Office: Bio IV 314A
Faculty page: http://www.umassmed.edu/faculty/show.cfm?faculty=1454
Frontotemporal dementia (FTD), a major clinical syndrome of frontotemporal lobar degeneration (FTLD), is an age-dependent neurodegenerative condition associated with focal atrophy of the frontal and/or temporal lobes. It is often associated with parkinsonism or amyotrophic lateral sclerosis (ALS), and is recognized now as the most common form of dementia before the age of 60. Unfortunately, the molecular pathogenesis of FTD remains largely unknown and effective treatments are not available. Recent exciting advances indicate that several proteins are involved in the pathogenesis of FTD and its related disorders, including CHMP2B, progranulin, TDP-43, and FUS. How these mutant proteins cause or contribute to neurodegeneration remains poorly defined.
Over the next a few years, we will use a combination of molecular, cellular, genetic, and behavioral approaches to further dissect the pathogenic mechanisms of mutant CHMP2B, progranulin and TDP-43, and identify common underlying pathways as potential targets for therapeutic interventions. To this end, multiple experimental systems will be utilized, including Drosophila, mouse models, and patient-specific induced pluripotent stem (iPS) cells.
List of Key papers
Lee A, Li W, Xu K, Bogert BA, Su K, Gao F-B. (2003) Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1. Development 130, 5543–5552.
Li W, Gao F-B. (2003) Actin filament–stabilizing protein tropomyosin regulates the size of dendritic fields. J. Neurosci. 23, 6171–6175.
Li W, Wang F, Menut L, Gao F-B. (2004) BTB/POZ-zinc finger protein Abrupt regulates dendritic branching in a neuronal subtype-specific and dosage-dependent manner. Neuron 43, 823–834.
Xu K, Bogert BA, Li W, Su K, Lee A, Gao F-B. (2004) The fragile X-related gene affects the crawling behavior of Drosophila larvae by regulating the mRNA level of the DEG/ENaC subunit Pickpocket1. Curr. Biol. 14, 1025–1034.
Li Y, Wang F, Lee J, Gao F-B. (2006) miRNA-9a ensures the precise specification of neuronal precursors in Drosophila. Genes Dev. 20, 2793–2805.
Sweeney NT, Brenman JE, Jan YN, Gao F-B. (2006) The coiled-coil protein Shrub controls neuronal morphogenesis in Drosophila. Curr. Biol. 16, 1006–1011.
Lee J-A, Beigneux A, Ahmad ST, Young SG, Gao F-B. (2007) ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr. Biol. 17, 1561–1567.
Xu, X, Li Y, Wang F, Gao F-B. (2008). The steady-state level of the nervous system-specific microRNA-124a is regulated by dFMR1 in Drosophila. J. Neurosci. 28:11883–11889.
Lee J-A, Gao F-B. (2009) Inhibition of autophagy induction delays neuronal cell loss caused by dysfunctional ESCRT-III in frontotemporal dementia. J. Neurosci. 29, 8506–8511.
Ahmad ST, Sweeney ST, Lee J-A, Sweeney NT, Gao F-B. (2009) A genetic screen identifies Serpin5 as a regulator of the Toll pathway and CHMP2B toxicity associated with frontotemporal dementia. Proc. Nat. Acad. Sci. USA. 106, 12168–12173.
Jiao J, Herl LD, Farese RV Jr, Gao F-B. (2010) MicroRNA-29b regulates the expression level of human progranulin, a secreted glycoprotein implicated in frontotemporal dementia. PLoS ONE 5, e10551.
Delaloy C, Liu L, Lee J-A, Su H, Shen F, Yang GY, Young WL, Ivey KN, Gao F-B. (2010) MicroRNA-9 coordinates proliferation and migration of human embryonic stem cells-derived neural progenitors. Cell Stem Cell 6, 323–335.
Xu XL, Zong R, Li Z, Biswas MH, Fang Z, Nelson DL, Gao F-B. (2011) FXR1P but not FMRP regulates the levels of mammalian brain-specific microRNA-9 and microRNA-124. J. Neurosci. 13:13705–13709.