Education & Training
- B.S., East London University-Immunology/Medical Microbiology, 1985
- Ph.D., London School of Hygiene and Tropical Medicine-Immunology of Infectious Diseases, 1988
Research Interest Summary
Our primary focus is inhibitory immune mechanisms (ie inhibitory receptors, Tregs, etc). We can accept students that only want a ‘dry lab’ (computational biology project only) or combined ‘wet and dry lab’ project (integrated systems immunology project wherein the student will work with mouse models or patient samples to generate data sets for sophisticated computational analysis that they will perform themselves). Most projects will be co-mentored by another faculty member (depending on the project) who collaborates with the Vignali lab and is ‘deep rooted’ in computational approaches and expertise. Rotations available in our mouse or human labs, but the greater opportunities are in the former.
(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.
Huang 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 cells. Immunity 21:503-13 [PMID: 15485628].
Li N, Wang Y, Forbes K, Vignali KM, Heale BS, Saftig P, Hartmann D, Black R, Rossi JJ, Blobal C, Dempsey PJ, Workman CJ, Vignali DAA (2007). Metalloproteases regulate T cell proliferation and effector function via LAG-3. EMBOJ 26: 494-504 [PMCID:1783452].
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 molecules LAG-3 and PD-1 synergistically regulate T cell function to promote tumoral immune escape. Cancer Research 72:917-927 [PMCID: 3288154].
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. 2:eaah4569 [Not yet listed in PubMed].
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].
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].
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].
Turnis ME*, Sawant DV*, Szymczak-Workman A, Andrews LP, Delgoffe GM, Yano H., Beres AJ, Vogel P, Workman CJ, Vignali DAA (2015). Interleukin-35 limits anti-tumor immunity. Immunity. 44:316-29 [PMCID: 4758699].
Collison LW, Pillai MR, Chaturvedi V, Vignali DAA (2009). Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner. J. Immunol. 182:6121-6128 [PMID:19414764; PMCID: 2698997].
Delgoffe GM*, Woo S-R*, Turnis ME, Gravano DM, Guy C, Overacre AE, Bettini ML, Vogel P, Finkelstein D, Bonnevier J, Workman CJ, Vignali DAA (2013). Stability and function of regulatory T cells is maintained by a neuropilin-1:semaphorin-4a axis. Nature 501:252-256 [PMCID: 3867145].
Overacre-Delgoffe AE, Chikina M, Dadey RE, Yano H, Brunazzi EA, Shayan G, Horne W, Moskovitz JM, Kolls JK, Sander C, Shuai Y, Normolle DP, Kirkwood J, Ferris RL, Delgoffe GM, Bruno TC, Workman CJ, Vignali DAA (2017). Interferon-g drives Treg fragility to promote anti-tumor immunity. Cell 169:1130-1141 [PMCID:5509332].