Brian R. Smith , MD Professor of Laboratory Medicine, Internal Medicine and Pediatrics Vice-Chair, Laboratory Medicine Director, Immunology and Flow Cytometry Laboratories Director, Hematopathology Fellowship Director, Immunohematology Research Training Program FMP 617 Phone: 203-688-2286 Fax: 203-688-4111 e-mail: brian.smith@yale.edu

1972 A.B., Princeton University
1976 M.D., Harvard Medical School
Residency and Fellowships: Brigham and Women's Hospital, Dana-Farber Cancer Institute, Children's Hospital, Boston

Research Activities

Dr. Smith's research interests fall into two related areas. First, the laboratory investigates the biology of hematopoietic cell adhesive interactions, especially platelet-leukocyte functional interdependency. The receptor-ligand pairs involved, the signal transduction mechanisms employed and the resultant alterations in functional cell phenotype are explored. A major interest in relating basic biological events to human pathophysiology has led the laboratory into studying the mechanisms and consequences of platelet activation and platelet-leukocyte conjugate formation during extracorporeal circulation, pre-eclampsia, and in hematologic disorders such as TTP. In the case of extracorporeal circulation, it seems clear that the complement system plays a major role in this process and hence translational research at the basic-clinical interface in the field of specific complement component blockade represents an ongoing direction. The importance of the subset of platelets most recently released from the circulation ("reticulated platelets") in these processes is explored through translational work in the area of platelet kinetic diagnostics in patients with thrombotic and hemostatic disorders.

References(A)

The second major area of interest in the laboratory is in understanding the immunology of stem cell transplantation, especially in the lymphoproliferative disorders. Lymphocyte interaction with endothelium and with accessory cells and the clonal recapitulation of immune ontogeny are areas of current investigation. Clinical translational research in these areas is also undertaken under the auspices of the laboratory with interest in understanding lymphomogenesis post-transplant and in the application of transplant to autoimmune diseases.

References(B)

The laboratory accepts graduate students directly through the Yale Program in Biomedical Engineering or as an adjunct laboratory through the Graduate School Combined Programs in Biological and Biomedical Sciences. Post-doctoral fellows (MD, PhD or MD/PhD) are also accepted, most commonly through the Departments of Laboratory Medicine, Pathology, Internal Medicine/Hematology, Internal Medicine/Oncology, Anesthesiology, Pediatrics/Hematology-Oncology, or Pediatrics/Infectious Diseases. Yale medical students may elect to work in the laboratory through the standard thesis mechanism and Yale undergraduate students may apply through the Molecular Biochemistry and Biophysics course 470a and 471b. To e-mail Dr. Smith, please click here.

Clinical and Teaching Activities
Dr. Smith sees adult hematology/oncology patients, stem cell transplantation patients, and carries out pathology interpretative clinical work through the Yale Faculty Practice. Teaching at the undergraduate level is carried out in MB&B 470a/471b, and in the Biomedical Engineering Seminar. At the graduate level, Dr. Smith is actively involved in the Laboratory Medicine teaching program at the Yale School of Medicine as well as those resident, fellow, post doctoral, graduate student and continuing education courses organized through the Yale Cancer Center, the Graduate School of Arts and Sciences Combined Programs in Biological and Biomedical Sciences, and the Departments of Internal Medicine and Pediatrics.

Other Activities
Dr. Smith has been and is active at the committee level in the following organizations:

• National Institutes of Health
• American Society of Hematology
• Leukemia Society of America
• American College of Physicians
• Academy of Clinical Laboratory Physicians and Scientists

Selected Recent Publications

References(A)

1. Smith BR. 1997. Interactions of Platelets and Endothelial Cells with Erythrocytes and Leukocytes in TTP. Sem Hematol 34:90-97.
2. Rinder CS, Rinder HM, Smith BR, Fitch JCK, Smith MJ, Tracey JB, Matis LA, Squinto SP, Rollins S. 1995. Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation. J Clin Invest 96:1564-1572. More
   
3. Smith BR. 1998. Interaction of Blood and Artificial Surfaces. In: Schafer AI, Loscalzo J. "Thrombosis and Hemorrhage, 2nd Edition" (Williams and Wilkins, Baltimore, MD) pp. 925-941. More
   
4. Rinder HM, Schuster, JE, Rinder CS, Wang C, Schweidler HJ, Smith BR. 1998. Correlation of Thrombosis with Increased Platelet Turnover in Thrombocytosis. Blood 91:1288-1294. More
   
5. Rinder HM. Tracey JB. Recht M. DeCastro L. Rinder CS. McHugh C. Smith BR. 1998. Differences in platelet alpha-granule release between normals and immune thrombocytopenic patients and between young and old platelets. Thrombosis & Haemostasis. 80(3):457-62 More
   
6. Rinder CS, Rinder HM, Johnson K, Smith M, Lee D, Tracey J, Polock G, Higgins P, Yeh CG, Smith BR. 1999. Role of C3 Cleavage in Monocyte Activation during Extracorporeal Circulation. Circulation 100:553-558 More
   
7. Rinder CS, Rinder HM, Smith MJ, Tracey JB, Fitch JCK, Li L, Rollins SA, Smith BR. 1999. Selective blockade of membrane attack complex formation during simulated extracorporeal circulation inhibits platelet but not leukocyte activation. J Cardiovasc Thor Surgery 118:460-466, 1999. More
   
8. Fitch JCK, Rollins S, Matis L, Alford B, Aranki S, Collard CD, Dewar M, Elefteriades J, Hines R, Kopf G, Kraker P, Li L, O'Hara R, Rinder C, Rinder H, Shaw R, Smith B, Stahl G, Sherman SK. Pharmacology and biological efficacy of a recombinant, humanized, single-chain antibody C5 complement inhibitor in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. Circulation 100:2499-2506, 1999. More
   

References(B)

1. Leitenberg D, Gilliand DG, Eisen R, Rinder H, Goldstein J, Stys P, Smith BR. 1995. Natural Killer Cell Lymphoproliferative Disease Associated with Chronic Demyelinating Neuropathy. Am J Med 99:99-102. More
   
2. Smith BR. 1999. Blood. In: "Microsoft Encarta Encyclopedia" (Microsoft Press, Redmond, WA).
   
3. Smith BR. 1997. Hematopoietic Stem Cell Transplantation. In: DeVita VT, Hellman S, Rosenberg SA. "Cancer: Principles and Practice of Oncology, 5th edition" (J.B. Lippincott Co., Philadelphia, PA) pp 2621-2639.
   
4. Ross GS, Wilson DJ, Erikson RP, Motulsky AG, Parkman R, Samulski RJ, Straus SE, Smith, BR. 1996. Gene Therapy in the United States: A 5 Year Status Report. Human Gene Therapy 7:1781-1790 More
   
5. Leitenberg D, Novak TJ, Farber D, Smith BR, Bottomly K. 1996. The Extracellular Domain of CD45 Controls Association with the CD4-T Cell Receptor Complex and the Response to Antigen-specific Stimulation. J Exp Med 183:249-259. More
   
6. Crouch J, Leitenberg D, Smith BR, Howe JG. 1997. Epstein-Barr Virus Suspension Cell Assay Using In Situ Hybridization and Flow Cytometry. Cytometry 29:50-57. More
   
7. Crotty PL, Smith BR, Tallini G. 1998. Morphologic, immunophenotypic and molecular evolution of bone marrow involvement in non-Hodgkin's lymphoma. Diag Mol Path 7(2):90-95. More