Robert B. Colvin, MD

Colvin Lab

“Pathogenesis of rejection and tolerance of organ transplants...”

Phone: 617-726-2588

Physician Profile

Overview

Robert B. Colvin, MD

Benjamin Castleman Distinguished Professor of Pathology,
Harvard Medical School (Formerly Chief of Pathology, 1991-2006)

Immunopathology Research Laboratory
Thier Building 8th Floor
Massachusetts General Hospital
Boston MA 02114
Phone: 617-724-3631
Fax: 617-724-5833
Email: rbcolvin@partners.org

The mechanisms of graft acceptance (tolerance) have been a major area of investigation in the transplant group at MGH, with mouse, pigs, non-human primates and most recently a clinical trial. Dr. Colvin is currently seeking the mechanisms of graft acceptance and the role of Foxp3+ Treg cells in mouse kidney allografts. These studies have revealed a novel Treg-rich organized lymphoid structure (TOLS) in accepted allografts that surround small arteries. Depletion of Treg causes dissolution of the TOLS and precipitates acute graft rejection. Further studies have revealed that mixed chimerism-induced tolerance leads to deletional tolerance of MHC antigens and regulatory tolerance of non-MHC antigens.

In studies in human kidney allografts, Dr. Colvin’s group was the first to describe chronic antibody-mediated rejection, now recognized as the most common cause of late graft dysfunction. He has shown that deposition of the classical complement component, C4d, in peritubular capillaries is a useful marker of acute and chronic antibody-mediated rejection. C4d is the most specific marker of these conditions. Through the efforts of Dr. Colvin and others, new categories of acute and chronic antibody-mediated rejection have been incorporated into the Banff criteria and have become the standard of care. Protocol biopsies from non-human primate studies have demonstrated sequential stages of chronic humoral rejection. Dr. Colvin leads the pathology core for several NIH and industry-sponsored clinical trials as well as an international NIH genomics project in renal allograft.

A major problem in long-term organ grafts is the development of a chronic arteriopathy, which has an unknown pathogenesis. Dr. Colvin and Dr. Paul Russell developed and characterized a model of the disease, using heart grafts in mice. Coronary arteries develop florid lesions over 4-8 weeks, resembling closely the lesions in human organ grafts. The group showed that chronic allograft arteriopathy can be produced by three distinct immune pathways, humoral antibody (passive transfer of anti-donor antibodies into RAG-1 knockout mice), T cells (male to female grafts) or natural killer cells (parental graft to F1 recipients). Such antibodies can mediate chronic arteriopathy in the absence of complement, through an NK cell dependent FcR mechanism.

The immunopathogenesis of renal diseases is Dr. Colvin’s other long-term interest. He has recently identified a new disease due to anti-brush border antibodies (ABBA) that deposit in the proximal tubules.  The publication led to the discovery of several other cases.  The nature of the antigen is under investigation with proteomic techniques.

 

 

Group Members

Lab Members

Alessandro Alessandrini, PhD  Associate Director, Pediatric Surgical Research Laboratories 
Ivy Rosales, MD  Fellow
Chao Yang, MD  Fellow
Patricia Della Pelle,   Laboratory Administrator
Catherine Adams,   Administrative Assistant to Dr. Colvin
Nicole Brousaides  Research Technologist
Rebecca White  Research Technician II
A. Bernard Collins  Technical Director
Dorothy Ndishabandi  Research Technician II

 

Research Projects

Dr. Colvin's laboratory is now primarily focused on the role of T regulatory cells (Foxp3+) in spontaneous acceptance of renal allografts in mice. Stable grafts have a characteristic T and B cell lymphoid aggregates around arteries with abundant Foxp3+ cells, which have been termed Treg-rich organized lymphoid structures (TOLS), believed to be important in acceptance. In recipients with stable renal allografts, transient depletion of Foxp3+ cells precipitates rapid and severe acute cellular rejection. 

The group is currently working on the mechanisms by which TOLS arise and the loss of Foxp3+ cells promotes rejection. New techniques include in vivo imaging of the cellular activity in renal allografts, using a minimally invasive, novel confocal multicolor endomicroscope developed by a co-investigator, Seok Yun, PhD, at Massachusetts General Hospital, which can detect cells labeled with fluorescent proteins and dyes.

Selected Publications

Bibliography of Robert B. Colvin via PubMed

 

Miyajima M, Chase CM, Alessandrini A, Farkash EA, Della Pelle P, Benichou G, Graham JA, Madsen JC, Russell PS, Colvin RB. Early acceptance of renal allografts in
mice is dependent on Foxp3+ cells.  Am J Pathol. 2011; 178:1635-45.

Akiyoshi T, Hirohashi T, Alessandrini A, Chase CM, Farkash EA, Neal Smith R, Madsen JC, Russell PS, Colvin RB. Role of complement and NK cells in antibody mediated rejection. Hum Immunol. 2012; 12:1226-32.

Hirohashi T, Chase CM, Della Pelle P, Sebastian D, Alessandrini A, Madsen JC, Russell PS, Colvin RB. A novel pathway of chronic allograft rejection mediated by NK
cells and alloantibody. Am J Transplant. 2012; 12:313-21.

Kawai T, Sachs DH, Sprangers B, Spitzer TR, Saidman SL, Zorn E, Tolkoff-Rubin N, Preffer F, Crisalli K, Gao B, Wong W, Morris H, LoCascio SA, Sayre P, Shonts B, Williams WW Jr, Smith RN, Colvin RB, Sykes M, Cosimi AB. Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am J Transplant. 2014; 14:1599-611.

Rosales IA, Collins AB, Alves do Carmo P, Tolkoff-Rubin N, Smith RN, Colvin RB. Immune complex tubulointerstitial nephritis due to autoantibodies to the proximal tubule brush border. J Am Soc Nephrol. 2016; 27:380-384.

Contact

Contact Us

Colvin Laboratory

Massachusetts General Hospital

Thier 831 Boston, MA 02114
  • Phone: 617-724-3631
  • Fax: 617-724-5833

Email: rbcolvin@partners.org

Phone: 617-726-2588

Physician Profile

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