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@upenn.edu

Specialty Division

Neuropathology, Immunobiology and Experimental Pathology

Research Expertise

My research aims to improve our understanding of Parkinson’s disease (PD), a progressive neurodegenerative condition that affects over 1 million individuals in the U.S. alone, and for which there is currently no cure. Our current efforts focus on three major themes in PD and related synucleinopathies such as dementia with Lewy bodies:

1) Role of Protein Misfolding in PD: 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) PD Drug Discovery: 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, I have 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
Cure Parkinsons Trust (UK), 2017 - Present
NIH/NINDS, 2017 - Present
Deutsche Forschungsgemeinschaft (DFG), 2017 - Present
Research Grants Council of Hong Kong, 2017 - Present

Web Links


Selected Publications

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

Ugras Scott, Daniels Malcolm J, Fazelinia Hossein, Gould Neal S, Yocum Anastasia K, Luk Kelvin C, Luna Esteban, Ding Hua, McKennan Chris, Seeholzer Steven, Martinez Dan, Evans Perry, Brown Daniel, Duda John E, Ischiropoulos Harry, EBioMedicine 31(): 307-319, 2018, PMID:29759483

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Lewy body-like alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration

Duffy Megan F, Collier Timothy J, Patterson Joseph R, Kemp Christopher J, Luk Kelvin C, Tansey Malú G, Paumier Katrina L, Kanaan Nicholas M, Fischer Luke D, Polinski Nicole K, Barth Olivia L, Howe Jacob W, Vaikath Nishant N, Majbour Nour K, El-Agnaf Omar M A, Sortwell Caryl E, Journal of Neuroinflammation 15(1): 129, 2018, PMID:29716614

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Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies.

Peng Chao, Gathagan Ronald J, Covell Dustin J, Medellin Coraima, Stieber Anna, Robinson John L, Zhang Bin, Pitkin Rose M, Olufemi Modupe F, Luk Kelvin C, Trojanowski John Q, Lee Virginia M-Y, Nature 557(7706): 558-563, 2018, PMID:29743672

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Differential α-synuclein expression contributes to selective vulnerability of hippocampal neuron subpopulations to fibril-induced toxicity.

Luna Esteban, Decker Samantha C, Riddle Dawn M, Caputo Anna, Zhang Bin, Cole Tracy, Caswell Carrie, Xie Sharon X, Lee Virginia M Y, Luk Kelvin C, Acta Neuropathologica, 2018, PMID:29502200

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Measurements of auto-antibodies to α-synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease.

Akhtar Rizwan S, Licata Joseph P, Luk Kelvin C, Shaw Leslie M, Trojanowski John Q, Lee Virginia M-Y, Journal of Neurochemistry, 2018, PMID:29500813

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Best Practices for Generating and Using Alpha-Synuclein Pre-Formed Fibrils to Model Parkinson's Disease in Rodents.

Polinski Nicole K, Volpicelli-Daley Laura A, Sortwell Caryl E, Luk Kelvin C, Cremades Nunilo, Gottler Lindsey M, Froula Jessica, Duffy Megan F, Lee Virginia M, Martinez Terina N, Dave Kuldip D, Journal of Parkinson's disease, 2018, PMID:29400668

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Critical appraisal of pathology transmission in the α-synuclein fibril model of Lewy body disorders.

Nouraei Negin, Mason Daniel M, Miner Kristin M, Carcella Michael A, Bhatia Tarun N, Dumm Benjamin K, Soni Dishaben, Johnson David A, Luk Kelvin C, Leak Rehana K, Experimental Neurology 299(Pt A): 172-196, 2018, PMID:29056362

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Induction of alpha-synuclein pathology in the enteric nervous system of the rat and non-human primate results in gastrointestinal dysmotility and transient CNS pathology.

Manfredsson Fredric P, Luk Kelvin C, Benskey Matthew J, Guezer Aysegul, Garcia Joanna, Kuhn Nathan C, Sandoval Ivette M, Patterson Joseph R, O'Mara Alana, Yonkers Reid, Kordower Jeffrey H, Neurobiology of Disease 112(): 106-118, 2018, PMID:29341898

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Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term.

Rey Nolwen L, George Sonia, Steiner Jennifer A, Madaj Zachary, Luk Kelvin C, Trojanowski John Q, Lee Virginia M-Y, Brundin Patrik, Acta neuropathologica 135(1): 65-83, 2018, PMID:29209768

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Modeling Parkinson's disease pathology by combination of fibril seeds and α-synuclein overexpression in the rat brain.

Thakur Poonam, Breger Ludivine S, Lundblad Martin, Wan Oi Wan, Mattsson Bengt, Luk Kelvin C, Lee Virginia M Y, Trojanowski John Q, Björklund Anders, Proceedings of the National Academy of Sciences of the United States of America 114(39): E8284-E8293, 2017, PMID:28900002

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