Michael Girardi MD, FAAD

Professor of Dermatology; Director, Residency Program

Research Interests

Cancer; Carcinogenesis; Cellular Immunology; Chemotherapy; Dermatology; DNA; Immunobiology; Immunology; Receptors; Tumor Immunology


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].

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

  • Modi B, Neustadter J, Binda E, Lewis J, Filler R, Roberts SJ, Kwong BY, Reddy S, Overton JD, Galan A, Tigelaar R, Cai L, Fu P, Shlomchik M, Kaplan DH, Hayday A, Girardi M. Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science 2012, 335(6064):104-8.
  • Lin WM, Lewis JM, Filler RB, Modi BG, Carlson KR, Reddy S, Thornberg A, Saksena G, Umlauf S, Oberholzer PA, Karpova M, Getz G, Mane S, Garraway LA, Dummer R, Berger CL, Edelson RL, Girardi M. Characterization of the DNA copy-number genome in the blood of cutaneous T-cell lymphoma patients. J Invest Dermatol. 2012;132(1):188-97
  • Girardi M, Choi J, Heald PW. “Extracorporeal Photochemotherapy” in Comprehensive Dermatologic Drug Therapy, S. Wolvertin, (ed), 3rd Ed. W.B. Saunders, Philadelphia, 2012.
  • Lott JP, Robinson D, Warren C, Klein R, Craiglow B, Girardi M. Dialogues in dermatology: Highlights from 2011. J Am Acad Dermatol. 2012;66(1):153-6
  • Girardi M, Kay J, Elston DM, LeBoit PE, Abu-Alfa A, Cowper SE. Nephrogenic systemic fibrosis: Clinicopathological definition and work-up recommendations. J Amer Acad Dermatol. 2011, 65(6):1095-1106.
  • Kwong BY, Roberts SJ, Silberzahn T, Filler RB, Neustadter JH, Galan A, Reddy S, Lin WM, Ellis PD, Langford CF, Hayday AC, Girardi M. Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis. J Invest Dermatol. 2010;130:1726-36.
  • Strid J, Roberts SJ, Filler RB, Kwong BY, Schpero W, Kaplan DH, Hayday AC, Girardi M. Acute upregulation of an NKG2D-ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis. Nat Immunol. 2008, 9:146-154.

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