Hua Xiao, M.D., Ph.D.

Hua Xiao, M.D., Ph.D.

1995-2000, Postdoctoral fellow, the Rockefeller University
1990-1995, Ph. D. in Molecular and Medical Genetics, University of Toronto
1978-1983, M.D. The Second Military Medical University, Shanghai, China

Research Interests
Precisely orchestrated gene expression results in proper cell differentiation, morphological development and immune responses to pathogens. Nearly all genes are regulated at the level of transcription. This process is controlled by an array of transcription factors at the end of signal transduction pathways. The fact that many oncogenes, tumor suppressor and viral regulatory genes encode RNA polymerase II transcription factors, highlights that perturbation of their normal regulation can have a devastating impact on gene expression, and hence the development of human diseases such as cancer. The overall objective of Xiao´s laboratory is to study the regulatory mechanisms and signal transduction pathways pertaining to the RNA polymerase II machinery and modulators of transcription such as estrogen receptors and transcription cofactors that are involved in tumorigenesis. Ultimately, our goal is to understand the transcriptional mechanisms underlying normal cell growth and apoptosis, and the dysregulation leading to tumorigenesis. Specifically, our on-going and proposed studies involve the characterization of a newly identified tumor suppressor TIP30, and its associated factor CIA (an estrogen receptor-interacting co-activator) and their role in the oncogenesis of breast and liver cancer.

The recent finding that TIP30 regulates the expression of genes involved in apoptosis and metastatic suppression indicates that there is a signaling pathway facilitated by TIP30 and its associated factors. Therefore, it is essential to identify proteins that are associated with TIP30 in order to unravel the regulatory hierarchies leading to TIP30 mediated apoptosis, as well as identify up-stream and down-stream genes in this signal pathway. The specific research projects are as follows: 1. Mechanism and Regulation of Gene Expression by Transcription Cofactors. 2. The role of a transcription factor, TIP30, in tumorigenesis. 3. Regulation of Estrogen-responsive gene expression and tumor suppression by transcriptional cofactors. 4. Development of therapeutic reagents for the treatment of hepatocellular carcinomas and breast ductal carcinomas.

Selected Publications

Chen F, Li A, Gao S, Hollern D, Williams M, Liu F, VanSickle E, Andrechek E, Zhang C, Yang C, Luo R, and Xiao H. Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression. Cell Death & Disease, 2014, 5:e1242.

Grieb BC, Grambling MW, Arrate, MP, Chen X, Haines DS, Xiao H, Eischen CM. Oncogenic Protein MTBP Interacts with MYC to Promote Tumorigenesis. Cancer Res. 2014, 74:3591-3602.

Wang Z, Humphries B, Xiao H, Jiang Y, Yang C. MicroRNA-200b Suppresses Arsenic-transformed Cell Migration by Targeting Protein Kinase Cα and Wnt5b-Protein Kinase Cα Positive Feedback Loop and Inhibiting Rac1 Activation. J Biol Chem. 2014, pii: jbc.M114.554246. [Epub ahead of print]

Gao S., Li A., Liu F., Chen F., Williams M., Zhang C., Kelley Z., Wu C-L., Luo R., and  Xiao H. (2013), NCOA5 Haploinsufficiency Results in Glucose Intolerance and Subsequent Hepatocellular Carcinoma. Cancer Cell, Volume 24, Issue 6, Pages 725–737.

Wang Z, Humphries B, Xiao H, Jiang Y, Yang C. (2013) Epithelial to mesenchymal transition in arsenic-transformed cells promotes angiogenesis through activating β-catenin-vascular endothelial growth factor pathway. Toxicol Appl Pharmacol. 271(1):20-9. doi: 10.1016/j.taap.2013.04.018. Epub 2013 Apr 30.

Li A, Zhang C, Gao S, Chen F, Yang C, Luo R, Xiao H. (2012) TIP30 loss enhances cytoplasmic and nuclear EGFR signaling and promotes lung adenocarcinogenesis in mice. Oncogene. 2012 Jun 25. [Epub ahead of print]

Zheng F, Zhou X, Xiao H, Wayman G, and Wang H.(2012) Regulation of Brain-derived Neurotrophic Factor Exon IV Transcription Through Calcium Responsive Elements In Cortical Neurons . PLoS One 2011;6(12):e28441. Epub 2011 Dec 9.

Wang Z, Yang J, Fisher T, Xiao H, Jiang Y, Yang C.(2011) Akt Activation is Responsible for Enhanced Migratory and Invasive Behavior of Arsenic-Transformed Human Bronchial Epithelial Cells 2011). Environmental Health Perspectives, 2012 Jan;120(1):92-7. Epub 2011 Sep 27.

Zhou, X, Xiao H, Wang H. (2011) Developmental changes of TrkB signaling in response to exogenous BDNF in primary cortical neurons Journal of Neurochemistry, Dec;119(6):1205-16.

Zhang C, Li A, Gao S, Zhang X, Xiao H. (2011) The TIP30 Protein Complex, Arachidonic Acid and Coenzyme A Are Required for Vesicle Membrane Fusion. PLoS One.;6(6):e21233. Epub 2011 Jun 24.

Zhang, C-L, Mori, M., Gao, S., Li, A-M., Hoshino, I., Aupperlee, M.D., Haslam, S. Z., and Xiao, H., Zhang C, Li A, Zhang X, Xiao H. (2011) A novel TIP30 protein complex regulates EGF receptor signaling and endocytic degradation. J Biol Chem. Mar 18;286(11):9373-81.Jan 20. [Epub ahead of print]

 Zhang C, Mori M, Gao S, Li A, Hoshino I, Aupperlee MD, Haslam SZ, Xiao H. (2010) Tip30 Deletion in MMTV-Neu Mice Leads to Enhanced EGFR Signaling and Development of Estrogen Receptor-Positive and Progesterone Receptor-Negative Mammary Tumors. Cancer Res. Dec. 15, 70:10224-10233

Zhang, H., Zhang, Y., Duan, H.-O., Kirley, S.D., McDougal , W., Xiao, H. and Chin-Lee Wu (2008) TIP30 Associated With Progression and Metastasis of Prostate Cancer. Int. J. Cancer. 123 (4): 810-816.

Pecha, J, Ankrapp, D. Jiang, C., Tang. W., Hoshino, I., Bruck, K., Wagner, K-U., Xiao, H., (2007). Deletion of Tip30 leads to rapid immortalization of murine mammary epithelial cells and ductal hyperplasia in the mammary gland. Oncogene, Nov 22;26(53):7423-31.

Jiang, C., Pecha, J., Hoshino, I., Ankrapp, D., Xiao, H. (2007) TIP30 mutant derived from hepatocelluar carcinoma specimens promotes growth of HepG2 cells through up-regulation of N-cadherien. Cancer Res. 67: 3574-3582. Selected as one of CANCER RESEARCH Highlights.

Alt J.R., Fernandez M. R., Bouska A., Xiao H. and Eischen C.M. (2005) Mdm2 Binds to Nbs1 at Sites of DNA Damage and Regulates Double-Strand Break Repair. J. Biol. Chem. 13; 280: 18771-81

Abbott K., Archambault J., Xiao H., Nguyen B.D., Roeder R.G., Greenblatt J., Omichinski J.G., Legault P. (2005) Interactions of HIV-1 Tat and RAP74 proteins with the RNA Polymerase II CTD phosphatase FCP1. Biochemistry. 44(8):2716-2731.

Ito M., Jiang C., Krumm ,K ., Zhang, X., Pecha, J., Zhao, J., Guo Y. Roeder RG., and Xiao H. (2003) TIP30 deficiency increases susceptibility to tumorigenesis.  Cancer Research, 63: 8763-7.

Jiang C., Ito M., Piening V., Bruck K., Roeder  R.G. and Xiao H. (2004) TIP30 interacts with an ERa-interacting coactivator, CIA  and regulates c-myc transcription. J. Biol. Chem. 279 (26), 27781-27789.

Estable M.C., Naghavi, M.H., Kato H., Xiao H., Qin J., Vahlne A., Roeder RG. (2002) MCEF, the newest member of The AF4 family of transcription factors involved in leukemia, is a P-TEFb-associated protein that can repress HIV-1.  J. Biomed.  Sci.  9, 234-45.

Yang Y., Dong  B., Mittelstadt, P.R., Xiao  H.  Ashwell J.D. (2002) HIV Tat binds Egr proteins and enhances Egr-Dependent transactivation of the Fas ligand promoter.  J. Biol. Chem.  277, 19482-7.

Wu C.L.,  Kirley S. D., Xiao H,  Chuang, D.C., Zukerberg L.R. (2001) Cables enhances cdk2 tyrosine 15 Phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers.  Cancer Res. 61, 7325-32.

Xiao H., Palhan V., Yang Y., and Roeder R.G.  TIP30 has an intrinsic kinase activity for up-regulation a subset of apoptotic genes (2000).  EMBO J.  19, 956-63.

Xiao  H, Tao, Y., Greenbaltt., J. and Roeder, R. G. A cofactor, TIP30 specifically enhances HIV-1 Tat activated Transcription (1998).  Proc. Natl. Acad.  USA.  95, 2146-51.

Xiao, H, Tao Y., and Roeder, R. G. The human homologue of Drosophila TRF-proximal protein is associated with An RNA polymerase II-SRB complex (1999). J. Biol. Chem. 274, 3937-40.

Luo Y., Ge H., Stevens S., Xiao H, and Roeder R. G., Coactivation by OCA-B: definition of critical regions and And synergism with general cofactos (1998). Mol. Cell Biol. 18, 3803-10.

Xiao H, Tao, Y., Greenbaltt., J. and Roeder, R. G. A cofactor, TIP30 specifically enhances HIV-1 Tat activated Transcription (1998). Proc. Natl. Acad. USA. 95, 2146-51.

Gupta R. Emli A, Pan G. Xiao H, Shales M., Geenblatt J., and Ingles C. J. Characterization of the Interaction between the acidic activation domain VP16 and the RNA polymerase II initiation factor TFIIB (1996). Nucleic Acids Res. 24, 2324-30.

Blau J., Xiao H., McCracken S., O'Hare P., Greenblatt J., and Bentley D. Three functional classes of Transcriptional activation domains (1996). Mol Cell Biol. 16, 2044-55.

Xiao H, Pearson A., Coulombe B., Truant R., Regier J., Triezenberg S J., Reinberg, Flores D. O., Ingles C. J, and Greenblatt J., Binding of a general transcription factor TFIIH to the acidic activation domain of VP16 and p53. (1994). Mol Cell Biol. 14, 7013-24.

Xiao H., Lis, J., Xiao H., Greenblatt J., and Friesen J.D., The upstream activator CTF/NF1 and RNA Polymerase II share a common element involved in transcriptional activation. (1994). Nucleic Acids Research 22, 1966-73.

Heng H.H.Q., Xiao H., Shi X-M, Greenblatt J., and Tsui L.P., Genes encoding general initiation factos for RNA Polymerase II transcription are dispersed iun the human genome. (1994). Human Molecular Genetics 3, 61-64.

Truant R., Xiao, H., Ingles C.J., and Greenblatt,J., Direct interaction between the transcriptional activation Domain of human p53 and the TATA box-binding protein. (1993). J. Biol. Chem. 268, 2284-87.

 Coulombe, B., Killen M., Liljelund P., Honda B., Xiao H., Ingles J., and Greenblatt J. Identification of three Mammalian proteins that bind to the yeast TATA box protein TFIID (1992). Gene Expression 2, 99-110.

 Xiao H., Kalman M., Ikehara K., Zemel S., Glazer G., and Cashel M., Residual Guanosine 3', 5'-Bispyrophosphate (ppGpp) Synthetic Activity of reIA Null Mutants Can Be Eliminated by spot Null Mutations. (1991). J. Biol. Chem.166, 5980-90.

Gentry D., Xiao H., Burgess R., and Cashel M., The Omega Subunit of Escherichia coli K-12 RNA Polymerase is Not Required for Stringent RNA Control In Vivo. (1991). J. of Bacteriology 173, 39001-03.

Sarubbi  E., Rudd  K., Xiao  H.,  Ikehara  K., Kalman  M., and Cashel  M. Characterization of the spoT gene of  Escherichia coli.  (1989)  J. Biol. Chem. 264, 15074-8.