Biomedical Sciences Graduate Program | University of California, San Francisco

Linda C. Giudice, MD, PhD, MSc
Normal and abnormal endometrial development

Selected Publications | Complete Publications

phone	(415) 476-2564
email	giudice@obgyn.ucsf.edu
additional websites
secondary research affiliation	Tissue/Organ Biology & Endocrinology

Our laboratory has had a long-standing interest in the role of normal and abnormal endometrial development and its relevance to implantation, miscarriage, fetal growth, and endometriosis in humans. We also study mechanisms underlying ovarian follicle development and steroidogenesis.

We study the roles of the insulin-like growth factor (IGF) system and the Wnt family in human endometrium, the role of the IGF system in human trophoblast invasion and function, and have numerous ongoing studies on functional genomics of human reproductive tissues.

We have pursued gene discovery in the window of implantation in endometrium from normal women and in women with endometrial disorders, including endometriosis, repetitiv miscarriage, and unexplained infertility. We have also performed molecular profiling of human endometrium across the menstrual cycle and in these disease states. These studies have resulted in identification of markers of diseases of the endometrium and potential targets for therapies. These studies have given insight into basic biologic processes in these conditions and have identified molecular markers and for targeted diagnostics and therapeutics.

We study mechanisms underlying endometrial differentiation in response to steroid hormones and cross-talk between the placenta and the maternal decidua, as well as putative endometrial stem cells and their relevance to endometrial regeneration and benign and malignant endometrial disorders. Some of these studies have revealed extensive roles for components of the immune system in reproductive disorders, which we are actively pursuing in translational studies. We are also investigating hESC differentiation down the trophoblast lineage and interactions between the human trophectoderm with endometrial epithelium in a model of the initial stage of implantation in humans.

Our studies in the ovary focus on the IGF system, using a mouse model in which PAPP-A has been deleted by homologous recombination. We also have conducted clinical trials, and most recently have been a site for the Reproductive Medicine Network for its Pregnancy and Polycystic Ovarian Syndrome trial.

Selected Publications

Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA, Giudice LC. Global gene profiling in human endometrium during the window of implantation. Endocrinology 2002;143:2119-2138.

Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice LC. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology 2003;144:2870-2881.

Tierney EP, Tulac S, Huang ST, Giudice LC. Activation of the protein kinase A pathway in human endometrial stromal cells reveals sequential categorical gene regulation. Physiol Genomics 2003 16; 16:47 -66.

Lathi RB, Hess AP, Tulac S, Nayak NR, Conti M, Giudice LC. Dose-dependent insulin regulation of insulin-like growth factor binding protein-1 in human endometrial stromal cells is mediated by distinct signaling pathways. J Clin Endocrinol Metab 2005;90:1599-1606.

Talbi S, Hamilton AE, Vo KC, Tulac S, Overgaard MT, Dosiou C, Le Shay N, Nezhat CN, Kempson R, Lessey BA, Nayak NR, Giudice LC. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006;147:1097-1121.

Tulac S, Overgaard MT , Hamilton AE, Jumbe NL, Suchanek E, Giudice LC. Dickkopf-1, an inhibitor of Wnt signaling, is regulated by progesterone in human endometrial stromal cells. J Clin Endocrinol Metab. 2006; 1:1453-1461.

Red-Horse K, Rivera J, Winn V, Kapidzic M, Dochman R, Vo KC, Giudice LC, McCune JM, Stoddart CA, Fisher SJ. A new in vivo model of human placental development reveals cytotrophoblast-mediated arterial apoptosis and lymphangiogenesis. J Clin Invest Clin Invest. 2006;16:2643-52.

Hess, AP, Dosiou, CD, Hamilton, AE, Talbi, S, Nyegaard, M, Genbacev-Krtolica, O, Mavrogianis, P, Ferrer, K, Kruessel, Jan, Fazleabas, AT, Fisher, SJ, and Giudice LC, Decidual Stromal Cell Response To Paracrine Signals From the Trophoblast: Amplification of Immune and Angiogenic Modulators. Biol of Repro. 2007; 76: 102-117.

Iinformation last updated March 2007