Post-transcriptional regulation in T cells

The National Institute of Allergy and Infectious Diseases awarded the University of Pittsburgh $218,728 on February 14, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to support postdoctoral research on post-transcriptional regulation of T cells.

The research investigates the role of an RNA-binding protein in T cell-driven inflammatory disease using graft-versus-host disease as a model system, and seeks to elucidate the mechanistic basis for how this protein post-transcriptionally regulates T cells. The work addresses therapeutic opportunities in T cell signaling pathways to improve long-term treatment of inflammatory and autoimmune disorders where patients show limited durable response to current immunosuppressive therapies. The funded activities include developing expertise in in vivo disease models, performing computational analyses of high-throughput sequencing data from immune cells, and establishing clinical and research mentorships aligned with the fellow's career objective in immune tolerance research.

The award supports work at the University of Pittsburgh, Pittsburgh, Pennsylvania, with performance through August 31, 2028. This is a project grant, the standard assistance type for investigator-initiated research under the program.

Abstract

T cell activation underlies the pathogenesis of many inflammatory disorders, including diseases of autoimmune and alloreactive background. Currently, many patients undergoing immunosuppressive therapy do not show a durable response, and are often refractory to second and third-line treatments. The identification of new targetable T cell signaling pathways may therefore pave the way for improved long-term treatment of inflammatory disease. Upon encountering their cognate antigen, T cells initiate a coordinated activation program involving changes in gene expression, epigenetics and protein synthesis to mount a rapid response, many of which are therapeutically targetable. Another critical mechanism for T cell regulation involves post- transcriptional control, including RNA processing and stability. We have identified an RNA-binding protein (RBP) that is induced following TCR activation, which exhibits previously uncharacterized roles in the post- transcriptional regulation of T cells. T cells deficient in this RBP showed defects in mrna translation, as well as proliferation and differentiation. The goals of this research proposal are to investigate the role of this RBP in T cell-driven inflammatory disease using graft-versus-host disease (GVHD) as a model (aim 1), and elucidate the mechanistic basis for how this RBP post-transcriptionally regulates T cells (aim 2). This project provides a unique opportunity for me to 1) gain expertise in an in vivo model of inflammatory disease (i.e. GVHD), 2) gain proficiency in computational analyses of high-throughput sequencing data of immune cells, and 3) form clinical and research mentorships tailored to my career goal of becoming a physician-scientist studying immune tolerance. This fellowship will allow me to create an early research niche within the field of immune tolerance which will be critical for my long-term objective to improve outcomes for patients with inflammatory disease.