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Brian Richard Smith, MD
Professor and Chair of Laboratory Medicine
Professor of
Internal Medicine and Pediatrics
Director,Immunology, Molecular Diagnostics and Flow Cytometry Laboratories
Director, Molecular
Diagnostics
Director, Hematopathology
Fellowship
Director, Immunohematology
Research Training Program
203-688-2286
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, Harvard Medical School, Boston,
MA
Community
of Science Biosketch
NIH Biosketch
Research
Interests
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,
tumor metastasis, and in hematologic disorders such as TTP and sickle
cell disease. 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.
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.
The
laboratory accepts graduate students 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 is boarded in Hematopathology and also in Internal Medicine,
Hematology and Medical Oncology. His clinical work encompases all
of these areas with the major current emphasis on advanced diagnostic
hematopathology (molecular diagnostics, flow cytometry). He carries
out pathology interpretative clinical work and sees adult hematology/oncology
patients through the Yale Medical
Group Yale Faculty Practice.
Teaching at the undergraduate level is carried out in MB&B 470a/471b,
and in the Biomedical Program 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.
References
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Rinder HM, Smith BR. Innovative Methods of Laboratory Medicine Resident Teaching. Clin Lab Med (in press).
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Wells A, Smith BR. The Goals of Resident Training in Laboratory Medicine in Combined AP/CP Programs: An Overview. Clin Laboratory Med (in press)
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Bizzarro MJ, Bhandari V, Krause DS, Smith BR, Gross IM. 2007. Circulating Stem Cells in Extremely Preterm Neonates. Acta Paediatrica (in press).
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Greilich PE, Brouse CF, Rinder HM, Jessen ME, Rinder CS, Whitten CW, Eberhart RC, Smith BR. 2007. Differential markers and time course of monocyte activation in on- versus off-pump coronary artery bypass surgery. Anesth Analgesia (in press).
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Smith, BR (editor). 2007. Education in Laboratory Medicine. Clinics in Laboratory Medicine. (in press)
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Rinder CS, Smith MJ, Rinder HM, Cortright DN, Brodbeck RM, Krause JE, Smith BR. 2007. Leukocyte effects of C5a Receptor Blockade during Simulated Extracorporeal Circulation. Ann Thorac Surg 83: 146-52.
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Rinder HM, Smith BR. 2007. Evolving Paradigms of Laboratory Medicine Resident Education and Consultation. Clin Chem 53: 1-2.
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Rinder CS, Rinder HM, Smith MJ, Fitch JCK, Tracey JB, Chandler WL, Rollins SA, Smith BR. 2006. Antithrombin reduces monocyte and neutrophil CD11b upregulation in addition to blocking platelet activation during extracorporeal circulation. Transfusion 46(7): 1130-1137.
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Smith BR, Rinder HM, Rinder CS. 2006. Chapter 59: Cardiopulmonary Bypass. In: Michaelson, A (ed) Platelets, 2nd Edition (Academic Press, New York) pp. 1077-1095
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Wells A, Smith BR, Sacks DB. 2006. The Challenge of Training Pathologists in the 21st Century. Hum Pathol 37: 932-33.
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Wells, A and Smith, BR. 2006. Counterpoint: Developing a Clinical Pathology Curriculum to meet Current and Future Needs. Clin Chem 52: 971-972.
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Smith BR, Wells A, Alexander CB, Bovill E, Campbell S, Dasgupta A, Fung M, Haller B, Howe JG, Parvin C, Peershke E, Rinder H, Spitalnik S, Weiss R, Wener M for the Academy of Clinical Laboratory Physicians and Scientists. 2006. Curriculum Content and Evaluation of Resident Competency in Clinical Pathology (Laboratory Medicine): A Proposal. Human Pathol 37: 934-68; Amer J Clin Pathol 125(Suppl 1): S3-S37; Clin Chem 52: 917-949. (simultaneous publication in three journals).
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Mathew JP, Rinder HM, Smith BR, Newman MF, Rinder CS. 2006. Transcerebral platelet activation after aortic cross-clamp release is associated with neurocognitive decline after cardiopulmonary bypass. Ann Thorac Surg 81: 1644.
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Fontes M, Mathew JP, Rinder HM, Zelterman D, Smith BR, Rinder CS. 2005. Atrial Fibrillation after Cardiopulmonary Bypass is Associated with Monocyte Activation. Anesthesia & Analgesia 101: 17-23.
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Rhoden KJ, Johnson C, Brandao G, Howe JG, Smith BR, Tallini G. 2004. Quantitative analysis of RET and its rearranged forms demonstartes marked variability in the mRNA expression levels of c-RET, RET/PTC1 and RET/PTC3 in papillary thyroid carcinoma. Laboratory Investigation 84: 1557-70.
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Wang S, Li N, Heald P, Fisk JM, Fadare O, Howe JG, McNiff JM, Smith BR. 2004.
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Flow Cytometry DNA ploidy analysis on peripheral blood from patients with Sezary syndrome: Detection of aneuploid neoplastic T cells in the blood is associated with large cell transformation in tissue. Am J Clin Pathol 122: 774-82.
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Zieske A, Smith BR. 2004. Biology of Hematopoietic Progenitor Cell Transplantation. In: "Cellular Therapy: A Physician's Handbook" (Snyder EL, Haley NR, eds), pp 1-10 , AABB Press.
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Howe JG, Crouch J, Cooper D, Smith BR. 2004. Real-Time Quantitative RT-PCR of Cyclin D1 mRNA for Mantle Cell Lymphoma Diagnosis in Blood, Marrow and Tissue Specimens. Clin Chem 50: 80-7.
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Greilich PE, Brouse CF, Rinder CS, Smith BR, Rinder HM, Sandoval BA, Eberhart RC, Jessen ME. 2004. Effects of Epsilon Aminocaproic Acid and Aprotinin on Leukocyte-Platelet Adhesion in Patients Undergoing Cardiac Surgery. Anesthesiology. 100: 225-33.
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Esposito C, Popescu W, Rinder HM, Schwartz J, Smith BR, Rinder CS. 2003. Increased leukocyte-platelet adhesion in patients with graft occlusion after peripheral vascular surgery. Thrombosis Haemostasis 90: 1128-34.
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H.M. Rinder, E.L. Snyder, J.B. Tracey, D. Dincecco, C. Wang, L. Baril, C.S. Rinder, and B.R. Smith. 2003. Reversibility of severe metabolic stress in stored platelets following in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival. Transfusion 43: 1230-7.
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Hui P, Howe JG, Crouch J, Nimmakayalu M, Qumsiyeh MB, Tallinni G, Flynn S, Smith BR. 2003. Real-time quantitative RT-PCR of Cyclin D1 mRNA expression in mantle cell lymphomas: comparison with FISH and immunohistochemistry. Leukemia & Lymphoma 44: 1385-94.
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Rinder CS, Mathew JP, Rinder HM, Smith BR. 2003. Neutrophil activation and CD11b Upregulation during cardiopulmonary bypass is associated with greater postoperative renal injury. Ann Thorac Surg 75: 899-905.
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Rinder HM, Smith BR. 2003. In Vitro Evaluation of Stored Platelets: Is there hope for predicting post-transfusion platelet survival and function? Transfusion 43:2-6.
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Rinder CS, Mathew JP, Rinder HM, Howe JG, Fontes M, Pfau S, Patel P, Smith BR. 2002. The platelet PLA2 polymorphism increases the risk of myocardial injury as reflected by troponin I release during cardiopulmonary bypass. Anesthesiology 97: 1118-22.
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Smith BR, Rinder CS, Rinder HM. 2002. Interaction of Blood and Artificial Surfaces. In: Loscalzo J, Schafer AI (eds) “Thrombosis and Hemorrhage, 3rd Edition” (Lippincott Williams & Wilkins, Philadelphia, PA) (pp 865-885).
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Smith BR, Rinder HM, Rinder CS. 2002. Chapter 48: Cardiopulmonary Bypass Platelet Physiology. In: Michaelson, A (ed) “Platelets” (Academic Press, New York) pp. 727-34.
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Wang C, Smith BR, Ault KA, Rinder HM. 2002. A new peripheral blood measure of stress thrombopoiesis predicts imminent platelet recovery following chemotherapy. Transfusion 42: 368-74.
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Griffin MJ, Rinder HM, Smith BR, Tracey JB, Kriz N, Rinder CS. 2001. Effects of Heparin, Protamine and Heparin-Protamine Reversal on Platelet Function under Conditions of Arterial Shear Stress. Anesthesia & Analgesia 93:20-7.
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Mathew JP, Rinder CS, Rinder HM, Howe JG, Crouch J, Newman MF, Fontes M, Phillips-Bute B, Smith BR and McSPI. 2001. Platelet GP IIIa PIA2 polymorphism enhances the risk of neurocognitive decline after cardiopulmonary bypass. Ann Thorac Surg 71: 663-6.
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 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 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
Smith BR. 1999. Blood. In: "Microsoft Encarta Encyclopedia" (Microsoft
Press, Redmond, WA). 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 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
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
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. 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 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. Smith
BR. 1997. Interactions of Platelets and Endothelial Cells with
Erythrocytes and Leukocytes in TTP. Sem Hematol 34:90-97. 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 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 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 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
Community
of Science Profile may be found at: http://myprofile.cos.com/smithb40
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