Using Genetically Modified Mice to Study the Role of Ubiquilin-1 in Alzheimer's Disease

Hongmin Wang, PhD
University of South Dakota (Vermillion, SD)
Year Awarded:
2014
Grant Duration:
July 1, 2014 to June 30, 2017
Disease:
Alzheimer's
Award Amount:
$250,000
Grant Reference ID:
A2014420S
Award Type:
Standard
Award Region:
US Northwestern

Using Mouse Models to Study the Role of Ubiquilin-1 in Alzheimer’s Disease

Summary

A protein named ubiquilin-1 has long been considered to play a role in Alzheimer's disease. However, the exact role of the protein in Alzheimer's disease remains unclear. This research project is to investigate whether increase or depletion of the ubiquilin-1 protein in genetically modified mice changes the signs and conditions of Alzheimer's disease.

Details

The goal of this project is to determine whether the onset and progression of Alzheimer’s disease (AD) in mice can be altered by the manipulation of a protein called ubiquilin-1. One major manifestation of AD is the accumulation of unwanted amyloid proteins in brain tissues. Previous studies conducted by these scientists have indicated that the ubiquilin-1 protein helps cell remove unwanted proteins; therefore, ubiquilin-1 may play a protective role for nerve cells affected by AD.

Dr. Wang’s group has produced genetically modified mice that either express excessive levels of ubiquilin-1 or are deficient in their expression of that protein. The scientists are currently crossing these mice with an AD mouse model, a group of mice whose specific genetic makeup allows them to serve as a model for the conditions of AD in humans. This crossbreeding will produce mice that exhibit the features of both original groups; the offspring will be AD mice that either express excessive ubiquilin-1 or lack the protein expression. Dr. Wang’s team will then investigate whether increasing or decreasing of ubiquilin-1 protein levels alters AD symptoms and progression, brain tissue structures, or the breakdown of the major AD-related proteins in the animals. The results of this study will help Dr. Wang’s team determine whether ubiquilin-1 affects the onset and progression of AD and whether the protein is a target for designing drugs to treat AD.

About the Researcher

Dr. Wang is an assistant professor in the Division of Basic Biomedical Sciences at the University of South Dakota Sanford School of Medicine in Vermillion, SD. He received his postdoctoral training at Johns Hopkins University School of Medicine in Baltimore, MD, and obtained his PhD from the University of Idaho in Moscow, ID. Dr. Wang’s laboratory uses genetically modified mouse models and different cell culture models, including induced pluripotent stem cells, to study AD and other disorders caused by nerve cell death in order to identify new strategies for treating such diseases.