A5065921839- Reproductive System and Pregnancy
- Endometriosis Research and Treatment
- Endometrial and Cervical Cancer Treatments
- Growth Hormone and Insulin-like Growth Factors
- Uterine Myomas and Treatments
- Estrogen and related hormone effects
- Pregnancy and preeclampsia studies
- Reproductive Biology and Fertility
- TGF-β signaling in diseases
- Reproductive Physiology in Livestock
- Gynecological conditions and treatments
- Ovarian function and disorders
- Single-cell and spatial transcriptomics
- Reproductive tract infections research
- Pregnancy and Medication Impact
- Virus-based gene therapy research
- Protease and Inhibitor Mechanisms
- Reproductive Health and Contraception
- Cancer Genomics and Diagnostics
- Blood Coagulation and Thrombosis Mechanisms
- Metabolism and Genetic Disorders
- Birth, Development, and Health
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
University of California, San Francisco
2015-2025
Reproductive Science Center
2012-2023
University of California System
2015-2016
City College of San Francisco
2014
Stanford University
1992-2002
Stanford Medicine
1991-2002
Baylor College of Medicine
1998
Nagoya Institute of Technology
1994
Huntington Medical Research Institutes
1989-1993
Case Western Reserve University
1991-1992
Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing biology and enabling new insights into the physiology human organs. We created a reference atlas comprising nearly 500,000 cells from 24 different tissues organs, many same donor. This enabled molecular more than 400 types, their distribution across tissues, tissue-specific variation in gene expression. Using multiple single donor identification clonal T between mutation rate B cells,...
IGFBP-1 is elevated in fetuses with long-term, chronic hypoxia and intrauterine growth restriction. We investigated the hypothesis that regulates human fetus vivo gene expression protein vitro . Umbilical artery levels (mean ± SEM) from term babies respiratory acidosis (acute hypoxia), normal babies, those mixed respiratory/metabolic (more profound prolonged hypoxia) were measured using an immunoradiometric assay. similar ( n = 12) acutely hypoxic 6) (189.1 71.8 vs. 175.8 45.9 ng /ml,...
We have studied the interaction between growth factors and sex steroids in regulating human endometrial stromal cell differentiation using an vitro serumfree culture model system. None of [epidermal factor (EGF), basic fibroblast (bFGF), insulin, insulin-like factor-I (IGF-I), IGF-II, or platelet-derived factor] stimulated cells grown progestin-free medium. However, progestin-treated cultures was dramatically increased by EGF, bFGF, factor, but not IGF-I, IGF-II. Estrogen could substitute...
Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties mesenchymal stem cells (MSCs), has been characterized. The MSC (eMSC) is likely the precursor fibroblast. goal this study was determine transcriptome and signaling pathways in eMSC understand its functional phenotype. Endometrial oocyte donors (n = 20) patients undergoing benign gynecologic...
Endometriosis (E), an estrogen-dependent, progesterone-resistant, inflammatory disorder, affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, expensive approaches. Because uterine lining (endometrium) women with E has altered molecular profiles, we tested whether classification this tissue can distinguish stage disease. We developed classifiers using genomic data n...
Human endometrium undergoes cyclic regeneration involving stem/progenitor cells, but the role of resident endometrial mesenchymal stem cells (eMSC) as progenitors stromal fibroblasts (eSF) has not been definitively demonstrated. In endometriosis, eSF display progesterone (P4) resistance with impaired decidualization in vivo and vitro. To investigate eMSC precursors whether endometriosis P4 is inherited from eMSC, we analyzed transcriptomes eutopic isolated by fluorescence-activated cell...
STUDY QUESTIONDo endometrial stromal fibroblasts (eSF) in women with polycystic ovary syndrome (PCOS) (eSFpcos) exhibit altered estrogen and/or progesterone (P4) responses, which may explain some of the adverse reproductive outcomes and pathologies these women?
Abstract Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept identify cell types origin using the Tabula Sapiens transcriptomic atlas as well individual atlases in combination with Human Protein Atlas consensus dataset. define type signature scores, which allow inference that contribute cell-free for a variety diseases.
The IGF family plays an important role in implantation and placental physiology. IGF-II is abundantly expressed by trophoblasts, binding protein (IGFBP)-4, a potent inhibitor of actions, the second most abundant IGFBP bed, exclusively maternal decidua. Proteolysis IGFBP-4 results decreased affinity for peptides, thereby enhancing actions. In current study, we have identified protease its human trophoblast decidualized endometrial stromal cell cultures, investigated their regulation effort to...
Oestradiol is important in the growth of uterine leiomyomata and may act primarily or secondarily through mediators such as factors, including insulin-like factors (IGF-I IGF-II), mitogenic peptides. IGF binding proteins (IGFBPs) modulate actions at their target cells. The objective this study was to examine possible steroid dependence IGF, IGFBP receptor gene expression synthesis leiomyomata, using tissues from women cycling normally made hypo-oestrogenic by a gonadotrophin-releasing...
Insulin-like growth factor binding protein-1 (IGFBP-1) can bind to the α5β1 integrin and stimulate cellularmigration in Chinese hamster ovary (CHO) cells. IGFBP-1 is a major product of endometrium pregnancy (decidua), may interact with invading cytotrophoblasts expressing modulate their invasion. The present study investigated interaction cytotrophoblast integrin, its effects on trophoblast attachment fibronectin invasion into decidualized endometrial stromal cell multilayers. incubated...
The implantation process begins with attachment of the trophectoderm (TE) blastocyst to maternal endometrial epithelium. Herein we have investigated transcriptome mural TE cells from 13 human blastocysts and compared these those embryonic stem cell (hESC)-derived-TE (hESC(troph)). transcriptomes hESC(troph) at Days 8, 10, 12 had greatest consistency TE. Among genes coding for secreted proteins are several molecules known be involved in process, as well novel ones, such CXCL12, HBEGF, inhibin...
Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity cancer.We hypothesized that an endocrine/metabolic environment PCOS may result "disease phenotype" affecting the of different cell populations, including stem cells their differentiated progeny.This was a prospective study conducted at academic medical center.Proliferative-phase endometrium obtained from 6 overweight/obese...
Human endometrium undergoes major gene expression changes, resulting in altered cellular functions response to cyclic variations circulating estradiol and progesterone, largely mediated by transcription factors nuclear receptors. In addition classic modulators, epigenetic mechanisms regulate during development environmental some diseases have roles steroid hormone action. Herein, we tested the hypothesis that DNA methylation plays a role regulation human different hormonal milieux. High...
Endometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune lesion clearance, pro-inflammatory endometrial environment, systemic inflammation. Comprehensive understanding endometriosis pathophysiology in different hormonal milieu disease severity has been hampered by limited direct characterization populations endometrium, blood, lesions. Simultaneous deep...
Abstract Endometriosis is a leading cause of pain and infertility affecting millions women globally. Herein, we characterize variation in DNA methylation (DNAm) its association with menstrual cycle phase, endometriosis, genetic variants through analysis genotype data endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% the endometriosis captured by DNAm identify significant differences profiles associated stage III/IV sub-phenotypes including opening window for...
Proteinases are likely effectors of endometrial menstrual breakdown. We have investigated proteinase production by human stromal cells subjected in vitro to progesterone (P) withdrawal, the physiologic stimulus for menstruation. Culture media exposed estradiol, P, or estradiol plus P had low levels proteolytic activity similar cultures maintained absence steroids. addition RU486 P-treated cultures, stimulated secretion. The cell was characterized gelatin zymography, inhibitor profile, and...
Endometrial stromal cells undergo decidual transformation, in response to epidermal growth factor (EGF) and progesterone. Since insulin-like factors (IGFs) IGF-binding proteins (IGFBPs) are believed be involved endometrial differentiation, insulin regulates IGFBP production a variety of cells, we have investigated the modulatory roles EGF, progesterone, on secretion by long term cultures human cells. Without insulin, principal secreted into conditioned medium, detected Western ligand...