![Alexandra Whiteley](/certificate/iqbiology/sites/default/files/styles/small/public/people/alexandra_whiteley.jpg?itok=Kdpq4EDL)
Office:ÌýJSCBB B222
³¢²¹²ú:ÌýJSCBB B250
Education
±Ê³ó¶Ù:ÌýBiomedical Sciences, Advisor: Jeoung Sook Shin, PhD. UCSF, 2008-2013
Postdoctoral Fellow:ÌýImmunology and Infectious Diseases, Advisor: Rick Brown, MD. Genentech, Inc., 2014-2016
Postdoctoral Fellow:ÌýCell 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 toÌýeukaryotic life through the regulation of protein degradation.ÌýUbiquitinatedÌýproteins bind to the proteasome via ‘intrinsic ubiquitin receptors’ – subunitsÌýof the proteasome capÌýwhich promote docking of ubiquitinated substrate to theÌýproteasome for subsequent degradation. In animal models,Ìýthese subunits areÌýessential to proper development and survival. In addition to intrinsic receptors, mammals alsoÌýexpress ‘extrinsicÌýubiquitin receptors’; these proteins are not subunits of the proteasome but areÌýcapable ofÌýsimultaneously and reversibly binding ubiquitinated proteins and theÌýproteasome. The largest family of extrinsicÌýubiquitin receptors are calledÌýUbiquilins (Ubqlns), which facilitate degradation of a poorly defined subset ofÌýubiquitinated proteins. Since their discovery, multiple Ubqlns have beenÌýimplicated inÌýcancerÌýand neurodegenerative disease. In particular, mutations in Ubqln2, which is highlyÌýexpressed inÌýneurons and muscle, were recently identified as the cause of anÌýX-linked, dominant form of familial AmyotrophicÌýLateral Sclerosis (fALS).Ìý
Recent work has shownÌýthat Ubqlns play a crucial role in the ubiquitin-proteasome system, which isÌýcentral toÌýcellular health, but major questions remain: do Ubqlns regulate theÌýsame clients regardless of cell type or stimulus?ÌýHow does the accumulation ofÌýthese clients impact cellular health? And how do these clients lead toÌýin vivoÌýpathology when Ubqln function isÌýlost? My laboratory aims to address these crucial questions using unbiased,Ìýmass-spectrometry based proteomics paired withÌýin vivoÌýand cell biological methods.
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