Kelvin C Luk, PhD

faculty photo
Research Assistant 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 Parkinson’s disease (PD), a progressive neurodegenerative condition that affects over 1 million individuals in the U.S. alone, and for which there is currently no cure. Over the past 10 years, efforts have been focused on three major themes in PD:

1) Role of Protein Misfolding in PD: 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) PD Drug Discovery: 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, I have been developing high-throughput screening assays to identify small molecules and biologics that inhibit or neutralize abnormal α-syn species.

3) Biology of midbrain dopamine neurons: PD is primarily a movement disorder that results from the loss of dopamine-producing neurons in the midbrain. The reasons why this subpopulation is particularly vulnerable in PD is unclear. By characterizing the pathways that govern their development and maintenance, we and others have shown that a susceptible dopamine cells are defined by specific transcription factors that regulate their survival in adulthood.

Selected Publications

Rey Nolwen L, George Sonia, Steiner Jennifer A, Madaj Zachary, Luk Kelvin C, Trojanowski John Q, Lee Virginia M-Y, Brundin Patrik: Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term. Acta neuropathologica 135(1): 65-83, Jan 2018.

Manfredsson Fredric P, Luk Kelvin C, Benskey Matthew J, Guezer Aysegul, Garcia Joanna, Kuhn Nathan C, Sandoval Ivette M, Patterson Joseph R, O'Mara Alana, Yonkers Reid, Kordower Jeffrey H: Induction of alpha-synuclein pathology in the enteric nervous system of the rat and non-human primate results in gastrointestinal dysmotility and transient CNS pathology. Neurobiology of disease Jan 2018.

Nouraei N, Mason DM, Miner KM, Carcella MA, Bhatia TN, Dumm B, Soni D, Johnson DA, Luk KC, Leak RK : Critical appraisal of pathology transmission in the α-synuclein fibril model of Lewy body disorders. Experimental Neurology 299(Pt A): 172-196, Oct 2017 Notes: doi: 10.1016/j.expneurol.2017.10.017. [Epub ahead of print]

Thakur Poonam, Breger Ludivine S, Lundblad Martin, Wan Oi Wan, Mattsson Bengt, Luk Kelvin C, Lee Virginia M Y, Trojanowski John Q, Björklund Anders: Modeling Parkinson's disease pathology by combination of fibril seeds and α-synuclein overexpression in the rat brain. Proceedings of the National Academy of Sciences of the United States of America 114(39): E8284-E8293, Sep 2017.

Haenseler W, Zambon F, Lee H, Vowles J, Rinaldi F, Duggal G, Houlden H, Gwinn K, Wray W, Luk KC, Wade-Martins R, James W, Cowley S : Excess α-synuclein compromises phagocytosis in iPSC-derived macrophages. Scientific Reports 7(1): 9003, Aug 2017 Notes: doi: 10.1038/s41598-017-09362-3.

Tapias V, Hu X, Luk KC, Sanders LH, Lee VMY, Greenamyre JT: Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via inos-mediated nitric oxide production. Cellular and Molecular Life Sciences 74(15): 2851-2874, May 2017.

Luk KC, Covell DJ, Kehm VM, Zhang B, Song IY, Byrne MD, Pitkin RM, Decker SC, Trojanowski JQ, Lee VM: Molecular and Biological Compatibility with Host Alpha-Synuclein Influences Fibril Pathogenicity. Cell Reports 16(12): 3373-87, Sep 2016.

Rey NL, Steiner JA, Maroof N, Luk KC, Madaj Z, Trojanowski JQ, Lee VM, Brundin P: Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson's disease. Journal of Experimental Medicine 213(9): 1759-78, Aug 2016.

Mason DM, Nouraei N, Pant DB, Miner KM, Hutchison DF, Luk KC, Stolz JF, Leak RK: Transmission of α-synucleinopathy from olfactory structures deep into the temporal lobe. Molecular Neurodegeneration 11(1): 49, Jun 2016 Notes: doi: 10.1186/s13024-016-0113-4.

Paumier KL, Luk KC, Manfredsson FP, Kanaan NM, Lipton JW, Collier TJ, Steece-Collier K, Kemp CJ, Celano S, Schulz E, Sandoval IM, Fleming S, Dirr E, Polinski NK, Trojanowski JQ, Lee VMY, Sortwell CE: Intrastriatal injection of pre-formed mouse α-synuclein fibrils into rats triggers α-synuclein pathology and bilateral nigrostriatal degeneration. Neurobiology of Disease 82: 185-199, Oct 2015 Notes: No issue number. doi: 10.1016/j.nbd.2015.06.003. Epub 2015 Jun 17.

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Last updated: 01/29/2018
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