A5008079002- Angiogenesis and VEGF in Cancer
- Developmental Biology and Gene Regulation
- Vascular Malformations and Hemangiomas
- Kruppel-like factors research
- Lymphatic System and Diseases
- Vascular Malformations Diagnosis and Treatment
- Reproductive System and Pregnancy
- Cancer-related gene regulation
- Cancer Immunotherapy and Biomarkers
- Pregnancy and preeclampsia studies
- Epigenetics and DNA Methylation
- Vascular Tumors and Angiosarcomas
- Congenital heart defects research
- Hedgehog Signaling Pathway Studies
- Atherosclerosis and Cardiovascular Diseases
- Immune cells in cancer
- Cerebrovascular and genetic disorders
- Digital Imaging in Medicine
- Liver physiology and pathology
- Estrogen and related hormone effects
- Organ and Tissue Transplantation Research
- Renal and related cancers
- Reproductive Biology and Fertility
- Cell Adhesion Molecules Research
- Surgical Sutures and Adhesives
Columbia University
2014-2024
Columbia University Irving Medical Center
2013-2024
Creative Commons
2017-2023
DermSurgery Associates
2023
NewYork–Presbyterian Hospital
2015-2021
New York Hospital Queens
2015-2021
Morgan Stanley Children's Hospital
2020-2021
Presbyterian Hospital
2021
Boston Children's Hospital
2016
Harvard University
2016
Rulang Jiang, Yu Lan, Harry D. Chapman, Carrie Shawber, Christine R. Norton, David V. Serreze, Gerry Weinmaster, and Thomas Gridley The Jackson Laboratory, Bar Harbor, Maine 04609 USA; Department of Biological Chemistry, University California, Los Angeles (UCLA), School Medicine, Angeles, California 90024 USA
ABSTRACT Notch controls cell fate by inhibiting cellular differentiation, presumably through activation of the transcriptional regulator human C promoter Binding Factor (CBF1), which transactivates hairy and Enhancer split (HES-1) gene. However, we describe constitutively active forms Notch1, inhibit muscle differentiation but do not interact with CBF1 or upregulate endogenous HES-1 expression. In addition, Jagged-Notch interactions that prevent expression specific genes involve upregulation...
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...
The Notch family of cell surface receptors and its ligands are highly conserved proteins that regulate fate determination, including those involved in mammalian vascular development. We report induces VEGFR-3 expression vitro human endothelial cells vivo mice. In vitro, complex with the DNA-binding protein CBF-1/suppressor hairless/Lag1 (CSL) bound promoter transactivated specifically cells. Through induction VEGFR-3, increased responsiveness to VEGF-C, promoting survival morphological...
Abstract Notch signaling is required for vascular development and tumor angiogenesis. Although inhibition of the ligand Delta-like 4 can restrict growth disrupt neovasculature, effect inhibiting receptor function on angiogenesis has yet to be defined. In this study, we generated a soluble form Notch1 (Notch1 decoy) assessed its in vitro vivo. decoy expression reduced stimulated by binding three distinct ligands inhibited morphogenesis endothelial cells overexpressing Notch4. Thus, functioned...
The discovery that Notch, a key regulator of cell fate determination, is functional in the vasculature has greatly improved our understanding differentiation and specialization vessels. Notch signaling been proven to be critical for arterial specification, sprouting angiogenesis, vessel maturation. In newly forming vascular sprouts, promotes distinction between leading "tip" endothelial growing "stalk" cell, cells eventually form new capillary. also implicated stability by regulating mural...
A proangiogenic role for Jagged (JAG)-dependent activation of NOTCH signaling in the endothelium has yet to be described. Using proteins that encoded different NOTCH1 EGF-like repeats, we identified unique regions Delta-like ligand (DLL)-class and JAG-class ligand-receptor interactions, developed decoys function as ligand-specific inhibitors. N110-24 decoy blocked JAG1/JAG2-mediated signaling, angiogenic sprouting vitro, retinal angiogenesis, demonstrating JAG-dependent signal promotes...
Although most nephron segments contain one type of epithelial cell, the collecting ducts consists at least two: intercalated (IC) and principal (PC) cells, which regulate acid-base salt-water homeostasis, respectively. In adult kidneys, these cells are organized in rosettes suggesting functional interactions. Genetic studies mouse revealed that transcription factor Tfcp2l1 coordinates IC PC development. induces expression specific genes, including H+-ATPase subunits Jag1. Jag1 turn,...
In development, lymphatic endothelial cells originate within veins and differentiate via a process requiring Prox1. Notch signaling regulates cell-fate decisions, expression studies suggested that Jag1/Notch1 functions in during specification. Using an inducible Prox1CreERT2 driver, was suppressed by deleting Notch1 or expressing dominant-negative Mastermind-like Prox1+ cells. Either loss of reduced increased progenitor cell numbers the veins, leading to incomplete separation venous vessels....
Background: Infantile hemangiomas can cause significant morbidity during proliferation, yet there is no U.S. Food and Drug Administration–approved treatment. They are believed to form from hemangioma stem cells, which differentiate toward a endothelial cell phenotype. Recently, propranolol has demonstrated effectiveness in treating complicated infantile hemangiomas. The authors hypothesize that facilitates their involution by altering cellular behavior both cells. Methods: Hemangioma cells...
Hepatic Notch signaling is inappropriately activated in obese/insulin-resistant mouse models. Genetic or pharmacologic inhibition of hepatic obese mice simultaneously improves glucose tolerance and reduces triglyceride content. As such, we predicted that human liver would be positively associated with insulin resistance steatosis. Here, systematically survey biopsy specimens, show active lean adults, expression multiple receptors ligands. In morbidly patients undergoing bariatric surgery,...
In the vasculature, Notch signaling functions as a downstream effecter of Vascular Endothelial Growth Factor (VEGF) signaling. VEGF regulates sprouting angiogenesis in part by inducing and activating matrix metalloproteases (MMPs). This study sought to determine if regulation MMPs was mediated via how influenced endothelial cell morphogenesis.We assessed relationship between cultured human umbilical vein cells. Overexpression VEGF-induced Notch4 ligand, Dll4, activated signaling, altered...
The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of than age-matched non-pregnant women, the risk feto-placental infection is low. Using cohort 66 COVID-19-positive in late pregnancy, we correlated clinical parameters with severity, placental histopathology, and expression viral entry Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None demographic or...
Abstract T-cell position in the tumor microenvironment determines probability of target encounter and killing. CD8+ exclusion from parenchyma is associated with poor response to immunotherapy, yet biology that underpins this distinct pattern remains unclear. Here we show vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised integrity periphery, leading impaired infiltration core. The spatial regulation ANGPT2 whole cross-sections was analyzed conjunction distribution,...