I. Raul Badell Will Use NIH K08 to Study Mechanisms of DSA Formation Following Kidney Transplantation

July 2017

NIH K08 awards provide the opportunity for promising clinician scientists with demonstrated aptitude to develop into independent investigators. Emory transplant surgeon I. Raul Badell, MD, will apply his recently received K08 — which obtained an impact score of 10 — to studying the poorly understood processes that generate anti-human leukocyte antigen (HLA) donor-specific antibodies (DSA). DSA plays a significant role in the development of chronic rejection and fibrosis and can lead to late renal allograft loss.

HLA are proteins located on the surface of white blood cells. There are three general groups of HLA, and various subtypes within those. If the recipient and donor's HLA are different, the recipient's immune system can detect the donor kidney's HLA as foreign antigen, and produce donor-specific antibodies against the donor HLA on the surface of the transplanted tissue.

Dr. Badell believes that gaining a better understanding of the cellular interactions responsible for DSA formation after transplantation could guide the optimization of current immunosuppressive strategies and the development of novel therapies to control its production. For the study, he will engage in a series of interrelated experiments in a murine skin transplant model to examine the costimulatory and coinhibitory mechanisms that drive T follicular helper (Tfh) cell-mediated DSA responses in the setting of CD28 costimulation blockade, and then test methods of improving inhibition of these responses.

The Emory-based mentors for this project and for assisting Dr. Badell in launching his independent research career are primary mentor Mandy Ford, PhD, scientific director of the Emory Transplant Center, and co-mentors Christian Larsen, MD, DPhil, an internationally acknowledged leader in transplant immunology research, and hematologic cancer researcher Larry Boise, PhD. Dr. Larsen was also Dr. Badell's mentor during his post-doctoral research fellowship in transplant immunology at the Emory Transplant Center.

As Dr. Badell works through this study and beyond, he hopes to acquire the advanced skills in experimental mouse models that will allow him to realize bench-to-bedside translation of novel approaches to controlling DSA in kidney transplant recipients.

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