Xi Chen, Ph.D.

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Xi Chen, Ph.D.

Cullen Duncan McAshan Endowed Chair in Cancer Research

Email

xi.chen@bcm.edu

Positions

Cullen Duncan McAshan Endowed Chair in Cancer Research: Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas United States

Associate Professor and CPRIT Scholar in Cancer Research: Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas United States

Member: 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 how cancer and its immune microenvironment sense and respond to stresses and therapeutic insults to evade immune surveillance and develop drug resistance. We specialize in ER stress, Unfolded Protein Response (UPR), immunology, cancer biology, biochemistry, transgenic and preclinical animal models. Our research aims to elucidate the significance and mechanisms of stress responses in therapy resistance and anti-tumor immunity, and develop mechanism-based novel therapies to overcome therapy resistance and transform cancer to a manageable chronic disease (Nat Rev Cancer, 2021). Our 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. Our efforts in understanding proteostasis regulation revealed the direct cross-talk between oncogenic signaling and the protein quality control machinery and uncovered the mechanisms that account for the proteostasis rewiring in response to KRAS inhibition, allowing the drug-resistant cells to escape oncogenic KRAS addiction and gain resistance (Science, 2023). 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

Lv X, Lu X, Cao J, Luo Q, Ding Y, Peng F, Pataer A, Lu D, ....Chen Y, Yao W, Chang EC, Catic A, Lin X, Miles G, Huang P, Sun Z, Burt B, Wang H, Wang J, Yao QC, Zhang B, Roth JA, O'Malley BW, Ellis MJ, Rimawi MF, Ying H, Chen X. "Modulation of the proteostasis network promotes tumor resistance to oncogenic KRAS inhibitors." Science. 2023 Sep 8;381(6662) Pubmed PMID: 37676964
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 Oct 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 Nov 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 Jul 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 Oct;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 Mar;38(4):431-40. Pubmed PMID: 16518401