The Harvard Reproductive Endocrine Sciences Center has been dedicated to translational research in reproduction for the past 20 years. The Center uses interdisciplinary approaches to define the genetic control of puberty and reproduction in the human incorporating techniques from clinical investigation, human genetics, molecular biology, and bioinformatics. Broadly, the Center aims to continue its discovery program to find novel genes that control reproductive function and elucidate their biology to enhance the diagnostics, treatment, and counseling of patients with infertility and reproductive disorders. PROJECT 1 (Pl: Crowley) will utilize modern genetic and genomic tools to identify genes involved in the biology of GnRH neuronal development capitalizing on our unique cohort of >1,300 patients/families with isolated GnRH deficiency that has been assembled by our Phenotyping, Genotyping, &Bioinformatics Core (Core B). It will then chart the genotype-phenotype spectrum of these new genes and determine their role in both congenital GnRH deficiency and more common reproductive disorders. PROJECT 2 (Pl: Seminara) will utilize human genetics and murine studies to elucidate the interplay of the Neurokinin B and KISS1/KISS1R pathways. These studies will also draw on our unique cohort of GnRH deficient patients as well as targeted gene deletions of these systems in mice. PROJECT 3 (Pl: Kaiser) will explore the molecular biology of G-coupled protein receptors (GPCRs) and the mechanisms by which they impact human reproduction. Using mutations in both ligands and their cognate GPCRs, including those from Project 1, Project 3 will chart their biologic activity and use in vitro techniques to elucidate their cellular actions and the effects of mutations on identified reproductive pathways. CORE A: will provide organizational, logistical, and administrative support for the center investigators;CORE B: will recruit patients for genetic studies/detailed phenotyping and manage the Progeny database;CORE C: will provide web based patient centered information on reproductive disorders and will link other investigators to our Progeny database.
This project aims to identify and study the genes which control puberty and reproduction in the human. Better understanding the genetic control of reproduction will enable us to develop better diagnostic tests, treatments, and counseling for patients with infertility and reproductive disorders.
|Sidhoum, Valerie F; Chan, Yee-Ming; Lippincott, Margaret F et al. (2014) Reversal and relapse of hypogonadotropic hypogonadism: resilience and fragility of the reproductive neuroendocrine system. J Clin Endocrinol Metab 99:861-70|
|Martin, Cecilia; Navarro, Víctor M; Simavli, Serap et al. (2014) Leptin-responsive GABAergic neurons regulate fertility through pathways that result in reduced kisspeptinergic tone. J Neurosci 34:6047-56|
|Ahow, Maryse; Min, Le; Pampillo, Macarena et al. (2014) KISS1R signals independently of G?q/11 and triggers LH secretion via the ?-arrestin pathway in the male mouse. Endocrinology 155:4433-46|
|Thompson, Iain R; Kaiser, Ursula B (2014) GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression. Mol Cell Endocrinol 385:28-35|
|Noel, Sekoni D; Abreu, Ana Paula; Xu, Shuyun et al. (2014) TACR3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients. FASEB J 28:1924-37|
|Min, Le; Soltis, Kathleen; Reis, Ana Claudia S et al. (2014) Dynamic kisspeptin receptor trafficking modulates kisspeptin-mediated calcium signaling. Mol Endocrinol 28:16-27|
|Salian-Mehta, S; Xu, M; Knox, A J et al. (2014) Functional consequences of AXL sequence variants in hypogonadotropic hypogonadism. J Clin Endocrinol Metab 99:1452-60|
|Kaiser, Ursula B (2014) Editorial: advances in neuroscience: the BRAIN initiative and implications for neuroendocrinology. Mol Endocrinol 28:1589-91|
|Macedo, Delanie B; Abreu, Ana Paula; Reis, Ana Claudia S et al. (2014) Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3. J Clin Endocrinol Metab 99:E1097-103|
|Beneduzzi, Daiane; Trarbach, Ericka B; Min, Le et al. (2014) Role of gonadotropin-releasing hormone receptor mutations in patients with a wide spectrum of pubertal delay. Fertil Steril 102:838-846.e2|
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