Kelvin C. Luk, PhD
Research Assistant Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine
Contact Information3600 Spruce St
1 Maloney Building
Philadelphia, PA 19104
Neuropathology, Immunobiology and Experimental Pathology
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.
Neurodegeneration, Parkinson's disease, drug discovery, cell-models, animal models
BSc (Microbiology and Immunology), McGill University, 1997
PhD (Pathology), McGill University, 2004
MTR (Translational Research), University of Pennsylvania, 2013
Postdoctoral fellowship, University of Pennsylvania, 2005-2009
Awards and Honors
Doctoral Research Award / Canadian Institutes for Health Research, 2000-2003
Teuber-Neysmith Graduate Research Award, Montreal Neurological Institute, 2002
Research Fellowship, University of Pennsylvania Institute for Translational Medicine and Therapeutics (ITMAT), 2010-2012
Memberships and Professional Organizations
Society for Neuroscience, 2004 - Present
Parkinson's UK, 2013 - Present
Fonds National de la Recherche Luxembourg, 2014 - Present
Luk KC, Covell DJ, Kehm VM, Zhang B, Song IY, Byrne MD, Pitkin RM, Decker SC, Trojanowski JQ, Lee VM, Cell Reports 16(12): 3373-87, 2016, PMID:27653697
Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson's disease
Rey NL, Steiner JA, Maroof N, Luk KC, Madaj Z, Trojanowski JQ, Lee VM, Brundin P, Journal of Experimental Medicine 213(9): 1759-78, 2016, PMID:27503075
Mason DM, Nouraei N, Pant DB, Miner KM, Hutchison DF, Luk KC, Stolz JF, Leak RK, Molecular Neurodegeneration 11(1): 49, 2016, PMID:27363576
Intrastriatal injection of pre-formed mouse α-synuclein fibrils into rats triggers α-synuclein pathology and bilateral nigrostriatal degeneration
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, Neurobiology of Disease 82(): 185-199, 2015, PMID:26093169
In vivo imaging demonstrates progressive aggregation of alpha-synuclein and selective degeneration of Lewy inclusion-bearing neurons in a mouse model of parkinsonism
Osterberg VR, Spinelli KJ, Weston LJ, Luk KC, Woltjer RL, Unni V, Cell Reports 10(8): 1252-60, 2015, PMID:25732816
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
Volpicelli-Daley LA, Luk KC, Lee VMY, Nature Protocols 9(): 2135-2146, 2014
Alpha-synuclein immunotherapy blocks uptake and templated propagation of misfolded a-synuclein and neurodegeneration
Tran HT, Chung CH, Iba M, Zhang B, Trojanowski JQ, Luk KC, Lee VMY, Cell Reports 7(): 2054-65, 2014, PMID:24931606
Luk KC, Lee VMY, Parkinsonism & related disorders 20 Suppl 1(): S85-7, 2014, PMID:24262196
The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress.
Luk KC, Rymar VV, van den Munckhof P, Nicolau S, Steriade C, Bifsha P, Drouin J, Sadikot AF, Journal of Neurochemistry 125(9): 932, 2013, PMID:23331067
Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.
Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM, Science 338(6109): 949, 2012, PMID:23161999