Possible Rotation Projects:
- Bridging sequence to expression and state representations models to identify therapeutic targets for immune cells in the tumor microenvironment
- Designing targeted degrader platforms for therapeutically modulating protein targets using in vitro systems
- Studying antitumor immunity using immune-competent spheroid models
Training Technologies Used:
- Single-cell genomics
- Deep learning and machine learning
- In vitro experiments with spheroid culture systems
- In vitro experiments with targeted degraders
- B.S., Cell Biology and Biochemistry, Bucknell University- 2010
- Ph.D., Molecular Virology and Microbiology, University of Pittsburgh- 2016
Daley JD, Mukherjee E, Ferraro D, Bhaskar S, Green A, Meyer EM, Tawbi H, Burgess M, Bruno TC, Cillo AR, Bailey KM. SARC028 Samples Reveal an Interplay between TGF-β, IFN Signaling, and Low HLA Class I Expression as Contributors to Ewing Sarcoma Checkpoint Blockade Resistance. Clin Cancer Res. 2025 Sep 2;31(17):3805-3816. doi: 10.1158/1078-0432.CCR-24-3882. PubMed PMID: 40627445; PubMed Central PMCID: PMC12402801.
Cillo AR, Cardello C, Shan F, Karapetyan L, Kunning S, Sander C, Rush E, Karunamurthy A, Massa RC, Rohatgi A, Workman CJ, Kirkwood JM, Bruno TC, Vignali DAA. Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8(+) T cells to promote antitumor immunity. Cell. 2024 Aug 8;187(16):4373-4388.e15. doi: 10.1016/j.cell.2024.06.036. PubMed PMID: 39121849; PubMed Central PMCID: PMC11346583.
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. LAG-3 and PD-1 synergize on CD8(+) T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity. Cell. 2024 Aug 8;187(16):4355-4372.e22. doi: 10.1016/j.cell.2024.07.016. PubMed PMID: 39121848; PubMed Central PMCID: PMC11323044.
Shan F, Cillo AR, Cardello C, Yuan DY, 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. Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells. Sci Immunol. 2023 Sep 15;8(87):eadf6717. doi: 10.1126/sciimmunol.adf6717. Epub 2023 Sep 15. PubMed PMID: 37713508; PubMed Central PMCID: PMC11045170.
Cillo AR, Mukherjee E, Bailey NG, Onkar S, Daley J, Salgado C, Li X, Liu D, Ranganathan S, Burgess M, Sembrat J, Weiss K, Watters R, Bruno TC, Vignali DAA, Bailey KM. Ewing Sarcoma and Osteosarcoma Have Distinct Immune Signatures and Intercellular Communication Networks. Clin Cancer Res. 2022 Nov 14;28(22):4968-4982. doi: 10.1158/1078-0432.CCR-22-1471. PubMed PMID: 36074145; PubMed Central PMCID: PMC9669190.
Kürten CHL, Kulkarni A, Cillo AR, Santos PM, Roble AK, Onkar S, Reeder C, Lang S, Chen X, Duvvuri U, Kim S, Liu A, Tabib T, Lafyatis R, Feng J, Gao SJ, Bruno TC, Vignali DAA, Lu X, Bao R, Vujanovic L, Ferris RL. Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing. Nat Commun. 2021 Dec 17;12(1):7338. doi: 10.1038/s41467-021-27619-4. PubMed PMID: 34921143; PubMed Central PMCID: PMC8683505.
Chuckran CA, Cillo AR, Moskovitz J, Overacre-Delgoffe A, Somasundaram AS, Shan F, Magnon GC, Kunning SR, Abecassis I, Zureikat AH, Luketich J, Pennathur A, Sembrat J, Rojas M, Merrick DT, Taylor SE, Orr B, Modugno F, Buckanovich R, Schoen RE, Kim S, Duvvuri U, Zeh H, Edwards R, Kirkwood JM, Coffman L, Ferris RL, Bruno TC, Vignali DAA. Prevalence of intratumoral regulatory T cells expressing neuropilin-1 is associated with poorer outcomes in patients with cancer. Sci Transl Med. 2021 Dec 8;13(623):eabf8495. doi: 10.1126/scitranslmed.abf8495. Epub 2021 Dec 8. PubMed PMID: 34878821; PubMed Central PMCID: PMC9022491.
Cillo AR, Somasundaram A, Shan F, Cardello C, Workman CJ, Kitsios GD, Ruffin AT, Kunning S, Lampenfeld C, Onkar S, Grebinoski S, Deshmukh G, Methe B, Liu C, Nambulli S, Andrews LP, Duprex WP, Joglekar AV, Benos PV, Ray P, Ray A, McVerry BJ, Zhang Y, Lee JS, Das J, Singh H, Morris A, Bruno TC, Vignali DAA. People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden. Cell Rep Med. 2021 Dec 21;2(12):100476. doi: 10.1016/j.xcrm.2021.100476. Epub 2021 Dec 2. PubMed PMID: 34873589; PubMed Central PMCID: PMC8636386.
Ruffin AT, Cillo AR, Tabib T, Liu A, Onkar S, Kunning SR, Lampenfeld C, Atiya HI, Abecassis I, Kürten CHL, Qi Z, Soose R, Duvvuri U, Kim S, Oesterrich S, Lafyatis R, Coffman LG, Ferris RL, Vignali DAA, Bruno TC. B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma. Nat Commun. 2021 Jun 7;12(1):3349. doi: 10.1038/s41467-021-23355-x. PubMed PMID: 34099645; PubMed Central PMCID: PMC8184766.
Cillo AR, Kürten CHL, Tabib T, Qi Z, Onkar S, Wang T, Liu A, Duvvuri U, Kim S, Soose RJ, Oesterreich S, Chen W, Lafyatis R, Bruno TC, Ferris RL, Vignali DAA. Immune Landscape of Viral- and Carcinogen-Driven Head and Neck Cancer. Immunity. 2020 Jan 14;52(1):183-199.e9. doi: 10.1016/j.immuni.2019.11.014. Epub 2020 Jan 7. PubMed PMID: 31924475; PubMed Central PMCID: PMC7201194.
Our research group focuses on understanding how immune cells make cell fate decisions, how intercellular communication influences these cell fate decisions, and the ways in which cell-cell interactions shape community dynamics in the tumor microenvironment. We address these questions in three major ways:
i) Computational approaches: developing, validating, and implementing computational tools to study cell-type specific drivers of differentiation and intercellular communication in vitro and in vivo;
ii) Mechanistic models: development of in vitro models focused on dissecting specific aspects of cellular differentiation and intercellular communication;
iii) Translational studies: applying high-dimensional approaches including spectral flow cytometry, single-cell multi-omics and spatial transcriptomics as part of translational studies in patients with solid tumors.
Through the approaches described above, we are defining the contributions of individual immune populations to antitumor immunity as well as their aggregate behavior within the tumor microenvironment. Better understanding the individual and community dynamics of immune populations will allow us to dissect why current immunotherapies fail in some patients and it will enable identification of new therapeutic strategies to promote antitumor immunity.
