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
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 Parkinson’s disease (PD), a progressive neurodegenerative condition that affects over 1.5 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. Through the development of novel biophysical, cell-based, and animal models, my work has sought to indentify factors that initiate α-Syn misfolding. Recently, we have 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.

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 unit headed by Dr. Kurt Brunden, I have been developing high-throughput screening assays to identify small molecules and biologics that inhibit the formation of 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

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, June 2015.

Osterberg VR, Spinelli KJ, Weston LJ, Luk KC, Woltjer RL, Unni V : In vivo imaging demonstrates progressive aggregation of alpha-synuclein and selective degeneration of Lewy inclusion-bearing neurons in a mouse model of parkinsonism. Cell Reports 10(8): 1252-60, March 2015.

Volpicelli-Daley LA, Luk KC, Lee VMY: Addition of exogenous α-Synuclein Pre-formed fibrils to Primary Neuronal Cultures to seed recruitment of endogenous α-Synuclein to Lewy body and Lewy Neurite-like aggregates. Nature Protocols 9: 2135-2146, August 2014.

Tran HT, Chung CH, Iba M, Zhang B, Trojanowski JQ, Luk KC, Lee VMY: Alpha-synuclein immunotherapy blocks uptake and templated propagation of misfolded a-synuclein and neurodegeneration. Cell Reports 7: 2054-65, June 2014.

Luk KC, Lee VMY: Modeling Lewy pathology propagation in Parkinson's disease. Parkinsonism & related disorders 20 Suppl 1: S85-7, Jan 2014.

Luk KC, Rymar VV, van den Munckhof P, Nicolau S, Steriade C, Bifsha P, Drouin J, Sadikot AF: The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress. Journal of Neurochemistry 125(9): 932, June 2013.

Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM: Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338(6109): 949, November 2012.

Luk, K.C., Kehm, V.M., Zhang, B., O’Brien, P., Trojanowski, J.Q. and Lee, V.M.Y.: Intracerebral inoculation of pathologic alpha-synuclein initiates a rapidly progressive synucleinopathy in mice. Journal of Experimental Medicine May 2012.

Volpicelli-Daley Laura A, Luk Kelvin C, Patel Tapan P, Tanik Selcuk A, Riddle Dawn M, Stieber Anna, Meaney David F, Trojanowski John Q, Lee Virginia M-Y: Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death. Neuron 72(1): 57-71, Oct 2011.

Watt Brenda, van Niel Guillaume, Fowler Douglas M, Hurbain Ilse, Luk Kelvin C, Stayrook Steven E, Lemmon Mark A, Raposo Graça, Shorter James, Kelly Jeffery W, Marks Michael S: N-terminal domains elicit formation of functional Pmel17 amyloid fibrils. The Journal of biological chemistry 284(51): 35543-55, Dec 2009.

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Last updated: 09/28/2016
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