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
Philadelphia, PA 19104
Office: 215-615-3202
Fax: 215-615-3206
Lab: 215-662-3292
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

Pang CCC, Sørensen MH, Lee K, Luk KC, Trojanowski JQ, Lee VMY, Noble W, Chang RCC.: Investigating key factors underlying neurodegeneration linked to alpha-synuclein spread. Neuropathol Appl Neurobiol Oct 2022 Notes: doi: 10.1111/nan.12829.

Miner KM, Jamenis AS, Bhatia TN, Clark RN, Rajasundaram D, Sauvaigo S, Mason DM, Posimo JM, Abraham N, DeMarco BA, Hu X, Stetler RA, Chen J, Sanders LH, Luk KC, Leak RK: α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans. Prog Neurobiol Page: 216:102307, Sep 2022 Notes: doi: 10.1016/j.pneurobio.2022.102307.

Diaz-Ortiz ME, Seo Y, Posavi M, Carceles Cordon M, Clark E, Jain N, Charan R, Gallagher MD, Unger TL, Amari N, Skrinak RT, Davila-Rivera R, Brody EM, Han N, Zack R, Van Deerlin VM, Tropea TF, Luk KC, Lee EB, Weintraub D, Chen-Plotkin AS: GPNMB confers risk for Parkinson's disease through interaction with α-synuclein. Science 377: eabk0637, Aug 2022 Notes: doi: 10.1126/science.abk0637.

Rahayel S, Mišić B, Zheng YQ, Liu ZQ, Abdelgawad A, Abbasi N, Caputo A, Zhang B, Lo A, Kehm V, Kozak M, Yoo HS, Dagher A, Luk KC: Differentially targeted seeding reveals unique pathological alpha-synuclein propagation patterns. Brain Jun 2022 Notes: Brain. 2022 Jun 3;145(5):1743-1756. doi: 10.1093/brain/awab440.

Sossi V, Patterson JR, McCormick S, Kemp CJ, Miller KM, Stoll AC, Kuhn N, Kubik M, Kochmanski J, Luk KC, Sortwell CE.: Dopaminergic Positron Emission Tomography Imaging in the Alpha-Synuclein Preformed Fibril Model Reveals Similarities to Early Parkinson's Disease. Mov Disord May 2022.

Hlushchuk I, Barut J, Airavaara M, Luk K, Domanskyi A, Chmielarz P.: Cell Culture Media, Unlike the Presence of Insulin, Affect α-Synuclein Aggregation in Dopaminergic Neurons. Biomolecules 12: 563, Apr 2022.

Steinkellner T, Conrad WS, Kovacs I, Rissman RA, Lee EB, Trojanowski JQ, Freyberg Z, Roy S, Luk KC, Lee VM, Hnasko TS.: Dopamine neurons exhibit emergent glutamatergic identity in Parkinson's disease. Brain 145: 879-886, Apr 2022.

Zhao J, Pan B, Fina M, Huang Y, Shimogawa M, Luk KC, Rhoades E, Petersson EJ, Dong DW, Kashina A.: α-Synuclein arginylation in the human brain. Transl Neurodegener 11: 20, Apr 2022.

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.

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.

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Last updated: 12/31/2022
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