1. 肿瘤免疫逃逸机制解析及药物靶标发现：
本课题组将以基础免疫学为切入点，借助转录组/代谢组测序以及转基因小鼠模型验证等技术手段，从代谢角度筛选和确证免疫逃逸驱动基因/蛋白，同时联合结构生物学、化学生物学以及药物化学等学科平台开发针对特定靶标的抗肿瘤药物；
2.肿瘤血管调控机制探究及药物靶标发现：
本课题组将基于前期工作基础，借助肿瘤样本检测、TCGA 数据库挖掘和蛋白组学分析等手段从多维度筛选/鉴定与肿瘤血管异常相关的基因和潜在药物干预靶点，利用 confocal、双光子显微镜、转基因小鼠等技术手段在多种肿瘤模型中验证效应靶标，最后针对特定靶标开发抗肿瘤靶向药物；
3. 肿瘤菌群代谢及药物干预：
以肿瘤微环境调控为导向，借助组学、细胞生物学、分子生物学等手段，深入剖析瘤内菌群代谢在肿瘤进展中的作用和调控机制，并针对关键基因和通路设计靶向干预药物；

(1) 明确肿瘤微环境中CH25H下调是效应性T细胞耗竭和凋亡的关键驱动因素，提出了恢复效应性T细胞CH25H用于肿瘤免疫治疗的新思路，并申请专利1项；
(2) 明确肿瘤微环境中CH25H下调是树突状细胞抗原交叉提呈失败的重要原因，为发展树突状细胞介导的肿瘤免疫治疗新策略奠定理论基础；
(3) 明确肿瘤微环境中CH25H下调在血管异常增生中的重要作用，发展了血管生成抑制剂联合放化疗的肿瘤治疗新策略;
截至目前，以第一作者（排一）在Cell Metab，Sci Transl Med，J Clin Invest，J Hepatol，Nat Commun 等国际权威杂志发表 SCI论文（非综述）7 篇，平均影响因子>18，单篇论文最高引用300余次，相关研究成果被宾夕法尼亚大学头条、美国科学技术学会（AAAS）、日本学术振兴会（JST）等国际媒体广泛报道。

第一作者：
1. Zhen Lu, Ioannis I. Verginadis, Motofumi Kumazoe, Gerry Castillo, Yao Yao, Rebecca Guerra, Sandra Bicher, Menghao You, Rong Qiu, Zebin Xiao, Zhen Miao, Subin S. George, Daniel P. Beiting, Takashi Nojiri, Yasutake Tanaka, Yoshinori Fujimura, Hiroaki Onda, Yui Hatakeyama, Akiko Nishimoto-Ashfield, Katrina Bykova, Wei Guo, Yi Fan, Nikolay M. Buynov, J. Alan Diehl, Ben Z. Stanger, Hirofumi Tachibana, Ellen Puré, Constantinos Koumenis, Elijah M. Bolotin, and Serge Y. Fuchs. Modified C-type natriuretic peptide normalizes tumor vasculature and improves solid tumor therapies. (Science Translational Medicine, in press). 2024; (IF=19.32)
2. Zhen Lu, Noreen McBrearty, Jinyun Chen, Vivek S. Tomar, Hongru Zhang, Gianluca De Rosa, Aiwen Tan, Aalim M. Weljie, Daniel P. Beiting, Zhen Miao, Subin S. George, Allison Berger, Gurpanna Saggu, J. Alan Diehl, Constantinos Koumenis, and Serge Y. Fuchs. ATF3 and CH25H regulate effector trogocytosis and anti-tumor activities of endogenous and immunotherapeutic cytotoxic T lymphocytes. Cell Metabolism. 2022;34, 1342–1358. (IF=31.3)
3. *Zhen Lu, *Jingyun chen, *Pengfei Yu, Matthew J. Atherton, Jun Gui, Vivek S. Tomar, Justin D. Middleton, Neil T. Sullivan, Sunil Singhal, Subin S. George, Tsonwin Hai, Evgeniy B. Eruslanov, and Serge Y. Fuchs. Tumor factors increase lysosomal activities to undermine antigen crosspresentation in lung cancer. Nature Communications. 2022; 13:6623. (*Co-first author, IF=16.6)
4. Zhen Lu, Eun-Ah Bae, Ioannis I. Verginadis, Hongru Zhang, Christina Cho, Noreen McBrearty, J. Alan Diehl, Constantinos Koumenis, Linda M. Bradley, and Serge Y. Fuchs. Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities. Cancer immunology, immunotherapy. 2022; Doi: 10.1007/s00262-022-03286-2. (IF=6.63)
5. Zhen Lu, Angelica Ortiz, Ioannis I. Verginadis, Amy R. Peck, Farima Zahedi, Christina Cho, Pengfei Yu, Rachel M. DeRita, Hongru Zhang, Ryan Kubanoff, Yunguang Sun, Andrew T. Yaspan, Elise Krespan, Daniel P. Beiting, Enrico Radaelli, Sandra W. Ryeom, J. Alan Diehl, Hallgeir Rui, Constantinos Koumenis, and Serge Y. Fuchs. Regulation of the intercellular biomolecule transfer-driven tumor angiogenesis and responses to anti-cancer therapies. Journal of Clinical Investigation. 2021;131(10):e144225. (IF=15.9)
6. Zhili Liu#, Zhen Lu#, Renwei Jing#, Bingfeng Zuo, Xianjun Gao, Gang Han, Han Qi, Li Wu, Yunde Liu, Haifang Yin. Alarmin augments the antitumor immunity of lentiviral vaccine in ectopic, orthotopic and autochthonous hepatocellular carcinoma mice. Theranostics. 2019;9(14):4006-4018. (#Co-first author, IF=12.4)
7. Zhen Lu#, Bingfeng Zuo#, Renwei Jing, Xianjun Gao, Quan Rao, Zhili Liu , Han Qi , Hongxing Guo, HaiFang Yin. Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models. Journal of Hepatology. 2017;67(4):739-748. (#Co-first author, IF=26.2)
共同作者：
1. Zebin Xiao, Leslie Todd, Li Huang, Estela Noguera-Ortega, Zhen Lu, Lili Huang, Meghan Kopp, Yue Li, Nimisha Pattada, Wenqun Zhong, Wei Guo, John Scholler, Maria Liousia, Charles-Antoine Assenmacher, Carl H June, Steven M Albelda, Ellen Puré. Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors. Nat Communications. 2023 Aug 22;14(1):5110. (IF=16.6)
2. Hongru Zhang, Pengfei Yu, Vivek S. Tomar1, Xiangjie Chen, Matthew J. Atherton , Zhen Lu, Hong-Guang Zhang, Shifeng Li, Angelica Ortiz , Jun Gui, N. Adrian Leu, Fangxue Yan, Andres Blanco, Mirella L. Meyer-Ficca , Ralph G. Meyer, Daniel P. Beiting, Jinyang Li , Selene Nunez-Cruz, Roddy S. O’Connor, Lexus R. Johnson, Andy J. Minn, Subin S. George, Constantinos Koumenis, J. Alan Diehl , Michael C. Milone , Hui Zheng  and Serge Y. Fuchs. Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors. Nature Cancer. 2022,11(1):1790. (IF=22.7)
3. Eric S. Lightcap, Pengfei Yu, Stephen Grossman, Keli Song, Mithun Khattar, Kristina Xega, Xingyue He, James M. Gavin, Hisashi Imaichi, James J. Garnsey, Erik Koenig, Hongru Zhang, Zhen Lu, Pooja Shah, Yu Fu, Michael A. Milhollen, Beryl A. Hatton, Jessica Riceberg, Vaishali Shinde, Cong Li, James Minissale, Xiaofeng Yang, Dylan England, Richard A. Klinghoffer, Steve Langston, Katherine Galvin, Gary Shapiro, Sai M. Pulukuri1, Serge Y. Fuchs, Dennis Huszar1*†. A small-molecule SUMOylation inhibitor activates antitumor immune responses and potentiates immune therapies in preclinical models. Science Translational Medicine. 2021,11(1):1790. (IF=19.32)
4. Bingfeng Zuo, Han Qi, Zhen Lu, Lu Chen, Bo Sun, Rong Yang, Yang Zhang, Zhili Liu , Xianjun Gao, Abin You, Li Wu , Renwei Jing, Qibing Zhou, HaiFang Yin. Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice. Nat Communications. 2020,11(1):1790. (IF=16.6)
5. Renwei Jing, Xiaoli Zhou, Jingwen Zhao, Yushuang Wei, Bingfeng Zuo, Abin You, Quan Rao, Xianjun Gao, Rong Yang, Lu Chen, Zhen Lu, Qibing Zhou, Ning Zhang, HaiFang Yin. Hepatology. 2018, 68(4):1391-1411. (IF=15.57)
6. Quan Rao, Bingfeng Zuo, Zhen Lu, Xianjun Gao, Abin You, Chenxuan Wu, Zhi Du, HaiFang Yin. Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro. Hepatology. 2016 Aug;64(2):456-72. (IF=15.57)

课题组长
陆振 教授
副教授/特聘研究员
陈欢副教授
杨云凯特聘副研究员
博士研究生
戴杭兵(2024级)
硕士研究生
王续年(2024级)