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 4001 E Fletcher Avenue
MDC36
Tampa FL 33613

Academic Email: thinakaran@usf.edu

Academic Phone:8139749214

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Education

Biography

For over twenty-five years, Dr. Thinakaran has directed an active and highly collaborative research group investigating mechanisms regulating Alzheimer’s disease (AD) pathogenesis and neuronal dysfunction. After twenty years at the University of Chicago, he moved to the University of South Florida in 2019 to become the Associate Dean of Neuroscience Research and the CEO of the Byrd Alzheimer’s Center and Research Institute. His research lab aims to gain insights from cutting-edge cell biology investigations and translate their discoveries to advance therapeutic strategies that can reduce the cerebral amyloid burden and mitigate cognitive deficits in AD. The Thinakaran lab has made outstanding contributions to our understanding of amyloid precursor protein trafficking and the biology of BACE1 and g-secretase, the two enzymes that sequentially cleave APP to generate Ab. In the past several years, they have characterized late-onset AD risk factors identified by GWAS efforts using cell-type-specific conditional knock-out and transgenic mice. They published key findings on the characterization of BIN1 as a risk factor in AD pathophysiology and microglial BIN1 function in neuroinflammation. Their study describing BIN1 regulation of region-specific tau pathogenesis and neurodegeneration in the PS19 model highlights BIN1’s role in promoting hippocampal tau pathophysiology. His lab uses 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 their goals. He has mentored over 25 post-doctoral fellows and students. Many have moved on to establish successful careers in academic research and medicine. Over the years, he has gained substantial administrative and leadership experience by serving on key committees within the University of Chicago and USF Morsani College of Medicine and participating 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 mechanisms regulating Alzheimer's disease (AD) pathogenesis. For over twenty years, we have investigated multiple aspects of AD cell biology. Our research has provided valuable insights into the regulation of APP trafficking and metabolism by APP secretases, cellular mechanisms involved in the generation of beta-amyloid peptides, and neuronal transcytosis of BACE1. Recently, we have characterized an essential function for the late-onset AD risk factor BIN1 in regulating synaptic vesicle dynamics that impacts on spatial learning and memory. We use an integrated approach that combines hypothesis-driven mutagenesis, biochemical characterization, detailed subcellular localization, advanced microscopy, live-cell imaging, and electrophysiology to accomplish our goals. Cultured non-neuronal cells, primary neurons and microglia, human iPSCs, and genetically-modified mice serve as experimental models in our investigation.

Memberships

• Member (International Society for Molecular Neurodegeneration, 2022 - Present)
• Member (Society for Neuroscience, 1994 - Present)

Recent Publications

• 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.

Awards/Honors

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