Prof Fu’s laboratory is interested in molecular mechanisms of cancer angiogenesis, metastasis and stem cell and iPS cell biology. His team is primarily working on a key regulator STAT3 and epigenetic regulation induced by cytokines. They have developed a number of in vivo and in vitro model systems for these studies. The major hypothesis is that STAT3 mediates essential inflammatory functions that can cause epigenetic changes leading to tumour transformation, angiogenesis and metastasis.
Dr. Xin-Yuan Fu’s laboratory has been working on the STAT SIGNALING PATHWAY since its discovery (See Fu, PNAS 1992). Now Fu lab focuses on STAT mediated epigenetic regulation of stem / cancer cells and other diseases. In the past, we first showed that STATs regulates cell growth and survival (Chin et al., 1996, Science, Su et al., Nature, 1997). Next, we demonstrated that STAT3 is an essential regulator of immunity and inflammation (Welte et al., PNAS, 2003. Kano et al., JEM 2003). For example, STAT3 has a negative role in regulation myeloid cell lineages and mice that are deficient STAT3 in immune cells will develop inflammation and autoimmune disorders. Dr. Fu’s laboratory in the CSI now focuses on the following new directions: 1) Signals and epigenetic regulation of inflammation and cancer development; 2) Biochemical pathways and signals that regulate stem cell functions and gene programming during early developmental stages; 3) Liver development, regeneration and cancer; 4) Development and Applications of stem cells and novel therapies in major human diseases.
- Dang Vinh Do, Jun Ueda, Chanchao Lorthongpanich, Wenjun Zhang , Akira Moh , Yi Zhou, Bo Feng, Guoji Guo, Peiyu J Lin, Md Zakir Hossain, Daniel M. Messerschmidt , Qiang Wu, Paul Robson, Huck Hui Ng, Lorenz Poellinger, Barbara B. Knowles, Davor Solter and Xin-Yuan Fu. A Genetic and Developmental Pathway from STAT3 to the OCT4-NANOG Circuit Essential for Maintenance of ICM Lineages in vivo. Genes & Development, 2013 Jun 15;27(12):1378-90. PMID: 23788624
- Mantel C, Messina-Graham S, Moh A, Cooper S, Hangoc G, Fu XY, Broxmeyer HE. Mouse hematopoietic cell-targeted STAT3 deletion: stem/progenitor cell defects, mitochondrial dysfunction,ROS overproduction, and a rapid aging-like phenotype. Blood. 2012 Sep 27; 120(13):2589-99.
- Wegrzyn J, Potla R, Chwae YJ, Sepuri NB, Zhang Q, Koeck T, Derecka M, Szczepanek K, Szelag M, Gornicka A, Moh A, Moghaddas S, Chen Q, Bobbili S, Cichy J, Dulak J, Baker DP, Wolfman A, Stuehr D, Hassan MO, Fu XY, Avadhani N, Drake JI, Fawcett P, Lesnefsky EJ, Larner AC. Function of mitochondrial Stat3 in cellular respiration. Science. 2009 Feb 6;323(5915):793-7.
- Kim BG, Li C, Qiao W, Mamura W, Kasperczak B, Anver M, Wolfraim L, Hong S, Mushinski E, Kim SG, Fu XY, Deng C, Letterio JJ. SMAD4 signaling in T cells is required for suppression of gastrointestinal cancer. Nature. 2006 Jun 22; 441(7096): 1015-9.
- Welte T, Leitenberg D, Dittel BN, al-Ramadi BK, Xie B, Chin YE, Janeway CA, Bothwell AL, Bottomly K, Fu XY. STAT5 interaction with the T cell receptor complex and stimulation of T cell proliferation. Science. 1999 Jan 8; 283(5399): 222-5.
- Su WCS, Kitagawa M, Xue N, Xie B, Garofalo S, Cho J, Deng C, Horton WA, Fu XY. Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism. Nature. 1997 Mar 20; 386(6622): 288-92.
- Chin EY, Kitagawa M, Su WS, You ZH, Iwamoto Y, Fu XY. Cell Growth Arrest and Induction of Cyclin Dependent Kinase Inhibitor p21WAF1/ CIP1 Mediated by STAT1. Science. 1996 May 3; 272(5262): 719-22.
- Fu XY, Zhang JJ. Transcription factor p91 interacts with the EGF receptor and mediates activation of the c-fos gene promoter. Cell. 1993 Sep 24, 74(6): 1135-1145.
- Fu XY. A transcription factor with SH2 and SH3 domains is directly activated by an interferon-alpha-induced cytoplasmic protein tyrosine kinase(s). Cell. 1992 Jul 24; 70(2): 323-335. (This paper described original discovery of the STAT signaling pathway).
- Fu XY, Schindler C, Improta T, Aebersold R, Darnell JE. The proteins of ISGF3, the IFN-alpha induced transcriptional activator, define a gene family involved in signal transduction. Proc. Natl. Acad. Sci. USA. 1992; 89: 7840-7843 (This paper described original identification and cloning of the STAT Gene Family).
|Affiliations||Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS
Director of International Relation (China), Yong Loo Lin School of Medicine, NUS
|Contact (Lab)||+65 66011760|
|Institute||Degree (if applicable)||Year(s)|
|Rockefeller University||Postdoctoral Training||1991|
|•||Senior Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore||2008 – Present|
|•||Professor, Department of Biochemistry, Yong Loo Lin School of Medicine||2008 – Present|
|•||Director of International Relation (China), Yong Loo Lin School of Medicine, NUS||2008 – Present|
|•||Professor, Microbiol and Immunology, Indiana University School of Medicine||2004 – Present|
|•||Member, Yale Cancer Center, Yale University, New Haven, CT||1996 – 2003|
|•||Associate Professor, Pathology and ImmunoBiology Program, Yale University School of Medicine||1996 – 2003|
|•||Assistant Professor, Pathology, Yale University School of Medicine||1994 – 1996|
|•||Assistant Professor, Mount Sinai School of Medicine, New York||1992 – 1994|
PhD Research Fellow
Study early liver progenitor cells with Foxa2-EGFP knockin mouse model; Study stat3 mediated epigenetic regulation in cancer biology, with focus on a novel methyltransferase family which plays roles in DNA damage pathway.
Study the collaboration of STAT5 and BHLHE40 in mouse T cell differentiation and autoimmune disorders.
Studying embryo/liver development by scRNA-seq technology.