A5067267440- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Steroid Chemistry and Biochemistry
- Estrogen and related hormone effects
- Biochemical and Molecular Research
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects of Natural Compounds
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Muscle metabolism and nutrition
- Nitric Oxide and Endothelin Effects
- Pulmonary Hypertension Research and Treatments
- Diagnosis and treatment of tuberculosis
- Cancer-related gene regulation
- Helicobacter pylori-related gastroenterology studies
- Menopause: Health Impacts and Treatments
- Cellular Mechanics and Interactions
- ATP Synthase and ATPases Research
- Fungal and yeast genetics research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Plant biochemistry and biosynthesis
- Biomarkers in Disease Mechanisms
- Nuclear Receptors and Signaling
- Caveolin-1 and cellular processes
Cornell University
2008-2023
New York State College of Veterinary Medicine
2017-2019
Ithaca College
2013
Sutter Davis Hospital
2010
The Ohio State University
2004-2006
Lung Institute
2006
Columbus Center
2006
University of Miami
2006
Inhibiting endothelial cell contractility reverses the deleterious effects of age-related matrix stiffening on normal function, which could help prevent development atherosclerosis.
Tumor microvasculature tends to be malformed, more permeable, and tortuous than vessels in healthy tissue, effects that have been largely attributed up-regulated VEGF expression. However, tumor tissue stiffen during solid progression, stiffness is known alter cell behaviors including proliferation, migration, cell-cell adhesion, which are all requisite for angiogenesis. Using vitro, vivo, ex ovo models, we investigated the of matrix on vessel growth integrity Our data indicate angiogenic...
Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) maintain infections in mammals but mechanisms proteins responsible for the import of acids Mtb were previously unknown. Here, we identify determine that uncharacterized protein Rv3723/LucA, functions integrate cholesterol acid uptake Mtb. Rv3723/LucA interacts with subunits Mce1 Mce4 complexes coordinate...
Summary Bacterial nutrition is an essential aspect of host–pathogen interaction. For the intracellular pathogen Mycobacterium tuberculosis (Mtb), causative agent in humans, fatty acids derived from lipid droplets are considered major carbon source. However, many other soluble nutrients available inside host cells and may be used as alternative sources. Lactate pyruvate abundant human fluids, particularly during inflammation. In this work, we study Mtb metabolism lactate combining classic...
Mycobacterium tuberculosis (Mtb) imports and metabolizes fatty acids to maintain infection within human macrophages. Although this is a well-established paradigm, the bacterial factors required for acid import are poorly understood. Previously, we found that LucA Mce1 in Mtb (Nazarova et al., 2017). Here, identified additional mutants have reduced ability fluorescent substrate during This screen novel genes as rv2799 rv0966c be necessary confirmed central role Rv3723/LucA putative components...
Despite the deployment of combination tuberculosis (TB) chemotherapy, efforts to identify shorter, nonrelapsing treatments have resulted in limited success. Recent evidence indicates that GSK2556286 (GSK286), which acts via Rv1625c, a membrane-bound adenylyl cyclase Mycobacterium tuberculosis, shortens treatment rodents relative standard care drugs. Moreover, GSK286 can replace linezolid three-drug, Nix-TB regimen. Given its therapeutic potential, we sought better understand mechanism action...
This study analyzed the regulation of α 2 -adrenoceptors (α -ARs) in human vascular smooth muscle cells (VSMs). Saphenous veins and dermal arterioles or VSMs cultured from them expressed high levels -ARs 2C > 2A , via RNase protection assay) responded to -AR stimulation [5-bromo- N-(4,5-dihydro-1 H-imidazol-2-yl)-6-quinoxalinamine (UK-14,304, 1 μM)] with constriction calcium mobilization. In contrast, aorta did not express neither nor intact UK-14,304. Although >> ) were detected...
There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics can disrupt cholesterol by Mtb vivo . Here we identify small molecule agonist (V-59) adenylyl cyclase Rv1625c, which stimulates 3’, 5’-cyclic adenosine monophosphate (cAMP) synthesis and inhibits Mtb. Similarly, using complementary genetic approach induces...
Mycobacterium tuberculosis (Mtb) uses a complex 3', 5'-cyclic AMP (cAMP) signaling network to sense and respond changing environments encountered during infection, so perturbation of cAMP might be leveraged disrupt Mtb pathogenesis. However, understanding pathways is hindered by the presence at least 15 distinct adenylyl cyclases (ACs). Recently, small molecule V-58 was shown inhibit replication within macrophages stimulate production in Mtb. Here we determined that rapidly directly...
Thrombospondin-1 (TSP-1) is an extracellular protein critical to normal lung homeostasis, and reported activate latent transforming growth factor-β (TGF-β). Because active TGF-β causally involved in fibrosis after bleomycin challenge, alterations TSP-1 may be relevant pulmonary fibrosis. We sought determine the effects of deficiency on susceptibility bleomycin-induced a murine model. Age-matched sex-matched C57BL/6 wild-type (WT) TSP-1-deficient mice were treated twice weekly for 4 weeks...
Women are at high risk of dying from unrecognized cardiovascular disease. Many differences in disease between men and women appear to be mediated by vascular smooth muscle cells (SMC). Because estrogen reduces the proliferation SMC, we hypothesized that activation receptor-alpha (ERalpha) agonists or growth factors altered SMC function. To determine effect factors, estrogen, ERalpha expression on differentiation, human aortic were cultured serum-free conditions for 10 days. had lower...
Upon infection, Mycobacterium leprae, an obligate intracellular bacillus, induces accumulation of cholesterol-enriched lipid droplets (LDs) in Schwann cells (SCs). LDs are promptly recruited to M. leprae-containing phagosomes, and inhibition this process decreases bacterial survival, suggesting that LD recruitment constitutes a mechanism by which host-derived lipids delivered leprae. We previously demonstrated leprae has preserved only the capacity oxidize cholesterol cholestenone, first...
The identification of small molecules that positively modulate the mitochondrial respiratory function has broad applications in fundamental research, therapeutic target validation, and drug discovery. We present an approach which primary screens for yeast are used to efficiently identify a subset high-value compounds can turn be rapidly tested against range mammalian cell lines. ability assay successfully high-throughput format hit increase membrane potential adenosine triphosphate (ATP)...
Abstract TGF-β plays an important role in the genesis and progression of pulmonary fibrosis. We sought to determine mononuclear phagocytes activation found that freshly isolated peripheral blood monocytes spontaneously released TGF-β. Stimulating these with GM-CSF or LPS, but not MCSF, augmented In human monocytes, free thiol compounds DTT NAC decreased activity TGF-β, without affecting mRNA transcription. Both lessened biological recombinant active a cell-free system. reduced dimeric from...
PURPOSE: A proprietary tart cherry juice blend (TCJB) has previously been shown to reduce functional and subjective markers of exercise-induced muscle damage in humans (Connolly et al 2006). The purpose this study was test the effect TCJB on blood horses assess potential antioxidant anti-inflammatory mechanisms. METHODS: Six untrained (mean age 10 yr, range 5-17 yr) were randomly divided into 2 groups a crossover design (2 week wash out) administered either or placebo blinded fashion. Horses...
Abstract Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts and Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol fatty acids) maintain infection in mammals. While the uptake of cholesterol by Mtb is mediated Mce4 transporter, route(s) acids remain unknown. Here, we demonstrate that an uncharacterized protein LucA, integrates assimilation both Mtb. LucA interacts with subunits Mce1 complexes coordinate activities these...
Abstract There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics can disrupt cholesterol by Mtb vivo . Here we identify small molecule agonist (V-59) adenylyl cyclase Rv1625c, which stimulates 3’, 5’-cyclic adenosine monophosphate (cAMP) synthesis and inhibits Mtb. Similarly, using complementary genetic approach...