PEOPLE

Kelvin C. Luk, PhD MTR

Research Associate Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania

Contact InformationHospital of the University of Pennsylvania
1 Maloney Building
3400 Spruce Street
Philadelphia, PA 19104
Office: 215-615-3202
Fax: 215-615-3206

Email: kelvincl@pennmedicine.upenn.edu

Specialty Division

Neuropathology, Cancer and Immunobiology

Research Expertise

My research aims to improve our understanding of the synucleinopathies, a group of neurodegenerative disorders that include Parkinson’s disease (PD), Lewy body dementia 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 Selective Vulnerability: Synucleinopathies are multisystem disorders that affects only specific cell populations. The reasons for this selective vulnerability is unclear. By characterizing the pathways that govern their development and maintenance, we and others have shown that a susceptible are defined by their connectivity and specific transcription profiles that regulate their function.

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
MSTR (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
Deutsche Forschungsgemeinschaft (DFG), 2017 - 2020
Research Grants Council of Hong Kong, 2017 - 2020
NIH, 2017 - 2023
Movement Disorders Society, 2018 - Present
Michael J. Fox Foundation, 2019 - Present
Austrian Science Fund, 2020 - Present
Parkinson's Foundation, 2020 - Present
International Parkinson and Movement Disorder Society, 2020 - Present
Multiple System Atrophy Coalition, 2022 - Present
NIH, 2022 - 2022
NIH, 2022 - 2022
Swiss National Science Foundation (SNSF), 2023 - present
Michael J. Fox Foundation, 2023 - present
NIH, 2023 - 2023
NIH, 2024 - present

Web Links


Selected Publications

O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology

Balana AT, Mahul-Mellier AL, Nguyen BA, Horvath M, Javed A, Hard ER, Jasiqi Y, Singh P, Afrin S, Pedretti R, Singh V, Lee VM, Luk KC, Saelices L, Lashuel HA, Pratt MR., Nature Chemical Biology, 2024, PMID:38347213

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Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons

Santhosh Kumar S, Naseri NN, Pather SR, Hallacli E, Ndayisaba A, Buenaventura C, Acosta K, Roof J, Fazelinia H, Spruce LA, Luk K, Khurana V, Rhoades E, Shalem O., Sci Adv 10(): eadj4767, 2024, PMID:38335281

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Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease

Arezoumandan S, Cousins KAQ, Ohm DT, Lowe M, Chen M, Gee J, Phillips JS, McMillan CT, Luk KC, Deik A, Spindler MA, Tropea TF, Weintraub D, Wolk DA, Grossman M, Lee V, Chen-Plotkin AS, Lee EB, Irwin DJ., Ann Clin Transl Neurol, 2024, PMID:38263854

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Transcriptomic profiling of early synucleinopathy in rats induced with preformed fibrils

Patterson JR, Kochmanski J, Stoll AC, Kubik M, Kemp CJ, Duffy MF, Thompson K, Howe JW, Cole-Strauss A, Kuhn NC, Miller KM, Nelson S, Onyekpe CU, Beck JS, Counts SE, Bernstein AI, Steece-Collier K, Luk KC, Sortwell CE., NPJ Parkinsons Dis 10(): 7, 2024, PMID:38172128

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Neuroinflammatory gene expression profiles of reactive glia in the substantia nigra suggest a multidimensional immune response to alpha synuclein inclusions

Stoll AC, Kemp CJ, Patterson JR, Howe JW, Steece-Collier K, Luk KC, Sortwell CE, Benskey MJ., Neurobiol Dis 191(): 106411, 2024, PMID:38228253

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Developmental exposure to the Parkinson's disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice

Boyd SL, Kuhn NC, Patterson JR, Stoll AC, Zimmerman SA, Kolanowski MR, Neubecker JJ, Luk KC, Ramsson ES, Sortwell CE, Bernstein AI., Toxicol Sci 196(): 99-111, 2023, PMID:37607008

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α-Synuclein aggregates amplified from patient-derived Lewy bodies recapitulate Lewy body diseases in mice

Uemura N, Marotta NP, Ara J, Meymand ES, Zhang B, Kameda H, Koike M, Luk KC, Trojanowski JQ, Lee VM., Nat Commun 14(): 6892, 2023, PMID:37898614

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The variance in phosphorylated, insoluble ⍺-synuclein in humans, rats, and mice is not mainly driven by biological sex

Miner KM, Jamenis AS, Bhatia TN, Clark RN, Abbas M, Luk KC, Leak RK., Acta Neuropathol, 2023, PMID:37568067

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A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy

Kim HY, Chia WK, Hsieh CJ, Saturnino Guarino D, Graham TJA, Lengyel-Zhand Z, Schneider M, Tomita C, Lougee MG, Kim HJ, Pagar VV, Lee H, Hou C, Garcia BA, Petersson EJ, O'Shea J, Kotzbauer PT, Mathis CA, Lee VM, Luk KC, Mach RH., J Med Chem 66(): 12185-12202, 2023, PMID:37651366

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