Skip to main content

Dario A. A. Vignali Ph.D.

  • Chair and Distinguished Professor, Department of Immunology
  • Frank Dixon Chair in Cancer Immunology
  • Co-Director of the Cancer Immunology Training Program
  • Associate Director for Scientific Strategy, UPMC Hillman Cancer Center
  • PMI Graduate Faculty

    Education & Training

  • Ph.D., Immunology of Infectious Diseases, University of London, 1988
  • BSc, Immunology and Medical Microbiology, North East London Polytechnic, 1985
Representative Publications

Cillo AR†, Cardello C, Shan F, Karapetyan L, Kunning SR, Sander C, Rush E, Li A, Karunamurthy A, Massa RC, Rohatgi A, Workman C, Kirkwood JM†, Bruno TC†, Vignali DAA† (2024). Relatlimab plus nivolumab rewires dysfunctional CD8+ T cells by coupling cytotoxic and exhaustion gene modules to promote antitumor immunity. Cell 187:4373-4388 [PMCID: 11346583].

Andrews LP*, Butler SC*, Cui J, Cillo AR, Cardello C, Liu C, Brunazzi EA, Baessler A, Xie B, Kunning SR, Ngiow SF, Huang YJ, Manne S, Sharpe AH, Delgoffe GM, Wherry EJ, Kirkwood JM, Bruno TC, Workman CJ, Vignali DAA (2024). LAG3 and PD1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFNγ-dependent anti-tumor immunity. Cell 187:4355-4372 [PMCID: 11323044].

Baessler A, Vignali DAA (2024). T Cell Exhaustion. Annual Reviews in Immunology 42:179-206 [PMCID: 38166256] [Invited Review].

Shan F, Cillo AR, Cardello C, Yuan D, Kunning SR, Cui J, Lampenfeld C, Williams AM, McDonough AP, Pennathur A, Luketich JD, Kirkwood JM, Ferris RL, Bruno TC, Workman CJ, Benos PV, Vignali DAA (2023). Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells. Science Immunology 8: eadf6717 [PMCID: 11045170].

Gocher-Demske AM, Cui J, Szymczak-Workman AL, Vignali KM, Latini JN, Pieklo GP, Kimball, JC, Avery L, Cipolla WL, Huckenstein BR, Hedden L, Meisel M, Alcorn JF, Kane LP, Workman CJ, Vignali DAA (2023).  Interferon gamma-induction of TH1-like regulatory T cells controls anti-viral responses. Nature Immunology 24: 841-854 [PMCID: 10224582].

Onkar SS, Cui J, Zou J, Cardello C, Cillo AR, Uddin MR, Sagan A, Joy M, Osmanbeyoglu HU, Pogue-Geile K, McAuliffe P, Lucas PC, Tsang GC, Lee AV, Bruno TC, Oesterreich S*, Vignali DAA* (2023). Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment. Nature Cancer 4: 516–534 [PMCID: Pending].

Grebinoski S*, Zhang Q*, Cillo AR, Manne S, Burnazzi EA, Tabib T, Cardello C, Lian C, Murphy GF, Lafyatis R, Wherry EJ, Das J, Workman CJ, Vignali DAA (2022). Autoreactive CD8+ T cells are restrained by a divergent exhaustion program. Nature Immunology 23:868-877 [PMCID: 9179227].

Guy C, Mitrea DM, Chou P-C, Temirov J, Vignali KM, Liu X, Zhang H, Kriwacki R, Bruchez M, Watkins S, Workman CJ†, Vignali DAA† (2022). LAG3 associates with TCR-CD3 complexes and suppresses signaling by driving co-receptor-Lck dissociation. Nature Immunology 23:757-767 [PMCID: 9106921].

Complete List of Publications

Research Interests
  • 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 and are insufficient in autoimmune disease.
  • We also have make heavy use of system immunology approaches, discovery-based efforts and development of novel antibody-based therapeutics aimed at identifying novel targets and pathways for therapeutic intervention.
  • We are 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 melanoma and head & neck).
  • My leadership efforts as Chair of Immunology and UPMC Hillman Cancer Center Associate Director for Scientific Strategy are directed toward providing a bridge between basic and transitional cancer immunology, and mentoring the next generation of immunologists.
  • We work extensively with large and start-up biopharmaceutical companies to bring novel therapeutics to the clinic.

 

Our research focuses on various aspects of T cell regulation and function:

(1)    Mechanistic Focus:

(a)    Immune Regulation: Inhibitory Receptors: Identification of novel inhibitory receptors (IR) and their mechanisms; immune modulation of T cell subsets by LAG3, PD1 and NRP1; PD1-LAG3 synergy; mechanism of CD8+ and CD4+ T cell exhaustion; role of IFNg; protein engineering to develop novel therapeutics.

(b)    Immune Regulation: Regulatory T cells (Tregs): Identification of novel Treg molecules and their function; mechanisms of Treg function and regulation of Treg stability. 

(c)    Systems Immunology: Single cell systems approaches (transcriptomic & epigenomic) to hypothesis test, hypothesis generate and discover; multispectral imaging; CRISPR screens.

(2)    Disease Focus:

(a)    Cancer: Biology of LAG3/PD1 and Tregs in mouse models of cancer and in samples from treatment-naive patients with cancer or immunotherapy recipients; primary focus on solid tumors – melanoma and head & neck; novel approaches for therapeutic translation; biomarker discovery.

(b)    Autoimmune and Inflammatory Disease: Impact, function & insufficiency of Tregs and IRs in several autoimmune and inflammatory disease with emphasis on models of autoimmune diabetes (NOD), EAE and asthma; development of therapeutic approaches to enhance Treg stability and development of IR agonists.