PEOPLE

Kelvin C. Luk, PhD

Research Assistant Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine

Contact Information3600 Spruce St
1 Maloney Building
HUP
Philadelphia, PA 19104
Office: 215-615-3202
Fax: 215-615-3206

Email: kelvincl@pennmedicine.upenn.edu

Specialty Division

Neuropathology, Immunobiology and Experimental Pathology

Research Expertise

My research aims to improve our understanding of the synucleinopathies, a group of neurodegenerative disorders that include Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). PD is a progressive neurodegenerative condition that affects over 1 million individuals in the U.S. alone, and for which there is currently no cure. Lewy bodies are also found in nearly half of all Alzheimer's disease patients examined at autopsy.

Our lab's current efforts focus on three major themes:

1) The Role of Protein Misfolding in PD and Related Synucleinopathies: Histopathological, genetic, and experimental evidence suggest that the aggregation and accumulation of alpha-synuclein (α-Syn), the primary component of Lewy bodies, underlies the symptoms seen in PD. We previously demonstrated that aggregated forms of α-Syn are transmissible entities that propagate and spread throughout the brain in a manner akin to prion diseases. This exciting discovery represents a significant shift in our understanding of PD etiology and progression. Through the development of novel biophysical, cell-based and animal models, my work seeks to identify factors that a) regulate α-Syn expression and misfolding, b) determine its route of transmission and c) modulate the toxicity of α-Syn pathology.

2) Novel Therapeutics Against Synucleinopathies: Present PD treatments provide temporary relief to motor impairments but do not alter the neurodegenerative process. In collaboration with UPenn’s Center for Neurodegenerative Disease Research Drug Discovery group, our team has been developing high-throughput screening assays to identify small molecules and biologicals that inhibit the accumulation and transmission of abnormal α-syn species or neutralize their action.

3) Biology of Midbrain Dopamine Neurons: PD is primarily a movement disorder that results from the loss of dopamine-producing neurons in the midbrain. The reasons why this subpopulation is particularly vulnerable in PD is unclear. By characterizing the pathways that govern their development and maintenance, we and others have shown that a susceptible dopamine cells are defined by specific transcription factors that regulate their survival in adulthood. More recently, we have also examined the mechanisms underlying the selective vulnerability in other non-dopamine neuron subpopulations.

This research is conducted by a talented and dedicated team of research specialists, postdoctoral researchers, and students. We are regularly in search of new members.

Itmat Expertise

Neurodegeneration, Parkinson's disease, drug discovery, cell-models, animal models, dementia, alpha-synuclein

Graduate Groups

Neuroscience

Education

BSc (Microbiology and Immunology), McGill University, 1997
PhD (Pathology), McGill University, 2004
MTR (Translational Research), University of Pennsylvania, 2013

Specialty Certification

Postgraduate Training

Postdoctoral fellowship, University of Pennsylvania, 2005-2009

Awards and Honors

Doctoral Research Award / Canadian Institutes for Health Research, 2000-2003
Teuber-Neysmith Graduate Research Award, Montreal Neurological Institute, 2002
Research Fellowship, University of Pennsylvania Institute for Translational Medicine and Therapeutics (ITMAT), 2010-2012

Memberships and Professional Organizations

Society for Neuroscience, 2004 - Present
Parkinson's UK, 2013 - Present
Fonds National de la Recherche Luxembourg, 2014 - Present
Medical Research Council, UK, 2015 - Present
Cure Parkinsons Trust (UK), 2017 - Present
Research Grants Council of Hong Kong, 2017 - Present
NIH/NINDS, 2017 - Present
Deutsche Forschungsgemeinschaft (DFG), 2017 - Present
Michael J. Fox Foundation, 2019 - Present
Austrian Science Fund, 2020 - Present

Web Links


Selected Publications

Neuronal activity modulates alpha-synuclein aggregation and spreading in organotypic brain slice cultures and in vivo

Wu Q, Shaikh MA, Meymand ES, Zhang B, Luk KC, Trojanowski JQ, Lee VM, Acta Neuropathologica, 2020, PMID:33021680

Read article

Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau

Darwich NF, Phan JM, Kim B, Suh E, Papatriantafyllou JD, Changolkar L, Nguyen AT, O'Rourke CM, He Z, Porta S, Gibbons GS, Luk KC, Papageorgiou SG, Grossman M, Massimo L, Irwin DJ, McMillan CT, Nasrallah IM, Toro C, Aguirre GK, Van Deerlin VM, Lee EB, Science, 2020, PMID:33004675

Read article

GDNF/RET Signaling Pathway Activation Eliminates Lewy Body Pathology in Midbrain Dopamine Neurons

Chmielarz P, Er Ş, Konovalova J, Bandres L, Hlushchuk I, Albert K, Panhelainen A, Luk K, Airavaara M, Domanskyi A, Movement Disorders, 2020, PMID:32964492

Read article

Perturbation of in vivo Neural Activity Following α-Synuclein Seeding in the Olfactory Bulb

Kulkarni AS, Del Mar Cortijo M, Roberts ER, Suggs TL, Stover HB, Pena-Bravo JI, Steiner JA, Luk KC, Brundin P, Wesson DW, Journal of Parkinsons Disease, 2020, PMID:32925105

Read article

Snca-GFP knock-in mice reflect patterns of endogenous expression and pathological seeding

Caputo A, Liang Y, Raabe TD, Lo A, Horvath M, Zhang B, Brown HJ, Stieber A, Luk KC, eNeuro, 2020, PMID:32788297

Read article

Impact of α-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized α-synuclein rat model of PD

Hoban DB, Shrigley S, Mattsson B, Breger LS, Jarl U, Cardoso T, Nelander Wahlestedt J, Luk KC, Björklund A, Parmar M, PNAS, 2020, PMID:32541058

Read article

Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of α-synuclein-preformed fibril-induced toxicity and motor deficits

Gezer AO, Kochmanski J, VanOeveren SE, Cole-Strauss A, Kemp CJ, Patterson JR, Miller KM, Kuhn NC, Herman DE, McIntire A, Lipton JW, Luk KC, Fleming SM, Sortwell CE, Bernstein AI, Neurobiology of Disease, 2020, PMID:32422283

Read article

Characterization of novel conformation-selective alpha-synuclein antibodies as potential immunotherapeutic agents for Parkinson's disease

Henderson MX; Covell DJ; Chung CH; Pitkin RM; Sandler RM; Decker SC; Riddle DM; Zhang B; Gathagan RJ; James MJ; Trojanowski JQ; Brunden KR; Lee VMY; Luk KC, Neurobiology of Disease 136(): https://doi.org/10.1016/j.nbd.2019.104712, 2019, PMID:31837422

Read article

Intrastriatal Alpha-Synuclein Fibrils in Monkeys: Spreading, Imaging and Neuropathologic Changes

Chu Y, Muller S, Tavares A, Barret O, Alagille D, Seibyl J, Tamagan G, Marek K, Luk KC, Trojanowski JQ, Lee VMY, Kordower JH, Brain, 2019, PMID:31580415

Read article

Slow Progressive Accumulation of Oligodendroglial Alpha-Synuclein (α-Syn) Pathology in Synthetic α-Syn Fibril-Induced Mouse Models of Synucleinopathy

Uemura N, Uemura MT, Lo A, Bassil F, Zhang B, Luk KC, Lee VM, Takahashi R, Trojanowski JQ, J Neuropathol Exp Neurol 78(10): 877-890, 2019, PMID:31504665

Read article

Search PubMed for articles