Kawai Lab

Overview

We have been conducting both preclinical and clinical studies to address two major challenges in organ transplantation: the need for lifelong immunosuppression and the shortage of donor organs.

Research Projects

Immunological Tolerance

Short-term outcomes following organ transplantation have improved significantly with the development of increasingly effective immunosuppressive agents. However, chronic immunosuppression is associated with substantial morbidity, including cardiovascular disease, infection, malignancy, de novo diabetes, and other metabolic complications. Moreover, current immunosuppressive regimens often fail to prevent chronic rejection, even when administered at toxic levels. For these reasons, the induction of immunological tolerance—defined as the absence of destructive immune responses to a transplanted organ without the need for ongoing immunosuppressive therapy—remains the ultimate goal of transplantation.

Our laboratory translated this concept from murine models to nonhuman primates and ultimately to clinical application in human leukocyte antigen (HLA)-mismatched kidney transplantation. Using this approach, we achieved durable renal allograft tolerance, with the longest graft survival now exceeding 12 years without immunosuppression. This work represents a seminal translational achievement, culminating in the first reproducibly successful induction of renal allograft tolerance in humans, as reported in The New England Journal of Medicine in 2008 and 2013.

Building on these results, we are currently conducting a clinical trial using a revised conditioning regimen designed to induce tolerance more efficiently and safely (NCT06972069). In parallel, we are extending this strategy to deceased donor transplantation—including kidney, heart, and lung—through a newly developed “delayed tolerance” protocol (NCT05900401).

Xenotransplantation

Another major challenge is the shortage of donor organs. Currently, over 108,000 individuals in the United States are awaiting transplantation, yet fewer than 40,000 transplants are performed annually. To address this unmet healthcare need, we are investigating the use of porcine organs for human transplantation.

Recent advances in genetic engineering have enabled kidney xenograft survival exceeding 600 days in nonhuman primates using only one or two immunosuppressive agents. In collaboration with eGenesis, we have evaluated porcine kidney xenografts incorporating triple carbohydrate antigen knockout (3KO) and multiple human transgenes (HTGs), and have identified specific gene edits associated with survival beyond two years in nonhuman primates (Anand et al., Nature, 2023).

A porcine kidney xenograft incorporating these genetic modifications was subsequently transplanted into a human with end-stage renal disease—the first such case worldwide (Kawai T, et al., New England Journal of Medicine, 2025). We have since performed three additional transplants in human recipients and continue to refine genetic modifications to further improve outcomes.

Research Projects

1. The Kawai Laboratory is leading the following research projects:
2. Bcl-2 inhibition to promote mixed chimerism and allograft tolerance.
3. Delayed tolerance strategies to expand the clinical applicability of tolerance induction protocols.
4. The role of efferocytosis in transplant tolerance.
5. Engineering hematopoietic stem cells to achieve chimerism without genotoxic conditioning.
6. Evaluation of genetic modifications in pigs for xenotransplantation.
7. Gene editing during normothermic machine perfusion of donor organs.

Lab Members

Principal Investigator

Tatsuo Kawai, MD, PhD
Senior Investigator/Head, Kawai Laboratory
A. Benedict Cosimi Chair in Transplant Surgery, Massachusetts General Hospital
Professor of Surgery, Harvard Medical School
Director, Legorreta Center for Clinical Transplant Tolerance

Tatsuo Kawai, MD, PhD, is a Professor of Surgery at Harvard Medical School and the A. Benedict Cosimi Chair in Transplant Surgery at MGH, where he directs the Legorreta Center for Clinical Transplant Tolerance. He has pioneered clinical protocols for immunological tolerance in kidney transplantation and leads research in xenotransplantation using genetically modified porcine organs.

Co-Investigator

Alban Longchamp, MD, PhD
Assistant Professor, Harvard Medical School
Transplant Surgeon, Massachusetts General Hospital

Dr. Longchamp is an expert of organ perfusion and developed
numerous research project to prevent ischemia reperfusion injuries, in both rodents, porcine kidney transplantation model, and in human. Recently, his team achieved successful multi-days kidney perfusion. He is currently working on advanced organ preservation techniques with biomarker-based monitoring to improve graft viability, long-term outcomes, and allow feasible protocols for immunological tolerance induction and xenotransplantation.

Kouta Niizuma, PhD
Instructor, Harvard Medical School
Center for Transplantation Sciences

He is specialized in transplant immunology and stem cell biology. One of his works is to elucidate innate barriers to xenogeneic tolerance by dissecting
the macrophage axis that limits donor chimerism in interspecies chimeric animals.

Postdoctoral Research Fellows

Andre Souffrant, MD
Avery Wison, MD
Bryar Hansen, DO
Yu Zhang, MD
Abbas Dehnadi, DMD

Research Technologist

David Barnes

Research Nurse (Legorreta Center)

Kerry Crisalli, RN
Dana Nasso, RN
Paula Arigg, RN

Research Coordinator

Gabriel Imrepsso

Advisors

A.Benedict Cosimi, MD Emeritus Professor of Surgery, Harvard Medical School
David H Sachs, MD, Emeritus Professor of Surgery, Harvard Medical School and Columbia University

Former Members

Ahmad Karadagi, MD (Karolinska Institute, Sweden), PhD, Toshihide Tomosugi, MD, Ryo Otsuka, PhD (Chugai Pharma, Japan), Grace Lassiter, MD (St. Elizabeth Hospital), Takayuki Hirose, MD (Hokkaido Univ.), Tetsu Oura, MD (Hokkaido Univ.), Kiyohiko Hotta, MD (Hokkaido Univ.), Masatoshi Matsunami, MD (Kameda General Hospital), Svjetlan Boskovic, MD, Ognjenka Nadazdin, MD, Yohei Yamada, MD (Keio University), Aki Aoyama, MD (Kyoto University), Soyoung Lee, MD (University of Pittsburgh Medical Center), Derek Klarin, MD (Mass General), Toru Murakami, MD (Tokyo Women’s Medical University), Takanori Ochiai, MD (Tokyo Medical and Dental University), John Mercer, MD, Ichiro Koyama, MD (Tokyo Women’s Medical University), Nahel Elias, MD (Mass General), Hiroshi Sogawa, MD (Yale University, Transplant Center), Gregory Abrahamian, MD (University of Texas)