A5031393659- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Estrogen and related hormone effects
- Nuclear Receptors and Signaling
- Reproductive Biology and Fertility
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genomics and Chromatin Dynamics
- Renal and related cancers
- Animal Genetics and Reproduction
- Tissue Engineering and Regenerative Medicine
- Reproductive System and Pregnancy
- Retinoids in leukemia and cellular processes
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Sperm and Testicular Function
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Congenital heart defects research
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Prenatal Screening and Diagnostics
- Ubiquitin and proteasome pathways
- Sexual Differentiation and Disorders
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
Baylor College of Medicine
2010-2021
Baylor University
2019
The University of Texas at Austin
2016-2018
Dell Children's Medical Center of Central Texas
2016-2018
The University of Texas MD Anderson Cancer Center
2011-2016
Weatherford College
2011
Pediatrics and Genetics
1994-2011
Rice University
2011
University of Louisville
2008
Qilu Hospital of Shandong University
2008
In the mammalian ovary, progressive activation of primordial follicles from dormant pool serves as source fertilizable ova. Menopause, or end female reproductive life, occurs when follicle is exhausted. However, molecular mechanisms underlying are poorly understood. We provide genetic evidence that in mice lacking PTEN (phosphatase and tensin homolog deleted on chromosome 10) oocytes, a major negative regulator phosphatidylinositol 3-kinase (PI3K), entire becomes activated. Subsequently, all...
Alignment of natural chicken ovalbumin upstream promoter transcription factor (COUP-TF) response elements shows that, in addition to the predominant direct repeat GGTCA motif with a 2-bp spacing, there are other functional COUP variations orientation and spacing. We systematically analyzed binding vitro-synthesized COUP-TFs showed that COUP-TF is capable oligonucleotides containing both repeats palindromes different spacings repeats. Subsequently, we four possible mechanisms proposed explain...
To maintain the female reproductive lifespan, majority of ovarian primordial follicles are preserved in a quiescent state order to provide ova for later life. However, molecular mechanism that maintains long quiescence is poorly understood. Here we genetic evidence show tumor suppressor tuberous sclerosis complex 1 (Tsc1), which negatively regulates mammalian target rapamycin (mTORC1), functions oocytes follicles. In mutant mice lacking Tsc1 gene oocytes, entire pool activated prematurely...
Oct4 plays an essential role in maintaining the inner cell mass and pluripotence of embryonic stem (ES) cells. The expression is regulated by proximal enhancer promoter epiblast distal at all other stages pluripotent lineage. Here we report that orphan nuclear receptor LRH-1, which expressed undifferentiated ES cells, can bind to SF-1 response elements gene activate reporter expression. LRH-1 colocalized with embryos early developmental stages. Disruption results loss stage death. Using...
Oocyte-specific deletion of ovarian genes using Cre/loxP technology provides an excellent tool to understand their physiological roles during folliculogenesis, oogenesis, and preimplantation embryonic development. We have generated a transgenic mouse line expressing improved Cre recombinase (iCre) driven by the growth differentiation factor-9 (GDF-9) promoter. The resulting was named GDF-9-iCre mice. Using floxed ROSA reporter mice, we found that expressed in postnatal ovaries, but not...
The chicken ovalbumin upstream promoter transcription factor (COUP-TF) is a member of the steroid/thyroid hormone receptor superfamily about which little known its functional role in cell. However, it able to repress hormonal induction target genes by vitamin D3 (VDR), thyroid (TR), and retinoic acid (RAR). We have shown previously that COUP-TF can bind wide variety A/GGGTCA repeats. This promiscuous recognition response elements correlates with ability I other receptors repeats different...
Completion of the Rattus norvegicus genome sequence enabled a global inventory and analysis nuclear receptors (NRs) in three mammalian species. Forty-nine NR members were found mouse, 48 human. Forty-seven rat, with gaps at locations expected for other two. Pairwise comparisons their distribution human identified 11 syntenic gene blocks, including small clusters two or closely related genes, each spanning 40 kb to 1700 kb. The exon structure ligand-binding domain suggests that shuffling has...
Embryonic stem (ES) cell pluripotency and differentiation are controlled by a network of transcription factors signaling molecules. Transcription such as Oct4 Nanog required for self-renewal maintain the undifferentiated state ES cells. Decreases in expression these indicate initiation Inactivation gene encoding orphan nuclear receptor GCNF showed that it plays an important role repression somatic cells during early embryonic development. GCNF−/− were isolated to study function...
Delineating the signaling pathways that underlie ESC pluripotency is paramount for development of applications in both research and clinical settings. In culture maintained by leukemia inhibitory factor (LIF) stimulation two separate axes: Stat3/Klf4/Sox2 PI3K/Tbx3/Nanog, which converge regulation Oct4 expression. However, LIF not required vivo self-renewal, thus alternate axes likely mediate these pathways. Additional factors promote gene expression have been identified, including direct...
Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) genes encode transcription factors belonging to the orphan subfamily of steroid/thyroid hormone receptor superfamily. Two COUP-TF counterparts have been cloned from mouse. In an attempt study function these in developing central nervous system (CNS), spatiotemporal expression patterns two mouse examined by situ hybridization. Both are widely expressed CNS, with that overlapping yet distinct each other. The differential murine...
The Wip1 gene is a serine/threonine phosphatase that induced in p53-dependent manner by DNAdamaging agents.We show here message expressed moderate levels all organs, but present at very high the testes, particularly postmeiotic round spermatid compartment of seminiferous tubules.We have confirmed mRNA ionizing radiation mouse tissues manner.To further determine normal biological function mammalian organisms, we generated Wip1-deficient mice.Wip1 null mice are viable variety postnatal...
We have cloned a novel member of the nuclear receptor superfamily that has been identified from complementary DNA libraries derived mouse tissues using low stringency cross hybridization strategy. The deduced protein sequence contains 495 amino acids and consists characteristic DNA-binding ligand-binding domains superfamily. primary this new orphan is distinct those previously members subgroups. Analysis properties in vitro synthesized revealed binds to TCAAGGTCA includes steroidogenic...
How tumor suppressor p53 selectively responds to specific signals, especially in normal cells, is poorly understood. We performed genome-wide profiling of chromatin interactions and target gene expression human embryonic stem cells (hESCs) response early differentiation, induced by retinoic acid, versus DNA damage, caused adriamycin. Most p53-binding sites are unique each state define stimulus-specific responses hESCs. Differentiation-activated targets include many developmental...
Embryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks sequentially reactivated as somatic reprogram to achieve pluripotency. How epigenetic regulators modulate this process contribute cell reprogramming is not clear. Here we performed functional RNAi screen identify the earliest required for reprogramming. We identified components of SAGA histone acetyltransferase complex, particular Gcn5,...
Significance Compared with microRNAs (miRNAs) enriched in cardiac and skeletal muscles, little is known about miRNAs expressed early progenitors. Here, we show that mesoderm posterior 1 (Mesp1) transactivates a large number of may promote cardiomyocyte formation. The miR-322/-503 cluster has the highest enrichment Mesp1 lineage progenitor cells, specifically developing heart tube, drives precocious formation by targeting an RNA-binding factor, CUG-binding protein Elav-like family member...
Background : Mammalian first lineage segregation generates trophectoderm (TE) and pluripotent inner cell mass (ICM), which provides an ideal model for studying the mechanisms of maintenance loss pluripotency. In mouse, transcription factor OCT4 restricts to ICM plays a key role in TE/ICM specification regulatory networks. However, pig, does not restrict cells, suggesting different molecular basis Results To explore porcine networks, we examined expression pattern pluripotency factors,...
Significance The p53 family member deltaNp63 (ΔNp63) is required for transcriptional activation of the microprocessor complex subunit DGCR8 in epidermal cells, leading to terminal differentiation tissues such as epidermis. We show here that loss ΔNp63 leads generation cells with self-renewing but limited capacity. When reexpressed deficient ΔNp63, these can terminally differentiate into all three germ layers. dubbed induced multipotent stem because their remarkable plasticity and ability...
The dynamic embryonic expression of germ cell nuclear factor (GCNF), an orphan receptor, suggests that it may play important role during early development. To determine the physiological GCNF, we have generated a targeted mutation GCNF gene in mice. Germ line proves receptor is essential for survival and normal GCNF−/− embryos cannot survive beyond 10.5 days postcoitum (dpc), probably due to cardiovascular failure. Prior death, suffer significant defects posterior Unlike GCNF+/+ embryos, do...
COUP-TF, an orphan member of the nuclear receptor superfamily, has been proposed to play a key role in regulating organogenesis, neurogenesis, and cellular differentiation during embryonic development. Since heterodimierization is common theme within superfamily demonstrated modulate transcriptional properties heterodimeric partners via allosteric interactions, we have devised strategy examine silencing function COUP-TF context. We find that intrinsic active repression not affected by...