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*(MCOM-Grad-Current-Neuroscience-Profile)

Gopal Thinakaran

Gopal Thinakaran, Ph.D.

Eric Pfeiffer Endowed Chair in Alzheimer's Res, Morsani College of Medicine

Ceo Byrd Alzheimer's Center, and Research Institute

Professor, Morsani College of Medicine, Molecular Medicine

Contact Info

Education

  • Ph.D., Molecular Biology and Genetics, University of Guelph, CANADA, 1992
  • M.Sc, Biotechnology, Madurai Kamaraj University, Madurai, INDIA, 1987
  • B.Sc, Biology, Madurai Kamaraj University, Madurai, INDIA, 1985

Biography

For over twenty-five years, I have led an active and highly collaborative research group investigating mechanisms that regulate Alzheimer’s disease (AD) pathogenesis and neuronal dysfunction. After twenty years at the University of Chicago, I moved to the University of South Florida in 2019 to serve as the Associate Dean of Neuroscience Research and the CEO of the Byrd Alzheimer’s Center and Research Institute. Our research aims to gain insights from cutting-edge cell biology investigations and translate our discoveries to advance therapeutic strategies that can reduce cerebral amyloid burden and mitigate cognitive deficits in AD. For many years, our research centered on amyloid precursor protein trafficking and the biology of BACE1 and gamma-secretase, the two enzymes that sequentially cleave APP to generate beta-amyloid peptides. More recently, we have focused our research on characterizing late-onset AD risk factors identified by GWAS studies, using cell-type-specific conditional knock-out and transgenic mouse models. We have made significant contributions to the AD field and have been quite successful in terms of our funding and publications (157 publications; >16,643 citations; h-index 61). More importantly, I have been fortunate to mentor over 30 post-doctoral fellows and graduate students. Many have gone on to establish successful careers in academic research and medicine. Over the years, I have gained substantial administrative and leadership experience through service on key Committees within the University of Chicago and USF Morsani College of Medicine, as well as participation in several Federal, Private, and Public Advisory Committees.

Interdisciplinary and Emerging Signature Programs

  • Cellular and Molecular Biology
  • Neurodegenerative Disease
  • Neuroscience

Research Interests

  • My lab (www.thinakaranlab.org) investigates the mechanisms regulating Alzheimer's disease (AD) pathogenesis. Over the past several years, we have characterized late-onset AD risk factors identified through GWAS efforts using cell-type-specific conditional knock-out and transgenic mice. We found that the late-onset AD risk factor BIN1 plays an essential role in neuronal function by regulating synaptic vesicle dynamics that impact spatial learning and memory. We also discovered a role for microglial BIN1 in neuroinflammation. Our study, which examined how BIN1 regulates region-specific tau pathogenesis and neurodegeneration in the PS19 model, highlights that BIN1 promotes hippocampal tau pathology. Recently, we published key findings on how PICALM functions as a risk factor in AD. My lab employs an integrated approach that combines molecular neuropathology analyses, biochemical characterization, detailed subcellular localization, advanced microscopy and live-cell imaging, RNAseq and spatial transcriptomics, electrophysiology, and behavioral tests to accomplish our goals. Cultured primary hippocampal neurons, microglia, oligodendrocytes, established cell lines, hiPSC lines, transgenic mice, and conditional knock-out mice serve as experimental models in our investigation.

Awards/Honors

  • Outstanding Research Achievement Award (University of South Florida - 2023)
  • John Trojanowski Memorial Award (Coins for Alzheimer’s Research Trust - 2023)

Memberships

  • Member (Society for Neuroscience, 1994 - Present)
  • Member (International Society for Molecular Neurodegeneration, 2022 - Present)
  • Member (International Society for Proteinopathies, 2025 - Present)
  • Member (Indian Academy of Neurosciences, 2025 - Present)

Recent Publications

  • Kozlova A*, Zhang S*, Sudwarts A*, Zhang H, Smirnou S, Byeon SK, Thapa C, Sun X, Stephenson K, Zhao X, Jamison B, Ponnusamy M, He X, Schneider JA, Pandey A, Bennett DA, Pang ZP, Sanders AR, Bellen HJ, Thinakaran G†, and Duan J†. PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia Nature. 646(8087) : 1178-1186, 2025.
  • Wang S*, Ponnusamy M*, Patel O, Hansen M, Collier L, Collier S, and Thinakaran G. Spatiotemporal transcriptomic profiling reveals metabolic dysfunction prior to overt tauopathy in the PS19 mouse model Experimental Molecular Medicine. In press., 2025.
  • Blazier DM, Lewandowski EM, Ram N, Zhang X, Wang S, Patel O, Collier L, Defilippi P, Chen Y, and Thinakaran G. A biophysical and molecular characterization of the interaction between the Alzheimer risk factor BIN1 and the neuronal scaffold protein p140Cap J Biol Chem. 301(10) : 110665, 2025.
  • Zhao X, Li Y, Zhang S; Sudwarts A, Zhang H, Kozlova A, Moulton MJ, Goodman LD, Pang ZP, Sanders AR, Bellen HJ, Thinakaran G, and Duan J. Alzheimer’s disease protective allele of Clusterin modulates neuronal excitability through lipid-droplet-mediated neuron-glia communication Molecular Neurodegeneration. 20(1) : 51, 2025.
  • McMillan JD, Wang S, Wohlfahrt J, Guergues J, Stevens SM Jr., and Thinakaran G. Proteomic characterization of the Alzheimer’s disease risk factor BIN1 interactome Molecular and Cellular Proteomics. 24(9) : 101055, 2025.
  • Moreira-Silva D, Yuksel M, Ponnusamy M, Hansen MT, McMillan JD, Geethakrishnan S, Wang S, Collier LA, and Thinakaran G. Amylin exacerbates tau pathology in the visual cortex of diabetic mice by impairing lysosomal activity Genes & Diseases. , 2025.
  • Sudwarts A., and Thinakaran G. Alzheimer’s genes in microglia: a risk worth investigating Molecular Neurodegeneration. 18(1) : 90, 2023.
  • Aow J, Huang, T-R, Goh, Y-T, Xu A, Sun Y, Thinakaran G, and Koo EH. Evidence for a clathrin-independent endocytic pathway for APP internalization in the neuronal somatodendritic compartment. Cell Reports. 42(7) : 112774. doi: 10.1016/j.celrep.2023.112774, 2023.
  • Ulku I, Liebsch F, Akerman SC, Schulz JF, Kulic L, Hock C, Pietrzik C, Di Spiezio A, Thinakaran G, Saftig P, and Multhaup G. Mechanisms of amyloid-β34 generation indicate a pivotal role for BACE1 in amyloid homeostasis. Scientific Reports. 13(1) : 2216. doi: 10.1038/s41598-023-28846-z, 2023.
  • Ponnusamy M, Wang S, Yuksel M, Hansen MT, Blazier DM, McMillan JD, Zhang X, Dammer EB, Collier L, and Thinakaran G. Loss of forebrain BIN1 attenuates hippocampal pathology and neuroinflammation in a tauopathy model Brain. 146(4) : 1561-1579. doi: 10.1093/brain/awac318, 2023.
  • Sudwarts S, Ramesha S, Gao T, Ponnusamy P, Wang S, Hansen M, Kozlova A, Bitarafan S, Kumar P, Beaulieu-Abdelahad D, Zhang X, Collier L, Szekeres C, Wood LB, Duan J, Thinakaran G, and Rangaraju S. BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia Molecular Neurodegeneration. 17(1) : 33. doi: 10.1186/s13024-022-00535-x, 2022.
  • Rynearson KD, Ponnusamy M, Prikhodko O, Xie Y, Zhang M, Nguyen P, Hug B, Sawa M, Becker A, Spencer B, Florio J, Mante M, Salehi B, Arias C, Galasko D, Head BP, Johnson G, Lin J, Duddy SK, Rissman RA, Mobley WC, Thinakaran G, Tanzi RE, and Wagner SL. Preclinical validation of a potent γ-secretase modulator for Alzheimer’s disease prevention Journal of Experimental Medicine. 218(4) : e20202560. doi: 10.1084/jem.20202560, 2021.
  • De Rossi P, Nomura T, Andrew RJ, Masse NY, Sampathkumar V, Musial TF, Sudwarts A, Aleksandra J Recupero1. Thomas Le Metayer1, Hansen MT, Ha-Na Shim H-N, Sofia V Krause SV, Freedman DJ, Vytas P Bindokas VP, Narayanan Kasthuri N, Nicholson DA, Contract Neuronal BIN1 regulates presynaptic neurotransmitter release and memory consolidation Cell Reports. 30(10) : 3520-3535.e7. doi: 10.1016/j.celrep.2020.02.026, 2020.