Philippa MELAMED (Associate Professor) Contact Information: Dept of Biological Sciences National University of Singapore Science Drive 4 Singapore 117543 Tel: 65161688 Fax: 67792486 email : dbsmp@nus.edu.sg

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Research Areas

Molecular endocrinology; transcriptional regulation; chromatin remodeling; pituitary hormones.

Research Interests

The focus of our research is the transcriptional regulation of pituitary hormones. We are especially interested in the molecular mechanisms regulating expression of the gonadotropins by the hypothalamic and gonadal regulatory hormones, and how differential regulation of the three target genes is achieved. This includes examining how the regulatory hormones induce covalent modifications of histone tails and the resulting changes in protein recruitment to these gene loci. Our model is primarily the mouse pituitary for which we are able to utilize the extensive protein and genome databases and implement, in particular, work of biomedical relevance. In addition, the fish pituitary is used for a comparative approach and because of the organized cell distribution in the pituitary, and the vast temporal changes in expression of many of these hormones.

Current research

1. Promoter analysis of the FSH b and gonadotropin a subunit genes is currently underway. Interactions between transcription factors activating all three genes are being studied.

2. Subtractive hybridization is being used to elucidate transcripts in the up-regulated in response to GnRH treatment. 2-D gel analysis is being used to study proteins differentially expressed in gonadotropes of varying maturity in order to discover novel proteins regulating gonadotropin gene expression.

3. Research is underway to identify cofactors recruited by DNA-bound transcription factors and the mechanisms through which they are recruited.

4. HDACs involved in repressing gonadotropin genes have been largely identified, but the intricate interactions within the repressive complex and the involvement of corepressors has yet to be determined.

5. We are starting a new project to eaxamine the role of the GnRH in stimulating proliferation of the immature gonadotropes and why this is attenuated with completion of cell differentiation.

Awards:

Selected Publications:

1. Lim, S., Koh, M., Luo, M., Yang, M., Abdul Kadir, M.N., Ye, Z., Wang, W. and Melamed, P. Distinct histone deacetylase complexes repress expression of the two gonadotropin b- subunit genes in the immature gonadotrope, and their actions are overcome by GnRH through diverse mechanisms. (submitted to Mol. Cell. Biol.)

2. Melamed, P. Abdul Kadir, M.N., Wijeweera, A. and Seah, S. (2006) Transcription of gonadotropin b subunit genes involves cross-talk between the transcription factors and co-regulators that mediate actions of the regulatory hormones. Mol. Cell. Endocrinol. 252:167-183.

3. Melamed, P., Zhu, Y., Tan, S.H., Xie, M. and Koh. M. (2006) Gonadotropin releasing hormone activation of c-jun, but not Egr-1, stimulates transcription of a luteinizing hormone b subunit gene. Endocrinology 147:3598-3605.

4. Luo, M., Koh, M., Feng, J., Wu, Q. and Melamed, P. (2005) Cross-talk in hormonally-regulated gene transcription through induction of estrogen receptor ubiquitylation. Mol.Cell. Biol. 25:7386-7398.

5. Melamed, P., Xue, Y.K., Poon, J.F., Wu, Q., Xie H., Yeo, J., Foo, T.W. and Chua H.K. (2005) The male seahorse synthesizes and secretes a novel C-type lectin into the brood pouch during early pregnancy. FEBS J. 272: 1221-1235.

6. Chong, K.L. Wang, S. and Melamed, P. (2004) Isolation and characterization of the follicle- stimulating hormone b subunit gene and 5’ flanking region of the Chinook salmon. Neuroendocrinology 80: 158-170.

7. Melamed, P., Chong, K.L. and Johansen, M.V. (2004) Evidence for lateral gene transfer from Salmonids to two Schistosome species. Nature Genetics 36: 786-787.

8. Yaron, Z., Gur, G., Melamed, P., Rosenfeld, H. and Elizur, A. and Levavi-Sivan, B. (2003) Regulation of fish gonadotropins. Int. Rev. Cytol. 225:131-185.

9. Melamed, P., Koh, M., Preklathan, P., Bei, L. and Hew, C.L. (2002) Multiple mechanisms for Pitx- 1 transactivation of a luteinizing hormone b subunit gene. J. Biol. Chem. 277: 26200-26207.