Case Western Reserve University

Hung-Ying Kao, Ph.D.

Associate Professor

Education

• Ph.D.: University of Minnesota, 1996
• Postdoc: The Salk Institute for biological studies, 2001

Research Interests

Our lab is interested in transcriptional regulation in human health and diseases. Currently, we have three ongoing projects:

• 1. Characterizing the biological function of histone deacetylase 7 (HDAC7) and its interacting proteins including alpha actinin 4 (ACTN4).
  HDAC7 is a member of class II HDACs. Precise regulation of the subcellular distribution of class II HDACs plays a pivotal role in cell differentiation and animal development. ACTN4 is an HDAC7 interacting protein and mutations in ACTN4 are associated with focal segmental glomerulosclerosis (FSGS), a kidney disease characterized by proteinuria. We are investigating the function and regulation of HDAC7 and ACTN4 in endothelial cells and podocytes.
• 2. Elucidating the mechanisms underlying tamoxifen-resistant breast cancer.
  The selective estrogen receptor modulator (SERM) tamoxifen is an important agent in the treatment of ER-positive breast cancer. SMRT and N-CoR are two closely-related transcriptional corepressors that mediate transcriptional repression by ER and are required for tamoxifen-mediated anti-proliferative activity. We hypothesize that decreased expression of SMRT or N-CoR contributes to tamoxifen-resistant breast cancer. We are interested in elucidating the mechanisms underlying stability control of the transcriptional corepressor SMRT in breast cancer.
• 3. Investigating the function and regulation of promyelocytic leukemia protein (PML).
  PML is a tumor suppressor protein that control many cellular processes including apoptosis, cell proliferation, senescence, and transcription. PML is subjected to several post-translational modifications such as phosphorylation, sumoylation, acetylation, ubiquitination, and isgylation. We are interested in the following questions:
  • How post-translational modifications regulate PML function?
  • How the post-translational modifications of PML cross-talk with each other?
  • How PML target genes mediate its cellular function?

Selected References

• Khurana S., Chakraborty S., Cheng X., Su Y. T., and Kao H. Y.
  “The Actin-binding Protein, Actinin Alpha 4 (ACTN4), Is a Nuclear Receptor Coactivator that Promotes Proliferation of MCF-7 Breast Cancer Cells”
  J Biol Chem 286 (3): 1850-9 (2011).
• Du Z., Song J., Wang Y., Zhao Y., Guda K., Yang S., Kao H. Y., Xu Y., Willis J., Markowitz S. D., Sedwick D., Ewing R. M., and Wang Z.
  “DNMT1 stability is regulated by proteins coordinating deubiquitination and acetylation-driven ubiquitination”
  Sci Signal 3 (146): ra80 (2010).
• Gao C., Liu Y., Lam M., and Kao H. Y.
  “Histone deacetylase 7 (HDAC7) regulates myocyte migration and differentiation”
  Biochim Biophys Acta 1803 (10): 1186-97 (2010). Read article in PubMedCentral
• Reineke E. L., Liu Y., and Kao H. Y.
  “Promyelocytic leukemia protein controls cell migration in response to hydrogen peroxide and insulin-like growth factor-1”
  J Biol Chem 285 (13): 9485-92 (2010). Read article in PubMedCentral
• Cheng X. and Kao H. Y.
  “G protein pathway suppressor 2 (GPS2) is a transcriptional corepressor important for estrogen receptor alpha-mediated transcriptional regulation”
  J Biol Chem 284 (52): 36395-404 (2009). Read article in PubMedCentral
• Reineke E. L. and Kao H. Y.
  “PML: An emerging tumor suppressor and a target with therapeutic potential”
  Cancer Ther 7 (A): 219-26 (2009). Read article in PubMedCentral
• Reineke E. L. and Kao H. Y.
  “Targeting promyelocytic leukemia protein: a means to regulating PML nuclear bodies”
  Int J Biol Sci 5 (4): 366-76 (2009). Read article in PubMedCentral
• Stanya K. J. and Kao H. Y.
  “New insights into the functions and regulation of the transcriptional corepressors SMRT and N-CoR”
  Cell Div 4: 7 (2009). Read article in PubMedCentral
• Gao C., Cheng X., Lam M., Liu Y., Liu Q., Chang K. S., and Kao H. Y.
  “Signal-dependent regulation of transcription by histone deacetylase 7 involves recruitment to promyelocytic leukemia protein nuclear bodies”
  Mol Biol Cell 19 (7): 3020-7 (2008). Read article in PubMedCentral
• Gao C., Ho C. C., Reineke E., Lam M., Cheng X., Stanya K. J., Liu Y., Chakraborty S., Shih H. M., and Kao H. Y.
  “Histone deacetylase 7 promotes PML sumoylation and is essential for PML nuclear body formation”
  Mol Cell Biol 28 (18): 5658-67 (2008). Read article in PubMedCentral
• Reineke E. L., Lam M., Liu Q., Liu Y., Stanya K. J., Chang K. S., Means A. R., and Kao H. Y.
  “Degradation of the tumor suppressor PML by Pin1 contributes to the cancer phenotype of breast cancer MDA-MB-231 cells”
  Mol Cell Biol 28 (3): 997-1006 (2008). Read article in PubMedCentral
• Stanya K. J., Liu Y., Means A. R., and Kao H. Y.
  “Cdk2 and Pin1 negatively regulate the transcriptional corepressor SMRT”
  J Cell Biol 183 (1): 49-61 (2008). Read article in PubMedCentral