Faculty

Kelvin C Luk, PhD MTR

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.
MSTR (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), 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.

Selected Publications

Gallagher E, Hou C, Zhu Y, Hsieh CJ, Lee H, Li S, Xu K, Henderson P, Chroneos R, Sheldon M, Riley S, Luk KC, Mach RH, McManus MJ.: Positron Emission Tomography with [(18)F]ROStrace Reveals Progressive Elevations in Oxidative Stress in a Mouse Model of Alpha-Synucleinopathy. Int J Mol Sci 25(9): 4943, May 2024 Notes: DOI: 10.3390/ijms25094943.

Fredlund F, Jimenez-Ferrer I, Grabert K, Belfiori L, Luk KC, Swanberg M.: Ciita Regulates Local and Systemic Immune Responses in a Combined rAAV-α-synuclein and Preformed Fibril-Induced Rat Model for Parkinson's Disease. J Parkinsons Dis May 2024.

Stoll AC, Kemp CJ, Patterson JR, Kubik M, Kuhn N, Benskey M, Duffy MF, Luk KC, Sortwell CE.: Alpha-synuclein inclusion responsive microglia are resistant to CSF1R inhibition. Journal of Neuroinflammation 21(1): 108, Apr 2024 Notes: DOI: 10.1186/s12974-024-03108-5.

Centner A, Del Priore I, Chambers N, Cohen SR, Terry ML, Coyle M, Glinski J, Stoll AC, Patterson JR, Kemp CJ, Miller KM, Kubik M, Kuhn N, Luk KC, Sortwell CE, Bishop C.: Deficits in basal and evoked striatal dopamine release following alpha-synuclein preformed fibril injection: An in vivo microdialysis study. Eur J Neurosci 59(7): 1585-1603, Apr 2024 Notes: DOI: 10.1111/ejn.16275.

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.: O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology. Nature Chemical Biology 20(5): 646-655, Feb 2024 Notes: DOI: 10.1038/s41589-024-01551-2.

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.: Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons. Science Advances 10(6): eadj4767, Feb 2024.

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.: Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease. Ann Clin Transl Neurol 11(3): 673-685, Jan 2024 Notes: DOI: 10.1002/acn3.51988.

Singh A, Panhelainen A, Reunanen S, Luk KC, Voutilainen MH.: Combining fibril-induced alpha-synuclein aggregation and 6-hydroxydopamine in a mouse model of Parkinson's disease and the effect of cerebral dopamine neurotrophic factor on the induced neurodegeneration. Eur J Neurosci 59(1): 132-153, Jan 2024.

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.: Transcriptomic profiling of early synucleinopathy in rats induced with preformed fibrils. NPJ Parkinsons Dis 10(1): 7, Jan 2024 Notes: DOI: 10.1038/s41531-023-00620-y.

Stoll AC, Kemp CJ, Patterson JR, Howe JW, Steece-Collier K, Luk KC, Sortwell CE, Benskey MJ.: Neuroinflammatory gene expression profiles of reactive glia in the substantia nigra suggest a multidimensional immune response to alpha synuclein inclusions. Neurobiol Dis 191: 106411, Jan 2024 Notes: DOI: 10.1016/j.nbd.2024.106411.

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Last updated: 05/23/2024
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