Research & Publications
Clinical Expertise: Dr. Girardi is Co-Director of the Yale Cutaneous Lymphoma Group, Director of the Photopheresis Unit, and Director of the Phototherapy Unit at the Yale Comprehensive Cancer Center and Yale-New Haven Hospital. Dr. Girardi is also an active member of the national and international organizations (United States Cutaneous Lymphoma Consortium, International Society of Cutaneous Lymphoma) that formulate and publish the criteria guidelines for the diagnosis and treatment CTCL, and is executing the largest clinical database for CTCL. He has published over 150 scientific manuscripts, clinical reports, and chapters, including on the genetic basis of CTCL and a Medical Progress Report for the New England Journal of Medicine. Dr. Girardi was recently awarded the 2017 Zeligman Award by Johns Hopkins University for his expertise in understanding the genetic and immunologic mechanisms that cause CTCL, and he has delivered over 100 national and international lectures including at the National Institutes of Health, U.S. Food and Drug Administration, Harvard University, University of Pennsylvania, Memorial Sloan Kettering Cancer Center, Moffitt Cancer Center, Kings College London, and Northwestern University. Dr. Girardi is currently Professor, Vice Chair, Residency Director, and NIH T32 Research Fellowship Director for the Department of Dermatology, Yale School of Medicine.
Disease expertise: the diagnosis and management of cutaneous lymphoma and related conditions, including: mycosis fungoides (MF) cutaneous T cell lymphoma (CTCL) [variants of which include folliculotropic MF, follicular mucinosis MF, hypopigmented (hypomelanotic) MF, pagetoid reticulosis (Woringer-Kolopp disease), tumor-stage (T3) MF, and transformed MF (T-MF), and Sézary syndrome (SS)]; lymphomatoid papulosis (LyP); CD4+ small/medium/pleomorphic T cell lymphoma (CD4+ SMPTCL); cutaneous B cell lymphoma (CBCL) [variants of which include primary cutaneous marginal zone B cell lymphoma (PCMZBCL) and primary cutaneous follicle center B cell lymphoma (PCFLBCL); lymphocytoma cutis (pseudolymphoma); parapsorias (including large plaque and small plaque variants); subcutaneous panniculitic T cell lymphoma (SCPTCL); cutaneous CD8+ cytotoxic T cell lymphoma; cutaneous gd+ T cell lymphoma; and cutaneous NK/T cell lymphoma.
Laboratory Research: During more than 15 years leading an NCI-funded research program at Yale, Dr. Girardi’s laboratory is credited with major contributions to our understanding of skin biology immunology and skin cancer development, including the elucidation of roles for gamma-delta T cells, NKG2D ligands, and Langerhans cells. Dr. Girardi has served as the Co-Director for the Yale Comprehensive Cancer Center’s Immunology and Immunotherapy Program, and is the holder/filer of 4 biomedical patents on cancer diagnosis and treatment and co-founder of two Yale startup companies.
Dr. Girardi’s current research projects include:
- The role of local immune cells in the development of cutaneous carcinogenesis. Using state-of-the-art genetically engineered mice, immunobiology techniques, and confocal imaging, the Girardi laboratory is dissecting how various immune cells, resident within and recruited to the skin, contribute the skin cancer development.
- Novel approaches to the diagnosis and treatment of cutaneous T cell lymphoma (CTCL). Overseeing one of the largest centers for CTCL, Dr. Girardi and colleagues use genetic sequencing and acoustic transfer to enhance diagnosis and to screen and develop new pharmaceutical agents in the treatment of this malignancy.
- Biodegradable nanotechnology in the prevention and treatment of skin cancer. In collaboration with W.M. Saltzman (Professor, Yale Biomedical Engineering) and Douglas Brash (Professor, Genetics), Dr. Girardi’s lab is developing novel strategies for skin cancer prevention and treatment.
Dr. Girardi’s prior research projects have included:
(1) Elucidation of Langerhans cell (LC) facilitation of chemical mutagenesis and photo-carcinogenesis. The Girardi lab elucidated a critical, entirely unforeseen, role for LC in cutaneous carcinogenesis and established a paradigm for resident dendritic cell influences on mutagenesis within epithelial tissues more generally [Science 2012], while definitively demonstrating that LC exert major influences in both stimulating KC mutagenesis as well as facilitating tumor promotion [J Invest Dermatol 2015a]. In addition, they revealed a major and again unanticipated influence for LC in UVB-induced p53 mutant keratinocyte clonal expansion [J Invest Dermatol, 2015b]. In collaboration with W.M. Saltzman (Professor, Yale Biomedical Engineering), the Girardi lab developed a translational sub-program of nanoparticle-based prevention of keratinocyte mutagenesis [Nature Mat, 2015].
- Modi BG, et al.… Girardi M. (2012). Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science. 335:104-108.
- Lewis JM, et al…. Girardi M. (2015). Mechanisms of chemical cooperative carcinogenesis by epidermal Langerhans cells. J Invest Dermatol. 135:1405-1414.
- Lewis JM, et al…. Girardi M. (2015). Langerhans facilitate UVB-induced epidermal carcinogenesis. J Invest Dermatol. 135:2824-2833.
- Deng Y, et al… Girardi M, Saltzman WM. (2015). A sunblock based on bioadhesive nanoparticles. Nat Mater. 14:1278-1285.
(2) Identification of the role of gamma-delta T cells in the regulation of cutaneous malignancy. The Girardi lab demonstrated the critical contribution of gd T cells to the regulation of cutaneous malignancy [Science, 2001; J Exp Med, 2003a], and their in-depth studies elucidated the differential contributions of gd T cells relative to ab T cells [J Exp Med, 2003b; J Invest Dermatol, 2004]. These findings were made at a time when there was considerable skepticism about the capacity of lymphocytes to control malignancy, and therefore helped define tumor immunology as a biological and clinical force. They went on to define major roles for these local immune cells in the regulation of the cutaneous stress response fundamental to carcinogenesis [Nat Immunol 2006; Nat Genet 2008].
- Girardi M, et al. (2001). Regulation of cutaneous malignancy by gamma-delta T cells. Science. 294:605-609.
- Girardi M, et al. (2003). The distinct contributions of murine TCRgamma-delta+ and TCRalpha-beta+ T cells to different stages of chemically induced skin cancer. J Exp Med. 198:747-755.
- Girardi M, et al. (2006). Environmentally responsive and reversible regulation of epidermal barrier function by gamma-delta T cells. J Invest Dermatol. 126:808-814.
- Boyden, et al. (2008). Skint1, the prototype of a newly identified Ig superfamily gene cluster, positively selects epidermal gamma-delta T cells. Nat Genet.;40:656-662.
(3) Elucidation of the immunoregulation of cutaneous inflammation and barrier function. The Girardi laboratory also has made several major contributions to the understanding of epidermal homeostasis and to the development and progression of skin cancer, while providing insight into cutaneous biology and epithelial malignancy more generally. These processes may be further understood in terms of their more physiologic roles in the regulation the epidermal stress response (ESR). In that regard, they were revealed that gd T cells are major regulators of the ESR, including via secretion of lymphoid-thymosin-b4 [J Exp Med, 2002; Immunology, 2004; J Invest Dermatol, 2006], and that critical to this communication is keratinocyte expression of NKG2D-ligands and detection by NKG2D-expressing innate immune cells, including the coordinated response of multi-partite skin immune components: epidermal gd+ T cells, natural killer T (NKT) cells, and Langerhans cells (LC) [Nature Immunol, 2005; Nature Immunol, 2008].
- Girardi M, et al. (2002). Resident skin-specific gammadelta T cells provide local, nonredundant regulation of cutaneous inflammation. J Exp Med. 195:855-867.
- Girardi M, et al. (2003). Anti-inflammatory effects in the skin of thymosin-beta4 splice-variants. Immunology.109:1-7.
- Oppenheim DE, et al….Girardi M, Hayday A. (2005). Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance. Nat Immunol. 6:928-937.
- Strid J, et al…. Girardi M. (2008). Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis. Nat Immunol. 9:146-154.
(4) Discerning the tumor-protective versus tumor-promoting contributions of ab T cells in chemical carcinogenesis. The Girardi lab identified and characterized a novel population of CD8+ tumor-promoting T cells (T-pro) [PNAS 2007] that drives cancer progression, proving that pro-tumor immune components are not confined to regulatory function but also the proactive local production of factors that promote tumor growth [J Invest Dermatol 2010].
- Roberts SJ, et al….Girardi M. (2007). Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis. Proc Natl Acad Sci U S A. 104:6770-6775.
- Wakabayashi Y….Girardi M, Balmain A. (2007). Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice. Nature. 445:761-765.
- Kwong BY, et al….Girardi M. (2010). Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis. J Invest Dermatol. 130:1726-1736.
- Girardi M, et al. (2004). Characterizing the protective component of the ab T cell response to transplantable squamous cell carcinoma. J Invest Dermatol. 122:699-706.
(5) Identification of genetic drivers of cutaneous T cell lymphoma (CTCL) and therapeutic innovation for the treatment of CTCL. In 2012, the Girardi lab had provided the most comprehensive description of gene copy number alterations in CTCL [J Invest Dermatol, 2012]. They collaborated (with R. Lifton, Professor and Chair, Yale Genetics, and Panel Co-Chair of the NIH Precision Medicine Initiative) to more fully elucidate the genetic driver’s of CTCL [Nature Genetics, 2015], and continue to be engaged in studies to characterize several therapeutic approaches to CTCL, including research into mechanisms underlying extracorporeal photopheresis.
- Lin WM, et al….Girardi, M. (2012) Characterization of the DNA copy-number genome in the blood of cutaneous T-cell lymphoma patients. J Invest Dermatol. 132:188-197.
- Choi J, et al….Girardi M, Lifton R. (2015). Genomic landscape of cutaneous T cell lymphoma. Nature Genetics. 47:1011-1019.
- Gibson JF, et al....Girardi M. (2016). Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vβ chain restriction. J Am Acad Dermatol. 74:870-877.
- Weed J….Girardi M. FISH Panel for Leukemic CTCL. (2017) J Invest Dermatol. 137:751-753.
Education & Training
- MDYale University (1992)
- BSBrown University, Biology & Computer Science (1988)
- Research FellowYale University School of Medicine, New Haven, CT
- ResidentYale University School of Medicine, New Haven, CT
- Research FellowYale University School of Medicine, New Haven, CT
- InternYale-New Haven Hospital, New Haven, CT
Honors & Recognition
|Yale Innovation Blavatnik Award||Blavatnik Fund||2018|
|Spatz Foundation Award for Cutaneous Lymphoma||Drs. Martin & Dorothy Spatz Charitable Foundation||2018|
|Zeligman Lectureship Award||Johns Hopkins University||2017|
|Elected to the American Society of Clinical Investigation||American Society of Clinical Investigation||2009|
|Duhring Lectureship Award||University of Pennsylvania||2009|