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News
Research
The XU Lab’s research focus is centered on the identification of mechanisms of cancer drug resistance and novel drug targets.

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, 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. In our lab, we aim to understand how best to personalize and maximize current cancer immunotherapy and targeted therapy efforts.

To this end, 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-naïve 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.

Our research holds not only biological significance by providing new insights into the fundamental biology discoveries, but also clinical significance to benefit cancer patients through exploration of areas such as clinical validation, drug target discovery and novel drug combinations.
People
描述
Education:
Scientific Interests:
B.Sc. Northeast Normal University;
Ph.D. Institute of Biophysics, Chinese Academy of Sciences 
Mechanisms of drug resistance in cancer
Outside Interests:
Reading and food
Lab Manager
Talin Suo, Ph.D.
Guotai Xu, Ph.D.
Principal Investigator
描述
Email: xuguotai  AT nibs.ac.cn
Education:
Scientific Interests:
Outside Interests:
B.Sc. Institute of Immunopharmacology and Immunotherapy, Shandong University;
Master in Medicine, Institute of Immunopharmacology and Immunotherapy, Shandong University;
Ph.D.  the Netherlands Cancer Institute (NKI) and Faculty of Medicine at VU University Amsterdam;
Mechanisms of Drug Resistance in Cancer & Discovery of Novel Drug Targets, DNA Damage Repair in Cancer, Cancer Epigenetics.
Basketball and food
描述
Lingling Wang
Experimenter
Outside Interests:
Reading, baking and cooking
描述
Education:
Scientific Interests:
B.Sc. Zhejiang University;
Novel therapy strategies for cancer; Novel technologies to dissect DNA Damage 
Outside Interests:
Workout
Aodi Ma
Ph.D. student
描述
Yue Qin
Ph.D. student
Education:
Scientific Interests:
B.Sc. Wuhan University
Interested in oncogenic signaling network and ready to find the Achilles' Heel of cancer. 
Outside Interests:
I love running and am a really digital fan
Stargazing, walking and movies
描述
Education:
Scientific Interests:
B.Sc. Hebei Normal University;
Ph.D. Computer Network Information Center, Chinese Academy of Sciences 
Cancer Genomics and Informatics; Bioinformatics algorithm and integrative mining from NGS data to uncover mechanisms of cancer drug resistance
Outside Interests:
Badminton, running and music
Post-doctoral Fellow
Xiaoyu He, Ph.D.
描述
Siming Chen
Ph.D. student
Education:
Scientific Interests:
B.Sc. Huazhong Agricultural University
Discovery of predictive biomarkers for PARP inhibitor sensitivity in BRCA-mutated and BRCA-non-mutated cancers
Outside Interests:
Silencing, swimming, music (Britpop) and my cat
描述
Jia'nan Jing
Education:
Scientific Interests:
B.S.Shanxi Agricultural University
M.S.China Agricultural University
Mechanisms of drug resistance in cancer
Outside Interests:
food and travelling
Ph.D. Student
Ph.D. Student
      Current members
描述
Feifei Ji
Education:
Scientific Interests:
M.S. Weifang Medical University
Exploration of the mechanism of drug sensitivity and resistance in gynecological tumors
Outside Interests:
Table Tennis, Chinese chess
Student
Visting Master Student
描述
Wang Li
Education:
Scientific Interests:
B.Sc. Southern University of Science and Technology
Mechanisms of drug resistance in cancer
Outside Interests:
Basketball, badminton
Ph.D. Student
Ph.D. Student
描述
Shiqi Li
Education:
Scientific Interests:
B.Sc. China Pharmaceutical University 
M.Sc. University College London 
Mechanisms of drug resistance in cancer; Bioinformatics; Cancer epigenetic
Outside Interests:
Motorcycles, modeling
research assistant
Research Assistant
描述
Haoran Wang
Education:
Scientific Interests:
B.Sc.  Capital Normal University & China Agricultural University
M.Sc.  China Agricultural University
Mechanisms of drug resistance in cancer
Outside Interests:
Volleyball
Ph.D. Student
Ph.D. Student
描述
Chunying Huang
Education:
Scientific Interests:
B.Sc. Southwest University 
M.Sc. Shanxi Normal University
Mechanisms of drug resistance in cancer and cancer therapy   
Outside Interests:
Ping Pong，badminton and food
Ph.D. Student
Ph.D. Student
描述
Wenxin Zhang
Education:
Scientific Interests:
B.Sc. Dalian Ocean University 
M.Sc. Shanghai Tech University
Mechanisms of drug resistance in cancer
Outside Interests:
Dancing, swimming
research assistant
Research Assistant
描述
Mingfeng Zou
Education:
Scientific Interests:
B. Sc. Zhejiang Ocean University
M. Sc. Sun Yat-sen University
Mechanism of drug resistance in cancer Novel drug target discovery Anti-cancer drug development
Outside Interests:
Reading, running and cycling
Ph.D. Student
Ph.D. Student
描述
Ruoqi Pan
Education:
Scientific Interests:
B.Sc. Zhejiang University / University of Edinburgh
Bioinformatics; revealing underlying epigenetic mechanisms of cancer drug resistance by multi-omics analysis
Outside Interests:
Photography, music and food
Ph.D. Student
Ph.D. Student
描述
Peijie Zhang
Education:
Scientific Interests:
B.Sc. Beijing Normal University
Bioinformatics; Multiomics data mining and integration to uncover mechanisms of target- and immuno-therapy resistance in cancer
Outside Interests:
Sci-fi and walking around
Ph.D. Student
Ph.D. Student
描述
Bo Yu
Education:
Scientific Interests:
B.Sc. Zhejiang University
Mechanisms of tumorigenesis and tumor progression; Immunotherapy and other promising therapy that may contribute to the treatment of cancer; Developmental biology
Outside Interests:
Food, comedy and music
Ph.D. Student
Ph.D. Student
描述
Peiwen Ding
Education:
Scientific Interests:
B.Sc. Shangdong University
Endocrine therapy resistance in ER+ breast cancer
Outside Interests:
K-pop, cats and talk show
Ph.D. Student
Ph.D. Student
描述
Xiaofeng Huang
Education:
Scientific Interests:
B.Sc.  Anhui Medical University 
M.Sc. Nanjing Medical University
Mechanisms of drug resistance in cancer
Outside Interests:
Traveling and film
Ph.D. Student
Visiting Phd student(Capital Medical University)
描述
Jiaqi Bai
Education:
Scientific Interests:
B.Sc.  North China University of Science and Technology
M.Sc. Capital Medical University
Mechanisms of drug resistance in head and neck cancer.
Outside Interests:
Running and reading
Ph.D. Student
Visiting Phd student(capital medical university)
描述
Xinyuan Ding
Education:
Scientific Interests:
B.Sc. College of pharmacy, Soochow University 
Master in Medicine, College of pharmacy, Soochow University
Ph.D. Institutes for Translational Medicine, Soochow University
clinical fellow
clinical fellow (Suzhou Municipal Hospital)
Mechanisms of Drug Resistance in Cancer, Clinical Translation of New Drug Targets
Ping Pong, Playing Cards
Outside Interests:
Name
Position
描述
Current Institute or School
Name
Position
描述
Current Institute or School
Name
Position
描述
Current Institute or School
Name
Position
描述
Current Institute or School
Zhirong Zhang
Thoracic Surgeon，Clinical Fellow
描述
Beijing Chaoyang Hospital
     Lab Alumni
Publications
Genomic Alterations in PIK3CA-Mutated Breast Cancer Result in mTORC1 Activation and Limit the Sensitivity to PI3Ka Inhibitors.
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*
Cancer Research, 2021 May 1;81(9):2470-2480.
Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers. 
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. 
Nature Communications, 2021 Aug 20;12(1):5053.
Line-Specific Network Models of ER + Breast Cancer Identify Potential PI3Kα Inhibitor Resistance Mechanisms and Drug Combinations. 
Jorge Gómez Tejeda Zañudo#*, Pingping Mao*, Clara Alcon, Kailey Kowalski, Gabriela N Johnson, Guotai Xu, Jose Baselga, Maurizio Scaltriti, Anthony Letai, Joan Montero*, Réka Albert*, Nikhil Wagle*.
Cancer Research, 2021 Sep 1;81(17):4603-4617.
Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex.
Wei Xie, Shengliu Wang, Juncheng Wang, M Jason de la Cruz, Guotai Xu, Maurizio Scaltriti, Dinshaw J Patel.
Proc Natl Acad Sci U S A, 2021 Feb 23;118(8): e2024512118.
ARID1A Determines Luminal Identity and Therapeutic Response in Estrogen-Receptor-Positive Breast Cancer.
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*.
Nature Genetics, 2020 Feb;52(2):198-207.
PI3K Inhibition Activates SGK1 via a Feedback Loop to Promote Chromatin-Based Regulation of ER-Dependent Gene Expression. 
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*. 
Cell Reports, 2019 Apr 2;27(1):294-306.
The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers.
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* .
Cancer Cell, 2018 Sep 10;34(3):427-438.
HELB Is a Feedback Inhibitor of DNA End Resection. 
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*.
Molecular Cell, 2016 Feb 4; 61(3):405-18.
Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs.
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*. 
EMBO Journal, 2015 Dec 14; 34(24): 2993-3008.
REV7 counteracts DNA double-strand break resection and affects PARP inhibition.
Guotai Xu, J. Ross Chapman#, Inger Brandsma#, Jingsong Yuan, Martin Mistrik, Peter Bouwman, Jirina Bartkova, Ewa Gogola, Daniël 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*. 
Nature, 2015 May 28; 521(7553): 541-4.
CopywriteR: DNA copy number detection from off-target sequence data.
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.
Genome Biology, 2015 Feb 27; 16:49.
BRCA2-deficient sarcomatoid mammary tumors exhibit multidrug resistance. 
Janneke E. Jaspers, Wendy Sol, Ariena Kersbergen, Andreas Schlicker, Charlotte Guyader, Guotai Xu, Lodewyk Wessels, Piet Borst, Jos Jonkers, Sven Rottenberg*. 
Cancer Research, 2015 Feb 15; 75(4): 732-41.
Proteomics of genetically engineered mouse mammary tumors identifies fatty acid metabolism members as potential predictive markers for cisplatin resistance.
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*. 
Mol Cell Proteomics, 2013 May; 12(5): 1319-34.
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.
Book Chapter
Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors.
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*.
Science, 2019 Nov 8;366(6466):714-723.
Enhancing CAR T-cell therapies against solid tumors: Mechanisms and reversion of resistance.
Yue Qin and Guotai Xu
Frontiers in Immunology,  2022 Dec 8;13:1053120.
Lab Fun
Position
02
Postdoctoral Fellow
Successful candidates should have a PhD. A strong background in immunology, DNA damage response and epigenetics, or bioinformatics is preferred.
03
Bioinformatician
We are looking for a bioinformatician to lead analyses on genomics and epigenomics analyses such as (WES, WGS, ChIP-seq, ATAC-seq and RNA-seq) and single cell (RNA-seq and ATAC-seq) analyses in cancer models. The successful candidate will become a fundamental component of this multidisciplinary team with mentorship in both computational and biological processes affecting therapeutic response in cancer.
We are looking for highly motivated and enthusiastic people interested in contributing to precision oncology.
We have openings for the following positions:
01
PhD Student
Our lab welcomes applications for rotations from graduate students from the PTN program (joint program by Peking University, Tsinghua University and NIBS), TIMBR program (Tsinghua Institute of Multidisciplinary Biomedical Research), and other NIBS programs.
04
Visiting PhD Student (full-time)
We may have openings for visiting PhD students from other universities or institutes to join our team. Successful candidates should have the willingness to stay at the lab for at least 2 years to conduct cancer-related research. 
05
Visiting Postdoctoral Fellow (full-time)
Successful candidates should have a PhD. Successful candidates should have the willingness to stay at the lab for at least 2 years to conduct cancer-related research. A strong background in immunology, DNA damage response and epigenetics, or bioinformatics is preferred.
06
Visiting Clinical Fellows (full-time)
Clinicians from any hospitals are welcomed to apply. Successful candidates should have the willingness to stay at the lab for at least 1 year to conduct cancer-related research. Some prior research experience is highly preferred.
Application Requirements for all candidates except PhD students:
CV, cover letter, and the contacts of 2~3 references emailed at xuguotai AT nibs.ac.cn
Contact
Email: 
Address:
xuguotai AT nibs.ac.cn
National Institute of Biological Sciences, No. 7, Science Park Road, Zhongguancun Life Science Park, Beijing
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