Xi Chen, Ph.D.
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Xi Chen, Ph.D.
Cullen Duncan McAshan Endowed Chair in Cancer Research
Positions
- Cullen Duncan McAshan Endowed Chair in Cancer Research
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Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas United States
- Associate Professor & CPRIT Scholar in Cancer Research
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Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas United States
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Education
- Postdoctoral Fellowship at Laurie Glimcher Lab, Weill Cornell Medical College
- 01/2015 - New York, New York United States
- Postdoctoral Fellowship at Laurie Glimcher Lab, Harvard School of Public Health/Harvard Medical School
- 09/2012 - Boston, Massachusetts United States
- PhD from Huck Hui Ng Lab, Genome Institute of Singapore, A*STAR/National University of Singapore
- 02/2009 - Singapore, Singapore
Honors & Awards
- CPRIT Scholar in Cancer Research
- Cancer Prevention Research Institute of Texas (CPRIT) (03/2015 - 02/2019)
- Leukemia & Lymphoma Society Career Development Fellow Award
- Leukemia & Lymphoma Society (07/2009 - 07/2012)
- NIH MERIT Award for Early Stage Investigator
- NCI/NIH (07/2018 - 06/2023)
Professional Interests
- ER protein quality control; Tumor Microenvironment; Cancer Immunology; Therapy resistance; Stem Cell Maintenance; Unfolded Protein Response; Endoplasmic Reticulum-Associated Degradation;
Professional Statement
The Chen laboratory studies the function and mechanism of Endoplasmic Reticulum (ER) protein quality control machinery in cancer progression, metastasis and therapy resistance. We specialize in ER stress, Unfolded Protein Response (UPR), biochemistry, transgenic and preclinical animal models, cancer biology and immunology. Our research aims to understand the molecular mechanism underlying the oncogenic signaling regulated proteostasis and its significance in cancer progression, therapy resistance, and anti-tumor immunity, and developing mechanism-based novel therapies to overcome therapy resistance and transform cancer to a manageable chronic disease (Nat Rev Cancer, 2021). Our recent study published in JCI revealed a critical role of the IRE1a/XBP1 branch of the UPR in mediating chemotherapy resistance and led to the first-in-human clinical trial of IRE1a RNase inhibitor. Another research area of the Chen laboratory focuses on ER Associated Degradation (ERAD). We recently discovered the crosstalk between ERAD complex and UPR in maintaining proteostasis and niche interactions (Nat Cell Biol, 2020, eLife, 2021).Selected Publications
- Xu L, Liu X, Peng F, Zhang W, Zheng L, Ding Y, Gu T, Lv K, Wang J, Ortinau L, Hu T, Shi X, Shi G, Shang G, Sun S, Iwawaki T, Ji Y, Li W, Rosen JM, Zhang XH, Park D, Adoro S, Catic A, Tong W, Qi L, Nakada D, Chen X "Protein quality control through endoplasmic reticulum-associated degradation maintains haematopoietic stem cell identity and niche interactions." Nat Cell Biol. 2020 October 22; 22 (10): 1162-1169. Pubmed PMID: 32958856
- Zhao N, Cao J ,Xu LY, Tang QZ, Dobrolecki L, Lyu XD, Talukdar M, Lu Y, Wang XR, Wang YF, Liu X, Bu W, Sun Z, Ying HQ, Lin X, Feng XH, Hartig S, Li F, Shen HF, Chen YW, Han L, Zeng QP, Patterson J, Putluri N, Sicheri F, Rosen J, Lewis MT, Chen X "Pharmacological targeting of MYC-regulated IRE1/XBP1 pathway suppresses MYC-driven breast cancer." J Clin Invest. 2018 128 (4): 1283-1299. Pubmed PMID: 29480818
- Chen X#, Cubillos-Ruiz JR#. "Endoplasmic reticulum stress signals in the tumour and its microenvironment." Nat Rev Cancer. 2020 November 19; (#: Corresponding Author): Pubmed PMID: 33214692
- Liu X, Yu J, Xu L, Umphred-Wilson K, Peng F, Ding Y, Barton BM, Lv X, Zhao MY, Sun S, Hong Y, Qi L, Adoro S, Chen X "Notch-induced endoplasmic reticulum-associated degradation governs mouse thymocyte β-selection." eLife. 2021 July 9; : Pubmed PMID: 34240701
- Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, Hatziapostolou M, Lim E, Tam W, Ni M, Chen Y, Mai J, Shen H, Hu DZ, Adoro Z, Hu B, Song M, Landis MD, Ferrari M, Brown M, Chang JC, Liu XS, Glimcher LH "XBP1 promotes triple negative breast cancer by controlling the HIF1α pathway." Nature. 2014 508 (7494): 103-7. Pubmed PMID: 24670641
- Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH "Integration of external signaling pathways with the core transcriptional network in embryonic stem cells." Cell. 2008 133 (6): 1106-17. Pubmed PMID: 18555785
- Liu L, Zhao M, Jin X, Ney G, Yang KB, Peng F, Cao J, Iwawaki T, Del Valle J, Chen X, Li Q "Adaptive endoplasmic reticulum stress signalling via IRE1α-XBP1 preserves self-renewal of haematopoietic and pre-leukaemic stem cells." Nat Cell Biol. 2019 21 (3): 328-337. Pubmed PMID: 30778220
- Zheng ZY, Anurag M, Lei JT, Cao J, Singh P, Peng J, Kennedy H, Nguyen NC, Chen Y, Lavere P, Li J, Du XH, Cakar B, Song W, ......Chen X, Banks KC, Lanman RB, Shafaee MN, Zhang XH, Vasaikar S, Zhang B, Hilsenbeck SG, Li W, Foulds CE, Ellis MJ, Chang EC "Neurofibromin Is an Estrogen Receptor-α Transcriptional Co-repressor in Breast Cancer." Cancer Cell. 2020 37 (3): 387-402.. Pubmed PMID: 32142667
- Tam WL, Lu H, Buikhuisen J, Soh BS, Lim E, Reinhardt F, Wu ZJ, Krall JA, Bierie B, Guo W, Chen X, Liu XS, Brown M, Lim B, Weinberg RA "Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells." Cancer Cell. 2013 24 (3): 347-64. Pubmed PMID: 24029232
- Martinon F, Chen X, Lee AH, Glimcher LH "TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages." Nat Immunol. 2010 11 (5): 411-8. Pubmed PMID: 20351694
- Dong H, Adams NM, Xu Y, Cao J, Allan DSJ, Carlyle JR, Chen X, Sun JC, Glimcher LH "The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc." Nat Immunol. 2019 20 (7): 865-878. Pubmed PMID: 31086333
- Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, Glimcher LH "T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt." Nat Immunol. 2011 12 (1): 96-104. Pubmed PMID: 21151104
- Chen X, Fang F, Liou YC, Ng HH "Zfp143 regulates Nanog through modulation of Oct4 binding." Stem Cells. 2008 26 (11): 2759-67. Pubmed PMID: 18687992
- Chen X, Vega VB, Ng HH "Transcriptional regulatory networks in embryonic stem cells." Cold Spring Harb Symp Quant Biol.. 2008 73 : 203-9. Pubmed PMID: 19022762
- Wu Q*, Chen X*, Zhang J, Loh YH, Low TY, Zhang W, Zhang W, Sze SK, Lim B, Ng HH "Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells." J Biol Chem. 2006 281 (34): 24090-4. Pubmed PMID: 16840789
- Zou W, Chen X, Shim JH, Huang Z, Brady N, Hu D, Drapp R, Sigrist K, Glimcher LH, Jones D. "The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono-ubiquitylation of Goosecoid." Nat Cell Biol.. 2011 13 (1): 59-65.
- Chen K, Chen Z, Wu D, Zhang L, Lin X, Su J, Rodriguez B, Xi Y, Xia Z, Chen X, Shi X, Wang Q, Li W. "Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes." Nat Genet. 2015 October ; 47 (10): 1149-57. Pubmed PMID: 26301496
- Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH "The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells." Nat Genet. 2006 March ; 38 (4): 431-40. Pubmed PMID: 16518401
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