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 Neuronal Selective Vulnerability: PD is multisystem disorder that affects only specific neuronal populations, including non-dopaminergic cells. 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
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
Deutsche Forschungsgemeinschaft (DFG), 2017 - Present
NIH, 2017 - Present
Michael J. Fox Foundation, 2019 - Present
Austrian Science Fund, 2020 - Present
International Parkinson and Movement Disorder Society, 2020 - Present
NIH, 2022 - 2022
NIH, 2022 - 2022

Web Links


Selected Publications

Differentially targeted seeding reveals unique pathological alpha-synuclein propagation patterns

Rahayel S, Mišić B, Zheng YQ, Liu ZQ, Abdelgawad A, Abbasi N, Caputo A, Zhang B, Lo A, Kehm V, Kozak M, Soo Yoo H, Dagher A, Luk KC, Brain, 2021, PMID:34910119

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Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice

Johnson ME, Bergkvist L, Stetzik L, Steiner JA, Meyerdirk L, Schulz E, Wolfrum E, Luk KC, Wesson DW, Krainc D, Brundin P., Neurobiol Dis, 2021, PMID:34536552

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LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies

Emmenegger M, De Cecco E, Hruska-Plochan M, Eninger T, Schneider MM, Barth M, Tantardini E, de Rossi P, Bacioglu M, Langston RG, Kaganovich A, Bengoa-Vergniory N, Gonzalez-Guerra A, Avar M, Heinzer D, Reimann R, Häsler LM, Herling TW, Matharu NS, Landeck N, Luk K, Melki R, Kahle PJ, Hornemann S, Knowles TPJ, Cookson MR, Polymenidou M, Jucker M, Aguzzi A., EMBO Mol Med 13(): e14745, 2021, PMID:34309222

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Heat Shock Protein 70 as a Sex-Skewed Regulator of α-Synucleinopathy

Bhatia TN, Clark RN, Needham PG, Miner KM, Jamenis AS, Eckhoff EA, Abraham N, Hu X, Wipf P, Luk KC, Brodsky JL, Leak RK., Neurotherapeutics, 2021, PMID:34528172

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Poly (ADP-ribose) Interacts With Phosphorylated α-Synuclein in Post Mortem PD Samples

Puentes LN, Lengyel-Zhand Z, Lee JY, Hsieh CJ, Schneider ME Jr, Edwards KJ, Luk KC, Lee VM, Trojanowski JQ, Mach RH., Front Aging Neurosci 13(): 704041, 2021, PMID:34220490

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Potent inhibitors of toxic alpha-synuclein identified via cellular time-resolved FRET biosensors

Braun AR, Liao EE, Horvath M, Kalra P, Acosta K, Young MC, Kochen NN, Lo CH, Brown R, Evans MD, Pomerantz WCK, Rhoades E, Luk K, Cornea RL, Thomas DD, Sachs JN., NPJ Parkinsons Dis 7(): 52, 2021, PMID:34183676

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Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein

Howe JW, Sortwell CE, Duffy MF, Kemp CJ, Russell CP, Kubik M, Patel P, Luk KC, El-Agnaf OMA, Patterson JR., Parkinsonism Relat Disord 89(): 41-47, 2021, PMID:34218047

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Cerebral Dopamine Neurotrophic Factor Reduces α-Synuclein Aggregation and Propagation and Alleviates Behavioural Alterations in vivo

Albert K, Raymundo DP, Panhelainen A, Eesmaa A, Shvachiy L, Araújo GR, Chmielarz P, Yan X, Singh A, Cordeiro Y, Palhano FL, Foguel D, Luk KC, Domanskyi A, Voutilainen MH, Huttunen HJ, Outeiro TF, Saarma M, Almeida MS, Airavaara M, Molecular Therapy, 2021, PMID:33940158

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Striatal afferent BDNF is disrupted by synucleinopathy and partially restored by STN DBS

Miller KM, Patterson JR, Kochmanski J, Kemp CJ, Stoll AC, Onyekpe CU, Cole-Strauss A, Steece-Collier K, Howe JW, Luk KC, Sortwell CE, J Neuroscience, 2021, PMID:33472823

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α-Synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson's disease

Cole TA, Zhao H, Collier TJ, Sandoval I, Sortwell CE, Steece-Collier K, Daley BF, Booms A, Lipton J, Welch M, Berman M, Jandreski L, Graham D, Weihofen A, Celano S, Schulz E, Cole-Strauss A, Luna E, Quach D, Mohan A, Bennett CF, Swayze EE, Kordasiewicz HB, Luk KC, Paumier KL., JCI Insight 6(): 135633, 2021, PMID:33682798

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