Rex Neal Smith, MD, PhD

Smith Lab

“Investigating the causes of acute and chronic rejection...”

Overview

 Rex Neal Smith, MD, PhD

Professor of Pathology, Harvard Medical School
Pathologist, Massachusetts General Hospital

Pathology Service
Massachusetts General Hospital
55 Fruit Street
Boston, MA 02140
Phone: 617-726-1835
Fax: 617-726-2365
Email: rnsmith@partners.org

 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 Harvard community, national consortia, and the Transplant Biology Research Program at MGH 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 have been able to establish 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. 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. With Dr. M. Soares investigations are ongoing into the mechanism of cerebral malaria. New work with Dr. E. Zorn and J Fraser seeks to identify new alloantibodies in graft rejection by novel proteomic approaches.

 

Group Members

Patricia Della Pelle  
Nicole Brousaides

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.

Selected Publications

Bibliography of Dr. Rex Neal Smith via PubMed

Roth, AJ, Brown, MC, Smith, RN, A.K. Badhwar, AK, Parente, O,. Chung, HC, Bunch, DO, McGregor, JG, Hogan, SL, Hu, Y, Yang, JJ, Berg, EA, Niles, J, Jennette, JC, Preston, GA, and Falk, RJ. Anti-LAMP-2 Antibodies Are Not Prevalent in Patients With Antineutrophil Cytoplasmic Autoantibody Glomerulonephritis. J Am Soc Nephrol, 2012; 23(3):545-555.

Wang, H., Smith, R.N., Spooner, AE, Isselbacher, EM, Cambria, RP, MacGillivray, RE,  Stone, JH, and Stone, JR. Giant cell aortitis of the ascending aorta without signs or symptoms of systemic vasculitis is associated with elevated risk of distal aortic events. Arthritis Rheum. 2012; 1: 317-319.

Herlitz, L.C., Bomback, A.S.. Markowitz, G.S., Stokes, M.B., Smith, R.N., Colvin, R.B., Appel, G.B., and D'Agati, V.D. Pathology after Eculizumab in Dense Deposit Disease and C3 GN. Journal of the American Society of Nephrology: JASN 2012; 23:1229-1237.

Smith, R.N., Malik, F., Goes, N., Farris, A.B., Zorn, E., Saidman, S., Tolkoff-Rubin, N., Puri, S., and Wong, W. 2012. Partial Therapeutic Response to Rituximab for the Treatment of Chronic Alloantibody Mediated Rejection of Kidney Allograft. Transplant Immunology. 2012; 27 (2): 107-113.

Nadazdin, O., S. Boskovic, S.L. Wee, H. Sogawa, I. Koyama, R.B. Colvin, R.N. Smith, G. Tocco, D.H. O'Connor, J.A. Karl, J.C. Madsen, D.H. Sachs, T. Kawai, A.B. Cosimi, and G. Benichou. Contributions of direct and indirect alloresponses to chronic rejection of kidney allografts in nonhuman primates. J Immunol., 2011; 187:4589-4597.

Primo VC, Marusic S, Franklin CC, Goldman WH, Achaval CG, Smith RN, Arnaout MA, Nikolic B. Anti-PR3 immune responses induce segmental and necrotizing glomerulonephritis. Clinical and Experimental Immunology 2010; 159: 327.

Contact

Contact Us

Smith Laboratory

Massachusetts General Hospital

55 Fruit StreetPathology Service, WRN 501D Boston, MA 02114
  • Phone: 617-726-1835
  • Fax: 617-726-2365

Email: rnsmith@partners.org

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