Web page: http://repromed.ucsd.edu/faculty/rmmellon.html

Special Honors:

• MENTOR Award from the NIH NICHD (2003-2013)

• Elected to the Council of the Endocrine Society (2001-2004)

• MERIT Award from the NIH NICHD (1997-2006)

• The Ernst Oppenheimer Memorial Award of the Endocrine Society, for Meritorious Research in the Field of Endocrinology. (1997)

• The Young Investigator Award of the Pituitary Society for Outstanding Research (1997)

Teaching:

Service:

• Director of the NICHD Center for Reproductive Science and Medicine
• Director of the UCSD Transgenic Mouse and Embryonic Stem Cell Core
• Director of the NIH Training Program in Reproductive Sciences
• Director of the Women’s Reproductive Health Research Training Center
• Chair of the Awards Committee, Women in Endocrinology
• Council of the Endocrine Society (2001-2004)
• Annual Meeting Steering Committee of the Endocrine Society (1999-2001)
• Chair of the NIH Endocrinology Study Section (1996-1998) (Member 1994-1998)
• Chair (Organizer), Gordon Research Conference on Hormone Action, 1995 (Vice-Chair, 1994)

General Area of Interest: Molecular Neuroendocrinology

The brain controls the body’s physiology through neurohormones secreted from the hypothalamus.  In particular, reproduction is regulated by the decapeptide gonadotropin-releasing hormone (GnRH).  GnRH is produced by as few as 800 specialized neurons in the hypothalamus.  Its function is to control release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary.  These hormones in turn control gametogenesis, puberty, menopause, menstrual cycles, and fertility. 

We study the regulation of these hormone genes at the molecular level both by hormones and neurotransmitters and throughout development. We use an integrated program of molecular approaches including:  1) Analysis in transgenic and knock-out mice; 2) Generation of novel pituitary and hypothalamic cell lines; 3) Investigation of the transcriptional regulatory proteins that control development, cellular identity, gene expression, and hormonal response; 4) Pulsatile secretion and circadian rhythms; and 5) Genomic approaches including DNA array analysis.

Using targeted oncogenesis in transgenic mice, we have created a variety of cultured cell models for pituitary endocrine cells and hypothalamic neurons.   The impact of the development of these models has been enormous, creating entirely new directions for molecular research in reproductive neuroendocrinology.  The creation of a series of pituitary cell lines representing sequential stages in development within several of the anterior pituitary endocrine cell lineages has allowed us to significantly illuminate the developmental and hormonal regulation of hormone gene expression, synthesis and secretion.  The creation of immortal hypothalamic GnRH neurons has facilitated rapid advances in understanding the roles of neurotransmitters and transcriptional regulators in hypothalamic function.  For example, this model allowed the demonstration that the GnRH pulse generator is intrinsic to the GnRH neuron, since secretion is pulsatile in these clonal cells in culture.  In addition to Dr. Mellon's own important contributions, researchers around the world are using her cultured cell models to study key issues in neuroendocrinology that were previously unapproachable.  The impact of these model systems has produced a revolution in the approaches used to study the neuroendocrinology of reproduction.

Recent Publications:

Chappell, P. E., White, R. S., Mellon, P. L. (2003). Circadian Gene Expression Regulates Pulsatile Gonadotropin-Releasing Hormone (GnRH) Secretory Patterns in the Hypothalamic GnRH-Secreting GT1-7 Cell Line. Journal of Neuroscience 23, 11202-11213. http://www.jneurosci.org/cgi/content/full/23/35/11202

Coss , D., Jacobs, S. B. R., Bender, C. E., Mellon, P. L. (2004). A Novel AP-1 Site is Critical for Maximal Induction of the Follicle-Stimulating Hormone Beta Gene by Gonadotropin-Releasing Hormone. Journal of Biological Chemistry 279, 152-162. http://www.jbc.org/cgi/content/full/279/1/152

Spady , T. J., Shayya, R., Thackray, V. G., Ehrensberger, L., Bailey, J. S., Mellon, P. L. (2004). Androgen Regulates Follicle-Stimulating Hormone Beta Gene Expression in an Activin-Dependent Manner in Immortalized Gonadotropes. Molecular Endocrinology 18, 925-940. http://mend.endojournals.org/cgi/content/full/18/4/925

Bailey, J. S., Rave- Harel, N., Coss, D., McGillivray, S. M., Mellon, P. L. (2004). Activin Regulation of the Follicle-Stimulating Hormone Beta subunit Gene Involves Smads and the TALE Homeodomain Proteins Pbx1 and Prep1. Molecular Endocrinology 18, 1158-1170. http://mend.endojournals.org/cgi/content/full/18/5/1158

Rave-Harel, N., Givens,* M. L., Nelson,* S. B., Duong, H. A., Coss, D., Clark, M. E., Hall, S. B., Kamps, M. P., and Mellon, P. L. (2004). TALE Homeodomain Proteins Regulate Gonadotropin-Releasing Hormone Gene Expression Independently and Via Interactions with Oct-1. Journal of Biological Chemistry 279, 30287-30297. *equivalent contributions
http://www.jbc.org/cgi/content/full/279/29/30287

Givens,* M. L., Kurotani,* R., Rave- Harel, N., Miller, N. L. G., Mellon, P. L. (2004). Phylogenetic Footprinting Reveals Evolutionarily Conserved Regions of the Gonadotropin-Releasing Hormone Gene that Enhance Cell-Specific Expression.  Molecular Endocrinology 18, 2950-2966.  *equivalent contributions

McGillivray,* S. M., Bailey,* J. S., Ramezani, R., Kirkwood, B. J., Mellon, P. L. (2005). Mouse GnRH Receptor Gene Expression is Mediated by the LHX3 Homeodomain Protein. Endocrinology 146, 2180-2185. *equivalent contributions http://endo.endojournals.org/cgi/content/full/146/5/2180

Givens, M. L., Rave- Harel, N., Goonewardena, V. D., Kurotani, R., Berdy, S. E., Swan, C., Rubenstein,* J. L. R., Robert,* B., Mellon, P. L. (2005). Developmental Regulation of Gonadotropin-Releasing Hormone Gene Expression by the Msx and Dlx Homeodomain Protein Families. Journal of Biological Chemistry 280, 19156-19165. *equivalent contributions http://www.jbc.org/cgi/reprint/280/19/19156

Rave- Harel, N., Miller,* N. L. G., Givens,* M. L., Mellon, P. L. (2005). The Groucho-Related Gene Family Regulates the Gonadotropin-releasing Hormone Gene through Interaction with the Homeodomain Proteins Oct 1 and Msx-1. Journal of Biological Chemistry 280, 30975-30983. *equivalent contributions http://www.jbc.org/cgi/reprint/280/35/30975

Coss , D., Thackray, V. G., Deng, C. X., Mellon, P. L. (2005). Activin Regulates Luteinizing Hormone Beta-Subunit Gene Expression through Smad-binding and Homeobox Elements. Molecular Endocrinology 19, 2610-2623. http://mend.endojournals.org/cgi/content/full/19/10/2610

Tang, Q., Mazur, M., Mellon, P.L. (2005). The Protein Kinase C Pathway Acts Through Multiple Transcription Factors to Repress Gonadotropin-Releasing Hormone Gene Expression in Hypothalamic GT1-7 Neuronal Cells. Molecular Endocrinology 19, 2769-2779. http://mend.endojournals.org/cgi/content/full/19/11/2769

Arial;Thackray,* V. G., McGillivray,* S. M., Mellon, P. L. (2006). Androgens, Progestins and Glucocorticoids Induce Follicle-Stimulating Hormone Beta-Subunit Gene Expression at the Level of the Gonadotrope. Molecular Endocrinology 20, 2062-2079. *equivalent contributions http://mend.endojournals.org/cgi/content/full/20/9/2062

Zhang, H., Bailey, J. S., Coss, D., Lin, B., Tsutsumi, R., Lawson, M.A., Mellon, P. L., Webster, N. J. G. (2006). Activin modulates the transcriptional response of LbetaT2 cells to GnRH and alters cellular proliferation. Molecular Endocrinology 20, 2909-2930. http://mend.endojournals.org/cgi/content/full/20/11/2909

McGillivray, S. M., Thackray, V. G., Coss, D., Mellon, P. L. (2007). Activin and Glucocorticoids Synergistically Activate Follicle-Stimulating Hormone Beta-Subunit Gene Expression in the Immortalized LBetaT2 Gonadotrope Cell Line. Endocrinology 148, 762-773. http://endo.endojournals.org/cgi/content/full/148/2/762

Sasson , R., Dearth, R. K., White, R. S., Chappell, P. E., Mellon, P. L. (2007). Orexin A Induces GnRH Gene Expression and Secretion from GT1-7 Hypothalamic GnRH Neurons. Neuroendocrinology, In Press.

Lawson, M. A., Tsutsumi, R., Zhang, H., Talukdar, I., Butler, B. K., Santos, S. J., Mellon, P. L., Webster, N. J. G. (2007). Pulse Sensitivity of the LH Beta Promoter is Determined by a Negative Feedback Loop Involving Egr1 and Nab1/2. Molecular Endocrinology, In Press.

Key Earlier Publications:

Mellon, P.L., Windle, J.J., Goldsmith ,P., Pedula, C., Roberts, J. and Weiner, R.I. (1990). Immortalization of Hypothalamic GnRH Neurons by Genetically Targeted Tumorigenesis. Neuron 5, 1-10.

Windle, J. J., Weiner, R. I., and Mellon, P. L. (1990).  Cell Lines of the Pituitary Gonadotrope Lineage Derived by Targeted Oncogenesis in Transgenic Mice.  Molecular Endocrinology 4, 597-603.

Belsham , D.D., Wetsel, W.C., and Mellon P.L. (1996). Regulation of Gonadotropin-releasing Hormone Gene Expression in GT1 Hypothalamic Neurons by NMDA and Nitric Oxide Through the cGMP Signal Transduction Pathway. EMBO Journal 15, 538-547.

Turgeon , J., Kimura, Y., Waring, D. W., and Mellon, P. L. (1996). Steroid and Pulsatile Gonadotropin-Releasing Hormone (GnRH) Regulation of Luteinizing Hormone and GnRH Receptor in a Novel Gonadotrope Cell Line. Molecular Endocrinology 10, 439-450.

Alarid, E. T., Windle, J. J., Whyte, D. B., and Mellon, P. L. (1996). Immortalization of Pituitary Cells at Discrete Stages of Development by Directed Oncogenesis in Transgenic Mice. Development 122, 3319-3329. http://dev.biologists.org/cgi/reprint/122/10/3319

Laboratory Personnel:

Djurdjica Coss, Ph.D.Assistant Project Scientist

Varykina Thackray, Ph.D.Postdoctoral Scholar

Rachel Larder, Ph.D. Postdoctoral Scholar

Brian Cherrington, Ph.D. Postdoctoral Scholar

Melissa Brayman, Ph.D. Postdoctoral Scholar

Kellie Breen, Ph.D. Postdoctoral Scholar

Anita Iyer, Ph.D. Postdoctoral Scholar

Nichol Miller, B.S. Ph.D. Student in Biomedical Sciences

Sara Berdy, B.S. Ph.D. Student in Biomedical Sciences

Alejandro Diaz, B.S. M.D. Ph.D. Student in Biomedical Sciences

Dan Clark, B.S. Ph.D. Student in Biological Sciences

Cameron Hand, B.S. Masters Student in Biological Sciences

Susan Mayo, M.S.      Staff Research Associate

Aisha Memon Undergraduate Researcher

Amy Tran Undergraduate Researcher

Ronit Lyon Undergraduate Researcher

Heather Ely Undergraduate Researcher

Michelle Pacer Undergraduate Assistant

John Yang Undergraduate Assistant

Gary Liu Undergraduate Assistant

Administrative Vicki Crowningshield

           e-mail: mellonadmin@ucsd.edu

Phone: (858) 534-1140 or (858) 822-1020