Office:听JSCBB B222
尝补产:听JSCBB B250
Education
笔丑顿:听Biomedical Sciences, Advisor: Jeoung Sook Shin, PhD. UCSF, 2008-2013
Postdoctoral Fellow:听Immunology and Infectious Diseases, Advisor: Rick Brown, MD. Genentech, Inc., 2014-2016
Postdoctoral Fellow:听Cell Biology, Advisor: Daniel Finley, PhD. Harvard Medical School, 2016-2019
Areas of Expertise
Cell Signaling, Proteins, and Enzymology
Research
Understanding Ubiquilins: Facilitators of protein degradation
The ubiquitin-proteasome system is essential to听eukaryotic life through the regulation of protein degradation.听Ubiquitinated听proteins bind to the proteasome via 鈥榠ntrinsic ubiquitin receptors鈥� 鈥� subunits听of the proteasome cap听which promote docking of ubiquitinated substrate to the听proteasome for subsequent degradation. In animal models,听these subunits are听essential to proper development and survival. In addition to intrinsic receptors, mammals also听express 鈥榚xtrinsic听ubiquitin receptors鈥�; these proteins are not subunits of the proteasome but are听capable of听simultaneously and reversibly binding ubiquitinated proteins and the听proteasome. The largest family of extrinsic听ubiquitin receptors are called听Ubiquilins (Ubqlns), which facilitate degradation of a poorly defined subset of听ubiquitinated proteins. Since their discovery, multiple Ubqlns have been听implicated in听cancer听and neurodegenerative disease. In particular, mutations in Ubqln2, which is highly听expressed in听neurons and muscle, were recently identified as the cause of an听X-linked, dominant form of familial Amyotrophic听Lateral Sclerosis (fALS).听
Recent work has shown听that Ubqlns play a crucial role in the ubiquitin-proteasome system, which is听central to听cellular health, but major questions remain: do Ubqlns regulate the听same clients regardless of cell type or stimulus?听How does the accumulation of听these clients impact cellular health? And how do these clients lead to听in vivo听pathology when Ubqln function is听lost? My laboratory aims to address these crucial questions using unbiased,听mass-spectrometry based proteomics paired with听in vivo听and cell biological methods.
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