徐國泰博士
- 基本信息
- 教育經(jīng)歷
- 工作經(jīng)歷
- 研究概述
- 發(fā)表文章
徐國泰 博士 研究員Guotai Xu, Ph.D.Assistant Investigator, NIBS, BeijingPhone: 80726688-8382Email: xuguotai AT nibs.ac.cnLab Website: Xulab.com.cn
導(dǎo)師：Prof. Sven Rottenberg & Prof. Piet Borst
10/2009-1/2016 PhD, the Netherlands Cancer Institute (NKI) and Faculty of Medicine at VU University Amsterdam, the Netherlands. Supervisors: Prof. Sven Rottenberg and Prof. Piet Borst. Promotor: Prof. Hein te Riele
2006.2-2009.6醫(yī)學(xué)碩士, 山東大學(xué)藥學(xué)院免疫藥理與免疫治療學(xué)研究所
導(dǎo)師：田志剛教授，張建教授
9/2006-6/2009 Master in Medicine, Institute of Immunopharmacology and Immunotherapy, Shandong University, China. Supervisors: Prof. Zhigang Tian & Prof. Jian Zhang
2002.9- 2006.7 工學(xué)學(xué)士, 山東大學(xué)藥學(xué)院
9/2002-7/2006 Bachelor in Engineering, School of Pharmaceutical Sciences, Shandong University, China
2020.10- Assistant Investigator, NIBS, Beijing
2019.1-2020.10，副研究員（博士后），紐約紀(jì)念斯隆凱特琳癌癥中心
導(dǎo)師：Dr. Maurizio Scaltriti
1/2019-10/2020 Postdoctoral Research Associate, Memorial Sloan Kettering Cancer Center (MSKCC), Maurizio Scaltriti laboratory, New York
2016.1-2019.1，助理研究員（博士后），紐約紀(jì)念斯隆凱特琳癌癥中心
導(dǎo)師：Prof. Jose Baselga & Dr. Maurizio Scaltriti
1/2016-1/2019 Postdoctoral Research Fellow, Memorial Sloan Kettering Cancer Center (MSKCC), Jose Baselga and Maurizio Scaltriti Laboratory
過去幾十年尤其是在靶向治療和免疫治療不斷取得突破, 患者的生存期也得到顯著的提升。但是，幾乎所有的癌癥病人都會(huì)出現(xiàn)耐藥，并且由于耐藥機(jī)制不明，大部分病人沒有合適的藥物替代方案。因此，探索腫瘤耐藥機(jī)制不僅可以使我們發(fā)現(xiàn)新的生物學(xué)現(xiàn)象并闡明其分子機(jī)制，由此而針對(duì)性設(shè)計(jì)的逆轉(zhuǎn)耐藥的方案對(duì)可能擴(kuò)大腫瘤藥物在臨床上的適用范圍也有較強(qiáng)的臨床意義。
為達(dá)到研究目的，我們首先通過兩種互補(bǔ)的研究路徑來篩選出腫瘤耐藥相關(guān)分子：1）一種是利用實(shí)驗(yàn)室在功能基因組學(xué)篩選（例如體內(nèi)體外CRISPR/Cas9 sgRNA篩選）方面的專長(zhǎng)，發(fā)現(xiàn)與耐藥相關(guān)的分子；2）第二種路徑是從收集臨床樣本（例如成對(duì)的治療前藥物敏感樣本和治療后耐藥樣本），然后通過高通量的方法學(xué)，包括蛋白質(zhì)組學(xué)和下一代測(cè)序，推測(cè)出可能的耐藥相關(guān)機(jī)制。然后，我們會(huì)建立和優(yōu)化各種腫瘤模型包括腫瘤細(xì)胞系，類器官和病人腫瘤樣本和異體移植、以及可精確模擬人自然病程的自發(fā)小鼠腫瘤等模型，結(jié)合細(xì)胞生物學(xué)，分子生物學(xué)，生物信息學(xué)等相關(guān)技術(shù)， 來驗(yàn)證我們的生物學(xué)發(fā)現(xiàn)并闡明其分子機(jī)制。最后，根據(jù)其分子機(jī)制合理設(shè)計(jì)逆轉(zhuǎn)耐藥方案，并最終發(fā)掘臨床轉(zhuǎn)化的潛能。
我們實(shí)驗(yàn)室長(zhǎng)期招聘免疫學(xué)，分子生物學(xué)，生物信息方向的博士后、研究助理，每年也通過北生所統(tǒng)一招生招收博士生，歡迎有興趣的科學(xué)家加入到我們的隊(duì)伍！詳情見實(shí)驗(yàn)室網(wǎng)站: Xulab.com.cn。
My diverse research experience has reinforced my strong commitment to pursue the identification of mechanisms of cancer drug resistance and novel drug targets. I aim to develop highly effective therapeutic strategies to treat cancer. More specifically, targeting both cancer and immune cells is a novel and promising method with great potential to simultaneously eliminate the patient’s tumor and harness their immune system to more effectively combat cancer. In our lab, we aim to understand how best to personalize and optimize current cancer immunotherapy and targeted therapy efforts.
There has been rapid progress in the fields of cancer immunotherapy and targeted therapy in the past few decades: how we treat cancer has undergone a complete revolution, leading to greater success in cancer survival and enhanced quality-of-life for patients. However, there is still much to be learned beyond what we already know about cancer treatment. The number of long-term survivors still remains limited, and many cancer patients do not respond to treatment, develop resistance, or relapse after initial responsiveness. Mechanisms of cancer drug resistance are still largely unknown, mostly due to tumor inter-/intra- heterogeneity and/or the tumor micro-/macro- environment. Therefore, our research holds not only scientific significance in terms of its contributions to the development of novel biology discoveries, but also clinical significance through exploration of areas such as clinical validation, drug target discovery and novel drug combinations.
We first plan to identify players associated with drug response by employing two complementary approaches: 1) via functional genomic approaches (e.g. in vitro/In vivo CRISPR/cas9 sgRNA screens) with pre-clinical models; and 2) via high-throughput approaches (e.g. Proteomics) with clinical models (e.g. paired drug-na?ve tumors and drug-resistant samples). Next, we will dissect the putative mechanisms of drug resistance from multiple directions, including but not limited to modeling (e.g. cell lines, organoids, PDXs and/or spontaneous mouse tumor models) and molecular validation. Uncovering this novel biology will be essential for us to ultimately identify druggable pathways and biomarkers that may improve clinical decision-making for patients. LINK: Xulab.com.cn
Publications
(1)?? Ninghui Mao, Zeda Zhang, Young Sun Lee, Danielle Choi, Aura Agudelo Rivera, Dan Li, Cindy Lee, Samuel Haywood, Xiaoping Chen, Qing Chang, Guotai Xu, Hsuan-An Chen, Elisa de Stanchina, Charles Sawyers, Neal Rosen, Andrew C Hsieh, Yu Chen, Brett S Carver. Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers. Nature Communications, 2021 Aug 20;12(1):5053.
(2)?? Jorge Gómez Tejeda Za?udo#*, Pingping Mao*, Clara Alcon, Kailey Kowalski, Gabriela N Johnson, Guotai Xu, Jose Baselga, Maurizio Scaltriti, Anthony Letai, Joan Montero*, Réka Albert*, Nikhil Wagle*. Line-Specific Network Models of ER + Breast Cancer Identify Potential PI3Kα Inhibitor Resistance Mechanisms and Drug Combinations. Cancer Research, 2021 Sep 1;81(17):4603-4617.
(3)?? Yanyan Cai#*, Guotai Xu#, Fan Wu, Flavia Michelini, Carmen Chan, Xuan Qu, Pier Selenica,?Erik Ladewig, Pau Castel, Yuanming Cheng, Alison Zhao, Komal Jhaveri, Eneda Toska,?Marta Jimenez, Alexandra Jacquet, Alicia Tran-Dien, Fabrice Andre, Sarat Chandarlapaty,?Jorge S. Reis-Filho, Pedram Razavi, and Maurizio Scaltriti*.?Genomic Alterations in PIK3CA-Mutated Breast Cancer?Result in mTORC1 Activation and Limit the Sensitivity to?PI3Ka?Inhibitors. Cancer Research, 2021 May 1;81(9):2470-2480.
(4)?? Wei Xie, Shengliu Wang, Juncheng Wang, M Jason de la Cruz, Guotai Xu, Maurizio Scaltriti, Dinshaw J Patel. Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex. Proc Natl Acad Sci U S A, 2021 Feb 23;118(8): e2024512118.
(5) Guotai Xu#, Sagar Chhangawala#, Emiliano Cocco, Pedram Razavi, Yanyan Cai, Jordan Otto, Lorenzo Ferrando, Pier Selenica, Carmen Chan, Erik Ladewig, Arnaud Da Cruz Paula, Matthew Witkin, Yuanming Cheng, Jane Park, Cristian Serna-Tamayo, Huiyong Zhao, Fan Wu, Mirna Sallaku, Xuan Qu, Alison Zhao, Clayton Collings, Andrew R D’Avino, Komal Jhavery, Richard Koche, Ross L Levine, Jorge S. Reis-Filho, Cigall Kadoch, Maurizio Scaltriti, Christina S Leslie*, José Baselga*, Eneda Toska*. ARID1A Determines Luminal Identity and Therapeutic Response in Estrogen-Receptor-Positive Breast Cancer. Nature Genetics, 2020 Feb;52(2):198-207.
(6)?? Neil Vasan, Pedram Razavi#, Jared L. Johnson#, Hong Shao#, Hardik Shah, Alesia Antoine, Erik Ladewig, Alexander Gorelick, Ting-Yu Lin, Eneda Toska, Guotai Xu, Abiha Kazmi, Matthew T. Chang, Barry S. Taylor, Maura N. Dickler, Komal Jhaveri, Sarat Chandarlapaty, Raul Rabadan, Ed Reznik, Melissa L. Smith, Robert Sebra, Frauke Schimmoller, Timothy R. Wilson, Lori S. Friedman, Lewis C. Cantley, Maurizio Scaltriti*, and José Baselga*. Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors. Science, 2019 Nov 8;366(6466):714-723.
(7)?? Eneda Toska#*, Pau Castel#, Sagar Chhangawala, Amaia Arruabarrena-Aristorena, Carmen Chan, Vasilis C. Hristidis, Emiliano Cocco, Mirna Sallaku, Guotai Xu, Jane Park, Gerard Minuesa, Sophie G. Shifman, Nicholas D. Socci, Richard Koche, Christina S. Leslie, Maurizio Scaltriti, Jose Baselga*. PI3K Inhibition Activates SGK1 via a Feedback Loop to Promote Chromatin-Based Regulation of ER-Dependent Gene Expression. Cell Reports, 2019 Apr 2;27(1):294-306.
(8)?? Pedram Razavi#, Matthew T. Chang#, Guotai Xu, Chaitanya Bandlamudi, Dara S. Ross, Neil Vasan, Yanyan Cai, Craig M. Bielski, Mark T.A. Donoghue, Philip Jonsson, Alexander Penson, Ronglai Shen, Fresia Pareja, Ritika Kundra, Sumit Middha, Michael L. Cheng, Ahmet Zehir, Cyriac Kandoth, Ruchi Patel, Kety Huberman, Lillian M. Smyth, Komal Jhaveri, Shanu Modi, Tiffany A. Traina, Chau Dang, Wen Zhang, Britta Weigelt, Bob T. Li, Marc Ladanyi, David M. Hyman, Nikolaus Schultz, Mark E. Robson, Clifford Hudis, Edi Brogi, Agnes Viale, Larry Norton, Maura N. Dickler, Michael F. Berger, Christine A. Iacobuzio-Donahue, Sarat Chandarlapaty, Maurizio Scaltriti, Jorge S. Reis-Filho, David B. Solit*, Barry S. Taylor*,? Jose Baselga* . The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers. Cancer Cell, 2018 Sep 10;34(3):427-438.
(9)?? Jan Tkac#, Guotai Xu#, Hemanta Adhikary, Jordan T.F. Young, David Gallo, Cristina Escribano-Diaz, Jana Krietsch, Alexandre Orthwein, Meagan Munro, Wendy Sol, Abdallah Al-Hakim, Zhen-Yuan Lin, Jos Jonkers, Piet Borst, Grant W. Brown, Anne-Claude Gingras, Sven Rottenberg, Jean-Yves Masson, Daniel Durocher*. HELB Is a Feedback Inhibitor of DNA End Resection. Molecular Cell, 2016 Feb 4; 61(3):405-18.
(10)Rosa Planells-Cases, Darius Lutter, Charlotte Guyader, Nora M. Gerhards, Florian Ullrich, Deborah A. Elger, Asli Kucukosmanoglu, Guotai Xu, Felizia K. Voss, S. Momsen Reincke, Tobias Stauber, Vincent A. Blomen, Daniel J. Vis, Lodewyk F. Wessels, Thijn R. Brummelkamp, Piet Borst, Sven Rottenberg* and Thomas J. Jentsch*. Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs. EMBO Journal, 2015 Dec 14; 34(24): 2993-3008.
(11)Guotai Xu, J. Ross Chapman#, Inger Brandsma#, Jingsong Yuan, Martin Mistrik, Peter Bouwman, Jirina Bartkova, Ewa Gogola, Dani?l Warmerdam, Marco Barazas, Janneke E. Jaspers, Kenji Watanabe, Mark Pieterse, Ariena Kersbergen, Wendy Sol, Patrick H. N. Celie, Philip C. Schouten, Bram van den Broek, Ahmed Salman, Marja Nieuwland, Iris de Rink, Jorma de Ronde, Kees Jalink, Simon J. Boulton, Junjie Chen, Dik C. van Gent, Jiri Bartek, Jos Jonkers, Piet Borst, Sven Rottenberg*. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature, 2015 May 28; 521(7553): 541-4.
(12)Thomas Kuilman,?Arno Velds,?Kristel Kemper,?Marco Ranzani,?Lorenzo Bombardelli,?Marlous Hoogstraat,?Ekaterina Nevedomskaya, Guotai Xu, Julian de Ruiter,?Martijn P Lolkema,?Bauke Ylstra,?Jos Jonkers,?Sven Rottenberg,?Lodewyk F Wessels,?David J Adams,?Daniel S Peeper*, Oscar Krijgsman. CopywriteR: DNA copy number detection from off-target sequence data. Genome Biology, 2015 Feb 27; 16:49.
(13)Janneke E. Jaspers, Wendy Sol, Ariena Kersbergen, Andreas Schlicker, Charlotte Guyader, Guotai Xu, Lodewyk Wessels, Piet Borst, Jos Jonkers, Sven Rottenberg*. BRCA2-deficient sarcomatoid mammary tumors exhibit multidrug resistance. Cancer Research, 2015 Feb 15; 75(4): 732-41.
(14)Marc Warmoes#, Janneke E. Jaspers#, Guotai Xu, Bharath K. Sampadi, Thang V. Pham, Jaco C. Knol, Sander R. Piersma, Epie Boven, Jos Jonkers, Sven Rottenberg*, Connie R. Jimenez*. Proteomics of genetically engineered mouse mammary tumors identifies fatty acid metabolism members as potential predictive markers for cisplatin resistance. Mol Cell Proteomics, 2013 May; 12(5): 1319-34.
Book Chapter
(1) Guotai Xu, Jos Jonkers, Sven Rottenberg. PARP inhibitor resistance - what is beyond BRCA1 or BRCA2 restoration? Book Chapter. PARP Inhibitors for Cancer Therapy. In: Nicola Curtin & Ricky Sharma, eds. Cancer Drug Discovery and Development Series: Springer, 2015: 453-471.
