Gopal Thinakaran, Ph.D.


  • Professor, Department of Neurobiology, Committee on Molecular Medicine/MPMM, Committee on Cellular and Molecular Physiology, Committee on Neurobiology


Ph.D., University of Guelph, Canada, 1992
M.S., Madurai Kamaraj University, India, 1987
B.A., Madurai Kamaraj University, India, 1985


The University of Chicago
Knapp Center, JFK R212
924 East 57th Street
Chicago, Illinois 60637

Phone:  (773) 834-3752


Cellular and Molecular Biology of Alzheimer's Disease

Alzheimer’s disease (AD) is the major cause of dementia in the elderly and the seventh-leading cause of death. This devastating disorder for which no cure is presently available, strikes someone in the United States every 70 seconds. More than half the population over 80 years of age suffers from AD. The number of Americans living with AD at present is estimated at 5.3 million. As the lifespan of humans continues to increase in industrialized societies and emerging economies, AD is becoming an ever-increasing social burden for the health care system and emotional burden for the immediate family members.

A little over one hundred years ago, Alois Alzheimer, a German psychiatrist and neuropathologist, first presented the case study of patient who suffered from the devastating illness that now bears his name. In a paper published in 1907, Alzheimer wrote: "Scattered through the entire cortex, especially in the upper layers, one found miliary foci that were caused by the deposition of a peculiar substance." Eighty years later, the "peculiar substance" was characterized as ~38-42 amino acid-long beta-amyloid peptides (Ab), which are derived from a larger type I transmembrane protein, termed amyloid precursor protein (APP). Cerebral deposition of Ab peptides in senile plaques is causally linked to AD. It is well established that Ab is associated with neuronal death and consequent memory loss.

The overarching goal of my research is to develop a better understanding of the molecular and cellular mechanisms that regulate Ab production. Specifically, my lab has been investigating the cell biology of two proteases, termed BACE1 and g-secretase, which sequentially cleave APP to generate Ab. BACE1 is a type I transmembrane aspartyl protease, whereas g-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 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 g-secretase microdomain localization and trafficking in cultured neurons and in mouse brain; 2) advanced live cell imaging of BACE1 trafficking and transport; 3) generating and characterizing animal models of p23, a negative regulator of Ab production, etc. In addition, we have been interested in the physiological functions of Stanniocalcin 2, a protein whose expression is induced by 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.

View Research Papers on PubMed