Investigator, Assoc Prof (M) Neurology, Mass General Research Institute

Associate Professor of Neurology Harvard Medical School

alzheimer's disease; amyloid beta-peptides; amyloid beta-protein precursor; amyloid precursor protein secretases; aspartic acid endopeptidases; ataxin-1; atxn1; gamma-secretase inhibitors; models biological; neurodegeneration; presenilin-1; signal transduction; γ-secretase inhibitors

Can (Martin) Zhang’s research is focused on identifying the mechanism of neurodegeneration in Alzheimer’s disease (AD), with the goal of identifying molecular targets and biomarkers that will translate into the development of novel therapeutic strategies for AD.

The pathogenesis of AD is believed to be primarily driven by amyloid-B (AB), the principal component of senile plaques in the brain. Zhang has discovered or characterized several genetic or pharmacologic modulators of AB production and clearance, including the AD risk gene ataxin-1 (ATXN1), the spice component curcumin and its analogs, and the cancer drug bexarotene.

Zhang elucidated the mechanism of a new class of highly promising AD treatments, the APP-selective γ-secretase modulators (GSMs). GSMs are a group of small molecules that lower plaque formation by specifically modulating the processing of APP to AB by the γ-secretase protease.

The GSMs, which function differently from non-selective γ-secretase inhibitors whose clinical development was stopped because of side effects, are expected to proceed into AD clinical trials in the coming years.

In addition, Zhang is currently studying the role of immune regulatory cytokines and dietary and environmental factors in the pathogenesis of AD in conventional cell and mouse models and in novel nanofiber-based single-cell models of the disease.