Pallavi Gopal, MD, PhD, and her lab are advancing research into TDP-43, a protein which plays important roles in cell function.
While TDP-43 is essential for healthy cell function, it can abnormally clump together in the nervous system. The buildup of TDP-43 is a hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and frontotemporal dementia.
Gopal, associate professor of pathology, and her lab are studying why TDP-43 malfunctions and loses its normal ability to protect cells. This loss leads to harmful clumping in nerve cells.
To support her work, Gopal recently received two major federal grants:
- 2026 Amyotrophic Lateral Sclerosis Research Program Therapeutic Idea Award from the Department of Defense. This grant backs high-risk, high-reward ideas that could lead to new ALS drugs and therapies.
- R21 grant from the National Institutes of Health/National Institute of Aging. This funding will be used to develop and test a new specialized peptide, aimed at blocking the harmful protein clumps from forming in the first place.
The lab recently published a computational pipeline to engineer peptide-based inhibitors, which are the foundation for both awards. These inhibitors can combat TDP-43 aggregation and restore normal splicing function.
Ultimately, Gopal aims to learn what triggers the TDP-43 protein to go awry and if there are ways to prevent the clumps from forming. She wants to know if they can intervene before the clumps form and if other unknown factors regulate the process.