The Huang laboratory studies transplantation immunology with a focus on developing clinically relevant protocols for the establishment of transplantation tolerance. Dr. Huang's research involves using basic immunologic approaches to develop clinically relevant strategies for regulating inflammation, overcoming transplant rejection and improving tumor immunotherapy.
Prolonged immunosuppression increases the risk of infection, fracture, cancer, and complications from drug toxicity. The morbidity of these drugs affects the quality of life, alters the risk profile and could jeopardize the benefits gained from a successful composite tissue allotransplant. Immunologic tolerance would allow for the long-term survival of these organs without the need for chronic immunosuppression. This would significantly impact the risk-ratio and allow for the more widespread use of VCA to reconstruct lost limbs and facial deformities.
VCA are comprised of different tissue types and have a significant skeletal muscle component which makes them particularly susceptible to ischemic injury. Strategies to prevent IRI could decrease rejection episodes, improve VCA outcomes and facilitate immune tolerance induction strategies. Galectin-3 (Gal3), a known inflammatory factor, is actively involved in ischemia-induced inflammation and fibrosis of various organs. We are investigating the role of Gal3 in VCA IRI. Gal3 may serve as a therapeutic target to prevent or reduce IRI and could also be used as a novel peripheral biomarker to predict the degree of ischemic damage and graft function following VCA transplantation.
Acute and chronic antibody-mediated rejection are major problems for transplant recipients because current immunosuppressive regimens are insufficient to control humoral immunity against the graft. Our preliminary data in the pre-clinical swine model demonstrate induction of stable B-cell tolerance following donor hematopoietic cell infusion using a novel low-toxicity protocol. We are studying the mechanistic basis for induction of stable B-cell tolerance to transplantation antigens in order to facilitate development of clinically relevant approaches to overcome humoral immunity to transplants.