A5082132858- Metabolism, Diabetes, and Cancer
- MicroRNA in disease regulation
- Intracranial Aneurysms: Treatment and Complications
- Cancer-related molecular mechanisms research
- Vascular Malformations Diagnosis and Treatment
- Kruppel-like factors research
- Intracerebral and Subarachnoid Hemorrhage Research
- PARP inhibition in cancer therapy
- Pancreatic function and diabetes
- Circular RNAs in diseases
- Bioinformatics and Genomic Networks
- Cancer-related gene regulation
- Cholesterol and Lipid Metabolism
- Gene expression and cancer classification
- Lung Cancer Treatments and Mutations
- Liver Disease and Transplantation
- Cancer, Hypoxia, and Metabolism
- Liver Disease Diagnosis and Treatment
- Pulmonary Hypertension Research and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Calpain Protease Function and Regulation
- Renin-Angiotensin System Studies
- Signaling Pathways in Disease
- Phytochemicals and Medicinal Plants
University of California, Riverside
2010-2024
Victor Valley College
2021-2024
University of California, San Diego
2011-2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
2023
First Hospital of Xi'an
2011-2019
Loma Linda University
2015-2018
St. Brendan's Hospital
2018
Peking University
2013-2016
J.P. Morgan
2016
California State University, San Bernardino
2016
The molecular basis for the focal nature of atherosclerotic lesions is poorly understood. Here, we explored whether disturbed flow patterns activate an innate immune response to form NLRP3 inflammasome scaffold in vascular endothelial cells via sterol regulatory element binding protein 2 (SREBP2). Oscillatory activates SREBP2 and induces cells. underlying mechanisms involve transactivating NADPH oxidase NLRP3. Consistently, SREBP2, 2, levels were elevated atheroprone areas mouse aortas,...
AMPK phosphorylates epigenetic factors to couple mitochondrial biogenesis and function with cellular energy needs.
Endothelial dysfunction plays an integral role in pulmonary hypertension (PH). AMPK (AMP-activated protein kinase) and ACE2 (angiotensin-converting enzyme 2) are crucial endothelial homeostasis. The mechanism by which regulates the endothelium its protective PH remain elusive.We investigated of phosphorylation Ser680 stability deciphered functional consequences this post-translational modification homeostasis PH.Bioinformatics prediction, kinase assay, antibody against phospho-ACE2 (p-ACE2...
Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role CCM pathogenesis serving major source VEGF during lesion formation. An increase astrocyte synthesis is driven nitric oxide (NO) generated consequence KLF2- KLF4-dependent elevation eNOS...
Cerebral cavernous malformations (CCMs) are neurovascular lesions caused by loss of function mutations in 1 3 genes, including
BACKGROUND: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities patients, suggests environmental, genetic, or biological factors act as disease modifiers. Still, underlying mechanisms are not entirely understood. Here, we report mild hypoxia accelerates CCM by promoting angiogenesis, neuroinflammation, vascular brains mouse models. METHODS: We used genetic studies, RNA sequencing,...
B-cell lymphoma-6 protein (Bcl-6) is a corepressor for inflammatory mediators such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 -3, which function to recruit monocytes endothelial cells upon inflammation. Poly [ADP ribose] polymerase 1 (PARP-1) proinflammatory, in part through its binding at the Bcl-6 intron suppress expression. We investigated mechanisms by PARP-1 dissociates from 1, ultimately leading attenuation of Analysis primary sequence suggested that...
Article23 April 2020Open Access Source DataTransparent process MicroRNA-483 amelioration of experimental pulmonary hypertension Jin Zhang Cardiovascular Research Center, School Basic Medical Sciences, Xi'an Jiaotong University Health Science Key Laboratory Environment and Genes Related to Diseases, Ministry Education China, University, Xian, China Search for more papers by this author Yangyang He State disease & FuWai Hospital, Chinese Academy Sciences Peking Union College, Beijing, Xiaosong...
Significance This work identifies mechanotransduction mechanisms by which blood flow regulates glycolysis in vascular endothelium. We demonstrate that atheroprotective pattern decreases glycolysis, an energy-demanding metabolic process, endothelium vitro and vivo. GCKR, inhibitor of glycolytic flux, is up-regulated flow, contrast to the down-regulation other genes. As a pioneer transcription factor induced KLF4 epigenetically remodels GCKR promoter thus transactivates GCKR. At...
Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose) polymerase 1 (PARP1). Biguanides angiotensin II receptor blockers (ARBs) such as metformin telmisartan have a vascular protective effect. We used cultured cells (ECs), diabetic hypertensive rodent models, AMPKα2-knockout mice to investigate whether beneficial effect on the endothelium via AMP-activated protein kinase (AMPK) phosphorylation of PARP1 thus inhibition activity....
Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such metformin, on COVID-19 outcomes remains unclear. Metformin increases expression angiotensin converting enzyme 2, known receptor severe acute respiratory syndrome 2. Data from people with T2DM hospitalized were test hypothesis that metformin use is associated improved survival in this population.Retrospective analyses...
Cortactin translocates to the cell periphery in vascular endothelial cells (ECs) on cortical-actin assembly response pulsatile shear stress. Because cortactin has putative sites for AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) deacetylation, we examined hypothesis that AMPK SIRT1 coregulate dynamics stress.Analysis of ability phosphorylate recombinant oligopeptides whose sequences matched consensus pointed Thr-401 as site phosphorylation. Mass spectrometry...
Significance This work identifies a mechanism by which atheroprone oscillatory shear and atheroprotective pulsatile differentially regulate microRNA (miR) biogenesis in the vascular endothelium. Nonphosphorylated nucleolin facilitates maturation of miR-93 miR-484, turn target Krüpple-like factor 2 endothelial nitric oxide synthase mRNAs. The translational significance these findings is provided identification elevated levels miR-484 sera from patients with coronary artery disease.
Type 2 diabetes mellitus (T2DM) is a frequent comorbidity of cancer. Hyperinsulinemia secondary to T2DM promotes cancer progression, whereas antidiabetic agents, such as metformin, have anticancer effects. However, the detailed mechanism for insulin and metformin-regulated cell proliferation remains unclear. This study identified by which upregulated expression c-Myc, sterol regulatory element-binding protein 1 (SREBP1), acetyl-coenzyme A (CoA) carboxylase (ACC1), are important regulators...
Lining the luminal surface of vasculature, endothelial cells (ECs) are in direct contact with and differentially respond to hemodynamic forces depending on their anatomic location. Pulsatile shear stress (PS) is defined by laminar flow predominantly located straight vascular regions, while disturbed or oscillatory (OS) localized branch points bifurcations. Such patterns have become a central focus diseases, such as atherosclerosis, because focal distribution dysfunction corresponds regions...
Background: Metabolic dysfunction–associated steatotic liver disease is a prevalent that affects nearly one-third of the global population. Recent genome-wide association studies revealed common missense variant in gene encoding mitochondrial amidoxime reducing component 1 (mARC1) associated with protection from metabolic disease, all-cause cirrhosis, and liver-related mortality suggesting role for mARC1 pathophysiology; however, little known about its function liver. In this study, we aimed...
AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine that activated by cellular perturbations associated with ATP depletion or stress. While AMPK modulates the activity of variety targets containing specific phosphorylation consensus sequence, number and their influence over processes currently thought to be limited.We queried human mouse proteomes for proteins sequences. Integration this database into Gaggle software facilitated construction probable AMPK-regulated...
Abstract Visualizing spatial assay data in anatomical images is vital for understanding biological processes cell, tissue, and organ organizations. Technologies requiring this functionality include traditional one-at-a-time assays, bulk single-cell omics experiments, including RNA-seq proteomics. The spatialHeatmap software provides a series of powerful new methods these needs, allows users to work with adequately formatted from public collections or custom images. It colors the features...
The function of the amyloid precursor protein (APP) in brain health remains unclear. This study elucidated a novel cytoprotective signaling pathway initiated by APP transcriptionally active intracellular domain (AICD) response to 27-hydroxycholesterol (27OHC), an oxidized cholesterol metabolite associated with neurodegeneration. cellular 27OHC was hormetic, such that low, but not high, doses promoted AICD transactivation microtubule serine/threonine kinase family member 4 (MAST4). MAST4 turn...
During limb development, fibroblast growth factors (Fgfs) govern proximal⁻distal outgrowth and patterning. FGFs also synchronize developmental patterning between the anterior⁻posterior axes by maintaining Sonic hedgehog (Shh) expression in cells of zone polarizing activity (ZPA) distal posterior mesoderm. Shh, turn, maintains Fgfs apical ectodermal ridge (AER) that caps tip bud. Crosstalk Fgf Shh signaling is critical for patterned but mechanisms underlying this feedback loop are not...
The transmembrane protein heart of glass1 (HEG1) directly binds to and recruits Krev interaction trapped 1 (KRIT1) endothelial junctions form the HEG1–KRIT1 complex that establishes maintains junctional integrity. Genetic inactivation or knockdown HEG1 KRIT1 leads upregulation transcription factors Krüppel-like 4 2 (KLF4 KLF2), which are implicated in vascular homeostasis; however, effect acute inhibition remains incompletely understood. Here, we report a high-throughput screening assay...