T cells are specialized immune cells that help protect the body from infections, control inflammation, and eliminate cancer cells. However, when T cells become overly inflammatory, they can contribute to chronic diseases such as inflammatory bowel disease (IBD). In contrast, when T cells lose their ability to effectively attack cancer cells. Developing ways to precisely control T-cell activity could lead to safer and more effective treatments for both inflammatory diseases and cancer.

Our research focuses on a protein called NRF2, which helps cells respond to stress and regulate antioxidant defenses. Recent studies from our laboratory have shown that NRF2 also plays an important role in controlling how T cells use nutrients and carry out their immune functions. In T cells, increasing NRF2 activity suppressed harmful inflammation in conditions like IBD, while reducing NRF2 activity enhanced the ability of T cells to kill tumor cells and reduce cancer growth.  We propose to develop innovative molecules called PROTACs for manipulating NRF2 levels in T cells. In this project, we will test whether T cell-specific NRF2-activating PROTACs can reduce inflammation and improve disease outcomes in preclinical models of inflammatory bowel disease. We will also determine whether T cell-specific NRF2-degrading PROTACs can enhance anti-tumor immune responses and improve the effectiveness of immunotherapy against melanoma. The long-term goal of this research is to develop precision immunotherapies that selectively reprogram T-cell function to treat inflammatory diseases and cancer while minimizing unwanted side effects. Successful completion of this project could lead to new therapeutic strategies for patients with IBD, melanoma, and other immune-mediated diseases.

Kalyani Pyaram, Ph.D., DNP, FNP-BC, WHNP-BC, APRN
Assistant Professor, Cancer Biology
Email: kpyaram@kumc.edu