权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of SMAD1 and SMAD5 in hormonal response, endometrial receptivity and glandular function

SMAD1 和 SMAD5 在激素反应、子宫内膜容受性和腺体功能中的作用

基本信息

批准号：
10468933
负责人：
Diana Monsivais
金额：
$ 24.4万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10468933
关键词：
Activins Affect Age Award BMP7 gene Binding Biological Bone Morphogenetic Proteins Cell Nucleus Cells Collaborations Complex Data Decidual Cell Reactions Defect Development Doctor of Philosophy Early Intervention Embryo Endometrial Endometrial Stromal Cell Endometrium Estrogen Receptors Estrogens Event Faculty Family Fellowship Female Female infertility Female sterility Fertility Follistatin Funding Gene Expression Genetic Transcription Genomics Goals Hormonal Hormones Human Immunology Impairment Incidence Infertility Institution Journals K-Series Research Career Programs Laboratories Lead Ligands Link MADH2 gene MADH4 gene Medical center Medicine Mentors Molecular Molecular Profiling Molecular Target Mothers Mus Mutant Strains Mice National Institute of Child Health and Human Development Organ Paper Pathology Pathway interactions Phase Phenotype Positioning Attribute Postdoctoral Fellow Pre-Eclampsia Pregnancy Prevention strategy Process Progesterone Progesterone Receptors Proteins Puberty Publishing Receptor Activation Reproduction Reproductive Biology Research Research Institute Research Personnel Research Priority Research Proposals Research Training Resources Role Sampling Scientist Signal Pathway Signal Transduction Site Study models TGF-beta type I receptor Texas Therapeutic Time Tissues Transgenic Mice United States National Institutes of Health Universities Uterine Gland Uterus Woman antagonist bone morphogenetic protein receptors career career development college design distinguished professor early pregnancy early pregnancy loss experience failure Implantation genome-wide genome-wide analysis gland development implantation improved inhibitor laboratory curriculum lectures meetings microbial disease mouse genetics mouse model natural Blastocyst Implantation novel prevent professor receptor receptor binding reproductive reproductive function reproductive tract research study response small molecule steroid hormone therapy development transcription factor transcriptome sequencing treatment strategy undergraduate student

项目摘要

Project Summary Despite the high incidence of early pregnancy loss among women, its causes are not well-understood and the treatment options are limited. The endometrium is the first site of contact between the embryo and mother, therefore, understanding the molecular signature of the endometrium at the time of embryo implantation will help us develop therapies to prevent early pregnancy loss in women. Bone morphogenetic proteins (BMPs) are highly conserved factors of the TGFb superfamily that signal by binding to a heterodimeric receptor complex composed of a BMP type 1 receptor and type 2 receptor complex. After receptor binding and activation, SMAD1 and SMAD5 proteins are phosphorylated, form a complex with SMAD4, and translocate to the nucleus to control gene expression. We recently showed that signaling components of the TGFb family (ALK3, ALK5, BMP7 and follistatin) are critical for endometrial receptivity by controlling the endometrial response to the steroid hormones, estrogen (E2) and progesterone (P4). However, the mechanism linking the TGFb pathway and the endometrial response to the steroid hormones is not understood. The goals of this proposal are to determine how the downstream signaling components of the BMP pathway, the SMAD1 and SMAD5 transcription factors, control the response to E2 and P4 in the endometrium during the process of embryo implantation. We will use transgenic mice and human endometrial samples to fully delineate how SMAD1 and SMAD5 control the endometrial response to E2 and P4 during early pregnancy. This award will support the career development of Diana Monsivais, Ph.D., a Postdoctoral Associate and IRACDA Fellow at Baylor College of Medicine. The candidate will be co-mentored by Dr. Martin Matzuk, the Stuart A. Wallace Chair, Robert L. Moody, Sr. Chair, and Professor in the Dept. of Pathology & Immunology at Baylor College of Medicine and by Dr. Masahito Ikawa, Distinguished Professor at the Research Institute for Microbial Diseases in Osaka University. Both co-mentors are outstanding researchers in the fields of reproduction and mouse genetics. The research will be primarily performed in Dr. Matzuk’s laboratory at Baylor College of Medicine, a top research institution in the Texas Medical Center, providing Dr. Monsivais with abundant research resources and access to collaborations. In the short-term, the award will provide Dr. Monsivais with career development and research training in reproductive biology and mouse genetics. In the long-term, this award will support the candidate’s transition into a faculty position as an independent investigator. Data from these studies will reveal the molecular events that orchestrate maternal and embryonic interactions during implantation, and will improve the therapeutic options for women experiencing infertility and early pregnancy loss.

项目总结