Transplantation Biology Research Center (TBRC) Laboratories

Overview

The Transplantation Biology Research Center (TBRC Labs) Laboratories in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital comprises two laboratories, the Genetic Engineering Laboratory and the Organ Transplantation Tolerance and Xenotransplantation Laboratory.

These laboratories utilize partially inbred miniature swine as preclinical large animal models in allotransplantation studies. Three herds of miniature swine homozygous for different sets of histocompatibility antigens at the major histocompatibility complex (MHC) have been developed by David H. Sachs, MD, former director of the TBRC. These animals show many similarities to human beings, both immunologically and physiologically, facilitating their potential use both as a model for allotransplantation studies and as xenograft donors.

Lab Members

Principal Investigator

David H. Sachs, MD  

Director, Transplantation Biology Research Center Laboratories
Immunologist, Massachusetts General Hospital
Professor of Surgery Emeritus, Harvard Medical School

Phone: 617-726-4065
Email: david.sachs@tbrc.mgh.harvard.edu

Dr. Sachs graduated from Harvard College in 1963, summa cum laude, with a Bachelor of Arts in chemistry, in 1964 with a DES in organic chemistry from the University of Paris and in 1968 with a Doctor of Medicine, magna cum laude, from Harvard Medical School.

From 1968 to 1970, Dr. Sachs trained as a surgical intern and research fellow in transplantation at Mass General. He then moved to the National Institutes of Health, where he developed a program in transplantation research. In 1991, he rturned to Mass General as director of the Transplantation Biology Research Center, now part of the CTS since 2015, and the first Paul S. Russell/Warner-Lambert Professor of Surgery at Harvard Medical School.

Dr. Sachs has published more than 700 articles in scientific journals. His research achievements include:

• Discovery of Ia (Class II) antigens in 1973
• Development of monoclonal antibodies to major histocompatibility complex (MHC) antigens
• Development of a unique large animal model for transplantation using miniature swine
• Use of mixed marrow reconstitution as a means of inducing specific transplantation tolerance
• Studies of specific transplantation tolerance of allografts and xenografts

Dr. Sachs is one of the three North American editors of Transplantation and was the founding editor of Xenotransplantation.

Dr. Sachs was elected to the Institute of Medicine of the National Academy of Sciences in 1996. He has received the Jean Borel Award in Transplantation, the ASTP/Novartis Established Investigator Award, The Medical Foundation Award and the Roche Ernest Hodge Memorial Award (formerly called the Roche AST Distinguished Achievement Award), the highest award bestowed by the American Society of Transplantation. Dr. Sachs was awarded an Honorary Degree from University of Nantes, France (2006), the Martin Prize for Excellence in Clinical Research (2009) and the Starzl Prize (2011). In 2014, he was honored with the Medawar Prize, awarded by the Transplantation Society.

Senior Executive Assistant

Rebecca Brophy

Phone: 617-726-4065
Email: rbrophy@partners.org

Senior Investigators

• Robert J. Hawley, PhD
• Kazuhiko Yamada, MD, PhD

Research Projects

The TBRC Laboratories' lead the following projects:

• Approaches to tolerance of allogeneic kidney and islet transplants: The major objectives of this project are to improve long-term outcomes following kidney and islet transplantation through research in clinically relevant, non-human primate models and to develop a tolerance-inducing strategy for curative treatment of end-stage diabetic nephropathy using living donor composite islet-kidney transplantation
• GalT-KO pigs expressing primate CD47 to facilitate organ xenografts: In these studies, we have produced GalT-KO pigs expressing primate CD47 via nuclear transfer. We are analyzing CD47 expression in these pigs, evaluating the efficacy of CD47 expression using in vitro systems, and performing proof-of-concept transplant experiments to validate the usefulness of this product in achieving mixed xenogeneic chimerism and tolerance
• Tolerance to vascularized allografts in miniature swine: These studies are directed towards the nature of cell populations responsible for adoptive transfer of tolerance, determining whether the thymus is required for breaking and/or reinforcing tolerance and examining the mechanism by which B cell immunity to class I antigens is controlled in animals tolerant of class I-mismatched renal allografts        
• A tolerance approach to xenotransplantation: The overall goal of this project is to develop a clinically applicable technology for xenotransplantation of porcine organs into primates. The three major approaches to this goal involve transplantation tolerance of the adaptive immune system, overcoming innate immune barriers and avoiding disordered thromboregulation
• Thymic rejuvenation for the induction of transplantation tolerance: The major objectives of this project are to identify cellular and humoral host elements responsible for thymic rejuvenation, determine their relative roles in this process and use this information to test the hypothesis that rejuvenation of an aged thymus will allow tolerance to be induced in adult animals by the same simple methodology that has been effective for juvenile animals