A5084644555- Caveolin-1 and cellular processes
- Ion Transport and Channel Regulation
- Signaling Pathways in Disease
- Eicosanoids and Hypertension Pharmacology
- Protease and Inhibitor Mechanisms
- Gastrointestinal motility and disorders
- Cardiac Ischemia and Reperfusion
- Ion channel regulation and function
- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Lipid metabolism and biosynthesis
- Virus-based gene therapy research
- Lipid metabolism and disorders
- CRISPR and Genetic Engineering
- Platelet Disorders and Treatments
- Cancer, Hypoxia, and Metabolism
- Mechanical Circulatory Support Devices
- Animal Virus Infections Studies
- Calcium signaling and nucleotide metabolism
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- Cell Adhesion Molecules Research
- Ion Channels and Receptors
- Photosynthetic Processes and Mechanisms
- Microbial Metabolic Engineering and Bioproduction
St. Jude Children's Research Hospital
2023-2024
University of Michigan–Ann Arbor
2021-2023
Imaging Center
2013-2023
University of Alberta
2012-2022
Princeton University
2011-2012
University of Calgary
2011
University of Arizona
2010
Instituto Nacional de Enfermedades Respiratorias
2009
Universidad Nacional Autónoma de México
2009
Instituto Nacional de Perinatología
2009
Background— Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in cardiac sarcomere determines systolic diastolic function. Loss of titin ischemic hearts has been reported, but mechanism degradation not well understood. Matrix metalloproteinase-2 (MMP-2) localized and, on activation ischemia/reperfusion injury, proteolyzes specific proteins. Here we determine whether an intracellular substrate for MMP-2 if its during contributes...
Abstract Aims Heart failure is a major complication in cancer treatment due to the cardiotoxic effects of anticancer drugs, especially from anthracyclines such as doxorubicin (DXR). DXR enhances oxidative stress and stimulates matrix metalloproteinase-2 (MMP-2) cardiomyocytes. We investigated whether MMP inhibitors protect against cardiotoxicity given role MMP-2 proteolyzing sarcomeric proteins heart remodelling extracellular matrix. Methods results Eight-week-old male C57BL/6J mice were...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for global COVID-19 pandemic, triggers formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks factors construct DMVs. We show that ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling replication, which leads productive infection....
The mannose-6-phosphate (M6P) biosynthetic pathway for lysosome biogenesis has been studied decades and is considered a well-understood topic. However, whether this regulated remains an open question. In genome-wide CRISPR/Cas9 knockout screen, we discover TMEM251 as the first regulator of M6P modification. Deleting causes mistargeting most lysosomal enzymes due to their loss modification accumulation numerous undigested materials. We further demonstrate that localizes Golgi required...
Contact sites between lipid droplets and other organelles are essential for cellular energy homeostasis upon metabolic demands. Detection of these contact at the nanometer scale over time in living cells is challenging. We developed a tool kit detecting based on fluorogen-activated bimolecular complementation CONtact sites, FABCON, using reversible, low-affinity split fluorescent protein, splitFAST. FABCON labels with minimal perturbation to organelle interaction. Via we quantitatively...
Matrix metalloproteinase-2 (MMP-2) has been extensively studied in the context of extracellular matrix remodeling but is also localized within cells and can be activated by prooxidants to proteolyze specific intercellular targets. Although there are reports MMP-2 mitochondria, a critical source cellular oxidative stress, these studies did not take into account presence their preparations mitochondria-associated membrane (MAM), subdomain endoplasmic reticulum (ER). We hypothesized that...
Matrix metalloproteinase (MMP)-2 is activated in aorta during endotoxemia and plays a role the hypocontractility to vasoconstrictors. Calponin-1 regulator of vascular smooth muscle tone with similarities troponin, cardiac myocyte protein that cleaved by MMP-2 myocardial oxidative stress injuries. We hypothesized calponin-1 may be proteolyzed endotoxemia-induced hypocontractility.Rats were given nonlethal dose bacterial lipopolysaccharide (LPS) or vehicle. Some rats MMP inhibitors ONO-4817...
Aims: Myocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms limit injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids dihydroxyeicosatrienoic protects from caused by myocardial infarction. Methods: sEH null and WT littermate mice were subjected surgical occlusion of left anterior descending artery or sham...
The murine jejunum and lower esophageal sphincter (LES) were examined to determine the locations of various signaling molecules their colocalization with caveolin-1 one another. Caveolin-1 was present in punctate sites plasma membranes (PM) all smooth muscles diffusely classes interstitial cells Cajal (ICC; identified by c-kit immunoreactivity), ICC-myenteric plexus (MP), ICC-deep muscular (DMP), ICC-serosa (ICC-S), ICC-intramuscularis (IM). In general, ICC also contained L-type Ca(2+)...
Persistent arterial hypotension is a hallmark of sepsis and believed to be caused, at least in part, by excess nitric oxide (NO). NO can combine with superoxide produce peroxynitrite, which activates matrix metalloproteinases (MMPs). Whether MMP inhibition vivo protects against vascular hyporeactivity induced endotoxemia unknown. Male Sprague-Dawley rats were administered either bacterial lipopolysaccharide (LPS, 4 mg/kg ip) or vehicle (pyrogen-free water). Later (30 min), animals received...
Reoviridae virus family members, such as mammalian orthoreovirus (reovirus), encounter a unique challenge during replication. To hide the dsRNA from host recognition, genome remains encapsidated in transcriptionally active proteinaceous core capsids that transcribe and release +RNA. De novo +RNAs proteins must repeatedly assemble into new progeny cores order to logarithmically amplify Reoviruses also produce outercapsid (OC) μ1, σ3 σ1 onto create highly stable infectious full virions....
Abstract Matrix metalloproteinase‐2 (MMP‐2) may play roles at intracellular and extracellular sites of the heart in ischaemia/reperfusion injury. Caveolins (Cav‐1, ‐2 ‐3) are lipid raft proteins which cell sig‐nalling. This study examined, using immunohistochemistry two photon confocal microscopy, if MMP‐2 caveolins co‐localize plasma membrane cardiac cells: cardiomyocytes (CM), fibroblasts (FB) capillary endothelial cells (CEC) left ventricle (LV) Cav‐1 +/+ −/− mouse heart. In LV...
ABSTRACT The rubella virus (RV) capsid is an RNA-binding protein that functions in nucleocapsid assembly at the Golgi complex, site of budding. In addition to its role assembly, pools associate with mitochondria, a localization not consistent assembly. Here we examined interaction mitochondria and showed this viral inhibits import processing mitochondrial precursor proteins vitro. Moreover, RV-infected cells were found contain lower intramitochondrial levels matrix p32. inhibiting...
Although mammals are thought to lose their capacity regenerate heart muscle shortly after birth, embryonic and neonatal cardiomyocytes in hyperplastic. During proliferation these cells need selectively disassemble myofibrils for successful cytokinesis. The mechanism of sarcomere disassembly is, however, not understood. To study this, we performed a series immunofluorescence studies multiple sarcomeric proteins proliferating rat ventricular myocytes correlated observations with biochemical...
Caveolins (Cav) are structural proteins that insert into the plasma membrane to form caveolae can bind molecules important in cardiac signal transduction and function. Cytochrome P450 epoxygenases metabolize arachidonic acid epoxyeicosatrienoic acids (EETs) which have known cardioprotective effects. Subsequent metabolism of EETs by soluble epoxide hydrolase reduces protective effect.(1) To assess effect ischemia-reperfusion injury on expression subcellular localization caveolins. (2) study...
Abstract Tissue culture medium routinely contains fetal bovine serum (FBS). Here we show that culturing human hepatoma cells in their native, adult (human serum, HS) results the restoration of key morphological and metabolic features normal liver cells. When moved to HS, these differential transcription 22–32% genes, stop proliferating, assume a hepatocyte-like morphology. Metabolic analysis shows Warburg-like profile, typical for FBS-cultured cells, is replaced by diverse profile consistent...
Some receptors and signaling molecules, such as Rho-kinase (ROCK), localize in caveolae. We asked whether the function of histamine (H 1 ) 5-hydroxytryptamine (serotonin) (5-HT 2A bovine tracheal smooth muscle are modified after caveolae disruption if so, altered ROCK activity plays a role this modification. Methyl-β-cyclodextrin (MβCD), used to deplete membrane cholesterol, was shown disrupt diminish sustained contractions (∼80%), 5-HT (100%), α-methyl-5-HT KCl (∼30%). Cholesterol-loaded...
Abstract In mouse intestine, caveolae and caveolin‐1 (Cav‐1) are present in smooth muscle (responsible for executing contractions) interstitial cells of Cajal (ICC; responsible pacing contractions). We found that a number calcium handling/dependent molecules associated with caveolae, including L‐type Ca 2+ channels, Na + ‐Ca exchanger type 1 (NCX1), plasma membrane pumps neural nitric oxide synthase (nNOS), close to the peripheral endo‐sarcoplasmic reticulum (ER‐SR). Also we this assemblage...