James F. Markmann, Md, PhD

Markmann Laboratory

The Markmann Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital examines the hypothesis that a small subset of B cells plays a beneficial or regulatory role in transplant tolerance within the elderly population.

Overview

The Markmann Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital examines the hypothesis that a small subset of B cells plays a beneficial or regulatory role in transplant tolerance.

The elderly are the fastest growing segment of the population, and soon the number of people older than 65 will outnumber the number of children under five. Our group is interested in the effect of age on transplant tolerance. Data suggest that with age comes a significant resistance to transplant tolerance, and we hypothesize that hormones play a role in this resistance. Our group is interested modulating the endocrine system to reverse this barrier to tolerance.

Group Members

Principal Investigators

James I. Kim, PhD
Senior Investigator/Co-Head, Kim/Markmann Laboratory, Center for Transplantation Sciences (CTS)
Assistant Immunologist, Massachusetts General Hospital
Assistant Professor of Surgery, Harvard Medical School

James F. Markmann, MD, PhD
Co-Director, CTS
Senior Investigator/Co-Head, Kim/Markmann Laboratory, CTS
Core Director, Specialized Services Facility for Isolated Pancreatic Islet Production, CTS
Chief, Division of Transplantation, MassGeneral
Claude E. Welch Professor of Surgery, Harvard Medical School

Postdoctoral Research Fellows

Beth Amundsen, MD
Hany Deirawan, MD

Research Projects

The Kim/Markmann Laboratory in the Center for Transplantation Sciences is leading the following 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, however, in the absence of B cells, graft survival is not prolonged. Since then, we and others have demonstrated that additional tolerance induction protocols are B cell-dependent, through a subpopulation of cells called regulatory B cells. We are working to understand the mechanism of regulatory B cell-mediated transplant tolerance. We hypothesize that TGF-β production by B cells is critical for tolerance induction. Our data suggests that regulatory B cells, through the production of TGF-β, induce regulatory T cells, and this interaction is necessary for prolonged graft survival
  • Immunosenescence in transplant tolerance: The elderly are the fastest growing segment of the population with end-stage organ disorders, and their numbers on the transplant waiting list continue to rise. In order for tolerance to become a goal for the majority of transplant patients, it is essential to understand the effects of aging on transplant tolerance. A short course of anti-CD45RB reliably induces stable, robust tolerance to various allogeneic grafts in young mice but never in aged mice. The thymus, an organ critical to immune function, shrinks beginning at the time of adolescence. Focusing on the role of thymic involution and the effect of hormonal manipulation in aged recipients, we discovered that chemical or surgical castration reverses the resistance to tolerance to the levels of a young recipient, and this correlates with thymic rejuvenation. In this model, we are exploring the basis of the age-dependent barrier to transplant tolerance and the mechanism by which endocrine modulation reverses this barrier

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