研究方向
恶性转移和复发是导致绝大多数癌症患者死亡的主要原因。对于早期肿瘤患者，虽然标准疗法可以去除原发性肿瘤，但恶性转移常在诊断治疗后的几个月至几年后发生。研究表明，癌细胞可能在原发肿瘤去除之前就已经扩散到远端器官。这些早期扩散的癌细胞停止增殖，进入休眠状态（metastatic dormancy，转移休眠）而不被临床诊断发现，直到重新苏醒并进展为恶性转移。靶向早期转移休眠期可以为阻断和预防晚期恶性转移提供非常重要的治疗窗口。
本实验室致力于研究肿瘤转移的调控机制，将运用分子生物学，生物化学，免疫学，生物信息学和多组学等多种实验技术手段，结合肿瘤动物模型，着重探究早期转移阶段肿瘤细胞内部和微环境中调节癌细胞休眠、苏醒和恶性进展的分子机制。主要研究方向包括：
1. 研究转移进展过程中调控癌细胞休眠、生存和免疫逃逸的分子信号通路
2. 探究转移休眠期癌细胞与微环境的相互作用及分子调控机制
3. 探索对肿瘤患者早期转移的诊断和治疗方法
代表性成果
1. Hu J, Sánchez-Rivera F, Wang Z, Johnson G, Ho Y, Ganesh K, Umeda S, Gan S, Mujal A, Delconte R, Hampton J, Zhao H, Kottapalli S, de Stanchina E, Iacobuzio-Donahue C, Pe’er D, Lowe S, Sun J, Massagué J. STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma. Nature. 2023, 616, 806-813.
Research highlighted by: Cancer Discovery, June 2023; Science Signaling, Apr 2023.
2. Tello-Lafoz M, Srpan K, Sanchez E, Hu J, Remsik J, Romin Y, Calò A, Hoen D, Bhanot U, Morris L, Boire A, Hsu K, Massagué J, Huse M, Er E. Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer. Immunity. 2021, 54(5):1037-1054
3. Laughney A, Hu J, Campbell N, Bakhoum S, Setty M, Lavallée V, Xie Y, Masilonis I, Carr A, Allaj V, Mattar M, Rekhtman N, Xavier J, Mazutis L, Poirier J, Rudin C, Pe’er D, Massagué J. Regenerative lineages and immune-mediated pruning in lung cancer metastasis. Nature Medicine. 2020, 26(2):259-269.
4. Huang Y, Hu J, Chen F, Lecomte N, Basnet H, David C, Witkin M, Allen P, Leach S, Hollmann T, Lacobuzio-Donahue, C Massagué J. ID1 mediates escape from TGF-β tumor suppression in pancreatic cancer. Cancer Discovery. 2020, 10(1):142-157.
5. Aragón E, Wang Q, Zou Y, Morgani S, Ruiz L, Kaczmarska Z, Su J, Torner C, Tian L, Hu J, Shu W, Agrawal S, Gomes T, Márquez J, Hadjantonakis A, Macias M, Massagué J. Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling. Genes & Development. 2019, 33(21-22):1506-1524.
6. Er E, Valiente M, Ganesh K, Zou Y, Agrawal S, Hu J, Griscom B, Rosenblum M, Boire A, Brogi E, Giancotti F, Schachner M, Malladi S, Massagué J. Pericyte-Like Spreading by Disseminated Cancer Cells Activates YAP and MRTF for Metastatic Colonization. Nature Cell Biology. 2018, 20(8): 966-978.
7. Yuan L, Zhai L, Qian L, Huang D, Ding Y, Xiang H, Liu X, Thompson W, Liu J, He YH, Chen XQ, Hu J, Kong QP, Tan M, Wang XF. Switching off IMMP2L Signaling Drives Senescence via Simultaneous Metabolic Alteration and Blockage of Cell Death. Cell Research. 2018, 28(6): 625-643. Cover article.
8. Hu J, Wang XF. HIF-miR-215-KDM1B promotes glioma-initiating cell adaptation to hypoxia. Cell Cycle. 2016, 15(15):1939-40.
9. Hu J, Sun T, Wang H, Chen Z, Wang S, Liu T, Yuan L, Li HR, Wang P, Feng Y, Wang Q, McLendon RE, Friedman AH, Keir ST, Bigner DD, Rathmell J, Fu SD, Li QJ, Wang H, Wang XF. miR-215 is induced post-transcriptionally via HIF-Drosha complex and mediates glioma-initiating cell adaptation to hypoxia by targeting KDM1B. Cancer Cell. 2016, 29(1): 49-60.
Research highlighted by Cell Cycle, Apr 2016; Science Signaling, Jan 2016.
10. Hu J, Markowitz GJ, Wang XF. Noncoding RNAs Regulating Cancer Signaling Network. Advances in Experimental Medicine and Biology. 2016;927:297-315.
11. Hu J, Markowitz GJ, Wang XF. Isolation of Glioma-Initiating Cells for Biological Study. Advances in Experimental Medicine and Biology. 2016;899:197-209.
12. Wang H*, Sun T*, Hu J*, Zhang R, Rao Y, Wang S, Chen R, McLendon RE, Friedman AH, Keir ST, Bigner DD, Li QJ, Wang H, Wang XF. miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways. Journal of Clinical Investigation. 2014, 124(10): 4489-502. *Equal contributions.
13. Tong X, Xia Z, Zu Y, Telfer H, Hu J, Yu J, Liu H, Zhang Q, Sodmergen, Lin S, Zhang B. ngs (notochord granular surface) gene encodes a novel type of intermediate filament family proein essential for notochord maintenance in zebrafish. Journal of Biological Chemistry. 2013, 288(4): 2711-20.
