Smith Lab

Overview

Dr. Smith’s research focuses primarily on the immunology of transplantation, with emphasis on the transplantation pathology of the heart, kidney, and pancreatic islets. He is particularly interested in how the acute and chronic rejection of allografts and xenografts come about. Studies involve patients and animal experimentation with heart, kidney and pancreatic islet grafts. With expertise in these areas, Dr. Smith is a consultant pathologist to investigators within the Harvard community, national consortia, and the Transplant Biology Research Program at Mass General with clinical and preclinical transplant programs. Dr. Smith is also a consultant to revisions of the classification scheme for human heart allograft biopsies.

Current emphasis and ongoing work includes studies of cellular and humoral rejection in cardiac allografts of humans and mice (hearts) and in kidneys of monkeys and humans. Dr. Smith has been able to correlate by indirect immunofluorescence C4d staining and the presence of alloantibodies in cardiac allografts. With investigators at other institutions, using clinical data, criteria are being established for the diagnosis of acute antibody-mediated rejection in human cardiac transplants. Dr. Smith and Dr. Colvin are studying the progression of monkey kidney allograft rejection that comes about with development of alloantibodies, chronic antibody-mediated rejection. They established that alloantibodies are the causative of the glomerulopathy of chronic humoral rejection in allografted kidneys, and established that chronic antibody-mediated rejection develops through four stages. Using RNA gene expression and statistical modelling, Dr. Smith has identified biologically important subgroups in allografts, including tolerance, which is not readily classified by just pathological review.

Dr. Smith, along with other investigators studying islet allograft survival, has established that portal vein-based islet allografts can undergo a non-immunological senescence. Dr. R Abdi and Dr. Smith are investigating why knockout of certain chemokine genes, dendritic cells, and stem cells affect graft rejection and donor dendritic cell migration. In some autologous stem cell transplants in mice, sarcomas developed. With AB Collins and Dr. JR Stone we have established the utility of immunofluorescence for the classification of amyloid deposits.

Research Projects

Current emphasis and ongoing work includes cellular and humoral rejection in humans (hearts) and monkeys (kidneys). Dr. Smith has been able to correlate in direct immunofluorescence C4d staining with alloantibodies by retrospective and prospective analysis of the cardiac allograft biopsies. This study establishes for the first time the correlation between C4d staining and the presence of alloantibodies. The Immunopathology laboratory is a reference site for this test.

Dr. Smith is also studying the progression of monkey kidney allograft rejection that comes about with development of alloantibodies and has established that alloantibodies strongly associate with and are likely causative of the glomerulopathy of chronic humoral rejection in allografted kidneys, thereby, establishing that chronic humoral rejection develops through stages.

Group Members

Meet our research team:

• Rex Neal Smith, MD, PhD
• Patricia Della Pelle  
• Nicole Brousaides

Selected Publications

Hotta K, Oura T, Dehnadi A, Boskovic S, Matsunami M, Rosales I, Smith RN, Colvin RB, Cosimi AB, Kawai T. Long-term Nonhuman Primate Renal Allograft Survival Without Ongoing Immunosuppression in Recipients of Delayed Donor Bone Marrow Transplantation. Transplantation. 2018 ;102(4):e128-e136.

Smith RN, Matsunami M, Adam BA, Rosales IA, Oura T, Cosimi AB, Kawai T, Mengel M, Colvin RB. RNA expression profiling of nonhuman primate renal allograft rejection identifies tolerance. Am J Transplant. 2017;18(6):1328-1339.

Smith RN, Adam BA, Rosales IA, Matsunami M, Oura T, Cosimi AB, Kawai T, Mengel M, Colvin RB. RNA expression profiling of renal allografts in a nonhuman primate identifies variation in NK and endothelial gene expression. Am J Transplant. 2017;17(3):646-656.

Fischer K, Ohori S, Meral FC, Uehara M, Giannini S, Ichimura T, Smith RN, Jolesz FA, Guleria I, Zhang Y, White PJ, McDannold NJ, Hoffmeister K, Givertz MM, Abdi R. Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation. m J Transplant. 2017; 17(7):1791-1801.

Bruneval P, Angelini A, Miller D, Potena L, Loupy A, Zeevi A, Reed EF, Dragun D, Reinsmoen N, Smith RN, West L, Tebutt S, Thum T, Haas M, Mengel M, Revelo P, Fedrigo M, Duong Van Huyen JP, Berry GJ. The XIIIth Banff Conference on Allograft Pathology: The Banff 2015 Heart Meeting Report: Improving Antibody-Mediated Rejection Diagnostics: Strengths, Unmet Needs, and Future Directions. Am J Transplant. 2017; 17(1):42-53.