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

1) 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 or neutralize abnormal α-syn species.

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.

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
Deutsche Forschungsgemeinschaft (DFG), 2017 - Present
Research Grants Council of Hong Kong, 2017 - Present
NIH/NINDS, 2017 - Present
Cure Parkinsons Trust (UK), 2017 - Present
Michael J. Fox Foundation, 2019 - Present

Web Links


Selected Publications

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

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Time course and magnitude of alpha-synuclein inclusion formation and nigrostriatal degeneration in the rat model of synucleinopathy triggered by intrastriatal α-synuclein preformed fibrils.

Patterson JR, Duffy MF, Kemp CJ, Howe JW, Collier TJ, Stoll AC, Miller KM, Patel P, Levine N, Moore DJ, Luk KC, Fleming SM, Kanaan NM, Paumier KL, El-Agnaf OMA, Sortwell CE, Neurobiology of Disease 130(): 104525, 2019, PMID:31276792

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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

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Seeding of protein aggregation causes cognitive impairment in rat model of cortical synucleinopathy.

Espa E, Clemensson EKH, Luk KC, Heuer A, Björklund T, Cenci MA, Movement Disorders, 2019, PMID:31449702

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Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders.

Schaser AJ, Osterberg VR, Dent SE, Stackhouse TL, Wakeham CM, Boutros SW, Weston LJ, Owen N, Weissman TA, Luna E, Raber J, Luk KC, McCullough AK, Woltjer RL, Unni VK, Scientific reports 9(1): 10919, 2019, PMID:31358782

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Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo.

Patterson JR, Polinski NK, Duffy MF, Kemp CJ, Luk KC, Volpicelli-Daley LA, Kanaan NM, Sortwell CE, Journal of visualized experiments : JoVE, 2019, PMID:31205308

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The center of olfactory bulb-seeded α-synucleinopathy is the limbic system and the ensuing pathology is higher in male than in female mice.

Mason DM, Wang Y, Bhatia TN, Miner KM, Trbojevic SA, Stolz JF, Luk KC, Leak RK, Brain pathology, 2019, PMID:30854742

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Stereotaxic Targeting of Alpha-Synuclein Pathology in Mouse Brain Using Preformed Fibrils.

Zhang B, Kehm V, Gathagan R, Leight SN, Trojanowski JQ, Lee VM-Y, Luk KC, Methods in molecular biology 1948(): 45-57, 2019, PMID:30771169

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Induction of the Immunoproteasome Subunit Lmp7 Links Proteostasis and Immunity in α-Synuclein Aggregation Disorders.

Ugras S, Daniels MJ, Fazelinia H, Gould NS, Yocum AK, Luk KC, Luna E, Ding H, McKennan C, Seeholzer S, Martinez D, Evans P, Brown D, Duda JE, Ischiropoulos H, EBioMedicine 31(): 307-319, 2018, PMID:29759483

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