Michael Girardi, MD, FAAD

Professor of Dermatology; Dermatology; Director, Residency Program; Vice Chair

Research Interests

Dermatology; DNA; Graft vs Host Disease; Immune System; Internship and Residency; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous; Carcinogenesis

Research Organizations

Dermatology: Medical Dermatology

Faculty Research

HTI

Immunology and Immunotherapy

Yale Cancer Center: Cancer Immunology

Office of Cooperative Research

Research Summary

Dr. Girardi’s principal research focus as a faculty member has been to investigate the relationship between the immune system and cancer from two complimentary perspectives: as a laboratory / translational investigator, and as a clinical scholar. He has published in high impact journals (Science, Nature, New England Journal, Nature Immunology, Journal of Experimental Medicine, Proceedings of the National Academy of Sciences). In addition, he has developed an internationally recognized clinical expertise in several areas including cutaneous T cell lymphoma (CTCL), nephrogenic systemic fibrosis (NSF), and the immunodulatory treatment extracorporeal photochemotherapy (ECP). His scientific and clinical scholarly accomplishments have been recently recognized by his elected membership into the American Society for Clinical Investigation. His laboratory has made several advances in our understanding of the immunoregulation of carcinogenesis. They are credited as the first lab to demonstrate the critical contribution of gamma/delta T cells to the regulation of cutaneous malignancy using three different skin cancer models [Science 2001]. This has directly led to the elucidation of the differential contributions of alpha/beta T cells relative to gamma/delta T cells [J Exp Med 2003]. Indicative of the influence of different alpha/beta T components on tumor growth, tumor cells populations reflect the immune status in that tumors developing in immunocompetent mice differed substantially from those developing in TCRbeta–/– or IFNgamma–/– mice by: (1) reduced expression of the natural killer receptor (NKG2D) ligand Rae-1, (2) overt regional necrosis reflected by an impoverished vasculature, and (3) reduced expression of a set of genes implicated in angiogenesis [J Invest Dermatol 2005]. We also identified and characterized a novel population of CD8+ tumor-promoting T cells (T-pro) [PNAS 2007] that drives cancer progression via local inflammatory influences. The identification of these T-pro cells adds substantially to the recognized association of inflammation and cancer, and has served as the basis for a translational study of human tumors [NCI SPORE].

Specialized Terms: Cancer; Carcinogenesis; Cellular Immunology; Chemotherapy; Dermatology; DNA; Immunobiology; Immunology; Receptors; Tumor Immunology

Extensive Research Description

Dr. Girardi’s principal research focus as a faculty member has been to investigate the relationship between the immune system and cancer from two complimentary perspectives: as a laboratory / translational investigator, and as a clinical scholar. He has published in high impact journals (Science, Nature, New England Journal, Nature Immunology, Journal of Experimental Medicine, Proceedings of the National Academy of Sciences). In addition, he has developed an internationally recognized clinical expertise in several areas including cutaneous T cell lymphoma (CTCL), nephrogenic systemic fibrosis (NSF), and the immunodulatory treatment extracorporeal photochemotherapy (ECP). His scientific and clinical scholarly accomplishments have been recently recognized by his elected membership into the American Society for Clinical Investigation. His laboratory has made several advances in our understanding of the immunoregulation of carcinogenesis. They are credited as the first lab to demonstrate the critical contribution of gamma/delta T cells to the regulation of cutaneous malignancy using three different skin cancer models [Science 2001]. This has directly led to the elucidation of the differential contributions of alpha/beta T cells relative to gamma/delta T cells [J Exp Med 2003]. Indicative of the influence of different alpha/beta T components on tumor growth, tumor cells populations reflect the immune status in that tumors developing in immunocompetent mice differed substantially from those developing in TCRbeta–/– or IFNgamma–/– mice by: (1) reduced expression of the natural killer receptor (NKG2D) ligand Rae-1, (2) overt regional necrosis reflected by an impoverished vasculature, and (3) reduced expression of a set of genes implicated in angiogenesis [J Invest Dermatol 2005]. We also identified and characterized a novel population of CD8+ tumor-promoting T cells (T-pro) [PNAS 2007] that drives cancer progression via local inflammatory influences. The identification of these T-pro cells adds substantially to the recognized association of inflammation and cancer, and has served as the basis for a translational study of human tumors [NCI SPORE]. Another laboratory focus is on the resident gamma/delta+ (Vgamma5+) dendritic epidermal T cells (DETC), and Dr. Girardi’s laboratory determined that DETC can kill SCC cells directly via the NKG2D ligand Rae-1. Induced epithelial expression of NKG2D ligand was shown to precipitate the reorganization of local immune components, including DETC, natural killer T (NKT) cells, and Langerhans cells [Nature Immunol 2008]. This may represent the earliest events in tumor immunosurveillance. This work supports the paradigm of the response of local immune components to the major stress molecules collectively known as NKG2D-ligands, describing the dynamic intraepithelial reorganization of T cells, dendritic cells, and NKT cells in skin and within early tumors. The findings of the protective effects of local T cells may be germane to the development of carcinoma across all epithelial tissues (e.g. colon and lung cancer), provide ananimal model for the surveillance of MICA+ tumors by local T cells, and have major implications for the identification of novel immune targets of cancer prevention and therapy for a spectrum of malignancies.

Selected Publications

Full List of PubMed Publications

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Contact Info

Michael Girardi, MD, FAAD
Patient Care Locations
Yale Dermatology AssociatesDoctors Building
2 Church Street South, Ste 305

New Haven, CT 06519
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Yale Hematology/Cutaneous LymphomaSmilow Cancer Hospital at Yale New Haven
35 Park Street, Ste 11th Floor

New Haven, CT 06511
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Mailing Address
PO Box 208059
333 Cedar Street

New Haven, CT 06520-8059

Curriculum Vitae

Girardi Lab