Hua Yu Lab

Hua Yu, Ph.D., is the Billy and Audrey L. Wilder Professor in Tumor Immunotherapy in the Department of Immuno-Oncology, and in the Irell and Manella Graduate School of Biological Sciences. She also serves as a Co-leader of the Cancer Immunotherapeutics Program within the City of Hope^® Comprehensive Cancer Center.

Dr. Hua Yu Lab has made groundbreaking contributions to understanding the role of STAT3 in cancer. The lab was the first to demonstrate STAT3 as a therapeutic target in vivo. Additionally, the lab pioneered research on STAT3’s critical role in promoting immunosuppression within the tumor microenvironment. Dr. Yu’s research also identified STAT3 as a key regulator of tumor angiogenesis and metastasis. In addition, her work uncovered STAT3’s interaction with other oncogenic pathways, such as NF-κB and S1PR1. Dr. Yu`s team developed siRNA-based technologies to target STAT3 and other intracellular molecules, opening new avenues for cancer therapy.  More recently, the Yu Lab has developed platforms to enable macromolecules, including antibodies, peptides, and CRISPR/Cas9 efficiently penetrate cells/nucleus, in vitro and in vivo. The team is now developing bivalent and bio-specific engineered macromolecule inhibitors to target the undruggable such as Myc and STAT3, with the goals to move towards clinical testing.

In addition to developing therapeutic reagents, one of the current research priorities in the Yu lab is on cancer reprogrammed lipid metabolism and/or other therapy resistance mechanisms in ovarian cancer, colorectal cancer and sarcomas. The group works closely with physician-scientists, including Drs Lorna Rodriguez, Janet Yoon and Ross Okimoto (UCSF).

• Marcin Kortylewski, PhD, Professor, Department of Immuno-Oncology, City of Hope
• Saul Priceman, PhD, Associate Professor at Keck School of Medicine of USC, and Founding Director of KSOM/NCCC Center for Cancer Cellular Immunotherapy Research
• Chunyan Zhang, PhD, Research Associate Professor, City of Hope
• Toshi Nagao, MD, Assistant professor, Tokyo Medical and Dental University
• Qianqian Zhao, PhD, Postdoctoral Fellow, AbbVie
• Tianyi Wang, PhD, Director of Corporate Alliances, Aureka Biotechnologies 
• Lin Wang, PhD, MD, Clinical Research Fellow, Genentech
• Veronica Lifshitz, PhD, Principal Research Scientist, AbbVie
• Chanyu Yue, PhD, Senior Scientist, Vividion Therapeutics
• Theresa Austria, PhD, Manager of Academic Programs and Training at Fox Chase Cancer Center
• Nigus Ambaye, PhD, Research Associate, Maryland School of Medicine
• Maryam Aftabizadeh, PhD, Staff Scientist. City of Hope
• Maciej Kujawski, PhD, Research Assistant Professor, City of Hope
• Jiehui Deng, PhD, Research Assistant Professor, NYU
• Greg Cherryholmes, PhD, Senior Clinical Development Scientist, Agilent Technologies
• Jieun Song, PhD, Senior Scientist, Aligos Therapeutics
• Wenzhao Li, PhD, Business Development Manager, GemPharmatech
• Heehyoung Lee, PhD, Managing Partner, LumeBio, Inc.
• Christoph Lahtz, PhD, Senior Director, Space Tango

• Li YJ, Chien SH, Huang R, Herrmann A, Zhao Q, Li PC, Zhang C, Martincuks A, Santiago NL, Zong K, Swiderski P, Okimoto RA, Song M, Rodriguez L, Forman SJ, Wang X, Yu H. A platform to deliver single and bi-specific Cas9/guide RNA to perturb genes in vitro and in vivo. Mol Ther. 2024, PubMed PMID: 39091030.
• Martincuks A, Zhang C, Austria T, Li YJ, Huang R, Lugo Santiago N, Kohut A, Zhao Q, Borrero RM, Shen B, Cristea M, Wang EW, Song M, Rodriguez-Rodriguez L, Yu H. Targeting PARG induces tumor cell growth inhibition and antitumor immune response by reducing phosphorylated STAT3 in ovarian cancer. J Immunother Cancer. 2024, PMID: 38580335.
• Li YJ, Zhang C, Martincuks A, Herrmann A, Yu H. STAT proteins in cancer: orchestration of metabolism. Nat Rev Cancer. 2023 PubMed PMID: 36596870.
• Ding L, Wang Q, Martincuks A, Kearns MJ, Jiang T, Lin Z, Cheng X, Qian C, Xie S, Kim HJ, Launonen IM, Färkkilä A, Roberts TM, Freeman GJ, Liu JF, Konstantinopoulos PA, Matulonis U, Yu H, Zhao JJ. STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer. J Immunother Cancer. 2023 PubMed PMID: 36609487; PubMed Central PMCID: PMC9827255.
• Li YJ, Fahrmann JF, Aftabizadeh M, Zhao Q, Tripathi SC, Zhang C, Yuan Y, Ann D, Hanash S, Yu H. Fatty acid oxidation protects cancer cells from apoptosis by increasing mitochondrial membrane lipids. Cell Rep. 2022. PubMed PMID: 35649368.
• Martincuks A, Song J, Kohut A, Zhang C, Li YJ, Zhao Q, Mak E, Rodriguez-Rodriguez L, Yu H, Cristea M. PARP Inhibition Activates STAT3 in Both Tumor and Immune Cells Underlying Therapy Resistance and Immunosuppression in Ovarian Cancer. Front Oncol. 2021 PMID: 34956861; PubMed Central PMCID: PMC8693573.
• Aftabizadeh M, Li YJ, Zhao Q, Zhang C, Ambaye N, Song J, Nagao T, Lahtz C, Fakih M, Ann DK, Yu H, Herrmann A. Potent antitumor effects of cell-penetrating peptides targeting STAT3 axis. JCI Insight. 2021. PMID: 33491667; PubMed Central PMCID: PMC7934871.
• Zhang C, Yue C, Herrmann A, Song J, Egelston C, Wang T, Zhang Z, Li W, Lee H, Aftabizadeh M, Li YJ, Lee PP, Forman S, Somlo G, Chu P, Kruper L, Mortimer J, Hoon DSB, Huang W, Priceman S, Yu H. STAT3 Activation-Induced Fatty Acid Oxidation in CD8(+) T Effector Cells Is Critical for Obesity-Promoted Breast Tumor Growth. Cell Metab. 2020. PMID: 31761565.
• Herrmann A, Nagao T, Zhang C, Lahtz C, Li YJ, Yue C, Mülfarth R, Yu H. An effective cell-penetrating antibody delivery platform. JCI Insight. 2019. PubMed PMID: 31341104; PubMed Central PMCID: PMC6675557.
• Wang T, Fahrmann JF, Lee H, Li YJ, Tripathi SC, Yue C, Zhang C, Lifshitz V, Song J, Yuan Y, Somlo G, Jandial R, Ann D, Hanash S, Jove R, Yu H. JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance. Cell Metab. 2018. PubMed PMID: 29249690; PubMed Central PMCID: PMC5777338.
• Kammertoens T, Friese C, Arina A, Idel C, Briesemeister D, Rothe M, Ivanov A, Szymborska A, Patone G, Kunz S, Sommermeyer D, Engels B, Leisegang M, Textor A, Fehling HJ, Fruttiger M, Lohoff M, Herrmann A, Yu H, Weichselbaum R, Uckert W, Hübner N, Gerhardt H, Beule D, Schreiber H, Blankenstein T. Tumour ischaemia by interferon-γ resembles physiological blood vessel regression. Nature. 2017 PMID: 28445461; PubMed Central PMCID: PMC5567674.
• Zhang C, Xin H, Zhang W, Yazaki PJ, Zhang Z, Le K, Li W, Lee H, Kwak L, Forman S, Jove R, Yu H. CD5 Binds to Interleukin-6 and Induces a Feed-Forward Loop with the Transcription Factor STAT3 in B Cells to Promote Cancer. Immunity. 2016 PMID: 27096320.
• Yu H, Lee H, Herrmann A, Buettner R, Jove R. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer. 2014. PubMed PMID: 25342631.
• Herrmann A, Priceman SJ, Swiderski P, Kujawski M, Xin H, Cherryholmes GA, Zhang W, Zhang C, Lahtz C, Kowolik C, Forman SJ, Kortylewski M, Yu H. CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells. J Clin Invest. 2014 PMID: 24892807.
• Priceman SJ, Shen S, Wang L, Deng J, Yue C, Kujawski M, Yu H. S1PR1 is crucial for accumulation of regulatory T cells in tumors via STAT3. Cell Rep. 2014 PMID: 24630990; PubMed Central PMCID: PMC3988983.
• Priceman SJ, Kujawski M, Shen S, Cherryholmes GA, Lee H, Zhang C, Kruper L, Mortimer J, Jove R, Riggs AD, Yu H. Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance. Proc Natl Acad Sci USA. 2013 PubMed PMID: 23878227; PubMed Central PMCID: PMC3740863.
• Deng J, Liu Y, Lee H, Herrmann A, Zhang W, Zhang C, Shen S, Priceman SJ, Kujawski M, Pal SK, Raubitschek A, Hoon DSB, Forman S, Figlin RA, Liu J, Jove R, Yu H. S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell. 2012. PubMed PMID: 22624714; PubMed Central PMCID: PMC3360884.
• Lee H, Zhang P, Herrmann A, Yang C, Xin H, Wang Z, Hoon DS, Forman SJ, Jove R, Riggs AD, Yu H. Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation. Proc Natl Acad Sci USA. 2012. PubMed PMID: 22547799; PubMed Central PMCID: PMC3356652.
• Anders K, Buschow C, Herrmann A, Milojkovic A, Loddenkemper C, Kammertoens T, Daniel P, Yu H, Charo J, Blankenstein T. Oncogene-targeting T cells reject large tumors while oncogene inactivation selects escape variants in mouse models of cancer. Cancer Cell. 2011 PMID: 22172721; PubMed Central PMCID: PMC3658305.
• Lee H, Deng J, Kujawski M, Yang C, Liu Y, Herrmann A, Kortylewski M, Horne D, Somlo G, Forman S, Jove R, Yu H. STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat Med. 2010 Dec;16(12):1421-8. doi: 10.1038/nm.2250. Epub 2010 Nov 21. PubMed PMID: 21102457; PubMed Central PMCID: PMC3088498.
• Hedvat M, Huszar D, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, Buettner R, Proia D, Kowolik CM, Xin H, Armstrong B, Bebernitz G, Weng S, Wang L, Ye M, McEachern K, Chen H, Morosini D, Bell K, Alimzhanov M, Ioannidis S, McCoon P, Cao ZA, Yu H, Jove R, Zinda M. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 2009. PMID: 19962667; PubMed Central PMCID: PMC2812011.
• Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009 Nov;9(11):798-809. doi: 10.1038/nrc2734. Review. PubMed PMID: 19851315; PubMed Central PMCID: PMC4856025.
• Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M, Lee H, Scuto A, Liu Y, Yang C, Deng J, Soifer HS, Raubitschek A, Forman S, Rossi JJ, Pardoll DM, Jove R, Yu H. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat Biotechnol. 2009 Oct;27; PubMed Central PMCID: PMC2846721.
• Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med. 2009 Jul 6;206(7):1457-64. doi: 10.1084/jem.20090207. Epub 2009 Jun 29. PubMed PMID: 19564351; PubMed Central PMCID: PMC2715087.
• Lee H, Herrmann A, Deng JH, Kujawski M, Niu G, Li Z, Forman S, Jove R, Pardoll DM, Yu H. Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. Cancer Cell. 2009. PubMed PMID: 19345327; PubMed Central PMCID: PMC2777654.
• Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, Drake C, Pardoll D, Yu H. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell. 2009. PubMed PMID: 19185846; PubMed Central PMCID: PMC2673504.
• Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007. Review. PubMed PMID: 17186030.
• Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, Niu G, Kay H, Mulé J, Kerr WG, Jove R, Pardoll D, Yu H. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005 PubMed PMID: 16288283.
• Yu H, Jove R. The STATs of cancer--new molecular targets come of age. Nat Rev Cancer. 2004. PubMed PMID: 14964307.
• Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S, Bhattacharya R, Gabrilovich D, Heller R, Coppola D, Dalton W, Jove R, Pardoll D, Yu H. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med. 2004. PubMed PMID: 14702634.
• Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R, Yu H. Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res. 1999. PubMed PMID: 10537273.