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 team'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 these disorders. We previously demonstrated that aggregated forms of α-Syn are transmissible entities that propagate and spread throughout the brain in a manner similar 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, our 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
Research Grants Council of Hong Kong, 2017 - 2020
Cure Parkinsons Trust (UK), 2017 - Present
NIH, 2017 - 2023
Deutsche Forschungsgemeinschaft (DFG), 2017 - 2020
Movement Disorders Society, 2018 - Present
Michael J. Fox Foundation, 2019 - Present
Austrian Science Fund, 2020 - Present
Parkinson's Foundation, 2020 - Present
International Parkinson and Movement Disorder Society, 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 - 2026
NIH, 2025 - 2025
Web Links
Selected Publications
Air-Liquid interface midbrain organoids model the pathological features of Parkinson's disease
Kälvälä S, Abushik P, Rezaie M, Dougalis A, Koistinaho J, Gardberg M, Luk KC, Malm T, Pelkonen A, Lehtonen Š., Neuroscience 612(): 220-233, 2026, PMID:42468771
Complement dysregulation during the early phases of synucleinopathy
Khan H, Gifford M, Kordbacheh A, Bury A, Panoushek S, Cole-Strauss A, Kemp CJ, Luk KC, Steece-Collier K, Kuhn NC, Kanaan NM, Sortwell CE, Patterson JR, Benskey MJ., Acta Neuropathol 152(): 7, 2026, PMID:42477211
IFNγ alters the aberrant phenotype of α-synuclein-treated microglia reducing the detrimental impact of their secretome on dopaminergic neurons
Niskanen J, Hakosalo V, Hämäläinen W, Kälvälä S, Hyvönen MT, Zhang Y, Luk KC, Koistinaho J, Lehtonen M, Goldsteins G, Albert K, Lehtonen Š., Neuroscience 603(): 201-213, 2026, PMID:41912064
Secreted GPNMB enhances uptake of fibrillar alpha-synuclein in a non-cell-autonomous process that can be blocked by anti-GPNMB antibodies
Carceles-Cordon M, Brody EM, Boucher ML, Gallagher MD, Skrinak RT, Unger TL, Penner CK, Berndt AJ, Das S, Lam K, Jaenisch R, Van Deerlin V, Lee EB, Brunden K, Luk KC, Chen-Plotkin AS, Neuron, 2026, PMID:42127911
Testing an inverse link between limbic alpha-synucleinopathy and myelin markers in mice and humans
Clark RN, Landes RE, Abbas M, Mistretta VG, Jhaveri JR, DeLoatch KA, Franks J, Chen J, Luk KC, Hu X, Leak RK., NPJ Parkinsons Dis 12(): 77, 2026, PMID:41702918
Clinically advanced NLRP3 inhibitor modulates microglial transcriptome and alleviates α-synuclein-induced progression of parkinsonism
Luque M, Matic M, Heras-Garvin A, Amo-Aparicio J, Luk KC, Haindl MT, Khalil M, Skouras DB, Dinarello CA, Stefanova N., J Neuroinflammation 23(): 76, 2026, PMID:41620763
Intestinal macrophages modulate synucleinopathy along the gut-brain axis
De Schepper S, Konstantellos V, Conway JA, Sokolova D, Zaccagnini L, Cowley MV, Sierksma A, Yudina M, Edmonds M, Gavriouchkina D, Geary B, Wallis A, Celikag M, Baykam Z, Vara-Pérez M, Crowley G, Hager FT, Bijnen M, Posner D, Luk K, Cerovic V, Clatworthy M, Videlock EJ, Jaunmuktane Z, Movahedi K, Greter M, Chain B, Alessi DR, Hong S, Bartels T., Nature, 2026, PMID:41606336
Synphilin-1 modulates alpha-synuclein assembly, release and uptake
Lázaro DF, Amen T, Gerhardt E, Song C, Burns R, Kruse N, Santos PI, Milovanovic D, Höglinger G, Mollenhauer B, Luk KC, Lee VM, Outeiro TF., NPJ Parkinsons Dis 11(): 326, 2025, PMID:41266386
Human microglia reduce alpha-synuclein aggregation and are neuroprotective in adult mouse brain
Albert K, Peltonen S, Vanne A, Kälvälä S, Syvänen V, Koistinaho J, Luk KC, Lehtonen Š., Brain Behav Immun, 2025, PMID:40912593
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
