Research

Research Focus: Stem cells, cell reprogramming, neurodegenerative diseases, and drug discovery

We are focused on gaining deeper insights into the biology of neurodegenerative and neurodevelopmental diseases, and in translating such knowledge into developing effective therapies. Existing literature highlight the role of mitochondrial dysfunction, oxidative stress, metabolic changes and aberrant proteostasis in the pathology of these diseases. However, it is still unclear what trigger these events at the onset of disease, and how are they orchestrated to cause neuronal damage. Toward addressing these fundamental questions we have developed human stem cell based (hiN, hiPSC, and hiPSC-derived brain organoid) “disease in a dish models” and complement those studies with a wide variety of in vivo animal experiments. We take an interdisciplinary approach by integrating functional genomics, proteomics and metabolomics to garner insights using the above model systems and then translate such knowledge into developing drugs. Using these strategies we recently showed how environment (e.g. pesticide exposure) and genes conspire in orchestrating aberrant cellular events leading to the apoptotic cell death in patient hiPSC-derived A9 dopaminergic neurons, the major cell type affected in Parkinson’s disease (PD) (Cell, 2013), and discovered novel lead compounds for therapeutic development in PD by targeting such “events” in an high-throughput small molecule screening (HTS) effort. We are taking similar strategies in studying Alzheimer’s disease (AD), Autism Spectrum Disorders (ASD) and neuronal damages observed in Mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes (MELAS) syndrome.

We are also actively involved in developing cell therapy for Parkinson’s disease and Stroke using our stem cell based platforms. We use optogenetics, in vivo imaging, behavioral read outs and histopathological assessments to evaluate/optimize our stem cell transplantation strategies in our animal models (Rats, Mice and African Green Monkeys). The NIH, CIRM and industrial partners on these projects support our efforts.