2011 Grants - Yu

Models, Imaging and Drugs for TDP-43 Pathobiology

Gang Yu, Ph.D.
University of Texas Southwestern Medical Center
Dallas, Texas

2011 Investigator-Initiated Research Grant

TDP-43 is a protein with numerous functions within cells. Altered forms of TDP-43 have been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia. Evidence for abnormal TDP-43 has also been found in cases of Alzheimer's disease and Parkinson's disease.

Gang Yu, Ph.D. and colleagues have been studying the functional roles of TDP-43. They have proposed to develop a strain of mice genetically modified to have a version of TDP-43 that can be visualized with a microscope. To achieve this, the researchers will use molecular biology techniques to change the TDP-43 gene so that the final protein contains specialized regions that fluoresce when exposed to light of a certain wavelength. They have already shown the ability to do this without affecting the function of TDP-43.

Using mice carrying the gene for fluorescent TDP-43, Dr. Yu and colleagues will determine where the protein is localized, how it aggregates, and how it is transported within cells. Finally, the researchers will use cells containing fluorescent TDP-43 to identify drug candidates that alter its properties. These studies will provide new insights into the function of TDP-43 and its role in disease, and they may help to identify potential new therapies for inhibiting some forms of neurodegeneration.