Yu Zhu, PhD

Regulation of tumor immunity by the vascular endothelium

Associations

• Immunology
• Tumor Microenvironment and Metastasis
• Immuno-Oncology Program

Our research is positioned at the interface of cancer immunology and vascular biology, with a central focus on how the vascular endothelium regulates cancer immune responses. Active areas of investigation include: (1) defining how endothelial cells sculpt the tumor microenvironment to control immune cell trafficking, (2) determining how cancer cells drive endothelial cell subset specialization to suppress lymphocyte recruitment, and (3) elucidating how endothelial cells in the draining lymph nodes regulate lymphocyte activation. Our ultimate goal is to uncover actionable mechanisms and develop effective vessel-targeting therapeutics to boost anti-tumor immunity.

• Zhu Y, Brulois KF, Dinh TT, Pan J, Butcher EC. COUP-TFII-mediated reprogramming of the vascular endothelium counteracts tumor immune evasion. Nat Commun. 2025 Aug.16(1):7457. Pubmedid: 40796746. Pmcid: PMC12343902.
• Zhu Y, Xiang M, Brulois KF, Lazarus NH, Pan J, Butcher EC. Endothelial cell Notch signaling programs cancer-associated fibroblasts to promote tumor immune evasion. Res Sq. 2024 Jun. Pubmedid: 38947054. Pmcid: PMC11213189.
• Dong X, Qi M, Cai C, Zhu Y, Li Y, Coulter S, Sun F, Liddle C, Uboha NV, Halberg R, Xu W, Marker P, Fu T. Farnesoid X receptor mediates macrophage-intrinsic responses to suppress colitis-induced colon cancer progression. JCI Insight. 2024 Jan.9(2). Pubmedid: 38258906. Pmcid: PMC10906220.
• Baer JM, Zuo C, Kang LI, de la Lastra AA, Borcherding NC, Knolhoff BL, Bogner SJ, Zhu Y, Yang L, Laurent J, Lewis MA, Zhang N, Kim KW, Fields RC, Yokoyama WM, Mills JC, Ding L, Randolph GJ, DeNardo DG. Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC. Nat Immunol. 2023 Sep.24(9):1443-1457. Pubmedid: 37563309. Pmcid: PMC10757749.
• Kim D, Tian W, Wu TT, Xiang M, Vinh R, Chang JL, Gu S, Lee S, Zhu Y, Guan T, Schneider EC, Bao E, Dixon JB, Kao P, Pan J, Rockson SG, Jiang X, Nicolls MR. Abnormal Lymphatic Sphingosine-1-Phosphate Signaling Aggravates Lymphatic Dysfunction and Tissue Inflammation. Circulation. 2023 Oct.148(16):1231-1249. Pubmedid: 37609838. Pmcid: PMC10592179.
• Dinh TT, Xiang M, Rajaraman A, Wang Y, Salazar N, Zhu Y, Roper W, Rhee S, Brulois K, O'Hara E, Kiefel H, Dinh TM, Bi Y, Gonzalez D, Bao EP, Red-Horse K, Balogh P, Gábris F, Gaszner B, Berta G, Pan J, Butcher EC. An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression. Nat Commun. 2022 Dec.13(1):7448. Pubmedid: 36460642. Pmcid: PMC9718832.
• Zhu Y, Herndon JM, Sojka DK, Kim KW, Knolhoff BL, Zuo C, Cullinan DR, Luo J, Bearden AR, Lavine KJ, Yokoyama WM, Hawkins WG, Fields RC, Randolph GJ, DeNardo DG. Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression. Immunity. 2017 Aug.47(2):323-338.e6. Pubmedid: 28813661. Pmcid: PMC5578409.
• Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, Nywening TM, Hawkins WG, Shapiro IM, Weaver DT, Pachter JA, Wang-Gillam A, DeNardo DG. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med. 2016 Aug.22(8):851-860. Pubmedid: 27376576. Pmcid: PMC4935930.
• Zhu Y, Hawkins WG, DeNardo DG. Regramming myeloid responses to improve cancer immunotherapy. Oncoimmunology. 2015 Jun.4(6):e974399. Pubmedid: 26155432. Pmcid: PMC4492504.
• Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J, Wang-Gillam A, Goedegebuure SP, Linehan DC, DeNardo DG. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014 Sep.74(18):5057-5069. Pubmedid: 25082815. Pmcid: PMC4182950.
• Liu Z, Chen S, Boyle S, Zhu Y, Zhang A, Piwnica-Worms DR, Ilagan MX, Kopan R. The extracellular domain of Notch2 increases its cell-surface abundance and ligand responsiveness during kidney development. Dev Cell. 2013 Jun.25(6):585-598. Pubmedid: 23806616. Pmcid: PMC3710456.
• Mitchem JB, Brennan DJ, Knolhoff BL, Belt BA, Zhu Y, Sanford DE, Belaygorod L, Carpenter D, Collins L, Piwnica-Worms D, Hewitt S, Udupi GM, Gallagher WM, Wegner C, West BL, Wang-Gillam A, Goedegebuure P, Linehan DC, DeNardo DG. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 2013 Feb.73(3):1128-1141. Pubmedid: 23221383. Pmcid: PMC3563931.