Summary
I am a Lecturer in the Department of Brain Sciences and an Academic Tutor for undergraduate Medicine at Imperial. I am also a Group Leader with a research team based at White City Campus and the UK DRI at Imperial.
Click here to visit The Ye lab website.
My research programme evolves around how toxic agents ("aggregates") that are associated with cell stress and neurodegeneration can be counterbalanced by the molecular recycling machines ("proteasomes") that are found abundantly in cells.
Click here for Selected Publications.
Read about my research to fight dementia in plain English.
Aggregation of misfolded proteins is a pathological process implicated in neurodegenerative disorders and dementia. While much research effort has focused on how aggregates are assembled, the reverse process of aggregate removal is less well-studied. Using advanced microscopy and cell biology approaches, my lab studies how proteasomes maintain cell homeostasis by targeting aggregates and how the ubiquitin-proteasome system is impaired in disease. Our recent results in vitro and in cells demonstrate that proteasomes restrict aggregate size and reorganise upon cell stress, assembling into foci around aggregates in a cytoskeleton-dependent manner. We are now focusing on the mechanisms underlying proteasome responses during aggregate formation in neurons, ultimately establish approaches to restrict and reverse dementia.
Our long-term goal is to identify distinct functions within the ubiquitin-proteasome system that will be amenable to therapeutic intervention at the different stages of neurodegeneration.
Professional Experience
2019- Principal Investigator and Fellow, UK DRI
Lecturer (Asst Professor), Imperial College London
2014-2018 Sir Henry Wellcome Research Fellow
Harvard Medical School and University of Cambridge
2012-2020 Research Fellow (JRF then Director of Studies in Natural Sciences), University of Cambridge
Education/Qualification
2012-2015 Junior Research Fellow (Henslow Research Fellowship, elected through open competition, sole awardee of >200 applicants)
University of Cambridge and Harvard Medical School
2008-2012 PhD candidate (Molecular Biology, Biochemistry and Biophysics) MRC Laboratory of Molecular Biology and University of Cambridge (St. John’s College)
2005-2008 BSc (Hons) Biochemistry/Biotechnology
Imperial College London
Short Biography
I (he/him) grew up in a small Nordic university town and have settled in the UK since undergraduate. Besides enjoying part of my postdoc fellowship in Boston in The Spirit of America, most of my time was spent in the nostalgic city of Cambridge. I am really thrilled to return to my alma mater and the innovative and diverse city of London.
Coming from a humble background, I have been immensely fortunate to have been guided by great mentors at various stages of my career. It is through their encouragement, as well as the unconditional support from my family, that I could pursue my goals without looking back.
When not busy in the lab, I enjoy racket sports, nature photography, tai chi (and others), chess (peak ecf 170, peak elo 1941) and beginner's Chinese calligraphy.
Selected Publications
Journal Articles
Morten MJ, Sirvio L, Rupawala H, et al., 2022, Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies., Proceedings of the National Academy of Sciences of the United States of America, Vol:119, ISSN:0027-8424, Pages:1-12
Mee Hayes E, Sirvio L, Ye Y, 2022, A potential mechanism for targeting aggregates with proteasomes and disaggregases in liquid droplets, Frontiers in Aging Neuroscience, Vol:14, ISSN:1663-4365
Ye Y, Klenerman D, Finley D, 2020, N-Terminal Ubiquitination of Amyloidogenic Proteins Triggers Removal of Their Oligomers by the Proteasome Holoenzyme, Journal of Molecular Biology, Vol:432, ISSN:0022-2836, Pages:585-596
Cliffe R, Sang JC, Kundel F, et al., 2019, Filamentous Aggregates Are Fragmented by the Proteasome Holoenzyme, Cell Reports, Vol:26, ISSN:2211-1247, Pages:2140-2149.e3
Zhang Y, Lippert AH, Lee JE, et al., 2018, Membrane potential regulates the dynamic localisation of mammalian proteasomes
Ye Y, Blaser G, Horrocks MH, et al., 2012, Ubiquitin chain conformation regulates recognition and activity of interacting proteins, Nature, Vol:492, ISSN:0028-0836, Pages:266-270