Aging and Organ Transplantation
Aging and Transplant Immunity
With an increasing aging population and prolonged life spans, there has been a significant increase in the number of older transplant recipients. At the same time, older patients represent the fastest growing cohort waiting for a transplant. Those older patients are treated in the same way as young recipients, yet their alloimmune responses differ substantially. This project aims to gain a solid understanding of age-specific changes in alloimmunity to provide treatments for older transplant recipients.
Rejuvenation of Old Organs for Transplantation
Many organs are currently not utilized mainly because of concerns about age-related functional compromise, loss of reserve, susceptibility to injury, and reduced repair capacities. Cellular senescence is a major driver of age-related dysfunction and contributes to a variety of chronic diseases. This project aims to understand how senescence critically drives immunogenicity, organ quality, and chronic graft deterioration while molding alloimmunity and targeting senescent cells has the potential to significantly improve organ utilization and transplant outcomes.
Interorgan Communication
Aging is a complex biological phenomenon that manifests at the cellular, tissue, and organismal levels. It is increasingly clear that rich dynamics underlie biological aging, yet the fundamental nature of this process remains poorly understood. Specifically, inter-tissue dynamics of biological age, and how this may change over the lifespan, have received little attention. This project aims to assess mechanisms of inter-organ aging dynamics and how these change during aging.
Biological Sex and Alloimmune Repsonse
Biological sex has an influence on a variety of physiological and pathological processes showing sex dependent differences in the occurrence of several diseases. In organ transplantation, donor and recipient sex are known to affect transplantation outcome. Women, receiving a kidney or heart transplant from male donors show inferior graft survival. This project aims to understand mechanisms that compromise access to transplantation and disadvantage female transplant recipients.
Metabolism and Alloimmunity
Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity and has been recommended for morbidly obese transplant recipients. We found that obese mice mounted augmented alloimmunity and rejected transplants faster than lean mice. This project aims to understand how obesity-related metabolic shift modulates alloimmunity and graft rejection.