A5101792678- Nitric Oxide and Endothelin Effects
- Atherosclerosis and Cardiovascular Diseases
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Endometriosis Research and Treatment
- Congenital heart defects research
- Gastrointestinal motility and disorders
- Galectins and Cancer Biology
- Sex and Gender in Healthcare
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroscience of respiration and sleep
- Biomarkers in Disease Mechanisms
- Cancer, Lipids, and Metabolism
- COVID-19 Clinical Research Studies
- Chemokine receptors and signaling
- Hemoglobin structure and function
- Pharmacological Effects of Natural Compounds
- Epigenetics and DNA Methylation
- Cardiovascular Disease and Adiposity
- Cardiovascular Issues in Pregnancy
- Inflammatory Biomarkers in Disease Prognosis
Duke University
2021-2022
University of Virginia
2014-2020
University of Pittsburgh
2014
San Francisco VA Medical Center
2006
University of California, San Francisco
2006
Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause death. However, we have limited understanding identity, origin, function many cells that make up late-stage lesions, as well mechanisms by which they control plaque stability.
Objective— Hemoglobin α (Hb α) and endothelial nitric oxide synthase (eNOS) form a macromolecular complex at myoendothelial junctions; the functional role of this interaction remains undefined. To test if coupling eNOS Hb regulates signaling, vascular reactivity, blood pressure using mimetic peptide to disrupt interaction. Approach Results— In silico modeling identified conserved sequence By mutating portions α, we specific that binds eNOS. A X) was generated complex. Using in vitro binding...
Background: Smooth muscle cells (SMCs) in atherosclerotic plaque take on multiple nonclassical phenotypes that may affect stability and, therefore, the likelihood of myocardial infarction or stroke. However, mechanisms by which these are only beginning to be explored. Methods: In this study, we investigated contribution inflammatory MCP1 (monocyte chemoattractant protein 1) produced both classical Myh11 (myosin heavy chain 11) + SMCs and have transitioned through an Lgals3 (galectin 3) state...
Background: The Myh11 promoter is extensively used as a smooth muscle cell (SMC) Cre-driver and regarded the most restrictive specific available to study SMCs. Unfortunately, in existing Myh11-CreER T2 mouse, transgene was inserted on Y chromosome precluding of female mice. Given importance including sex biological variable that numerous SMC-based diseases have sex-dependent bias, field has been tremendously limited by lack model both sexes. Here, we describe new autosomal mouse (referred...
Abstract Regional DNA hypermethylation and global hypomethylation are 2 epigenetic alterations associated with colorectal cancers. However, their correlation microsatellite instability (MSI) chromosomal (CIN) in cancer, relationship chromatin conformation histone modification not clear. In this study, we analyzed regional methylation 16 cell lines 64 primary We found that MSI CIN alternative events most tumors. Furthermore, also cases. observed a strong between hypomethylation. further...
The stem cell pluripotency factor Oct4 serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle (SMC) investment. Here, we show using Myh11-CreERT2 lineage-tracing with inducible SMC and pericyte (SMC-P) knockout of that regulates perivascular migration recruitment angiogenesis. Knockout in cells significantly impairs migration, increases death, delays endothelial promotes vascular leakage following corneal angiogenic stimulus. also perfusion...
Objective: Smooth muscle cells and pericytes display remarkable plasticity during injury disease progression. Here, we tested the hypothesis that perivascular give rise to Klf4 -dependent macrophage-like augment adipose tissue (AT) inflammation metabolic dysfunction associated with diet-induced obesity (DIO). Approach Results: Using Myh11-Cre ERT2 eYFP (enhanced yellow fluorescent protein) mice flow cytometry of stromovascular fraction epididymal AT, observed a large smooth lineage traced +...
Smooth muscle cells (SMC) are conventionally thought to promote atherosclerotic plaque stability by investing within the fibrous cap and protecting blood flow from harmful inflammatory core. However, lineage tracing studies have shown that SMC in can undergo a Klf4-dependent transition vivo macrophage-like state, characterized loss of markers expression multiple macrophage markers, lipid accumulation, phagocytic activity. Of major interest, induced state vitro cholesterol loading also show...
Smooth muscle cells (SMC) are not terminally differentiated but display remarkable plasticity to differentiate into other cell types in response injury or chronic disease states such as atherosclerosis. Of major significance, we previously demonstrated that nearly a third of the macrophage marker positive within advanced mouse and human atherosclerotic plaques SMC myeloid origin. These transitions phenotype dependent on stem pluripotency gene Klf4 play critical role overall lesion...
The development of atherosclerosis is regulated by heritable factors; however, the mechanisms through which many these genetic components affect plaque remain poorly understood. Recently, minor allele a SNP in coding region Inhibitor Differentiation 3 ( ID3 ) gene at rs11574 was associated with increased CVD risk. Mutation from major (G) to (A) changes 105 th amino acid an alanine threonine, attenuating ability antagonize bHLH transcription factors and prevent them binding DNA activating...
Background: Dysregulation of immunohematologic function (IHF) promotes cardiovascular disease and impairs protective responses to cancer infection. A pragmatic method identify those as risk due IHF could improve the precision preventive interventions provide insight into heterogeneity immunologic capacity. We developed validated a distill complete blood cell count data distinct profiles prognostic relevance. Methods: adapted latent profile analysis methods simultaneously groups patients with...