Gopal Thinakaran, Ph.D.

Professor of Neurobiology, Neurology, and Pathology

University of Chicago

Research in Dr. Thinakaran's lab investigates mechanisms that regulate Alzheimer's disease β-amyloid (Aβ) production and deposition. Specifically, they study the biology of BACE1 and γ-secretase, the two enzymes that sequentially cleave amyloid precursor protein (APP) to generate Aβ. Recent investigations in their lab center on the regulation of BACE1 and γ-secretase function by post-translational S-palmitoylation, live-cell analysis of dynamic membrane trafficking of BACE1, and the characterization of γ-secretase modulating protein p23. As a post-doctoral fellow, at The Johns Hopkins University School of Medicine Dr. Thinakaran participated in the early characterization of presenilin biology and investigations on how FAD mutations in PS1 affect Aβ production using cell culture and animal models. For over twelve years heI has been leading a group at the University of Chicago, investigating multiple aspects of Alzheimer's disease cell biology including, the physiological and pathological functions of presenilins, regulation of APP trafficking and metabolism, modulation of amyloid production/deposition by post-translational modification of APP secretases and interaction with associated proteins, and the characterization of subcellular sites and membrane microdomains involved in the generation of Aβ peptides.  They have been using an integrated approach that combines hypothesis driven mutagenesis, biochemical characterization, detailed subcellular localization, advanced live cell imaging, and electrophysiology to accomplish our goals. Cultured non-neuronal cells, primary hippocampal neurons, transgenic, knock-out and gene-targeted mice serve as experimental models in the investigation.

Funded Research

Project Description Researchers Funding
BIN1 in Alzheimer’s Disease Neuropathology

The goal of this proposal is to investigate how one of the recently identified late-onset Alzheimer’s disease risk genes, namely BIN1, contributes to neuropathology. BIN1 is an adaptor protein that regulates membrane dynamics in a variety of cellular contexts. Only limited information is available on BIN1 expression and function in the brain. As such, there is much to be learned about the precise biological and mechanistic connection between BIN1 and Alzheimer’s disease.

2015 to 2016

BACE1 transcytosis in Alzheimer’s disease pathogenesis

Many lines of evidence suggest that beta-amyloid peptides cause neuronal damage and affect fundamental memory processes early in the course of Alzheimer's disease (AD). Two membrane-associated enzymes, namely betasecretase (BACEl) and gamma-secretase are responsible for beta-amyloid production. Understanding the details regarding the cellular and molecular mechanisms involved in beta-amyloid production in neurons is a topic of central importance in molecular AD research.

2012 to 2013


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
Pierre De Rossi, Virginie Buggia-Prevot, Robert J Andrew, Sofia V Krause, Elizabeth Woo, Peter T Nelson, Peter Pytel, Gopal Thinakaran, BIN1 localization is distinct from Tau tangles in Alzheimer’s disease, Matters, 12 Jan 2017
Virginie Buggia-Prévot, Gopal Thinakaran, Significance of transcytosis in Alzheimer's disease: BACE1 takes the scenic route to axons, BioEssays, 37(7), June 2015