Caitlin Zebley Lab

Despite the promise of immunotherapy, a known limiting factor of durable therapeutic success is T-cell exhaustion – a state in which T cells lose their protective capacity due to prolonged exposure to an antigen. Our past and ongoing research demonstrates that it is possible to overcome these obstacles of exhaustion and engineer T cells with specific epigenetic programs that instill disease-relevant, long-lived immunological properties. Our examination of T-cell differentiation focuses on restricting the terminal exhaustion of CD4 and CD8 T cells to bolster immunotherapeutic effects and strengthen effective, long-term cellular therapies. 

Furthering our study of T-cell differentiation and exhaustion is our work to define the epigenetic regulators that restrict antitumor immunity during prolonged antigen exposure. Our laboratory examines mutations that occur during the premalignant state of clonal hematopoiesis (CH).

Our goal is to understand how disruption of key CH-associated epigenetic regulators impact T-cell differentiation and how we can target these regulators to block the progression of T cell exhaustion. We are working to design an ideal CD8 T cell population for adoptive transfer that is proliferative and maintains effector potential that provides a long-lasting anti-tumor response. My goal is to continue to expand my research program to implement our laboratory findings in future cellular therapies that directly benefit patients with catastrophic disease.