A5018317129- Angiogenesis and VEGF in Cancer
- Developmental Biology and Gene Regulation
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Congenital heart defects research
- MicroRNA in disease regulation
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Reproductive Biology and Fertility
- Reproductive System and Pregnancy
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Lymphatic System and Diseases
- Cell Adhesion Molecules Research
- Vascular Malformations and Hemangiomas
- Vascular Malformations Diagnosis and Treatment
- Organ and Tissue Transplantation Research
- Pregnancy and preeclampsia studies
- Digital Imaging in Medicine
- Cerebrovascular and genetic disorders
- Pregnancy-related medical research
- Hedgehog Signaling Pathway Studies
University of Illinois Chicago
2017-2025
Illinois College
2019-2025
University of Illinois Urbana-Champaign
2021-2024
Columbia University
2010-2023
Columbia University Irving Medical Center
2008-2017
United States University
2017
University Medical Center Groningen
2016
Wake Forest University
2016
Tokyo Medical and Dental University Hospital
2016
Institute of Molecular Biology and Biophysics
1997-2014
The Notch gene family encodes large transmembrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. To assess the role Notch4 gene, we generated Notch4-deficient mice by targeting. Embryos homozygous for this mutation developed normally, and mutant adults were viable fertile. However, displayed genetic interactions with a targeted related Notch1 gene. mutations both genes often more severe phenotype than embryos. Both Notch1/Notch4 double embryos...
We report the cloning and characterization of a new member Delta family Notch ligands, which we have named Dll4 . Like other genes, is predicted to encode membrane-bound ligand, characterized by an extracellular region containing several EGF-like domains DSL domain required for receptor binding. In situ analysis reveals highly selective expression pattern within vascular endothelium. The activity known actions members this suggest role in control endothelial cell biology.
We have demonstrated previously that a combination of signals from the neural tube and floor plate/notochord complex synergistically induce expression myogenic bHLH genes differentiation markers in unspecified somites. In this study we demonstrate Sonic hedgehog (Shh), which is expressed plate/notochord, subset Wnt family members (Wnt-1, Wnt-3, Wnt-4), are dorsal regions tube, mimic muscle inducing activity these tissues. combination, Shh either Wnt-1 or Wnt-3 sufficient to myogenesis...
ABSTRACT The int-3 oncogene was identified as a frequent target in Mouse Mammary Tumor Virus (MMTV)-induced mammary carcinomas and encodes the intracellular domain of novel mouse Notch gene. To investigate role proto-oncogene development carcinogenesis, we isolated cDNA clones corresponding to entire coding potential proto-oncogene. We propose name this gene Notch4 reserve nomenclature for references oncogenic form. deduced amino acid sequence contains conserved motifs found proteins;...
Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment the keratinocyte cell fate and/or maintenance epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation both mouse human through mechanism independent cycle withdrawal requiring down-modulation selected interferon-responsive genes, including IRF7 IRF3. In turn, elevated counteracts ability...
The bone marrow (BM) microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC) pool (Morrison Spradling, 2008Morrison S.J. Spradling A.C. Stem niches: mechanisms that promote maintenance throughout life.Cell. 2008; 132: 598-611Abstract Full Text PDF PubMed Scopus (1441) Google Scholar). We have previously demonstrated endothelial support proper regeneration system following myeloablation (Butler et...
Epicardial cells on the heart's surface give rise to coronary artery smooth muscle (caSMCs) located deep in myocardium. However, differentiation steps between epicardial and caSMCs are unknown as final maturation signals at arteries. Here, we use clonal analysis lineage tracing show that derive from pericytes, mural associated with microvessels, these present adults. During development following onset of blood flow, pericytes arterial remodeling sites upregulate Notch3 while endothelial...
Wnt signaling plays a critical role in development and oncogenesis. Although significant progress has been made understanding the downstream cascade of signaling, little is known regarding modification cell death machinery. Given that numerous oncogenes transform cells by providing survival function, we hypothesized may inhibit apoptosis. Here, report expressing Wnt-1 were resistant to cancer therapy–mediated inhibited cytochrome c release subsequent caspase-9 activation induced...
The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution to development ventral midbrain (VM) dopaminergic (DA) neurons. Our results show β-catenin is expressed in DA precursor cells signaling takes place these cells, as assessed TOPGAL [Tcf optimal-promoter β-galactosidase] reporter mice. We also found Wnt-1, -3a, -5a expression differentially regulated during partially purified distinctively VM...
Notch receptors and their ligands play important roles in both normal animal development pathogenesis. We show here that the F-box/WD40 repeat protein SEL-10 negatively regulates receptor activity by targeting intracellular domain of for ubiquitin-mediated degradation. Blocking endogenous was done expression a dominant-negative form containing only WD40 repeats. In case Notch1, this block leads to an increase signaling stimulated either activated Notch1 or Jagged1-induced through Notch1....
Notch proteins function as receptors for membrane-bound ligands (Jagged and Delta-like) to regulate cell-fate determination. We have investigated the role of signaling in embryonic endothelium mouse by expressing an activated form Notch4 protein vasculature under regulation Flk1 (VEGFR) locus. Expression results a growth developmental delay lethality at about 10 days postcoitum. The extent developing mutant embryos was restricted, fewer small vessels were seen, vascular networks...
Forkhead box O (Foxo) transcription factors govern metabolism and cellular differentiation. Unlike Foxo-dependent metabolic pathways target genes, the mechanisms by which these proteins regulate differentiation have not been explored. Activation of Notch signaling mimics effects Foxo gain function on Using muscle as a model system, we show that physically functionally interacts with promoting corepressor clearance from effector Csl, leading to activation genes. Inhibition myoblast...
Convincing evidence has accumulated to identify the Frizzled proteins as receptors for Wnt growth factors. In parallel, a number of secreted frizzled-like with conserved N-terminal frizzled motif have been identified. One these proteins, Frzb-1, binds Wnt-1 and Xwnt-8 antagonizes signaling in Xenopus embryos. Here we report that Frzb-1 blocks induced cytosolic accumulation β-catenin, key component pathway, human embryonic kidney cells. Structure/function analysis reveals complete removal...