On Nov. 14, 2024, Professor of Pathology Laura Hale, MD, PhD, and co-Principal Investigator Joseph Turek, MD, PhD, associate professor of Surgery, were awarded a $242,250 R21 grant from the National Institutes of Health (NIH) to develop ways to prevent rejection of transplanted pig organs. Their project is titled “Inducing Xenotolerance via Chimeric Thymus” and will span two years.
Xenotransplantation of organs from genetically modified pigs into humans has been proposed as a way to overcome the currently insufficient numbers of human organs suitable for transplant. However thus far, pig organs transplanted into humans survive for only a short time. The human recipients either reject the transplanted pig organs as foreign or they develop overwhelming infections resulting from the immunosuppression used to prevent rejection.
This project will study ways to create specific unresponsiveness of human T cells to donor pig tissues, a state called immunologic tolerance, that is typically generated when T cell precursors encounter self-molecules in the thymus. Self-molecules are components that the immune system is able to distinguish from foreign substances.
Hale and Turek will model these processes by implanting thymuses from donor pigs together with human T-cell precursors into immunodeficient mouse recipients. The pig thymus tissues will receive gene therapy prior to implantation so they will make human (rather than pig) versions of the proteins that attract human T-cell precursors to the thymus. The research team will monitor whether the human T cells enter the pig thymus and if so, how they develop in the chimeric (pig-human) thymus.
These studies build on the unparalleled expertise of Duke clinicians and researchers with thymus transplantation to advance development of strategies to induce tolerance toward transplanted organs. Success in these studies would be a major breakthrough that could make organ replacement via xenotransplantation accessible to the large number of patients who currently die while awaiting a suitable human donor.
Since 1995, Hale has served as Principal Investigator or co-investigator on over 40 NIH, Department of Defense (DOD), and privately-funded grants that studied mechanisms and novel therapies for immune-mediated diseases and cancer. In August 2023, she received a five-year grant award through the National Institute of Aging as part of a program project to determine mechanisms that control age-related thymic atrophy and changes in immune function and as well as to identify therapies that can rejuvenate immune responses in older individuals.
In March 2023, Hale and Turek received a two-year R21 grant titled “Transplantation of Cryopreserved Thymus” from the National Institute of Allergy, Immunology, and Infectious Diseases.
Hale has also been recognized for her commitment to excellence in teaching. In May 2024, she received the 2024 Gordon G. Hammes Faculty Teaching Award. It recognizes continuing excellence in teaching and mentoring and exemplary commitment to the education of graduate students within basic science departments and graduate training programs in the Duke School of Medicine.