Research & Publications
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), squamous cell carcinoma (SCC), 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.
Specialized Terms: Cancer; Carcinogenesis; Cellular Immunology; Chemotherapy; Dermatology; DNA; Immunobiology; Immunology; Lymphoma; Receptors; Tumor Immunology
Extensive Research Description
Dr. Girardi’s current research projects include:
1. Identification of genetic drivers of CTCL. Dr. Girardi's lab provided the most comprehensive description of gene copy number alterations in CTCL [J Invest Dermatol, 2012], and then more fully elucidated the genetic drivers of CTCL [Nature Genetics, 2015]. This is now part of an integrated data resource [J Invest Dermatol, 2018]. Dr. Girardi's lab also developed the first cytogenetics panel for CTCL [J Invest Dermatol, 2017], now implemented by Yale Clinical Genetics, and identified precancerous cells in the circulation of CTCL patients using dual single-cell RNA/TCR seq [Blood Adv., 2023].
A. Lin WM, Lewis JM, Filler RB…Dummer T, Berger CL, Edelson RL, Girardi M. (2012). Characterization of the DNA copy-number genome in the blood of cutaneous T-cell lymphoma patients. J Invest Dermatol. 132(1):188-197. PMCID: PMC3841973
B. Choi J, Goh G, Walradt T…Girardi M & Lifton RP. (2015). Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 47(9):1011-9. PMCID: PMC4552614
C. Weed J, Gibson J, Lewis J, Carlson K, Foss F, Choi J, Li P, Girardi M. (2017). FISH panel for leukemic CTCL. J Invest Dermatol. 137(3):751-753. PMCID: PMC5419071
D. Ren J, Qu R, Rahman NT, Lewis JM, King ALO, Liao X, Mirza FN, Carlson KR, Huang Y, Gigante S, Evans B, Rajendran BK, Xu S, Wang G, Foss FM, Damsky W, Kluger Y, Krishnaswamy S, Girardi M. Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations. Blood Adv. 2023;7(3):445-457. doi: 10.1182/bloodadvances.2022008168. PMID: 35947128
2. Innovation for the management and treatment of CTCL. Dr. Girardi's lab developed modified criteria for use of Vbeta panel flow cytometry diagnosis of CTCL [J Amer Acad Dermatol, 2016] now implemented by YNHH Flow Cytometry. His lab characterized BCL2 [Blood, 2015], BET [Oncotarget, 2018], JAK [Blood Adv, 2020], and proteosome [J Invest Dermatol, 2023] targeting activity against CTCL, and their defined their synergy with established anti-CTCL agents. Dr. Girardi's lab's current collaborative research efforts in this area include drug design using synergistic chemistry where single agents are developed with dual targeting and synergistic drug combinations for the treatment of advanced stage CTCL.
A. Cyrenne BM, Lewis JM, Weed JG, Carlson KR, Mirza FN, Foss FM, Girardi M. (2017). Synergy of BCL2 and histone deacetylase inhibition against leukemic cells from cutaneous T-cell lymphoma patients. Blood. 130(19):2073-2083. PMCID: PMC5680613
B. Kim SR, Lewis JM, Cyrenne BM, Mirza FN, Carlson KR, Foss FM, Girardi M. (2018). BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition. Oncotarget. 9(49):29193-29207. doi: 10.18632/oncotarget.25670. PMCID: PMC6044378
C. Yumeen S, Mirza FN, Lewis JM, King ALO, Kim SR, Carlson KR, Umlauf SR, Surovtseva YV, Foss FM, Girardi M. (2020) JAK inhibition synergistically potentiates BCL2, BET, HDAC, and proteasome inhibition in advanced CTCL. Blood Adv. 4(10):2213-2226. PMCID: PMC7252559
D. Xu S, Ren J, Lewis JM, Carlson KR, Girardi M. Proteasome inhibitors interact synergistically with BCL2, histone deacetylase, BET, and Jak inhibitors against cutaneous T-cell lymphoma cells. J Invest Dermatol. 2023 Jan 13:S0022-202X(23)00011-8. doi: 10.1016/j.jid.2022.12.017. Online ahead of print. PMID: 36642402
3. Novel strategies for the prevention and treatment of skin cancer. In collaboration with W. M. Saltzman, PhD, Dr. Girardi's lab developed a novel drug delivery system of bioadhesive biodegradable nanoparticles to prevent skin cancer [Nature Materials, 2015; Bioeng Transl Med, 2018], and improve the local delivery of chemotherapeutic and immunostimulatory agents to skin cancers [PNAS, 2021]. His current collaborative research efforts in this area include novel site-directed therapeutics for BCC and peritoneal carcinomatosis / ovarian cancer (with W.M. Saltzman, via Yale start-up Stradefy Biosciences).
A. Deng Y, Ediriwickrema A, Yang F, Lewis J, Girardi M & Saltzman WM. (2015). A sunblock based on bioadhesive nanoparticles. Nat Mater.14(12):1278-85. doi: 10.1038/nmat4422. Epub 2015 Sep 28. PMCID: PMC4654636
B. Suh HW, Lewis J, Fong L, Ramseier JY, Carlson K, Peng ZH, Yin ES, Saltzman WM & Girardi M. (2018). Biodegradable bioadhesive nanoparticle incorporation of broad-spectrum organic sunscreen agents. Bioeng Transl Med. 4(1):129-140. doi: 10.1002/btm2.10092. PMCID: PMC6336670
C. Hu JK, Suh H-W, Qureshi M, Lewis JM, Yaquoob S, Moscato ZM, Griff S, Lee AK, Yin ES, Saltzman WM & Girardi M. (2021). Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.2020575118. PMID: 33526595
D. Mai Y, Ouyang Y, Yu M, Qin Y, Girardi M, Saltzman WM, …Deng Y. Topical formulation based on disease-specific nanoparticles for single-dose cure of psoriasis. J Control Release. 2022 Jul 12;349:354-366. doi: 10.1016/j.jconrel.2022.07.006. PMID: 35817278
4. Elucidation of Langerhans cells (LC) role in skin homeostasis and carcinogenesis. Dr. Girardi's lab defined major roles for local immune cells in the regulation of the cutaneous stress response fundamental to carcinogenesis [Nat Immunol, 2006]. Dr. Girardi's lab established a paradigm for resident immune influences on mutagenesis within epithelial tissues [Science, 2012], while revealing that LC exert major influences in facilitating mutagenesis and tumor promotion [J Invest Dermatol, 2015; PNAS, 2021]. Dr. Girardi's current collaborative research efforts in this area include novel strategies for the inhibition of tumor promotion using topical RORgt inhibitors and miRNA target-based oligonucleotides (with Jeff Bender, MD, Yale Immunobiology).
A. 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. doi: 10.1038/ni1556. PMID: 18176566
B. 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
C. 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
D. Lewis JM, Mirza FN, Xu S, Yumeen S, Turban JL, Galan A, Girardi M. (2021). Chronic UV radiation-induced RORγt+ IL-22-producing lymphoid cells are associated with mutant KC clonal expansion. Proc Natl Acad Sci U S A. Sep 14;118(37):e2016963118. doi: 10.1073/pnas.2016963118. PMID: 34504008
5. alpha-beta and gamma-delta T cell regulation of inflammation and tumor promotion. Dr. Girardi and colleagues were the first to demonstrate the critical contribution of gd T cells to the regulation of cutaneous malignancy [Science, 2001; J Exp Med, 2003a], while elucidating the differential contributions of gd and ab T cells [PNAS, 2007; J Exp Med, 2003b].
A. 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. doi: 10.1126/science.1063916. PMID: 11567106
B. Girardi M, Lewis J, Glusac E, Filler RB, Geng L, Hayday AC, Tigelaar RE. (2002). Resident skin-specific gamma/delta T cells provide local, nonredundant regulation of cutaneous inflammation. J Exp Med. 195(7):855-67. doi: 10.1084/jem.20012000. PMCID: PMC2193718
C. 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
D. 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
Dermatology; DNA; Graft vs Host Disease; Immune System; Internship and Residency; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous; Carcinogenesis
- “Extracorporeal Photochemotherapy” in Comprehensive Dermatologic Drug TherapyGirardi M, Choi J, Heald PW. “Extracorporeal Photochemotherapy” in Comprehensive Dermatologic Drug Therapy, S. Wolvertin, (ed), 3rd Ed. W.B. Saunders, Philadelphia, 2012.