DF/HCC Program Affiliation

Cutaneous Oncology and Melanoma

Research Abstract

Keywords:
Leukocyte homing
Skin immunology
Skin cancer immunology

The Fuhlbrigge laboratory is currently involved in three primary research projects:
1) Using a unique method for assessment of adhesion to individual T cell glycoproteins developed in the lab, the Fuhlbrigge research group has identified several novel selectin ligands on skin homing T cells. Ongoing studies are directed toward establishing the structural properties of these ligands, characterizing their patterns of expression, defining the mechanisms by which their expression is regulated and correlating expression with specific skin disorders and/or functional T cell subsets. Inhibitory RNA methods are being developed to allow study of the relative contributions of the known E- selectin ligands on T cells.

2) Through examination of tumors from patients with malignant melanoma, the Fuhlbrigge lab has identified a defect in homing receptor expression that may explain the poor prognosis and resistance to immunotherapy seen in these patients. To study these issues, the Fuhlbrigge lab has developed a model of human melanoma growing in human skin transplanted onto immunodeficient mice, which is proving valuable for the study of tumor angiogenesis and the regulation of vascular adhesion receptors in melanoma. This unique strategy will provide not only a method for detailed studies of the mechanisms regulating the recruitment of immune cells to tumors in human tissues, but a means for testing new therapeutic strategies on human tissues that will be more directly applicable to use in real patients than existing models.

3) Although inoculation of skin with vaccinia virus (termed scarification) to prevent smallpox has been used successfully for over 200 years, little is known about the growth of vaccinia virus in skin after inoculation, how scarification promotes activation of the immune response or why this process results in more protective immune responses than more common methods of immunization. The Fuhlbrigge lab, in collaboration with the laboratories of Drs. Kupper and Liu in the Department, is studying how the immune response develops after scarification in mice, and the effects on the response to vaccinia of various cytokines expressed in skin. The Fuhlbrigge lab utilizes unique model for studying scarification, including use of immune deficient mice bearing human skin xenotransplants and mice engineered to overexpress immune modulating cytokines in skin.

Publications

• Bianchi T,Pincus LB,Wurbel MA,Rich BE,Kupper TS,Fuhlbrigge RC,Boes M.Maintenance of peripheral tolerance through controlled tissue homing of antigen-specific T cells in K14-mOVA mice.J Immunol 2009 Apr 15;182(8):4665-74.
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• Tian T,Liu L,Freyschmidt EJ,Murphy GF,Kupper TS,Fuhlbrigge RC.Overexpression of IL-1alpha in skin differentially modulates the immune response to scarification with vaccinia virus.J Invest Dermatol 2009 Jan;129(1):70-8.
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• Fuhlbrigge RC, Weishaupt C.Adhesion molecules in cutaneous immunity.Semin Immunopathol 2007 Apr;29(1):45-57.
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• Weishaupt C, Munoz KN, Buzney E, Kupper TS, Fuhlbrigge RC.T-cell distribution and adhesion receptor expression in metastatic melanoma.Clin Cancer Res 2007 May 1;13(9):2549-56.
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• Liu L, Fuhlbrigge RC, Karibian K, Tian T, Kupper TS.Dynamic programming of CD8+ T cell trafficking after live viral immunization.Immunity 2006 Sep;25(3):511-20.
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• Sackstein R, Fuhlbrigge R.The blot rolling assay: a method for identifying adhesion molecules mediating binding under shear conditions.Methods Mol Biol 2006;341:217-26.
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• Fuhlbrigge RC, King SL, Sackstein R, Kupper TS.CD43 is a ligand for E-selectin on CLA+ human T cells.Blood 2005 Nov 3.
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• Kupper TS, Fuhlbrigge RC.Immune surveillance in the skin: mechanisms and clinical consequences.Nat Rev Immunol 2004 Mar;4(3):211-22.
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• Chong BF, Murphy JE, Kupper TS, Fuhlbrigge RC.E-selectin, thymus- and activation-regulated chemokine/CCL17, and intercellular adhesion molecule-1 are constitutively coexpressed in dermal microvessels: a foundation for a cutaneous immunosurveillance system
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• Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS.Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells.Nature 1997 Oct 30;389(6654):978-81.
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