Academic and Clinical Interests
Dr. Canfield completed his doctoral training in the area of immunoglobulin structure and effector function with Dr. Sherie Morrison at UCLA. Following an internal medicine residency, he transitioned into T cell biology, studying the mechanisms by which activated T cells adhere to extracellular matrix (ECM) in a post-doctoral fellowship with Dr. Seth Lederman at the Columbia University College of Physicians and Surgeons. These studies led to the discovery that a receptor for laminin previously associated only with tumor metastasis mediates laminin adherence in activated CD4+ T lymphocytes.1
Dr. Canfield went on to pursue clinical training in the field of Allergy/Immunology at Columbia with Dr. Paul Rothman, during which time he developed a murine model recapitulating the genetic predisposition to asthma associated with single nucleotide polymorphisms in the human IL-4 receptor alpha chain. These studies led to the discovery of a novel IL-4 signaling pathway mediated by members of the MAP kinase signaling family.2 The murine model of IL-4 receptor SNP effects remains one of the ongoing research endeavors in Dr. Canfield’s lab.
In the past two years, the lab’s interests have moved in a translational direction with two projects directly examining the response of human peripheral blood T cells to a variety of antigen stimuli in vitro. One project, examining the effects of environmental tobacco smoke (ETS) on the development of allergies and asthma, focuses on a sample of children recruited from NYC neighborhoods with high rates of asthma and allergy. Current studies aim to characterize the T cell proliferative and cytokine response to these allergens among sensitized and non-sensitized individuals, and to identify effects of ETS exposure on the T cell allergen-specific response.
In a second translational study, Dr. Canfield has joined a collaborative effort with Drs. Chess and Jiang examining mechanisms of peripheral immune regulation. Previous work by Drs. Jiang and Chess in a murine model of autoimmunity identified a population of CD8+ T lymphocytes capable of suppressing autoreactive CD4+ effector T cells and preventing emergence of autoimmune disease. Evidence from this model regarding the mechanism by which CD4+ T cells are targeted for suppression suggests that this regulatory process may be important in the avoidance of a variety of “inappropriate” immune responses, including autoimmune and allergic responses in humans. The aim of these collaborative studies is to apply the evidence gathered in the mouse system to characterize the orthologous regulatory system in humans. Among the disease conditions under study are type 1 diabetes mellitus, allergic rhinitis, and asthma.
In summary, Dr. Canfield’s research interests involve both basic and translational approaches toward an overarching aim of elucidating the mechanisms underlying the maladaptive T cell immune responses that precipitate allergy and autoimmunity.
Selected Bibliography
Perzanowski, M. S., S. M. Canfield, G. L. Chew, R. B. Mellins, L. A. Hoepner, J. S. Jacobson, and I. F. Goldstein. 2008. Birth order, atopy, and symptoms of allergy and asthma among inner-city children attending Head Start in New York City. Clin Exp Allergy.
Chew, G. L., M. S. Perzanowski, S. M. Canfield, I. F. Goldstein, R. B. Mellins, L. A. Hoepner, M. Ashby-Thompson, and J. S. Jacobson. 2008. Cockroach allergen levels and associations with cockroach-specific IgE. J Allergy Clin Immunol 121:240-245.
Canfield, S., Y. Lee, A. Schroder, and P. Rothman. 2005. Cutting edge: IL-4 induces suppressor of cytokine signaling-3 expression in B cells by a mechanism dependent on activation of p38 MAPK. J Immunol 174:2494-2498.
Canfield, S. M., and A. Y. Khakoo. 1999. The nonintegrin laminin binding protein (p67 LBP) is expressed on a subset of activated human T lymphocytes and, together with the integrin very late activation antigen-6, mediates avid cellular adherence to laminin. J Immunol 163:3430-3440.
Sullivan, G. M., S. M. Canfield, S. Lederman, E. Xiao, M. Ferin, and S. L. Wardlaw. 1997. Intracerebroventricular injection of interleukin-1 suppresses peripheral lymphocyte function in the primate. Neuroimmunomodulation 4:12-18.
Tao, M. H., S. M. Canfield, and S. L. Morrison. 1991. The differential ability of human IgG1 and IgG4 to activate complement is determined by the COOH-terminal sequence of the CH2 domain. J Exp Med 173:1025-1028.
Canfield, S. M., and S. L. Morrison. 1991. The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region. J Exp Med 173:1483-1491.
Artandi, S. E., S. M. Canfield, M. H. Tao, K. L. Calame, S. L. Morrison, and V. R. Bonagura. 1991. Molecular analysis of IgM rheumatoid factor binding to chimeric IgG. J Immunol 146:603-610.
Morrison, S. L., S. Canfield, S. Porter, L. K. Tan, M. H. Tao, and L. A. Wims. 1988. Production and characterization of genetically engineered antibody molecules. Clin Chem 34:1668-1675. |