2024-08-27T15:35:02+08:002019-12-03|
Contact Information
Research Team
Name Position Office Phone Email
Nancy ZHENGResearch AssistantE12-3040nancyzheng@um.edu.mo
Jie KEPhD StudentE12-3043
Shuai LIUPhD StudentE12-3043
Wenqi ZHANGPhD StudentE12-3043
Shiwen WANGPhD StudentE12-3043
Qiaoyuan LIUPhD StudentE12-3043
Zijian SUNPhD Student
Xi YANGPhD Student
Education
PhD

(2004 – 2009)

University of Arizona, Tucson, Arizona, United States

PhD in Pharmacology and Toxicology

BSc

(1996 – 2000)

Sun Yat-Sen (Zhongshan) University, Guangzhou, China

BS in Microbiology

Positions
2020 – Present Associate Professor, Faculty of Health Sciences, University of Macau, Macao
2014 – 2020 Assistant Professor, Faculty of Health Sciences, University of Macau, Macao
2009 – 2014 Postdoctoral Research Fellow, UCSD Stem Cell Program, University of California San Diego, La Jolla, California, USA
Research Interests
Increasing evidence suggests that epigenetic regulation of chromatin states strongly influences gene expression and cell fate choices, and its deregulation could therefore be a critical aspect to development and disease. My research focuses on understanding how chromatin-modifying enzymes control cell fate decisions during pancreas development, and elucidating the epigenetic and transcriptional mechanisms that underlie pancreatic lesion. We utilized both mouse genetic approaches and a parallel hESC-based in vitro differentiation system which recapitulates the sequence of events observed during in vivo pancreas development, where pluripotent cells first commit to endoderm, then primitive gut tube, posterior foregut, and subsequently pancreas. Using this differentiation platform, we have begun to dissect the epigenetic events that drive pancreatic development. Additional ongoing research in my laboratory includes:

  1. Using high-throughput sequencing and genome-editing technologies to study the DNA and histone modifications in pancreatic cancer, elucidating the role of chromatin modification enzymes in mouse models, and exploring novel anti-cancer or preventive strategies by targeting key epigenetic pathways.
  2. In vitro differentiation of patient-specific iPS/hES cells as models of pancreatic diseases, such as diabetes mellitus
Representative Publications
  1.  Li J#, Wu X#, Ke J#, Lee M, Lan Q, Li J, Yu J, Huang Y, Sun D-Q*, Xie R*. TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation. Nat. Comm. 2022
  2. Zhao X#, Wang Y#, He J#, Huang X, Xie R*, Yu J*. LncRNA UCA1 maintains the low-tumorigenic and non-metastatic status by stabilizing E-cadherin in primary prostate cancer cells. Mol Carcinog. 2020, 59(10):1174-1187. (*co-corresponding author)
  3. Ye J#, Huang A#, Wang H, Zhang AMY, Huang X, Lan Q, Sato T, Goyama S, Kurokawa M, Deng C, Sander M, Schaeffer DF, Li W*, Kopp JL*, Xie R*. PRDM3 attenuates pancreatitis and pancreatic tumorigenesis by regulating inflammatory response. Cell Death & Disease. 2020, 11:187.
  4. Zhang T, Guan X, Choi U.L., Dong Q, Lam M.T., Zeng J, Xiong J, Wang X, Poon C.W., Zhang H, Zhang X, Wang H, Xie R, Zhu B, and Li G*. Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation. Epigenetics & Chromatin. 2019, 12:32.
  5. Zhang H, Wang Y, Dou J, Guo Y, He J, Li L, Liu X, Chen R, Deng R, Huang J, Xie R, Zhao X*, Yu J*. Acetylation of AGO2 promotes cancer progression by increasing oncogenic miR-19b biogenesis. Oncogene. 2019, 38(9):1410-1431.
  6. Wu X, Li G, Xie R*. Decoding the role of TET family dioxygenases in lineage specification. Epigenetics & Chromatin. 2018, 11(1):58.
  7. Li J#, Wu X#, Zhou Y#, Lee M, Guo L, Han W, Mo W, Cao WM, Sun D*, Xie R*, Huang Y*. Decoding the dynamic DNA methylation and hydroxymethylation landscapes in endodermal lineage intermediates during pancreatic differentiation of hESC. Nucleic Acids Res. 2018, 46(6):2883-2900. (*co-corresponding author)
  8. Ye J#, Yuen SM#, Murphy G, Xie R*, Kwok HF*. Anti-tumor effects of a ‘human & mouse cross-reactive’ anti-ADAM17 antibody in a pancreatic cancer model in vivo. Eur J Pharm Sci. 2017, 110:62-69. (*co-corresponding author)
  9. Niu Y, Li Q, Xie R, Liu S, Wang R, Xing P, Shi Y, Wang Y, Dong L*, Wang C*. Modulating the phenotype of host macrophages to enhance osteogenesis in MSC-laden hydrogels: Design of a glucomannan coating material. Biomaterials. 2017, 139:39-55.
  10. Shih HP#, Seymour PA#, Patel NA, Xie R, Wang A, Liu PP, Yeo GW, Magnuson MA, Sander M*. A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs Lineage Allocation of Foregut Progenitor Cells. Cell reports. 2015, 13(2):326-36.
  11. Wang A#, Yue F#, Li Y#Xie R, Harper T, Patel NA, Muth K, Palmer J, Qiu Y, Wang J, Lam DK, Raum JC, Stoffers DA, Ren B*, Sander M*. Epigenetic priming of enhancers predicts developmental competence of hESC-Derived endodermal lineage intermediates. Cell Stem Cell. 2015, 16(4):386-99
  12. Xie R, Carrano A, Sander M*. A systems view of epigenetic networks regulating pancreas development and β-cell function. Wiley Interdiscip Rev Syst Biol Med. 2015, 7(1):1-11
  13. Zhang F#, Xie R#, Lau SS, Monks TJ*. PARP-1 hyperactivation and reciprocal elevations in intracellular Ca2+ during ROS-induced non-apoptotic cell death. Toxicol. Sci. 2014, 140(1):118-34. (#co-first author)
  14. Xie R, Everett LJ, Lim HW, Patel NA, Schug J, Kroon E, Kelly OG, Wang A, D’Amour KA, Robins AJ, Won KJ, Kaestner KH, Sander M*. Dynamic chromatin remodeling mediated by Polycomb proteins orchestrates pancreatic differentiation of human embryonic stem cells. Cell Stem Cell. 2013, 12(2):224-37.
  15. van der Meulen, Xie R, Kelly OG, Vale WW, Sander M, Huising MO*. Urocortin 3 marks mature human primary and embryonic stem cell-derived pancreatic alpha and beta cells. PLOS One. 2012, 7(12): e52181.
  16. Morán I, Akerman I, van de Bunt M, Xie R, Benazra M, Nammo T, Arnes L, Nakić N, García-Hurtado J, Rodríguez-Seguí S, Pasquali L, Sauty-Colace C, Beucher A, Scharfmann R, van Arensbergen J, Johnson PR, Berry A, Lee C, Harkins T, Gmyr V, Pattou F, Kerr-Conte J, Piemonti L, Berney T, Hanley N, Gloyn AL, Sussel L, Langman L, Brayman KL, Sander M, McCarthy MI, Ravassard P, Ferrer J*. Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metab. 2012, 16(4):435-48.
  17. Seymour PA, Shih HP, Patel NA, Freude KK, Xie R, Lim CJ, Sander M*. A Sox9/Fgf feed-forward loop maintains pancreatic organ identity. Development. 2012, 139(18):3363-72.
  18. Monks TJ*, Xie R, Tikoo K, Lau SS. ROS-induced histone modifications and their role in cell survival and cell death. Drug Metab Rev. 2006, 38(4):755-67
  19. Xie R, Zhuang M, Ross LS, Gomez I, Oltean DI, Bravo A, Soberon M, Gill SS*. Single amino acid mutations in the cadherin receptor from Heliothis virescens affect its toxin binding ability to Cry1A toxins. J Biol Chem. 2005, 280(9):8416-25.
  20. Yu J, Xie R, Tan L, Xu W, Zeng S, Chen J, Tang M, Pang Y*. Expression of the full-length and 3′-spliced cry1Ab gene in the 135-kDa crystal protein minus derivative of Bacillus thuringiensis subsp. kyushuensis. Curr Microbiol. 2002, 45(2):133-8.
  21. Yu J, Xu W, Zeng S, Zhang X, Liu J, Xie R, Pang Y*. Cloning and expression of cyt2Ba7 gene from a soil-isolated Bacillus thuringiensis. Curr Microbiol. 2002, 45(5):309-14.
Research Grants
2020 – 2023 The Science and Technology Development Fund, Macao S.A.R (FDCT 0022/2019/AMJ, $1,875,000, PI). Functions of post-translational modifications of key epigenetic and transcriptional regulatory factors in malignant tumor development.
2020 – 2021 University of Macau Multi-Year Research Grant (MYRG2019-00126-FHS, $126,000, PI). Anti-tumour effects of an ADAM17 inhibitory antibody on pancreatitis-induced pancreatic ductal adenocarcinoma.
2019 – 2022 The Science and Technology Development Fund, Macao S.A.R (FDCT 0033/2019/A1, $2,248,000, PI). The anti-inflammatory mechanisms of Prdm3 in pancreatitis and pancreatic ductal adenocarcinoma.
2019 – 2020 The Science and Technology Development Fund, Macao S.A.R (FDCT 0025/2019/PS, $126,724, PI). The development of a sustainable cyanobacteria system for endocrine disrupting compounds degradation.
2018 – 2021 The Science and Technology Development Fund, Macao S.A.R (FDCT 170/2017/A3, $1,385,000, PI). The roles of PRDM16 in pancreatic ductal adenocarcinoma.
2018 – 2020 National Natural Science Foundation of China (NSFC 31701276, $240,000, PI). Dissecting the roles of TET hydroxylates in enhancer priming during endoderm lineage specification.
2017 – 2019 University of Macau Multi-Year Research Grant (MYRG2016-00065-FHS, $1,500,000, PI). Developing multicellular pancreatic endoderm clusters for cell replacement therapies in diabetes.
2014 – 2017 University of Macau Start-up Research Grant (SRG2014-00030-FHS, $150,000, PI). The role of PRDMs in epigenetic regulation of pancreas development.
Awards
2012 Scholarship Award, Beta Cell Biology Consortium Investigator Retreat
2011 Scholarship Award, Beta Cell Biology Consortium Investigator Retreat
2008 Conference Grant, PARP 17th International Symposium on Poly(ADP-reibosyl)ation
2008 Finalist and honorable mention for Carl C. Smith Mechanisms Specialty Section manuscript award, Society of Toxicology Annual Meeting
2007 Drug Discovery Specialty Section Travel Award, Society of Toxicology Annual Meeting
2006 Graduate Student Travel Award, American Society for Pharmacology and Experimental Therapeutics
Professional Activities
2014 – Present American Association for Cancer Research
2013 – Present International Society for Stem Cell Research
2020 – Present Macau Society for Stem Cell Research