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Directory > Faculty
Hua Xiao, MD., Ph.D.
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Associate Professor, Department of
Physiology
Genetics Program
Cell and Molecular Biology Program
MD., SMMU, China; Ph.D, in Molecular & Medical Genetics,
University of Toronto |
3193 BPS
Phone: 517-355-6475 Ext. 1146
E-mail: xiaoh@msu.edu
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.
SELECTIVE PUBLICATIONS:
| 1. |
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
In press. |
| 2. |
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. |
| 3. |
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. |
| 4. |
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. |
| 5. |
Jiang C., Ito M., Piening V., Bruck K., Roeder R.G. and
Xiao H. (2004) TIP30 interacts with an ER Alpha-interacting
coactivator, CIA and regulates c-myc transcription. J. Biol.
Chem. 279 (26), 27781-27789. |
| 6. |
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. |
| 7. |
Diehl J. A, Rimerman R. A., Xiao H., and Emili A. (2003)
Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent
protein kinase. Mol Cell Biol. 23(5):1764-74. |
| 8. |
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. |
| 9. |
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. |
| 10. |
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. |
| 11. |
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. |
| 12. |
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 |
| 13. |
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. |
| 14. |
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. |
| 15. |
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. |
| 16. |
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. |
| 17. |
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. |
| 18. |
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. |
| 19. |
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. |
| 20. |
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. |
| 21. |
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. |
| 22. |
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. |
| 23. |
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. |
| 24. |
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. |
Other Publications
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