Pamela Mellon
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Pamela L. Mellon, PhD Vice-Chair for Research Professor of Reproductive Medicine and Neuroscience Division of Reproductive Endocrinology Director of the Center for Reproductive Science and Medicine Telepho1ne: (858) 534-1312 |
Ph.D. in Molecular Biology, University of California, Berkeley, 1979
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: Neuroscience 268; Molecular and Cellular Neurobiology (Director of graduate course)
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 Postdoctoral 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, gonadal steroidogenesis, 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sasson, R., Dearth, R. K., White, R. S., Chappell, P. E., Mellon, P. L. (2006). Orexin A Induces GnRH Gene Expression and Secretion from GT1-7 Hypothalamic GnRH Neurons. Neuroendocrinology 84, 353-363.
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.
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 Luteinizing Hormone Beta Promoter Is Determined by a Negative Feedback Loop Involving Early Growth Response-1 and Ngfi-A Binding Protein 1 and 2. Molecular Endocrinology 21, 1175 - 1191.
Pitteloud,* N., Zhang,* C., Pignatelli, D., Li, J.-D., Raivio, T., Cole, L. W., Plummer, L., Jackobson-Dickson, E. E., Mellon, P. L., Zhou,* Q.-Y., Crowley,* W. F. Jr. (2007). Loss-of-function Mutations in the Prokineticin 2 Gene Cause Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism. (2007). Proceedings of the National Academy of Sciences USA 104, 17447-17452. *equivalent contributions
Coss, D., Hand, C. M., Yaphockun, K. K. J., Ely, H. A., and Mellon,
P. L. (2007). p38 Mitogen-Activated Protein Kinase is Critical for
Synergistic Induction of the FSHβ Gene by Gonadotropin-Releasing
Hormone and Activin through Augmentation of c-Fos Induction and Smad
Phosphorylation. Molecular Endocrinology 12, 3071-3086.
Lu, M., Tang, Q., Olefsky, J. M., Mellon, P. L., and Webster, N. J.
G. (2008). Adiponectin Activates AMPK and Decreases Luteinizing
Hormone Secretion in LβT2 Gonadotropes. Molecular Endocrinology 22,
760-771.
McMahon, H. E., Hashimoto, O., Mellon, P. L., and Shimasaki, S.
(2008). Oocyte-specific Over-expression of Mouse BMP-15 Leads to
Accelerated Folliculogenesis and an Early Onset of Acyclicity in
Transgenic Mice. Endocrinology 149, 812-817.
Thackray, V. G., Mellon, P. L. (2008). Synergistic Induction of
Follicle-Stimulating Hormone β-subunit Gene Expression by Gonadal
Steroid Hormone Receptors and Smad Proteins. Endocrinology 149,
1091-1102.
Sasson,* R., Luu,* S. H., Thackray, V. G., and Mellon P. L. (2008).
Glucocorticoids Induce Human Glycoprotein Hormone Alpha-Subunit Gene
Expression in the Gonadotrope. Endocrinology 149, 3643-3655.
*equivalent contributions.
Cherrington,* B. D., Bailey,* J. S., Diaz, A. L., and Mellon, P. L.
(2008). NeuroD1 and Mash1 Temporally Regulate GnRH Receptor Gene
Expression in Immortalized Mouse Gonadotrope Cells. Molecular and
Cellular Endocrinology 295, 106-114. *equivalent contributions.
Avelino-Cruz, J. E., Flores, A., Mellon, P. L., Felix, R., and
Monjaraz, E. (2009). Leptin Increases L-type Ca2+ Channel Expression
and GnRH-stimulated LH Release in LβT2 Gonadotropes. Molecular and
Cellular Endocrinology 298, 57-65.
Miller, N. L. G., Wevrick, R., and Mellon, P. L. (2009). Necdin, a
Prader-Willi Syndrome Candidate Gene, Regulates Gonadotropin-releasing
Hormone Neurons during Development. Human Molecular Genetics 18,
248-260.
Thackray, V. G., Hunnicutt, J. L., Memon, A. K., Ghochani, Y., and
Mellon, P. L. (2009). Progesterone Inhibits Basal and GnRH Induction
of Luteinizing Hormone β-Subunit Gene Expression. Endocrinology 150,
In press. 19106225
Laboratory Personnel
- Djurdjica Coss, Ph.D.
- Assistant Project Scientist
- Varykina Thackray, Ph.D.
- Assistant Adjunct Professor
- Rachel Larder, Ph.D.
- Postdoctoral Scholar
- Christine Glidewell-Kenney, Ph.D.
- Postdoctoral Scholar
- Melissa Brayman, Ph.D.
- Postdoctoral Scholar
- Kellie Breen, Ph.D.
- Postdoctoral Scholar
- Anita Iyer, Ph.D.
- Postdoctoral Scholar
- Dan Clark, B.S.
- Ph.D. Student in Biomedical Sciences
- Emily Witham, B.S.
- Ph.D. Student in Biomedical Sciences
- Susan Mayo, M.S.
- Staff Research Associate
- Jason Meadows, B.S.
- Animal Technician
- Patrick Corpuz, B,S,
- Master's Student
- Yasmin Ghochani, B.S.
- Master's Student
- Jonathon Aderinto
- Undergraduate Researcher
- Patricia Pepa
- Undergraduate Researcher
- Lacey Lindaman
- Undergraduate Researcher
- Tracy Hsu
- Undergraduate Researcher
- Anastasia Bendebury
- Undergraduate Assistant
- Mark Nguyen
- Undergraduate Assistant
- Paul Yu
- Undergraduate Assistant