Kelvin C. Luk, PhD MTR
Research Associate Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania
Contact InformationHospital of the University of Pennsylvania
1 Maloney Building
3400 Spruce Street
Philadelphia, PA 19104
Office: 215-615-3202
Fax: 215-615-3206
Email: kelvincl@pennmedicine.upenn.edu
Specialty Division
Neuropathology, Cancer and Immunobiology
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 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 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.
Itmat Expertise
Neurodegeneration, Parkinson's disease, drug discovery, cell-models, animal models, dementia, alpha-synuclein
Graduate Groups
Neuroscience
Education
BSc (Microbiology and Immunology), McGill University, 1997
PhD (Pathology), McGill University, 2004
MSTR (Translational Research), University of Pennsylvania, 2013
Specialty Certification
Postgraduate Training
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
Medical Research Council, UK, 2015 - Present
Cure Parkinsons Trust (UK), 2017 - Present
Research Grants Council of Hong Kong, 2017 - 2020
NIH, 2017 - 2023
Deutsche Forschungsgemeinschaft (DFG), 2017 - 2020
Movement Disorders Society, 2018 - Present
Michael J. Fox Foundation, 2019 - Present
Austrian Science Fund, 2020 - Present
International Parkinson and Movement Disorder Society, 2020 - Present
Parkinson's Foundation, 2020 - Present
NIH, 2022 - 2022
NIH, 2022 - 2022
Multiple System Atrophy Coalition, 2022 - Present
NIH, 2023 - 2023
Swiss National Science Foundation (SNSF), 2023 - present
NIH, 2024 - present
Web Links
Selected Publications
Uptake of alpha-synuclein preformed fibrils is suppressed by inflammation and induces an aberrant phenotype in human microglia
Niskanen J, Peltonen S, Ohtonen S, Fazaludeen MF, Luk KC, Giudice L, Koistinaho J, Malm T, Goldsteins G, Albert K, Lehtonen Š., Glia, 2025, PMID:39435593
Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread
Jang E, Hoxha K, Mozier D, Insana A, Farber E, Changolkar L, Zhang B, Chio TI, Crowe A, Chen R, Mercken M, Lee EB, Luk KC, Brunden KR, Lee VM, Xu H., J Neurosci 44(): e0877242024, 2024, PMID:39500576
Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
Lam I, Ndayisaba A, Lewis AJ, Fu Y, Sagredo GT, Kuzkina A, Zaccagnini L, Celikag M, Sandoe J, Sanz RL, Vahdatshoar A, Martin TD, Morshed N, Ichihashi T, Tripathi A, Ramalingam N, Oettgen-Suazo C, Bartels T, Boussouf M, Schäbinger M, Hallacli E, Jiang X, Verma A, Tea C, Wang Z, Hakozaki H, Yu X, Hyles K, Park C, Wang X, Theunissen TW, Wang H, Jaenisch R, Lindquist S, Stevens B, Stefanova N, Wenning G, van de Berg WDJ, Luk KC, Sanchez-Pernaute R, Gómez-Esteban JC, Felsky D, Kiyota Y, Sahni N, Yi SS, Chung CY, Stahlberg H, Ferrer I, Schöneberg J, Elledge SJ, Dettmer U, Halliday GM, Bartels T, Khurana V., Neuron 112(): 2886-2909, 2024, PMID:39079530
Positron Emission Tomography with [(18)F]ROStrace Reveals Progressive Elevations in Oxidative Stress in a Mouse Model of Alpha-Synucleinopathy
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., Int J Mol Sci 25(9): 4943, 2024, PMID:38732162
Ciita Regulates Local and Systemic Immune Responses in a Combined rAAV-α-synuclein and Preformed Fibril-Induced Rat Model for Parkinson's Disease
Fredlund F, Jimenez-Ferrer I, Grabert K, Belfiori L, Luk KC, Swanberg M., J Parkinsons Dis 14(4): 693-711, 2024, PMID:38728204
Alpha-synuclein inclusion responsive microglia are resistant to CSF1R inhibition
Stoll AC, Kemp CJ, Patterson JR, Kubik M, Kuhn N, Benskey M, Duffy MF, Luk KC, Sortwell CE., Journal of Neuroinflammation 21(1): 108, 2024, PMID:38664840
Deficits in basal and evoked striatal dopamine release following alpha-synuclein preformed fibril injection: An in vivo microdialysis study
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., Eur J Neurosci 59(7): 1585-1603, 2024, PMID:38356120
O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology
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., Nature Chemical Biology 20(5): 646-655, 2024, PMID:38347213
Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons
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., Science Advances 10(6): eadj4767, 2024, PMID:38335281
Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease
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., Ann Clin Transl Neurol 11(3): 673-685, 2024, PMID:38263854
