Liam L. Chen, M.D., Ph.D.
Primary Appointment in Pathology
My research interests focus on understanding the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. We use Drosophila, fruit fly, as a model to study the mechanisms underlying central nervous system malfunction in humans. We express pathological human genes in the fly to generate an abnormal phenotype, such as age-dependent learning and memory defect, slowed motor activity, neuronal or glial cell loss. This phenotype can then be used in conjunction with the rich genetic toolbox that Drosophila researchers have developed to identify pathways that contribute to this degeneration. Their small size, rapid generation time, and low costs for maintenance make fruit flies ideal for studying neurodegenerative disease. The Drosophila models provide a platform for genome-wide screens and unbiased genetic screens to identify components of pathological pathways.
Chen L, Periquet M, Wang X, Negro A, McLean PJ, Hyman BT, Feany MB. Tyrosine and serine phosphorylation of alpha-synuclein have opposing effects on neurotoxicity and soluble oligomer formation. J Clin Invest. 2009. 119(11):3257-65.
Nosho K, Shima K, Irahara N, Kure S, Firestein R, Baba Y, Toyoda S, Chen L, Hazra A, Giovannucci EL, Fuchs CS, Ogino S. SIRT1 histone deacetylase expression is associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Mod Pathol. 2009. 22(7):922-32.
Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci. 2005. 8(5):657-63.
Chen L, O'Keefe SL, Hodgetts RB. Control of Dopa decarboxylase gene expression by the Broad-Complex during metamorphosis in Drosophila. Mech Dev. 2002. 119(2):145-56.