Gopal Thinakaran, University of Chicago
Professor
Chicago, Illinois
gopal@uchicago.edu
Office:
(773) 834-3752
Expert In
Bio/Research
The overarching goal of my research is to develop a better understanding of the molecular and cellular mechanisms that regulate Aß production. Specifically, my lab has been investigating the cell biology of two proteases, termed BACE1 and gamma-secretase, which sequentially cleave APP to generate...
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Bio/Research
The overarching goal of my research is to develop a better understanding of the molecular and cellular mechanisms that regulate Aß production. Specifically, my lab has been investigating the cell biology of two proteases, termed BACE1 and gamma-secretase, which sequentially cleave APP to generate Aß. BACE1 is a type I transmembrane aspartyl protease, whereas gamma-secretase is a multiprotein transmembrane complex made of the catalytic subunit presenilin (PS1 or PS2) and three other integral subunits: nicastrin, APH-1, and PEN-2. We use cultured neuronal and non-neuronal cell lines, primary neurons, knock-out mice and transgenic mouse models of AD pathogenesis in our investigations.
In recent years, we have investigated the amyloidogenic processing of APP in cholesterol- and sphingolipid-rich membrane microdomains, termed lipid rafts. Ongoing investigations focus on: 1) the role of S-palmitoylation on BACE1 and gamma-secretase microdomain localization and trafficking in cultured neurons and in mouse brain; 2) advanced live cell imaging of BACE1 trafficking and transport; 3) understanding how risk factors identified by GWAS studies modify AD pathogenesis. In addition, we have been interested in the physiological functions of Stanniocalcin 2, a protein whose expression is induced by the cellular adaptive response to protein misfolding stress, termed the unfolded protein response. We have recently uncovered a molecular function for Stanniocalcin 2 in cellular calcium homeostasis and are now exploring the potential involvement of calcium homeostasis in Alzheimer’s disease pathogenesis using cell culture and animal models.
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In recent years, we have investigated the amyloidogenic processing of APP in cholesterol- and sphingolipid-rich membrane microdomains, termed lipid rafts. Ongoing investigations focus on: 1) the role of S-palmitoylation on BACE1 and gamma-secretase microdomain localization and trafficking in cultured neurons and in mouse brain; 2) advanced live cell imaging of BACE1 trafficking and transport; 3) understanding how risk factors identified by GWAS studies modify AD pathogenesis. In addition, we have been interested in the physiological functions of Stanniocalcin 2, a protein whose expression is induced by the cellular adaptive response to protein misfolding stress, termed the unfolded protein response. We have recently uncovered a molecular function for Stanniocalcin 2 in cellular calcium homeostasis and are now exploring the potential involvement of calcium homeostasis in Alzheimer’s disease pathogenesis using cell culture and animal models.
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