A5035207083- Adenosine and Purinergic Signaling
- Genetic and Kidney Cyst Diseases
- Cancer, Hypoxia, and Metabolism
- Respiratory Support and Mechanisms
- Neonatal Respiratory Health Research
- Liver physiology and pathology
- Neurological Complications and Syndromes
- Growth Hormone and Insulin-like Growth Factors
- Liver Disease Diagnosis and Treatment
- Acute Kidney Injury Research
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
- Immune Response and Inflammation
- Fibroblast Growth Factor Research
- Renal and related cancers
- Circular RNAs in diseases
- Neuroscience of respiration and sleep
- Circadian rhythm and melatonin
- Cancer, Stress, Anesthesia, and Immune Response
- Mitochondrial Function and Pathology
- Axon Guidance and Neuronal Signaling
- Apelin-related biomedical research
- Cellular Mechanics and Interactions
- Nuclear Receptors and Signaling
- Cancer Cells and Metastasis
University of Colorado Denver
2003-2018
University of Colorado Anschutz Medical Campus
2011-2017
University of Colorado Health
2000-2009
University Gastroenterology
2008
University of Colorado Cancer Center
2003
MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits by constraining the nlrp3 inflammasome. was increased in biopsies from patients with active IBD and preclinical models of inflammation. miR-223-/y mice presented exacerbated myeloid-driven experimental colitis heightened clinical, histopathological,...
Background While acute lung injury (ALI) contributes significantly to critical illness, it resolves spontaneously in many instances. The majority of patients experiencing ALI require mechanical ventilation. Therefore, we hypothesized that ventilation and concomitant stretch-exposure pulmonary epithelia could activate endogenous pathways important protection. Methods Findings To examine transcriptional responses during ALI, exposed cyclic stretch conditions—an vitro model resembling A...
Intercellular transfer of miR-223 from neutrophils to alveolar epithelial cells reduces lung inflammation in a mouse model ventilator-induced injury or pulmonary bacterial infection.
Abstract Myocardial ischemia–reperfusion injury (IRI) leads to the stabilization of transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, role HIF2-alpha remains elusive. Here we show that induces epithelial growth amphiregulin (AREG) elicit cardioprotection myocardial IRI. Comparing mice with inducible deletion Hif1a or Hif2a cardiac myocytes, loss Hif2-alpha increases infarct sizes....
NK cells are innate lymphoid important for immune surveillance, identifying and responding to stress, infection, and/or transformation. Whereas conventional (cNK) circulate systemically, many reside in tissues where they appear be poised locally regulate tissue function. In the present study, we tested contribution of tissue-resident (trNK) homeostasis by studying ischemic injury mouse kidney. Parabiosis experiments demonstrate that kidney contains a significant fraction trNK under...
Acute lung injury (ALI) is characterized by alveolar and uncontrolled inflammation. Since most cases of ALI resolve spontaneously, understanding the endogenous mechanisms that promote resolution important to developing effective therapies. Previous studies have implicated extracellular adenosine signaling in tissue adaptation wound healing. Therefore, we hypothesized a functional contribution for production during resolution. As model, administered intratracheal LPS observed peak at 3 d,...
A complex biologic network regulates kidney perfusion under physiologic conditions. This system is profoundly perturbed following renal ischemia, a leading cause of acute injury (AKI) — life-threatening condition that frequently complicates the care hospitalized patients. Therapeutic approaches to prevent and treat AKI are extremely limited. Better understanding molecular pathways promoting postischemic reflow could provide new candidate targets for therapeutics. Due its role in adapting...
Abstract Although acute lung injury (ALI) contributes significantly to critical illness, resolution often occurs spontaneously through endogenous pathways. We recently found that mechanical ventilation increases levels of pulmonary adenosine, a signaling molecule known attenuate inflammation. In this study, we hypothesized contribution transcriptionally controlled pathways adenosine receptor (ADOR) during ALI. gained initial insight from microarray analysis epithelia exposed conditions...
The signaling molecule adenosine has been implicated in attenuating acute lung injury (ALI). Adenosine is terminated by its uptake through equilibrative nucleoside transporters (ENTs). We hypothesized that ENT-dependent could be targeted to enhance adenosine-mediated protection. To address this hypothesis, we exposed mice high-pressure mechanical ventilation induce ALI. Initial studies demonstrated time-dependent repression of ENT1 and ENT2 transcript protein levels during examine the...
Abstract Acute lung injury (ALI) is an acute inflammatory disease that causes morbidity and mortality in critically ill patients. However, there are many instances where ALI resolves spontaneously through endogenous pathways help to control excessive inflammation. Previous studies have implicated the extracellular signaling molecule adenosine events A2B receptor protection. In this context, we hypothesized tissue-specific expression of responsible for previously described attenuation ALI. To...
Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on rhythm proteins in the heart indicated a role for Clock or Per2 cardiac metabolism. In contrast Clock−/−, Per2−/− mice have larger infarct sizes with deficient lactate production during myocardial ischemia. To test hypothesis that represents an important regulator metabolism ischemia, we measured reperfusion Per1−/−, wildtype mice. As measurements whole blood exclusive controlling next...
The netrin family of secreted proteins provides migrational cues in the developing central nervous system. Recently, netrins have also been shown to regulate diverse processes beyond their functions brain, incluing ochrestration inflammatory events. Particularly netrin-1 has implicated dampening hypoxia-induced inflammation. Here, we hypothesized an anti-inflammatory role endogenous acute kidney injury (AKI). As homozygous deletion is lethal, studied mice with partial (Ntn-1+/− mice) as a...
A wide search for ischemic preconditioning (IPC) mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2) to be cardioprotective. Studies on cardiac metabolism found a key role Per2 in mediating metabolic dependence carbohydrate metabolism. To profile mediated pathways following IPC mouse heart, we performed genome array and 352 abundantly expressed well-characterized dependent micro RNAs. One prominent result our silico analysis RNAs revealed...
Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known be involved in both inflammatory gene regulation and host-pathogen interactions key pathogenesis sepsis. The goal study was determine role miR-223 as a mediator kidney injury. Using knockout mice multiple models experimental sepsis, we found that differentially influences acute injury (AKI) based model used. In...
Proliferation of cyst-lining epithelial cells is an integral part autosomal dominant polycystic kidney disease (ADPKD) cyst growth. Cytokines and growth factors within fluids are positioned to induce Vascular endothelial factor (VEGF) a pleiotropic present in ADPKD liver (human 1,128 ± 78, mouse 2,787 136 pg/ml) and, lesser extent, renal 294 41, 191 90 pg/ml). Western blotting showed that receptors for VEGF (VEGFR1 VEGFR2) were both normal bile ducts pkd2(WS25/−) cells. Treatment with...
Ischemia and reperfusion significantly contributes to the morbidity mortality of liver surgery transplantation. Based on studies showing a critical role for adenosine signaling in mediating tissue adaptation during hypoxia, we hypothesized that events through receptors (ADORA1, ADORA2A, ADORA2B, or ADORA3) attenuates hepatic ischemia injury. Initial screening human biopsies obtained transplantation demonstrated selective robust induction ADORA2B transcript protein following reperfusion....
Pit-1/GHF-1 is a pituitary-specific, POU homeodomain transcription factor required for development of somatotroph, lactotroph, and thyrotroph cell lineages regulation the temporal spatial expression growth hormone, prolactin (PRL), thyrotropin-beta genes. Synergistic interaction Pit-1 with member Ets family factors, Ets-1, has been shown to be an important mechanism regulating basal Ras-induced lactotroph-specific rat (r) PRL promoter activity. Pit-1beta/GHF-2, alternatively spliced isoform...
The genetic and molecular mechanisms that initiate maintain pituitary tumorigenesis are poorly understood. Nonfunctioning tumors of the gonadotrope lineage represent 35% all tumors; usually macroadenomas, often resulting in hypopituitarism; have no medical treatments. Using expression microarrays combined with whole-genome copy number screens on individual human tumors, we identified mammalian sterile-20-like kinase (MST4) transcript, which was amplified within chromosome Xq26.2 one tumor...
Abstract A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment polymorphonuclear neutrophils (PMNs) into lungs, causing significant collateral tissue damage. Defining molecular and cellular steps that control neutrophil infiltration activation during ALI therefore important therapeutic relevance. Based on previous findings implicating transcription factor Tbet mucosal Th1-inflammation, we hypothesized a detrimental role for ALI. In line with our hypothesis,...
Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent genetic that results in cyst formation and liver. Cytokines growth factors secreted by the cyst-lining epithelia are positioned to initiate autocrine/paracrine signaling promote growth. Comparative analyses of human liver fluids revealed disparate cytokine/growth factor profiles. CXCR2 agonists, including IL-8, epithelial neutrophil-activating peptide (ENA-78), growth-related oncogene-alpha (GRO-alpha), potent...
The Ets-binding site within the basal transcription element (BTE) of rat prolactin (rPRL) promoter is critical for both and growth factor-regulated rPRL gene expression. Here we report purification identification factor that binds to BTE. This was purified from GH3 pituitary nuclear extracts using ammonium sulfate fractionation, heparin-Sepharose Mono Q chromatography, BTE-affinity magnetic beads. We two proteins 57 47 kDa identified 57-kDa protein by mass spectrometry as Ets GABPα. Western...