Robert Vassar, Ph.D.

Professor of Cell and Molecular Biology
Feinberg School of Medicine

Vassar's ongoing research focuses on the role of Aβ and BACE1 in normal biological processes and in disease mechanisms of relevance to AD. His lab is particularly interested in the functions of BACE1 and the homologue, BACE2, and the cell biology of Aβ in neurons. Cellular and molecular studies of BACE1 and BACE2 knockout mice will be important for elucidating the biological functions of these novel aspartic proteases and identifying their substrates. Finally, the lab is interested in the role of inflammation in AD pathophysiology, novel transgenic and knockout mouse models of AD, and molecular changes that may occur during brain aging leading to neurodegeneration.

Funded Research

Project Description Researchers Funding
The roles of Eps homology domain (EHD) proteins and synaptic activity in axon transport of the Alzheimer’s β-secretase BACE1 in the brain

The membrane-bound aspartic protease 13-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the 13-secretase enzyme that generates the first cleavage in the formation of the 13-amyloid (AI3) peptide from APP (1). Thus, BACE1 is a prime therapeutic target for Alzheimer's disease (AD). However, BACE1 inhibitors with drug-like properties that cross the blood-brain barrier (BBB) have proven difficult to develop.

2012 to 2013
$200,000
Investigations of the Mechanism of Action of TagretinR/Bexarotene on Amyloid Clearance in Transgenic Mouse Models

Recent studies from the laboratory of Dr. Gary Landreth (Cramer P. et. al (2012) Science 335) have demonstrated that Bexarotene (Targretin), a highly selective, blood-brain barrier-permeant, FDA-approved, RXR agonist for the treatment of cutaneous T-cell lymphoma, can rapidly reduce amyloid plaque burden and rescue behavioral deficits in transgenic mouse models of AD. The proposed mechanism of action is via transcriptional activation of PPARγ:RXR- and LXR:RXR-regulated genes, including ApoE, ABCA1 and ABCG1 expression, that facilitates Aβ clearance and promotes microglial phagocytosis.

2012
$50,343

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Riqiang Yan, Robert Vassar, Targeting the β secretase BACE1 for Alzheimer's disease therapy, The Lancet Neurology, 13(3), March 2014, 319 - 329