth in this model. Dr. Sas established that the beneficial effects of intraocular inflammation are secondary to influx of a distinct population of circulating white cells. He is presently isolating the specific molecular factors mediating the beneficial effects of these inflammatory cells.
Project Mentor: Benjamin Segal, M.D.