Gina Rayat, PhD
Office: 5-002C, Li Ka Shing Centre for Health Research Innovation
Mail: University of Alberta, Edmonton AB T6G 2E1
Associate Professor, Department of Surgery
Director – Surgical Medical Research Institute
Associate Director - Graduate Program in the Department of Surgery
Islet xenotransplantation, tansplantation tolerance, autoimmunity (type 1 diabetes)
Current Research Activities
Dr. Rayat’s research focus is to understand the mechanism(s) of islet xenograft rejection and to develop safer strategies for preventing rejection and induction of tolerance to islet xenografts.
Despite the current success in this field of islet transplantation, two major problems need to be addressed so that this therapy can be applied to the majority of individuals with type 1 diabetes. These problems are shortage of human islets for transplantation and the chronic use of immunosuppressive drugs to prevent rejection of the transplant.
One possible solution to the shortage of human islets is to use islets from animal sources. Newborn pigs are an attractive alternative source of islets because islets from newborn pigs are easily isolated in large numbers and they are capable of maturing and reversing diabetes in small and large animals. However, newborn pig islets are rapidly rejected in these animals without continuous administration of immunosuppressive drugs, which have harmful side effects and potential health risks.
Dr. Rayat and her group prevent rejection of newborn pig islets using short-term administration of strategic combinations of monoclonal antibodies that interfere with the interaction between T cells and antigen presenting cells (APCs) so that these cells will not be activated. Dr. Rayat’s studies will provide clinically useful method of preventing rejection of newborn pig islet xenografts without chronic use of immunosuppressive drugs.
Currently, projects on genetically engineered pig islets are underway in Dr. Rayat’s lab. These projects are funded by CIHR with Dr. Greg Korbutt as the PI and ADI translational team grant with Dr. Rayat as the PI.
Other Activities and Affiliations
Dr. Rayat was elected Council member of the International Xenotransplantation Association, Canadian Society of Immunology, Canadian Society of Transplantation, Cell Transplant Society, Transplantation Society, International Pancreas and Islet Transplant Association and the International Xenotransplantation Association.
Dr. Rayat received her Bachelor of Science degree major in Molecular Biology at the University of Winnipeg and completed her Master of Science degree in Transplantation Immunology at the University of Manitoba. She completed her PhD training at the University of Alberta under Dr. Ray V. Rajotte’s supervision and moved to Denver, Colorado, USA for a postdoctoral training under the supervision of Dr. Ron G. Gill at the Barbara Davis Center for Childhood Diabetes.
Dr. Rayat returned to Edmonton and was appointed Assistant Professor in the Department of Surgery at the University of Alberta.
Thompson P, Badell IR, Lowe M, Turner A, Cano J, Avila J, Azimzadeh A, Cheng X, Pierson R, Johnson B, Robertson J, Song M, Leopardi F, Strobert E, Korbutt G, Rayat G, Rajotte R, Larsen CP, Kirk AD. Alternative immunomodulatory strategies for xenotransplantation: CD40/154 pathway-sparing regimens promote xenograft survival. Am J Transplant 2012 (Epub ahead of print).
Ramji QA, Bayrack K, Arefanian H, Marcet-Palacios M, Bleackley RC, Rajotte RV, Rayat GR. Protection of porcine islet xenografts in mice using sertoli cells and monoclonal antibodies. Transplantation 2011; 92: 1309-1311.
Thompson P, Badell IR, Lowe M, Cano J, Song M, Leopardi F, Avila J, Ruhil R, Strobert E, Korbutt G, Rayat G, Rajotte R, Iwakoshi N, Larsen CP, Kirk AD. Islet xenotransplantation using Gal-deficient neonatal donors improves engraftment and function. Am J Transplant 2011; 11: 2592-2602.
Thompson P, Cardona K, Russell M, Badell IR, Shaffer V, Korbutt G, Rayat GR, Cano J, Song M, Jiang W, Strobert E, Rajotte RV, Pearson T, Kirk AD, Larsen CP. CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates. Am J Transplant 2011; 11: 947-957.
Arefanian H, Tredget EB, Rajotte RV, Gill RG, Korbutt GS, Rayat GR. Short-term administrations of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies induce tolerance to neonatal porcine islet xenografts in mice. Diabetes 2010; 59: 958-966.
Kobayashi T, Arefanian H, Harb G, Tredget EB, Rajotte RV, Korbutt GS, Rayat GR. Prolonged survival of microencapsulated neonatal porcine islets xenografts in immune-competent mice without anti-rejection therapy. Cell Transplant 2008; 17: 1243-1256.
Arefanian H, Tredget EB, Rajotte RV, Korbutt GS, Gill RG, Rayat GR. Combination of anti-CD4 with anti-LFA-1 and anti-CD154 monoclonal antibodies promotes long-term survival and function of neonatal porcine islet xenografts in spontaneously diabetic NOD mice. Cell Transplant 2007; 16:787-798.
Rayat GR, Gill RG. Indefinite survival of neonatal porcine islet xenografts by simultaneous targeting of LFA-1 and CD154 or CD45RB. Diabetes 2005; 54:443-451.
Rayat GR, Johnson ZA, Beilke JN, Korbutt GS, Rajotte RV, Gill RG. The degree of phylogenetic disparity of islet grafts dictates the reliance on indirect CD4 T cell antigen recognition for rejection. Diabetes 2003; 52: 1433-1440.
Rayat GR, Rajotte RV, Elliott JF, Korbutt GS. Expression of Galα(1,3)Gal on neonatal porcine islet beta cells and susceptibility to human-complement lysis. Diabetes 1998; 47:1406-1411.
Zhi Hao Xu