Dario A. Vignali, PhD
Campus: 200 Lothrop Street
Office: E1052 BSTWR
Lab: E1000-12B - 15A
Pittsburgh PA 15261
- BSc, Immunology and Medical Microbiology, North East London Polytechnic, 1985
- PhD, Immunology of Infectious Diseases, University of London, 1988
- Professor and Vice Chair
- Co-Leader of the Cancer Immunology Program
- Co-Director of the Tumor Microenvironment Center
Our research focuses on various aspects of T cell regulation and function:
(1) Mechanistic Focus:
(a) Immune Regulation: Regulatory T cells (Tregs): Identification of novel Treg molecules and their function; mechanism of Treg function; regulation of Treg stability via Nrp1 and other pathways; IL-35 signaling and mechanism of action; IL-35 production by other cell populations.
(b) Immune Regulation: Inhibitory Molecules: Identification of novel inhibitory mechanisms; immune modulation of T cell subsets by LAG3 and PD1; synergy between LAG3 and other inhibitory receptors, particularly PD1.
(c) Control of T cell receptor (TCR):CD3 complex signaling: Modulation and control of TCR signal transduction by inhibitory receptors and mechanisms; mechanism of TCR:CD3 signaling.
(2) Disease Focus:
(a) Cancer: Biology of LAG3/PD1, IL-35 and Nrp1 in mouse models of cancer and also in samples from treatment-naive patients or immunotherapy recipients; primary focus on solid tumors – head & neck, melanoma, lung, pancreatic, ovarian cancer, with some work on breast, GI and glioma cancers, and hematological malignancies; novel approaches for therapeutic translation.
(b) Autoimmune and Inflammatory Disease: Impact and function of Tregs and inhibitory receptors in the several autoimmune and inflammatory disease with emphasis on models of autoimmune diabetes (NOD mouse model), EAE and asthma; development of approaches to enhance Treg stability and function; therapeutic delivery approaches to promote IL-35, Nrp1 and Lag3 function.
Szymczak AL, Workman CJ, Wang Y, Vignali KM, Dilioglou S, Vanin E, Vignali DAA (2004). Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nature Biotechnology 22: 589-594 [PMID: 15064769].
Huan C-T, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Lavitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DAA (2004). Role of LAG-3 in regulatory T cellsw. Immunity 21: 503-13 [PMID: 15485628].
Holst J, Vignali KM, Burton AR, Vignali DAA (2006). Rapid analysis of T cell selction and function in vivo using T cell receptor retrogenic mice. Nature Methods 3: 191-197 [PMID: 16489336].
Collison LW, Workman CJ, Kuo TK, BOyd K, Wang Y, Vignali K, Cross R, Sehy D, Blumberg RS, Vignali DAA (2007). The inhibitory cytokine IL-35 contributes to regulatory T cell function. Nature 450: 566-569 [PMID: 18033300].
Holst J, Wang H, Durick-Eder K, Workman CJ, Boyd K, Baquet Z, Singh H, Forbes K, Chruscinski A, Smeyne R, van Oers NSC, Utz PJ, Vignali DAA (2008). Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity. Nature Immunology 9: 658-666 [PMID: 18469818].
Vignali DAA, Collison LW, Workman CJ (2008). How regulatory T cells work. Nature Reviews Immunology 8: 523-532 [PMID: 18566595; PMCID: 2665249].
Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, Finkelstein D, Forbes K, Workman CJ, Brown SA, Rehg JE, Jones ML, Ni H-T, Artis D, Turk MJ, Vignali DAA (2010). Interleukin-35-mediated induction of a potent regulatory T cell population. Nature Immunology 11: 1093-1101 [PMCID: 3008395].
Woo S-R*, Turnis ME*, Goldberg MV*, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Vogel P, Liu C-L, Tangsombatvisit S, Grosso, JF, Netto G, Smeltzer MP, Chaux A, Utz PJ, Workman CJ, Pardoll DM, Korman AJ, Drake CG, Vignali DAA (2012). Immune inhibitory molecular LAG-3 and PD-1 synergistically regulate T cell function to promote tumoral immune escape. Cancer Research 72: 917-927 [PMCID: 3288154].
Collison LC*, Delgoffe GM*, Guy C, Vignali KM, Chaturvedi V, Fairweather D, Satoskar AR, Garcia KC, Hunter CA, Drake CG, Murray PJ, Vignali DAA (2012). The composition and signaling of the IL-35 receptor are unconventional. Nature Immunology 13: 290-299 [PMCID: 3529151].
Vignali DAA, Kurchroo VK (2012). IL-12 Family Cytokines: Immunlogical Playmakers. Nature Immunology 13: 722-728 [PMID: 22814351; PMCID: 4158817].
Delgoffe GM*, Woo SR*, Turnis ME, Gravano DM, Guy C, Overacre AE, Bettini ML, Vogel P, Finkelstein D, Bonnevier J, Workman CJ, Vignali DAA. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature 2013 Sep 12; 501(7466):252-256 [PMCID: 3867145].
Guy C, Vignali KM, Temirov J, Bettini ML, Overacre AE, Smeltzer M, Zhang H, Huppa JB, Tsai Y-H, Lobry C, Xie J, Dempsey PJ, Crawford HC, Aifantis I, Davis MM, Vignali DAA. Distinct TCR signaling pathways drive proliferation and cytokine production in T cells. Nature Immunology 14:262-270, 2013. [Issue cover] [PMCID: 3577985].
Turnis ME*, Sawant DV*, Szymczak-Workman A, Andrews LP, Delgoffe GM, Yano H, Beres AJ, Vogel P, Workman CJ, Vignali DAA (2016). Interleukin-35 limits anti-tumor immunity. Immunity 44: 316-329 [PMCID: 4758699].
Zhang Q, Chikina M, Szymczak-Workman AL, Horne W, Kolls JK, Vignali KM, Normolle D, Bettini M, Workman CJ, Vignali DAA (2017). LAG-3 limits regulatory T cell proliferation and function in autoimmune diabetes. Science Immunology. In Press.
- Our research focuses on gaining a better understanding of the inhibitory mechanisms, including inhibitory receptors and regulatory T cells, that limit anti-tumor immunity in cancer patients.
- We also have discovery-based programs aimed at identifying novel targets for therapeutic intervention.
- We are also working with UPCI scientists and clinicians to facilitate the translation of novel therapeutic modalities with a focus on immunologically-impacted solid tumors (primarily head and neck, melanoma, lung, pancreatic cancer).
- My UPCI leadership efforts are directed toward providing a bridge between basic and transitional cancer immunology.
- We work extensively with large and start-up biopharmaceutical companies to bring novel therapeutics to the clinic.