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
NIH, 2017 - 2023
Research Grants Council of Hong Kong, 2017 - 2020
Deutsche Forschungsgemeinschaft (DFG), 2017 - 2020
Cure Parkinsons Trust (UK), 2017 - Present
Movement Disorders Society, 2018 - Present
Michael J. Fox Foundation, 2019 - Present
Parkinson's Foundation, 2020 - Present
International Parkinson and Movement Disorder Society, 2020 - Present
Austrian Science Fund, 2020 - Present
Multiple System Atrophy Coalition, 2022 - Present
NIH, 2022 - 2022
NIH, 2022 - 2022
NIH, 2023 - 2023
Swiss National Science Foundation (SNSF), 2023 - present
NIH, 2024 - present
Web Links
Selected Publications
Glycine-to-aspartic acid mutation at codon 51 in Snca disrupts the synaptic localisation of α-synuclein and enhances its propensity for synucleinopathy
West S, Natalwala A, Singh Dolt K, Lamont DJ, McMillan M, Luk K, Mashimo T, Kunath T., Brain Commun 7(): fcaf224, 2025, PMID:40574971
Blood α-Synuclein Separates Parkinson's Disease from Dementia with Lewy Bodies
Kannarkat GT, Zack R, Skrinak RT, Morley JF, Davila-Rivera R, Arezoumandan S, Dorfman K, Luk K, Wolk DA, Weintraub D, Tropea TF, Lee EB, Xie SX, Chandrasekaran G, Lee VM, Irwin D, Akhtar RS, Chen-Plotkin AS., Ann Neurol, 2025, PMID:40521808
GDNF reduces fibril-induced early-stage alpha-synuclein pathology after delivery of 20S proteasome inhibitor lactacystin
Er S, Parkkinen I, Trepczyk K, Seelbach A, Pasculli MS, De Lorenzo F, Luk K, Jankowska E, Chmielarz P, Domanskyi A, Airavaara M., Eur J Pharm Sci 208(): 107048, 2025, PMID:39988264
Intrastriatal injection of alpha-synuclein preformed fibrils to rats results in L-DOPA reversible sensorimotor impairments and alterations in non-motor function
Fleming SM, Scott S, Hamad EJ, Herman DE, Holden JG, Yan L, Linning-Duffy K, Kemp CJ, Patterson JR, Miller KM, Kubik M, Kuhn N, Stoll AC, Duffy MF, Steece-Collier K, Cole-Strauss A, Lipton JW, Luk KC, Sortwell CE., Front Neurosci 19(): 1556447, 2025, PMID:40236948
Fibril fuzzy coat is important for α-synuclein pathological transmission activity
Han Y, Li J, Xia W, Li Q, Sun Z, Zeng W, Hu Y, Luk KC, Liu C, Xiang S, He Z., Neuron, 2025, PMID:40215967
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
Lack of neuroprotection after systemic administration of the soluble TNF inhibitor XPro1595 in an rAAV6-α-Syn + PFFs-induced rat model for Parkinson's disease
Fredlund F, Fryklund C, Trujeque-Ramos O, Staley HA, Pardo J, Luk KC, Tansey MG, Swanberg M., Neurobiol Dis, 2025, PMID:39954745
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
