Kelvin C Luk, PhD

faculty photo
Research Associate Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
3600 Spruce St
1 Maloney Building
HUP
Philadelphia, PA 19104
Office: 215-615-3202
Fax: 215-615-3206
Lab: 215-662-3292
Education:
BSc (Microbiology and Immunology)
McGill University, 1997.
PhD (Pathology)
McGill University, 2004.
MTR (Translational Research)
University of Pennsylvania, 2013.
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Description of 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.

Selected Publications

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: Differentially targeted seeding reveals unique pathological alpha-synuclein propagation patterns. Brain Dec 2021 Notes: doi: 10.1093/brain/awab440.

Johnson ME, Bergkvist L, Stetzik L, Steiner JA, Meyerdirk L, Schulz E, Wolfrum E, Luk KC, Wesson DW, Krainc D, Brundin P.: Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice. Neurobiol Dis Sep 2021.

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.: LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies. EMBO Mol Med 13: e14745, Sep 2021.

Bhatia TN, Clark RN, Needham PG, Miner KM, Jamenis AS, Eckhoff EA, Abraham N, Hu X, Wipf P, Luk KC, Brodsky JL, Leak RK.: Heat Shock Protein 70 as a Sex-Skewed Regulator of α-Synucleinopathy. Neurotherapeutics Sep 2021.

Puentes LN, Lengyel-Zhand Z, Lee JY, Hsieh CJ, Schneider ME Jr, Edwards KJ, Luk KC, Lee VM, Trojanowski JQ, Mach RH.: Poly (ADP-ribose) Interacts With Phosphorylated α-Synuclein in Post Mortem PD Samples. Front Aging Neurosci 13: 704041, Jun 2021.

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.: Potent inhibitors of toxic alpha-synuclein identified via cellular time-resolved FRET biosensors. NPJ Parkinsons Dis 7: 52, Jun 2021.

Howe JW, Sortwell CE, Duffy MF, Kemp CJ, Russell CP, Kubik M, Patel P, Luk KC, El-Agnaf OMA, Patterson JR.: Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein. Parkinsonism Relat Disord 89: 41-47, Jun 2021.

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: Cerebral Dopamine Neurotrophic Factor Reduces α-Synuclein Aggregation and Propagation and Alleviates Behavioural Alterations in vivo. Molecular Therapy Apr 2021.

Miller KM, Patterson JR, Kochmanski J, Kemp CJ, Stoll AC, Onyekpe CU, Cole-Strauss A, Steece-Collier K, Howe JW, Luk KC, Sortwell CE: Striatal afferent BDNF is disrupted by synucleinopathy and partially restored by STN DBS. J Neuroscience Mar 2021.

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.: α-Synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson's disease. JCI Insight 6: 135633, Mar 2021.

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Last updated: 05/12/2022
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