A5015690059- Axon Guidance and Neuronal Signaling
- Apelin-related biomedical research
- Angiogenesis and VEGF in Cancer
- Cancer Mechanisms and Therapy
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Hippo pathway signaling and YAP/TAZ
- Hemoglobinopathies and Related Disorders
- HER2/EGFR in Cancer Research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Neuroscience of respiration and sleep
- Obstructive Sleep Apnea Research
- Cancer, Hypoxia, and Metabolism
- Sleep and Wakefulness Research
- Sarcoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Hemoglobin structure and function
- Cancer-related Molecular Pathways
- Kruppel-like factors research
- CRISPR and Genetic Engineering
- Global Cancer Incidence and Screening
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
- Eicosanoids and Hypertension Pharmacology
Duke University
2020
Vanderbilt University
2014-2017
Vanderbilt University Medical Center
2016
National Heart Lung and Blood Institute
2009-2013
National Institutes of Health
2009-2013
University of New Mexico
2007-2008
Rhabdomyosarcoma (RMS) is a childhood cancer originating from skeletal muscle, and patient survival poor in the presence of metastatic disease. Few determinants that regulate metastasis development have been identified. The receptor tyrosine kinase FGFR4 highly expressed RMS tissue, suggesting role tumorigenesis, although its functional importance has not defined. Here, we report identification mutations human tumors lead to activation present evidence it functions as an oncogene RMS. Higher...
Genome-wide analyses determined previously that the receptor tyrosine kinase (RTK) EPHA2 is commonly overexpressed in non-small cell lung cancers (NSCLCs). overexpression associated with poor clinical outcomes; therefore, may represent a promising therapeutic target for patients NSCLC. In support of this hypothesis, here we have shown targeted disruption EphA2 murine model aggressive Kras-mutant NSCLC impairs tumor growth. Knockdown human lines reduced growth and viability, confirming...
In clinical studies, sleep apnea is associated with hypertension, oxidative stress, and increased circulating endothelin-1 (ET-1). We previously developed a model of by exposing rats to eucapnic intermittent hypoxia (IH-C) during sleep, which increases both blood pressure plasma levels ET-1. Because similar protocols in mice increase tissue markers we hypothesized that IH-C generation reactive oxygen species (ROS) contributes the development ET-1-dependent hypertension rats. To test this,...
Basal-like/triple-negative breast cancers (TNBCs) are among the most aggressive forms of cancer, and disproportionally affects young premenopausal women African descent. Patients with TNBC suffer a poor prognosis due in part to lack molecularly targeted therapies, which represents critical barrier for effective treatment. Here, we identify EphA2 receptor tyrosine kinase as clinically relevant target TNBC. expression is enriched basal-like molecular subtype human cancers. Loss function both...
Abstract Dysregulation of receptor tyrosine kinases (RTK) contributes to cellular transformation and cancer progression by disrupting key metabolic signaling pathways. The EPHA2 RTK is overexpressed in aggressive forms breast cancer, including the HER2+ subtype, correlates with poor prognosis. However, role tumor metabolism remains unexplored. In this study, we used vivo vitro models HER2-overexpressing investigate mechanisms which ligand–independent promotes tumorigenesis absence its...
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates diverse array cellular processes, including cell growth, survival, metabolism, and cytoskeleton dynamics. mTOR functions in two distinct complexes, mTORC1 mTORC2, whose activities substrate specificities are regulated by complex specific cofactors, Raptor Rictor, respectively. Little known regarding the relative contribution versus mTORC2 vascular endothelial cells. Using mouse models or Rictor gene targeting,...
GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 a cofactor nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated African populations. We examined pain sickle cell anemia rs8007267 was risk factor crises discovery ( n = 228; odds ratio [OR] 2.26; P 0.009) replication 513; OR 2.23; 0.004) cohorts. In vitro , cells from subjects homozygous allele...
Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence tumor invasion adjacent structures or metastasis. LIM-only protein 4 (LMO4) LIM-domain binding 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial differentiation, been associated with increased metastasis, decreased shortened survival breast. Here, we implicate LDB1-binding proteins, single-stranded 2 (SSBP2) 3...
Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited tumors. Indeed, tumors upregulate proangiogenic molecules while simultaneously suppressing angiostatic pathways to recruit blood vessels for growth, survival, metastatic spread. Understanding how cancers exploit antiangiogenic signals a key step developing new, molecularly targeted therapies. While...
<ns4:p><ns4:bold>Background:</ns4:bold> The conventional dogma of treating cancer by focusing on the elimination tumor cells has been recently refined to include consideration microenvironment, which includes host stromal cells. Ephrin-A1, a cell surface protein involved in adhesion and migration, shown be suppressive context cell. However, its role not fully investigated. Here, we examine how ephrin-A1 deficiency affects growth metastasis murine model breast cancer.</ns4:p><ns4:p>...
<ns4:p><ns4:bold>Background:</ns4:bold> The conventional dogma of treating cancer by focusing on the elimination tumor cells has been recently refined to include consideration microenvironment, which includes host stromal cells. Ephrin-A1, a cell surface protein involved in adhesion and migration, shown be suppressive context cell. However, its role not fully investigated. Here, we examine how ephrin-A1 deficiency affects growth metastasis murine model breast cancer.</ns4:p><ns4:p>...
Rats exposed to intermittent hypoxia/hypercapnia (IH/HC) during sleep mimic apnea have increased mean arterial pressure (MAP) and endothelin 1 (ET-1). We previously reported that the superoxide dismutase mimetic tempol prevents this increase in blood circulating ET-1. Because (O2−) can stimulate ET-1 synthesis, we hypothesized IH/HC increases O2− rats MAP. To test this, were or air cycling (Sham) for 14 days. On day 14, mesenteric arteries dissected used evaluate effect of on generation....
Abstract Genome-wide analyses determined previously that the receptor tyrosine kinase (RTK) EPHA2 is commonly overexpressed in non-small cell lung cancers (NSCLCs). overexpression associated with poor clinical outcomes; therefore, may represent a promising therapeutic target for patients NSCLC. In support of this hypothesis, we have shown targeted disruption murine model aggressive KRAS-mutant NSCLC impairs tumor growth. Knockdown human lines reduced growth and viability, confirming...
<div>Abstract<p>Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited tumors. Indeed, tumors upregulate proangiogenic molecules while simultaneously suppressing angiostatic pathways to recruit blood vessels for growth, survival, metastatic spread. Understanding how cancers exploit antiangiogenic signals a key step developing new, molecularly...
<div>Abstract<p>Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited tumors. Indeed, tumors upregulate proangiogenic molecules while simultaneously suppressing angiostatic pathways to recruit blood vessels for growth, survival, metastatic spread. Understanding how cancers exploit antiangiogenic signals a key step developing new, molecularly...
<p>Supplemental Figure Legends</p>
<p>Supplemental Figure S1: Dose response for Slit2-mediated inhibition of VEGF-induced vascular assembly.</p>
<p>Supplemental Figure S2: Inhibiting Slit activity rescues VEGF-induced vascular assembly and migration in EphA2 knockdown human endothelial cells.</p>
<p>Supplemental Figure S3: Inhibiting Slit activity rescues tumor cell-induced EphA2-deficient endothelial cell migration.</p>