Alzheimer's disease is a debilitating and deadly disease that subverts our most basic mental functions including the ability to think and to recall memories and eventually to even care for our own basic bodily needs. It is not only the most common form of dementia but also the sixth leading cause of death in the United States. As the elderly population grows, the prevalence of Alzheimer's disease will increase dramatically, presenting a pressing need in medicine and in our society. Since its identification a century ago, considerable progress has been made in understanding the symptoms and risk factors of Alzheimer's disease. However, our understanding of its molecular mechanisms is still very limited, and as a result there are no disease-modifying interventions to prevent or even delay its progression. I propose to develop new tools and combine biochemical, biophysical, and bioengineering approaches to determine the molecular basis of Alzheimer's disease. Both the tools and the scientific results will then be used to develop new prototype therapeutic agents. The technology developed for this goal will also have far-reaching impact on elucidating mechanisms for a variety of proteins.

Public Health Relevance

Alzheimer's disease is a progressive, untreatable, and uniformly fatal brain disease affecting more than 5 million Americans; this number is expected to grow to 16 million by 2050 as our society ages. Many clues regarding the molecular mechanisms have emerged, but until pinpointed, a cure will remain elusive. We are developing novel molecular tools and have laid out a clear plan for not only determining the key molecular deficit in Alzheimer's disease, but also converting that new understanding directly into viable therapeutic agents.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2AG052940-01
Application #
8954527
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Yang, Austin Jyan-Yu
Project Start
2015-09-30
Project End
2020-08-31
Budget Start
2015-09-30
Budget End
2020-08-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Stanford University
Department
Biophysics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Latorraca, Naomi R; Fastman, Nathan M; Venkatakrishnan, A J et al. (2017) Mechanism of Substrate Translocation in an Alternating Access Transporter. Cell 169:96-107.e12