Explore This Lab


The Markmann Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital focuses on regulatory B cell-mediated transplant tolerance and meeting the need for donor liver allografts through pig-to-human liver xenotransplantation. While regulatory T cells have been evaluated in early-phase clinical trials for their capacity to curtail alloimmunity and achieve allograft survival without chronic immunosuppression, producing therapeutically relevant regulatory B cells (Bregs) remains a fertile area for progress and translation to clinical application. Delineation of Breg function and mechanisms of suppression remain to be clarified.

With extensive experience studying Bregs in diverse experimental models of tolerance to cell and tissue transplantation, as well as experience generating Bregs ex vivo and identifying key immunomodulatory pathways, the Markmann Lab aims to advance Breg-based treatments through the optimization and validation of several innovative approaches.

According to the U.S. Organ Procurement and Transplantation Network (OPTN), 105,846 candidates are currently waiting to receive an organ. By the end of 2022, roughly 40,000 transplants will take place, but over 10,000 patients will either die or become too sick to transplant. The only possible solution with the potential to address the inadequate organ supply in the near term appears to be use of animal organs, also known as xenotransplantation. The Markmann Lab is working to understand the immunological, and physiological barriers to liver xenotransplantation and determining the needed genetic modifications and immunosuppressive regimens necessary to achieve durable graft survival.

Lab Members

Principal Investigators

James F. Markmann, MD, PhD
Co-Director, Center for Transplantation Sciences (CTS)
Senior Investigator/Head, Markmann Laboratory, CTS
Principal Investigator, Pancreatic Islet Isolation Laboratory, CTS
Chief, Division of Transplantation, Massachusetts General Hospital
Claude E. Welch Professor of Surgery, Harvard Medical School

Christian LeGuern, PhD
Senior Investigator/Head, Molecular Biology Laboratory, CTS
Associate Immunologist, Massachusetts General Hospital
Associate Professor of Surgery & Immunology, Harvard Medical School
Professor, University Paris Sorbonne

Ji Lei, MD, MSc, MBA
Investigator/Director, Pancreatic Islet Isolation Laboratory, CTS
Associate Immunologist, Massachusetts General Hospital
Assistant Professor of Surgery, Harvard Medical School

Research Scientists

  • Kang Mi Lee, PhD

Postdoctoral Research Fellows

  • Daniel Firl, MD
  • Anil Kharga, MD

Research Technologists

  • Helen Deng, MD
  • Zhihong Yang, MD PhD

Doctoral Students

  • Minxue Liao, MD

Research Technicians

  • Kevin Deng, BS
  • Rudy Matheson, BS
  • Olivia Bourgeois, BS

Former Members

Qiang Fu, MD, PhD; Daniel Cloonan, MD; Nikolaos Serifis, MD; Taylor Coe, MD; Omar Haque, MD, MPH; Noel Feeney, BS; Guoli Huai, MD, PhD; Charles Rickert, MD, PhD; Dan Erdman, MS; Danielle Detelich, MD; Lisa Kojima, BS; Chen Dai, MD; Mohamed Aburawi, MD; Haley Tector, BS; Beth Amundsen, MD; Laura Washburn, BS; Hany Deirawan, MD.

Research Projects

Regulatory B cell-mediated transplant tolerance

Several years ago, our group first described a transplant tolerance protocol that was B cell-dependent. We determined that a short course of anti-CD45RB antibody treatment prolongs heart allografts indefinitely, but not in the absence of B cells. Since then, we and others have demonstrated that additional tolerance induction protocols are B cell-dependent, with the recovery and adoptive transfer of B cells from tolerant mice being sufficient to induce transplantation tolerance in naïve hosts.

To further understand the role and potential of regulatory B cells as a cell-based therapeutic, we have investigated methods of expanding naïve B cells ex vivo through Toll-like receptors (TLRs) and generating B cells with regulatory properties. In vitro and in vivo, these Bregs are capable of suppressing T cell proliferation, prolonging graft survival and inducing regulatory T cells. Phenotypically, our Bregs display upregulated markers of B cell activation, including CD80, CD86, MHC class II and CD38. In addition, greater expression of TIM1, CD25, PD-L1 and LAP (a surrogate for the anti-inflammatory cytokine, TGF-β) is observed. Through single cell RNA-sequencing, we have substantiated an important role for TGF-β-mediated signaling that may underlie the immunobiology of Bregs we term Bregs-TLR9/4.

With evidence in our lab exhibiting the advantage of antigen-specific Bregs, we strongly believe in our ability to advance the understanding of Breg mechanisms of differentiation and suppression, optimize Breg function and develop the potential of Bregs as a cell-based therapy.

Pig-to-primate liver xenotransplantation

In recent years, we have witnessed breakthroughs in xenotransplantation based on the use of organs from genetically modified pigs targeting antibody and complement-activation pathways. The focus of our research is on liver ex-vivo perfusion and orthotopic liver xenotransplantation. Transplantation of livers from GTKO miniature swine into baboon recipients performed at our center have shown the longest survival without evidence of rejection, inflammation or thrombotic microangiopathy (TMA) at 29 days. True long-term survival of liver xenotransplants has yet to be achieved and will require tackling key concerns such as identifying the most effective immunosuppression regimen, overcoming coagulation dysregulation and management of systemic inflammation and graft ischemia reperfusion injury (IRI). Our team aims to evaluate the impact of CRISPR-Cas9-induced gene panels on the incidence and severity of initial xenograft dysfunction.