Michael Girardi, MD, FAAD

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 Co-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), erythrodermic MF, tumor-stage (T3) MF, transformed MF (T-MF), large cell transformation MF (LCT-MF), and Sézary syndrome (SS)]; CD30+ lymphoproliferative disorders (CD30+ LPD) including lymphomatoid papulosis (LyP) and anaplastic large cell lymphoma (ALCL); 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 gamma-delta T cell lymphoma; and cutaneous NK/T cell lymphoma.

Laboratory Research: During more than 20 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 7 biomedical patents on cancer diagnosis and treatment and co-founder of two Yale startup companies. Watch a video with Dr. Michael Girardi >>

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 robotic 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. Identification of genetic drivers of CTCL. In 2012, we had provided the most comprehensive description of gene copy number alterations in CTCL [J Invest Dermatol, 2012]. More recently, we 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].

a. Lin WM, Lewis JM, Filler RB…Dummer T, 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):188-197. PMID: 21881587

b. Choi J, Goh G, Walradt T…Girardi M, Lifton RP.Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015;47(9):1011-9. PMID: 26192916

c. Chang LW, Patrone CC, Yang W, Rabionet R, Gallardo F, Espinet B, Sharma MK, Girardi M, Tensen CP, Vermeer M, Geskin LJ. An integrated data resource for genomic analysis of cutaneous T-cell lymphoma. J Invest Dermatol. 2018;S0022-202X(18)32294-2. PMID: 29981755

d. Kiessling MK, Oberholzer PA, Mondal C, Karpova MB, Zipser MC, Lin WM, Girardi M, … Dummer R. High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade. Blood. 2011 Feb 24;117(8):2433-40. PMID: 21209378

2. Innovation for the management and treatment of CTCL. Our lab has helped characterize BCL2 inhibition [Blood, 2015] and BET inhibition [Oncotarget, 2018] activity against patient-derived CTCL cells and the potential for synergism with established anti-CTCL agents. We have also collaborated to help decipher the mechanism of ECP/Photopheresis, the most commonly used immunotherapy for CTCL, and developed the first FISH panel for CTCL

a. Kim SR, Lewis JM, Cyrenne BM, Monico PF, Mirza FN, Carlson KR, Foss FM, Girardi M. BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition. Oncotarget. 2018;9(49):29193-29207. PMID: 30018745

b. Cyrenne BM, Lewis JM, Weed JG, Carlson KR, Mirza FN, Foss FM, Girardi M. Synergy of BCL2 and histone deacetylase inhibition against leukemic cells from cutaneous T-cell lymphoma patients. Blood. 2017;130(19):2073-2083. PMID: 28972015

c. Ventura A, Vassall A, Robinson E, Filler R, Hanlon D, Meeth K, Ezaldein H, Girardi M, Sobolev O, Bosenberg MW, Edelson RL. Extracorporeal photochemotherapy drives monocyte-to-dendritic cell maturation to induce anticancer immunity. Cancer Res. 2018;78(14):4045-4058. PMID: 29764863

d. Weed J, Gibson J, Lewis J, Carlson K, Foss F, Choi J, Li P, Girardi M. FISH panel for leukemic CTCL. J Invest Dermatol. 2017;137(3):751-753. PMID: 27836797

3. Clinical guidelines in the management of CTCL. As a member of the USCLC and ISCL, I have worked closely with other members to formulate diagnostic and treatment guidelines for CTCL.

a. Scarisbrick JJ, …Girardi M, …Kim YH. Cutaneous lymphoma international consortium study of outcome in advanced stages of mycosis fungoides and Sézary syndrome: Effect of specific prognostic markers on survival and development of a prognostic model. Clin Oncol. 2015 Nov 10;33(32):3766-73. PMID: 26438120

b. James E, Sokhn JG, Gibson JF, Carlson K, Subtil A, Girardi M, Wilson LD, Foss F. CD4 + primary cutaneous small/medium-sized pleomorphic T-cell lymphoma: a retrospective case series and review of literature. Leuk Lymphoma. 2015 Apr;56(4):951-7. PMID: 24996443

c. Lloyd S, Chen Z, Foss FM, Girardi M, Wilson LD. Acute toxicity and risk of infection during total skin electron beam therapy for mycosis fungoides. J Am Acad Dermatol. 2013 Oct;69(4):537-43. PMID: 23849563

d. Olsen EA, …Girardi M, B…Vonderheid EC; International Society for Cutaneous Lymphomas; United States Cutaneous Lymphoma Consortium; Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. Clin Oncol. 2011 Jun 20;29(18):2598-607. PMID: 21576639

4. Elucidation of immune contributions to carcinogenesis. We established a paradigm for resident immune influences on mutagenesis within epithelial tissues more generally [Science 2012], while definitively demonstrating that LC exert major influences in both stimulating mutagenesis as well as facilitating tumor promotion [J Invest Dermatol 2015a]. We also revealed a major influence for LC in UVB-induced p53 mutant keratinocyte clonal expansion [J Invest Dermatol, 2015b]. In collaboration with W.M. Saltzman, we have developed a translational sub-program of nanoparticle-based prevention of keratinocyte mutagenesis and the tumor-promoting effects of chemical and UVB exposure. This directly led to the development of a novel sunscreen characterized by superior safety and efficacy [Nature Mat, 2015].

a. Modi BG, Neustadter J, Binda E, Lewis J, Filler RB, Roberts SJ, Kwong BY, Reddy S, Overton JD, Galan A, Tigelaar RE, Cai L, Fu P, Shlomchik M, Kaplan DH, Hayday A, Girardi M. (2012). Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science. 335(6064):104-108. PMCID: PMC3753811

b. Lewis JM, Bürgler CD, Fraser JA, Liao H, Golubets K, Kucher CL, Zhao PY, Filler RB, Tigelaar RE, Girardi M. (2015). Mechanisms of chemical cooperative carcinogenesis by epidermal Langerhans cells. J Invest Dermatol. 135(5):1405-1414. PMCID: PMC4364923

c. Lewis JM, Bürgler CD, Freudzon M, Golubets K, Filler RB, Girardi M. (2015). Langerhans facilitate UVB-induced epidermal carcinogenesis. J Invest Dermatol;135(11):2824-2833. PMCID: PMC4640962

d. Strid J, Roberts SJ, Filler RB, Lewis JM, Kwon, BY, Schpero W, Kaplan DH, Hayday AC, Girardi, M. (2008). Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis. Nat Immunol. Feb;9(2):146-154. PMID: 18176566

5. Identification of the relative contributions of alpha/beta and gamma/delta T cells in the regulation of cutaneous malignancy. We were the first to demonstrate the critical contribution of gamma/delta T cells to the regulation of cutaneous malignancy [Science, 2001; J Exp Med, 2003a], and our in-depth studies elucidated the differential contributions of gamma/delta T cells relative to alpha/beta 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 we helped define tumor immunology as a biological and clinical force. We went on to define major roles for these local immune cells in the regulation of the cutaneous stress response so fundamental to carcinogenesis [Nat Immunol 2006; Nat Genet 2008]. We also 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].

1. Girardi M, Oppenheim DE, Steel CR, Lewis JM, Glusac E, Filler R, Hobby P, Sutton B, Tigelaar RE, Hayday AC. (2001). Regulation of cutaneous malignancy by gd T cells. Science. 294(5542):605-609. PMID: 11567106
2. Girardi M, Glusac E, Filler RB, Roberts SJ, Propperova I, Lewis JM, Tigelaar RE, Hayday AC (2003). The distinct contributions of murine TCRgd+ and TCRab+ T cells to different stages of chemically induced skin cancer. J Exp Med. 198(5):747-755. PMCID: PMC2194182
3. Roberts SJ, Ng BY, Filler RB, Lewis J, Glusac EJ, Hayday AC, Tigelaar RE, Girardi M. (2007). Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis. Proc Natl Acad Sci U S A. 104(16):6770-6775. PMCID: PMC1871860
4. Wakabayashi Y, Mao JH, Brown K, Girardi M, Balmain A. (2007). Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice. Nature. 445(7129):761-765. PMID: 17230190