2015

The New Investigator Awards in Alzheimer's Disease


Manu Sharma, PhD

Assistant Professor, Weill Cornell Medicine

Tau Proteostasis by Hsc70 Co-Chaperones

Microtubules are tiny tubular structures in cells that act like conveyor belts, moving vesicles, granules, chromosomes, and organelles such as mitochondria via special attachment proteins. Tau protein molecules stabilize these microtubules. But when tau proteins become defective, pathologies of the nervous system (such as Alzheimer’s disease) can develop. Defective tau proteins accumulate in the form of aggregates in the neurons of Alzheimer’s disease patients and consequently lead to neuron loss and cognitive decline.

The objective of Dr. Sharma’s research is to achieve a better understanding of the molecular machinery that suppresses tau aggregation in neurons. Dr. Sharma and his group will use biochemical, cell biological, and whole-animal approaches to investigate how Hsj1 (a co-chaperone protein) causes tau degradation, thus possibly reducing tau aggregation and pathology. They expect their research to give them a clear understanding, in molecular detail, of how Hsj1 acts to reduce tau in neurons. They also expect to clarify whether this action of Hsj1 protects against neurodegeneration driven by tau aggregation.

Dr. Sharma’s research, if successful, could make a huge impact on the treatment of Alzheimer’s disease by informing therapeutic strategies that mimic or boost the activity of cellular tau-degrading mechanisms.

More 2015 Recipients of this Grant

Todd Cohen, PhD

Novel Post-translational Mechanisms that Mediate Neurodegeneration in Aging and Alzheimer’s Disease

Jason Hinman, MD, PhD

Development of a Novel Mouse Model of Mixed Vascular- and Alzheimer’s -Caused Dementia

Marc Vermulst, PhD

Transcription errors in Alzheimer’s disease

Alon Zaslaver, PhD

Synaptic failure in AD during aging-associated proteostasis collapse