Project Grant F32AI197463

The National Institute of Allergy and Infectious Diseases awarded Duke University $172,160 on October 17, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to support investigator-initiated research on the role of PTEN in homeostatic repopulation after induction therapy in kidney transplantation, led by Principal Investigator Michael K. Okoreeh.

The funded research investigates how phosphatase and tensin homologue (PTEN) regulates memory T cell differentiation and expansion during lymphodepletion recovery in kidney transplant recipients. The project addresses a clinical limitation: while belatacept-based immunosuppressive regimens that block T cell costimulation offer improved graft function compared to calcineurin inhibitors, they are limited by higher early acute rejection rates driven by CD28-independent effector memory T cells. Preliminary data from transplant patients treated with T cell depletion using alemtuzumab plus belatacept and rapamycin (ABR regimen) show that approximately 50 percent of patients can discontinue rapamycin and maintain solely on belatacept, while those unable to discontinue rapamycin exhibit expansion of PTEN-negative effector memory T cells. The research hypothesizes that PTEN deficiency drives uncontrolled effector memory T cell proliferation resistant to costimulation blockade, and that rapamycin may serve as a PTEN surrogate. The project seeks to identify whether controlling PTEN-deficient memory T cell expansion could allow broader patient discontinuation of rapamycin and its associated off-target toxicities.

Work is performed at Duke University in Durham, North Carolina, with a period of performance from October 17, 2026, through June 30, 2028. This is a Project Grant, an assistance type supporting individual investigator-initiated research.