Tansey Lab

Microglia can contribute to the spread of misfolded proteins such as alpha-synuclein in neurodegenerative disorders including Parkinson’s and Alzheimer’s disease. The accumulation of aggregated protein is thought to drive disease progression, however the mechanisms by which microglia influence the spread of aggregation is not clear. We are investigating the role of cannabinoid signaling to regulate or restore microglial function as a potential therapeutic target for age-related neurodegenerative. Currently, we are using single-cell and organotypic tissue models to evaluate the mechanisms by which cannabinoid receptor 2 regulates microglia uptake and phagocytosis of aggregated alpha-synuclein and tau.

Microglia can contribute to the spread of misfolded proteins such as alpha-synuclein in neurodegenerative disorders including Parkinson’s and Alzheimer’s disease. The accumulation of aggregated protein is thought to drive disease progression, however the mechanisms by which microglia influence the spread of aggregation is not clear. We are investigating the role of cannabinoid signaling to regulate or restore microglial function as a potential therapeutic target for age-related neurodegenerative. Currently, we are using single-cell and organotypic tissue models to evaluate the mechanisms by which cannabinoid receptor 2 regulates microglia uptake and phagocytosis of aggregated alpha-synuclein and tau.

Bile acids are best known for their roles in digestion and metabolism, but emerging research reveals that they are also key regulators of the immune system.  Alterations in bile acid composition have been observed in neurodegenerative diseases, many of which are accompanied by gastrointestinal dysfunction. This connection highlights bile acids as a promising target for uncovering the mechanisms that drive neurodegeneration. Our research focuses on bile acid metabolism and signaling in the context of relapsing-remitting multiple sclerosis, with the goal of advancing new therapeutic strategies to support patient health.

Although the role of immune dysfunction, both in the CNS and in the periphery, has become increasingly more appreciated as causative in neurodegenerative diseases over the last decade, to date there has been considerable neglect on the role of an aging immune system in these diseases. Immune cell exhaustion, which is characterized as a suppression of the immune response and immune cell function, is associated with both chronic inflammation as well as an aging immune system. Recent publications from the Tansey lab have implicated both PD and FTD-associated genetic mutations with increased risk of immune cell exhaustion in both preclinical models and clinical samples. Multiple projects are ongoing in the Tansey lab to expand on this research to understand how an exhausted peripheral immune system may contribute to neurodegeneration, and how it may be targeted as a potential therapeutic and leveraged for biomarker development.

Krueger ME, Boles JS, Simon ZD, Alvarez SD, McFarland NR, Okun MS, Zimmermann EM, Forsmark CE, Tansey MG (2025). A comparative analysis of Parkinson’s disease and inflammatory bowel disease gut microbiomes highlights shared depletions in key butyrate-producing bacteria, NPJ Parkinson’s Disease March 19;11(1): 50 PMID: 40108151 DOI: 10.1038/s41531-025-00894-4

Wang HV, Xiang JF, Yuan C, Veire AM, Gendron TF, Murray ME, Tansey MG, Hu J, Gearing M, Glass JD, Jin P, Corces VG, McEachin ZT (2025). pTDP-43 levels correlate with cell type specific molecular alterations in the prefrontal cortex of C9orf72 ALS/FTD patients. PNAS March 4;122 (9): e2419818122 PMID: 40108151 DOI: 10.1038/s41531-025-00894-4 

Wallings RL, Gillett DA, Staley HA, Mahn S, Mark J, Neighbarger N, Kordasiewicz H, Hirst WD, Tansey MG.  (2025) ASO-mediated knockdown of GPNMB in mutant- GRN and Grn -deficient peripheral myeloid cells disrupts lysosomal function and immune responses. Mol Neurodegener. 2025 Apr 8;20(1):41. doi: 10.1186/s13024-025-00829-w.PMID: 40200337

Bolen ML, Gomes BN, Gill B, Menees KB, Staley H, Jernigan J, Tansey MG. (2025) Peripheral Blood Immune Cells from Individuals with Parkinson’s Disease or Inflammatory Bowel Disease Share Deficits in Iron Storage and Transport that are Modulated by Non-Steroidal Anti-Inflammatory Drugs. Neurobiol Dis 2025 Jan 11:106794.doi: 10.1016/j.nbd.2025.106794.

Jernigan JE, Staley HA, Baty Z, Bolen ML, Gomes BN, Holt J, Cole CL, Neighbarger NK, Dheeravath K, Merchak AR, Menees KB, Coombes SA, Tansey MG (2025) RGS10 attenuates systemic immune dysregulation induced by chronic inflammatory stress. J Neuroinflammation. 2025 Feb 24;22(1):49. doi: 10.1186/s12974-024-03322-1.PMID: 39994765

Christiansen JR, Ferreira SA, Szymkowski DE, Jakobsson J, Tansey MG, Romero-Ramos M. (2025) Peripherally administered TNF inhibitor is not protective against α-synuclein-induced dopaminergic neuronal death in rats. Neurobiol Dis. 2025 Mar;206:106803. doi: 10.1016/j.nbd.2025.106803. Epub 2025 Jan 10.PMID: 39800228 
Fredlung F, Fryklund C, Trujeque-Ramos O, Staley HA, Pardo J, Luk KC, Tansey MG, Swanberg M. (2025) 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. Neurobiol Dis 2025 Apr:207:106841.doi: 10.1016/j.nbd.2025.106841. Epub 2025 Feb 13. PMID: 39954745. DOI: 10.1016/j.nbd.2025.106841

Bolen ML, Menees KB, Gearing M, Gong J, Ren Y, Merchak AR, Murray ME, McEachin ZT and Tansey MG (2025) Multiplex digital spatial profiling identifies subregion dependent targeted proteome changes across variants of dementia NPJ Dement 1(1):10.doi: 10.1038/s44400-025-00010-6. Epub 2025 Jun 3. PMID: 40476255 PMCID: PMC12133586 DOI: 10.1038/s44400-025-00010-6

Mark JR, Titus AM, Staley HA, Alvarez S, Mahn S, McFarland NR, Wallings RL, Tansey MG (2025) Peripheral immune cell response to stimulation stratifies Parkinson's disease progression from prodromal to clinical stages. Commun Biol. 2025 May 8;8(1):716. doi: 10.1038/s42003-025-08088 7.PMID: 40341772

Bettcher BM, Ferreira de Oliveira F, Willette AA, Michalowska MM, Santos Machado L, Rajbanshi B, Borelli WV, Tansey MG, Rocha A, Suryadevara V, Hu W. (2025) Analysis and Interpretation of Inflammatory Fluid Markers in Alzheimer’s Disease: A Roadmap for Standardization, J Neuroinflammation, 2025 Apr 15;22(1):105.doi: 10.1186/s12974-025-03432-4.

Duggan MR, Morgan DG, Price BR, Rajbanshi B, Martin-Peña A, Tansey MG, Walker KA (2025) Immune modulation to treat Alzheimer's disease. Mol Neurodegener. 2025 Mar 31;20(1):39. doi: 10.1186/s13024-025-00828-x.PMID: 40165251

Luthra N, Mehta N, Munoz M, Fantuzzi G, Lamotte G, Haus J, McFarland N, Tansey MG, Gonzalez-Latapi P, Piso G, Kang U, and Corcos D. Aerobic Exercise-Induced Changes in Fluid Biomarkers in Parkinson’s Disease, NPJ Parkinson’s Disease, in press.

Sampson TR, Tansey MG, West AB, Liddle RA  (2025) Lewy body diseases and the gut. Mol Neurodegener. 2025 Jan 30;20(1):14. doi: 10.1186/s13024-025-00804-5.PMID: 39885558

Mark JR, Tansey MG. (2025) Immune cell metabolic dysfunction in Parkinson's disease. Mol Neurodegener. 2025 Mar 24;20(1):36. doi: 10.1186/s13024-025-00827-y.PMID: 40128809 

Michael T. Heneka, Wiesje van der Flier, Frank Jessen, Jeroen Hoozemanns, Dietmar Thal, Delphine Boche, Frederic Brosseron, Charlotte Teunissen, Henrik Zetterberg, Andreas Jacobs, Paul Edison, Alfredo Ramirez, Carlos Cruchaga, Jean-Charles Lambert, Ruiz Laza Agustin, Jose Vicente Sanchez-Mut, Andre Fischer, Sergio Castro Gómez, Thor Stein, Luca Kleineidam, Michael Wagner, Jonas Neher, Colm Cunningham, Sim K. Singhrao, Marco Prinz, Christopher K. Glass, Johannes Schlachetzki, Oleg Butovsky, Kilian Kleemann, Philip L. De Jaeger, Hannah Scheiblich, Guy Brown, Landreth, Gary, Moutinho Miguel, Jaime Grutzendler, Diego Gomez Nicola, Roisin McManus, Katrin Andreasson, Christina Ising, Deniz Karabag, Darren Baker, Shane Liddelow, Alexej Verkhratsky, Malú G. Tansey, Alon Monsonego, Ludwig Aigner, Guillaume Dorothee, Klaus-Armin Nave, Mikael Simons, Gabriela Constantin, Neta Rosenzweig, Alberto Pascual García, Gabor Petzold, Jonathan Kipnis, Carmen Venegas, Marco Colonna, Andrea J. Tenner, M Kerry O’Banion, Jörn Sternert, Douglas L. Feinstein, Magdalena Sastre, Kiran Bhaskar, Soyon Hong, Dori Schafer, Todd Golde, Richard Ransohoff, David Morgan, John Breitner, Renzo Mancuso, Sean-Patrick Riechers. Neuroinflammation in Alzheimer’s disease Nat Rev Immunol. 2024 Dec 9. doi: 10.1038/s41577-024-01104-7. Online ahead of print. PMID: 39653749 Review.

Merchak AR, Bolen ML, Tansey MG, Menees KB. (2024). Thinking outside the brain: Gut microbiome influence on innate immunity within neurodegenerative disease. Neurotherapeutics Oct;21(6):e00476. doi: 10.1016/j.neurot.2024.e00476. Epub 2024 Oct 31. PMID: 39482179 PMCID: PMC11585893 DOI: 10.1016/j.neurot.2024.e00476

Harms AN, Yang V, and Tansey MG. (2023) Central and Peripheral Innate and Adaptive Immunity in Parkinson’s disease, for Neuroimmunology Special Issue of Science Translational Medicine 2023 Nov 8;15(721):eadk3225.doi: 10.1126/scitranslmed.adk3225. Epub 2023 Nov 8.PMID: 37939158 DOI: 10.1126/scitranslmed.adk3225

Gillett, GA, Wallings, RL, Uriarte Huarte, O, and Tansey, MG. (2023) Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease J Neuroinflammation 2023 Nov 30;20(1):286.doi: 10.1186/s12974-023-02965-w.PMID: 38037070 PMCID: PMC10688479 DOI: 10.1186/s12974-023-02965-w

Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. (2022) Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol. 2022 Mar 4:1-17. doi: 10.1038/s41577-022-00684-6. Online ahead of print. PMID: 35246670. PMCID: PMC8895080

Helmreich, D.L. (2022) Profiles of women in science: Malú Gámez Tansey, Norman and Susan Fixel Professor of Neuroscience and Neurology, Co-Director of the Center for Translational Research in Neurodegenerative Disease and Director of the Parkinson's Foundation Research Center of Excellence, University of Florida College of Medicine European Journal of Neuroscience 55(2):350-353. doi: 10.1111/ejn.15578. Epub 2022 Jan 7.PMID: 34951072

Wikipedia Page

Medium Magazine Interview

Bright Focus- Bruce Willis has FTD- What are the symtpoms of FTD?

Flash Forward- Vanguard Series: The Future of the Aging Brain

VJ Neurology AD/PD 2021

INmune Bio - Innate Immunity and Inflammation

Oxford Brain Diagnostic Seminar Series

BRAIN Journals - The Brain Conference 2021

Cure Parkinson’s Trust 3P Webinar

Know Brainer Podcast Interview with Dr. Jaya Viswanathan