NAME: Xiao, Tian

POSITION TITLE: Associate Research Fellow, Shenzhen University School of Medicine

EDUCATION/TRAINING

A.   Personal Statement

My long-standing research interests fall in the function of histone methylation during lung cancer initiation and progression. We discovered that conditional knockout of a regulator of histone methylation, Paxip1, significantly accelerates Kras-driven lung cancer progression. Several cytokines may have important roles in this physiological process but the detailed mechanisms remain to be investigated. This work was supported by a regular grant of the National Natural Science Foundation in China (NSFC), the Outstanding Young Teachers Project in Colleges and Universities of Guangdong Province, and a Shenzhen Science and Technology Innovation Commission G rant.

B.   Positions and Honors

Positions and Employment

11/2012-12/2012     Research Assistant, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China

11/2012-06/2014    Associate Research Fellow, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

06/2014 -present      Assistant Professor, School of Medicine, Shenzhen University. Sh enzhen , China

07/2017 -present       Associate Research Fellow, School of Medicine, Shenzhen University. Shenzhen, China

Organizing International Meetings

Other Experience and Honors

C.   Contributions to Science (*: corresponding/co-corresponding author)

1.    Gene-ViroTherapy of Cancer Targeting Angiogenesis

Angiogenesis is a critical step in the progression of tumors from a small, localized focus to an enlarging tumor with the capability to metastasize. Thus, inhibition of angiogenesis is one of the most promising new anti-cancer strategies. Based on the achievements of gene therapy and virotherapy, we developed a new strategy for cancer therapy named “Targeting Gene-ViroTherapy of Cancer”. By combining the oncolytic effect of recombinant adenovirus and various functions of therapeutic genes, this new strategy exhibits potent antitumor efficiency.

ZD55 is an oncolytic adenovirus vector with a deletion in the E1B 55kDa gene. By inserting the expression cassette of vascular endothelial cell growth inhibitor (VEGI) or plasminogen kringle 5 K71R mutant (mK5) into ZD55, we have constructed two gene-viruses, ZD55-mK5 (BBRC 2008) and ZD55-VEGI-251 (Cell Res 2010). Both ZD55-mK5 and ZD55-VEGI-251 can selectively replicate in tumor cells and secreted mK5 or VEGI can potently inhibit endothelial cell proliferation, tube formation in vitro and angiogenesis of chick chorioallantoic membrane (CAM) in vivo. ZD55-mK5 or ZD55-VEGI-251 treatment can markedly suppress tumor xenograft growth in nude mice. Additionally, increased antiangiogenic activity of mK5 was observed in both in vitro and in vivo assays and ZD55-VEGI-251 can also directly induce tumor cell apoptosis in addition to its antiangiogenic effects. In conclusion, our findings indicate that tumor therapy based on targeting angiogenesis with antiangiogenic factors via an oncolytic adenovirus is efficient and prospective. Both ZD55-mK5 and ZD55-VEGI-251 are promising therapeutic agents for clinical cancer therapy.

1)     Xiao T^#, Fan JK^#, Huang HL, Gu JF, Li LY, Liu XY*. VEGI-armed oncolytic adenovirus inhibits tumor neovascularization and directly induces mitochondrial-mediated cancer cell apoptosis. Cell Res, 20(3): 367-378, 2010.

2)     Fan JK^#, Xiao T^#, Gu JF, Wei N, He LF, Ding M, and Liu XY*. Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor. Biochem Biophys Res Commun, 374(2): 198-203, 2008.

3. Liu XY, Huang WL, Qian QJ, Zou WG, Zi-Lai Zhang ZL, Chu L, Zhang KJ, Zhao LL, Zhang YH, Qiu SB, Zhang ZW, Xiao T, Fan JK, Wei N1, Liu XR, Cao X, Gu JF, Wei RC, Ding M, Wu S. Cancer Targeting Gene–Viro–Therapy and its Promising Future: A Trend in Both Cancer Gene Therapy and Cancer Virotherapy. Recent Advances in Cancer Research and Therapy, 33-83, Elsevier; 2012.

2.    Identification of an essential regulator for cancer glycolysis, miR-143

The “Warburg effect” describes the unique metabolic phenomenon that conversion of glucose into lactic acid is enhanced in cancer cells, even in the presence of oxygen. Cancer cells preferentially utilize this far less efficient glycolytic process for energy production. Whether the deregulation of miRNAs contributes to the Warburg effect remains largely unknown. Since miRNA regulates target genes at both mRNA and protein levels, traditional methods simply using gene expression values to predict gene-miRNA pairs deregulated in cancer may fail to pick up those genes exhibiting protein-level changes.

We developed a new method by assigning a gene with an activity measure dependent on the expression level of its functional associated genes based on a previously constructed gene functional association network (gNET). Then, we integratively analyzed the miRNA and gene expression profiling in lung cancer and identified the gene-miRNA pairs significantly deregulated in cancer glycolysis. We found that HK2, coding for the enzyme that catalyzes the first irreversible step of the glycolytic pathway, is one of the top genes predicted and potentially regulated by multiple miRNAs, including miR-143. Interestingly, miR-143 expression was inversely associated with HK2 protein levels but not mRNA levels in human lung cancer samples. miR-143, down-regulated by mammalian target of rapamycin activation, reduces glucose metabolism and inhibits cancer cell proliferation and tumor formation through targeting HK2. Collectively, we have not only established a novel methodology for gene-miRNA pair prediction but also identified miR-143 as an essential regulator of cancer glycolysis via targeting HK2 (JBC 2012). This work hopefully improves current understanding of the regulatory network of cancer metabolism and provides potential targets for the development of cancer therapeutic strategies. 

1)     Fang R,Xiao T*, Fang Z, Sun Y, Li F, Gao Y, Feng Y, Li L, Wang Y, Liu XL, Chen HQ, Liu XY*, Ji HB*. MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene. J Biol Chem, 287(27): 23227-23235, 2012.

D.   Research Support

Ongoing Research Support

The General Program of National Natural Science Foundation of China (81401849)

Tian Xiao, PI                                                               ¥ 560,000 (direct cost)              01/2018 to 12/2021

Functional and mechanistic study of histone methylation regulator PTIP on initiation and progression of non-small cell lung cancer

Outstanding Young Teachers Project in Colleges and Universities of Guangdong Province (YQ2015144)

Tian Xiao, PI                                                               ¥ 300,000                                  01/2016 to 12/2018

Functional and mechanistic study of PTIP on initiation and progression of non-small cell lung cancer

Guangdong Medical Science and Technology Research Foundation (A2016249)

Tian Xiao, PI                                                               ¥ 5,000                                      07/2016 to 06/2018

Applied research on function of NCAM^highCD44^low/- cell population in metastasis and clinical diagnosis of small cell lung cancer

Shenzhen Science and Technology Innovation Commission G rant (JCYJ20160307155641741),

Tian Xiao, PI                                                               ¥ 300,000                                      10/2016 to 06/2018

Study on function of NCAM^highCD44^low/- cell population in metastasis and clinical diagnosis of small cell lung cancer

Completed Research Support

The Young Scholars Fund of National Natural Science Foundation of China (81401849),

Tian Xiao, PI                                                               ¥ 230,000                               01/2015 to 12/2017

Functional and mechanistic study of phenotypic transition during malignant progression of small cell lung cancer

Research Start-up Project for Young Teachers of Shenzhen University (201406),

Tian Xiao, PI                                                               ¥ 60,000                                 06/2014 to 05/2016

 Functional and mechanistic study of phenotypic transition during malignant progression of small cell lung cancer

China Postdoctoral Science Foundation  (20100480639)

Tian Xiao, PI                                                               ¥ 30,000                                 08/2010 to 08/2012

Study on the function and regulation of NEDD9 in metastasis of human lung cancer

Shanghai Postdoctoral Scientific Program (11R21417100).

Tian Xiao, PI                                                               ¥ 30,000                                 10/2010 to 10/2011

The biological function and molecular mechanism of HEF1 in lung cancer metastasis

Postdoctor Research Program of Shanghai Institutes for Biological Sciences (2010KIP504)

Tian Xiao, PI                                                               ¥ 150,000                                 07/2010 to 07/2012

Functional study and regulation of NEDD9 in metastasis of lung cancer

Outstanding Youth Foundation of Shanghai Institutes for Biological Sciences (2013KIP102).

Tian Xiao, PI                                                               ¥ 210,000                                07/2013 to 06/2015

Phenotypic plasticity of small cell lung carcinoma and its biological function

E.    Peer-reviewed publications (*: corresponding author)

1)     Xiao T, Zhu JJ, Huang S, Peng C, He S, Du J, Hong R, Chen X, Bode AM, Jiang W, Dong Z*, Zheng D*. Phosphorylation of NFAT3 by CDK3 induces cell transformation and promotes tumor growth in skin cancer. Oncogene 2017; 36:2835-2845.

2)     Huang G^#, Li S^#, Yang N, Zou Y, Zheng D*, Xiao T*. Recent progress in circular RNAs in human cancers. Cancer Lett 2017; 404:8-18.

3)     Cao T^#, Xiao T^#, Huang G, Xu Y, Zhu JJ, Wang K, Ye W, Guan H*, He J*, Zheng D*. CDK3, target of miR-4469, suppresses breast cancer metastasis via inhibiting Wnt/beta-catenin pathway. Oncotarget 2017; 8(49):84917-84927.

4)     Han RF^#, Huang GQ^#, Wang YJ, Xu YF, Hu YM, Jiang WQ, Wang TF*, Xiao T*, Zheng D*. Increased gene expression noise in human cancers is correlated with low p53 and immune activities as well as late stage cancer. Oncotarget 2016;7:72011-72020

5)     Fang R,Xiao T*, Fang Z, Sun Y, Li F, Gao Y, Feng Y, Li L, Wang Y, Liu XL, Chen HQ, Liu XY*, Ji HB*. MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene. J Biol Chem, 287(27): 23227-23235, 2012.

6)     Huang HL^#, Xiao T^#, He LF, Ji HB, Liu XY*. Interferon-beta-armed oncolytic adenovirus induces both apoptosis and necroptosis in cancer cells. Acta Biochim Biophys Sin, 44(9): 737-745, 2012.

7)     Xiao T, Bao L*, Ji HB*. Finding biomarkers for non-small cell lung cancer diagnosis and prognosis. Front. Biol. 7(1): 14–23, 2012. (invited review)

8)     Xiao T^#, Fan JK^#, Huang HL, Gu JF, Li LY, Liu XY*. VEGI-armed oncolytic adenovirus inhibits tumor neovascularization and directly induces mitochondrial-mediated cancer cell apoptosis. Cell Res, 20(3): 367-378, 2010.

9)     Fan JK^#, Xiao T^#, Gu JF, Wei N, He LF, Ding M, and Liu XY*. Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor. Biochem Biophys Res Commun, 374(2): 198-203, 2008.