Dario A. Vignali, PhD

Research Interests

My 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 and are insufficient in autoimmune disease. I also have discovery-based programs aimed at identifying novel targets for therapeutic intervention. I am also working with UPMC Hillman Cancer Center scientists and clinicians to facilitate the translation of novel therapeutic modalities with a focus on immunologically impacted solid tumors (primarily head and neck and melanoma). My UPMC Hillman Cancer Center leadership efforts, in part as co-leader of the Cancer Immunology & Immunotherapy Program, are directed toward providing a bridge between basic and transitional cancer immunology. Lastly, I also work extensively with large and start-up biopharmaceutical companies to bring novel therapeutics to the clinic.

 

Selected Publications

  • 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].
  • 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].
  • 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].
  • Collison LW*, 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].
  • 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- drives Treg fragility to promote anti-tumor immunity. Cell 169:1130-1141 [PMCID: 5509332]
  • Sawant DV*, Yano H*, Chikina M, Zhang Q, Liao M, Liu C, Sun Z, Sun T, Tabib T, Pennathur A, Luketich JD, Lafyatis R, Chen W, Poholek A, Bruno TC, Workman CJ, Vignali DAA (2019). Adaptive plasticity of IL10+ and IL35+ regulatory T cells cooperatively promote intratumoral T cell exhaustion. Nature Immunology. 20:724-735 [PMCID: 6531353].
  • Sawant DV*, Yano H*, Chikina M, Zhang Q, Liao M, Liu C, Sun Z, Sun T, Tabib T, Pennathur A, Luketich JD, Lafyatis R, Chen W, Poholek A, Bruno TC, Workman CJ, Vignali DAA (2019). Adaptive plasticity of IL10+ and IL35+ regulatory T cells cooperatively promote intratumoral T cell exhaustion. Nature Immunology. 20:724-735 [PMCID: 6531353].
  • Liu C, Chikina M, Deshpande R, Menk AV, Wang T, Tabib T, Brunazzi EA, Vignali KM, Sun M, Stolz DB, Lafyatis RA, Chen W, Delgoffe GM, Workman CJ, Wendell SG, Vignali DAA (2019). Treg cells promote the SREBP1-dependent metabolic fitness of M2-like intratumoral macrophages via CD8+ T cells. Immunity 51:381-397 [PMCID: 6703933].
  • Andrews LP, Somasundaram A, Moskovitz JM, Szymczak-Workman AL, Liu C, Cillo AR, Lin H, Normolle DP, Moynihan KD, Taniuchi I, Irvine DJ, Kirkwood JM, Lipson EJ, Ferris RL, Bruno TC, Workman CJ, Vignali DAA (2020). Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding. Science Immunology. 5:eabc2728 [PMCID: 32680952].
  • Liu C, Somasundaram A, Manne S, Gocher AM, Szymczak-Workman AL, Vignali KM, Scott EN, Normolle DP, Wherry EJ, Lipson EJ, Ferris RL, Bruno TC, Workman CJ, Vignali DAA (2020). Neuropilin-1 is a T cell memory checkpoint limiting long-term anti-tumor immunity. Nature Immunology, 21:1010-1021 [PMCID: 7442600].
  • Cillo AR, Kürten C, Tabib T, Qi Z, Onkar S, Wang T, Liu L, Duvvuri U, Kim S, Soose RJ, Oesterreich S, Chen W, Lafyatis R, Bruno TC†, Ferris RL†, Vignali DAA† (2020). Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity, 52:183-199 [PMID: 31924475].
  • Andrews LA, Vignali KM, Szymczak-Workman AL, Burton AR, Brunazzi EA, Ngiow SF, Harusato A, Sharpe AH, Wherry EJ, Taniuchi I, Workman CJ, Vignali DAA (2021). An immunological toolbox to interrogate T cell subsets. Immunity. 54:2209-2217 [PMID: 34551314].
  • Chuckran CA, Cillo AR, Moskovitz J, Overacre-Delgoffe A, Somasundaram AS, Magnon GC, Abecassis I, Zureikat AH, Luketich J, Pennathur A, Sembrat J, Rojas M, Merrick DT, Taylor SE, Orr B, Modugno F, Bukanovich R, Schoen RE, Kim S, Duvvuri U, Zeh H, Edwards R, Kirkwood JM, Coffman L, Ferris RL, Bruno TC, Vignali DAA (2021). Neuropilin-1 Enforces Human Regulatory T cell Stability and Function in Solid Tumors. Science Translational Medicine. 13:eabf8495 [PMID: 34878821].