Co-Mentors: Taeho Kim, PhD and Ricardo Dolmetsch, PhD
Cambridge, Massachusetts, United States
Research in our group is focused on finding treatments for monogenic, orphan neurodegenerative diseases such as Friedreich’s Ataxia (FA), Frontotemporal Dementia (FTD) and Spinal Muscular Atrophy. We employ a variety of tools, e.g., iPS cell-derived neuronal models and next-generation sequencing, to develop disease-relevant cellular models, perform screens, and elucidate key pathways dysregulated in the disease state. While the high unmet medical need in these orphan diseases motivates our interest, we are also keen to elucidate common pathological mechanisms (including dysregulated proteostasis, inflammation, and mitochondrial dysfunction) driving neurodegenerative disease progression in general. We have recently developed robust cellular models to monitor neuronal and microglia dysfunction in FTD and have identified novel candidate pathways involved in these diseases. Furthermore, using innovative proteomic technology, we have identified unique approaches to interrogate signaling pathways implicated in neuronal survival and neuroinflammatory processes. Our current aim is to validate and investigate pathways that go awry in pathological conditions, with the ultimate goal of developing disease modifying therapies for FTD and related neurodegenerative disorders.
SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. Palacino J, Swalley SE, Song C, Cheung AK, Shu L, Zhang X1, Van Hoosear M, Shin Y, Chin DN, Keller CG, Beibel M, Renaud NA, Smith TM, Salcius M, Shi X, Hild M, Servais R, Jain M, Deng L, Bullock C, McLellan M, Schuierer S, Murphy L, Blommers MJ, Blaustein C, Berenshteyn F, Lacoste A, Thomas JR, Roma G, Michaud GA, Tseng BS, Porter JA, Myer VE, Tallarico JA, Hamann LG, Curtis D, Fishman MC, Dietrich WF, Dales NA, Sivasankaran R. Nat Chem Biol. 2015 Jul;11(7):511-7.