A Penn Medicine research team has been selected to receive funding through the Kissick Family Foundation Frontotemporal Dementia (FTD) Grant Program, administered in partnership with the Milken Institute's Science Philanthropy Accelerator for Research and Collaboration (SPARC). The program awarded $2.5 million across five research teams, all focused on accelerating foundational discoveries, advancing treatment options, and improving outcomes for people living with sporadic FTD. Together, the funded projects represent diverse approaches to understanding why FTD develops and progresses differently across individuals, with the shared goal of uncovering new biomarkers and therapeutic targets.
The Penn team — consisting of three IOA Members, Michael Guo, MD, PhD, Michael Haney, PhD, and Hong Xu, PhD — will receive funding for their project "Decoding somatic genome instability as a driver of selective neuronal vulnerability in FTD," which investigates how DNA mutations that accumulate in cells over time may contribute to the disease.
"Frontotemporal dementia causes certain brain cells to accumulate abnormal tau protein and degenerate, while other cells remain relatively protected," explained Dr. Guo. "A fundamental mystery in the field is why some cells are more resilient to tau, while others are vulnerable."
To investigate this question, the team will test whether differences in neuronal DNA mutations help explain this selective vulnerability. Using a combination of human brain tissue and a brain-in-a-dish model, they will examine whether tau drives DNA mutations and whether impaired DNA repair leaves certain neurons more susceptible to the protein. By identifying what distinguishes resilient neurons from vulnerable ones, their findings may reveal new strategies to protect brain cells and slow disease progression.
"We are deeply appreciative of the support from the Kissick Family Foundation," said Dr. Guo. "The support of this grant will enable our team to pursue a bold project examining whether DNA mutations may cause some neurons in the brain to become vulnerable to damage from tau proteins in FTD. Ultimately, we hope our project will generate novel insights into the causes of FTD and identify new strategies for therapies."