Postdoctoral Research Fellow in Surgery, Harvard Medical School
Department of Surgery, Brigham and Women’s Hospital
Shailesh Agarwal, MD
Associate Professor of Surgery, Harvard Medical School
Associate Surgeon, Division of Plastic and Reconstructive Surgery, Brigham and Women’s Hospital
Ulrich von Andrian, MD, PhD
Mallinckrodt Professor of Immunobiology, Harvard Medical School
Development of skin grafts which are protected from rejection through local, autonomous, regulatory T-cell recruitment
Tissue allotransplantation — the application of donated tissues to an injured recipient — presents a significant clinical reconstructive opportunity for individuals with devastating musculoskeletal trauma or burn injuries. However, subsequent therapies that involve suppressing the immune system to allow the tissue grafts to survive, pose a risk of adverse effects including infection, diabetes, and even the development of tumors. Recognizing this issue, Pratik Koirala, PhD, and his team developed a gene therapy that allows cells to “sense” tissue allotransplantation rejection and produces an immunosuppressant that only impacts the affected skin graft, reducing the likelihood of developing other harmful conditions. This gene therapy has a closed-loop expression system that enables the immunosuppressant to be turned “on” by the cytokines that form during tissue rejection and to be turned “off” when those cytokines are withdrawn. Therefore, this gene therapy, when delivered only to the skin graft, allows the transplanted tissue to regulate threats of rejection and prioritize its survival.
With Stepping Strong Center funding, Dr. Koirala will begin a trial study that delivers his gene therapy with the goal of protecting skin grafts from tissue allotransplantation rejection. Using the information gathered during the study, Dr. Koirala aims to proceed with further development to bring this therapy closer to human application.
Pratik Koirala, PhD, is a postdoctoral research fellow in surgery at Harvard Medical School and within the Department of Surgery at Brigham and Women’s Hospital. Dr. Koirala earned his degree at the University of Kansas, Lawrence, with a focus on the molecular biology of bacteria. During his studies, Dr. Koirala studied quorum sensing in bacteria to understand how they communicate with each other and regulate gene expression to compete against other environmental competitors. Dr. Koirala’s research interests are aimed toward developing closed-loop gene circuits which enable cells to autonomously produce therapeutic proteins in response to threatening environments.