A5087452663- Congenital heart defects research
- Angiogenesis and VEGF in Cancer
- Atherosclerosis and Cardiovascular Diseases
- Peptidase Inhibition and Analysis
- Kruppel-like factors research
- Eosinophilic Esophagitis
- Cardiovascular Disease and Adiposity
- IL-33, ST2, and ILC Pathways
- Chromatin Remodeling and Cancer
- Eosinophilic Disorders and Syndromes
- Protease and Inhibitor Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Estrogen and related hormone effects
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Lipid metabolism and disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phagocytosis and Immune Regulation
- Single-cell and spatial transcriptomics
- Academic Writing and Publishing
- Fibroblast Growth Factor Research
- Connective Tissue Growth Factor Research
- Cancer, Lipids, and Metabolism
- Cell Adhesion Molecules Research
University of Colorado Anschutz Medical Campus
2020-2024
University of Colorado Denver
2019-2023
Hypertension Institute
2023
Integrated Oncology (United States)
2023
Children's Hospital Colorado
2019
Eosinophilic esophagitis (EoE), a chronic food allergic disease, lacks sensitive and specific peripheral biomarkers. We hypothesized that levels of EoE-related biomarkers captured using 1-hour minimally invasive Esophageal String Test (EST) would correlate with mucosal eosinophil counts tissue concentrations these same aimed to determine whether EST accurately distinguishes active from inactive EoE or normal esophagus.In prospective, multisite study, children adults (ages 7-55 years)...
Resident vascular adventitial SCA1+ progenitor (AdvSca1) cells are essential in development and injury. However, the heterogeneity of AdvSca1 presents a unique challenge understanding signaling pathways orchestrating their behavior homeostasis injury responses. Using smooth muscle cell (SMC) lineage-tracing models, we identified subpopulation (AdvSca1-SM) originating from mature SMCs that undergo reprogramming situ exhibit multipotent phenotype. Here employed lineage tracing RNA-sequencing...
Vascular smooth muscle-derived Sca1+ adventitial progenitor (AdvSca1-SM) cells are tissue-resident, multipotent stem that contribute to progression of vascular remodeling and fibrosis. Upon acute injury, AdvSca1-SM differentiate into myofibroblasts embedded in perivascular collagen the extracellular matrix. While phenotypic properties AdvSca1-SM-derived have been defined, underlying epigenetic regulators driving AdvSca1-SM-to-myofibroblast transition unclear. We show chromatin remodeler...
Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific deletion promotes spontaneous vascular remodeling loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, overexpression reduces plaque area preserves SMC contractile protein expression atherosclerosis blunts Ang II (angiotensin II)-induced pathological remodeling, suggesting...
In recent years, fate-mapping lineage studies in mouse models have led to major advances vascular biology by allowing investigators track specific cell populations vivo. One of the most frequently used tracing approaches involves tamoxifen-inducible Cre
We previously established that vascular smooth muscle-derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response acute injury. However, the role of these chronic atherosclerosis has not been defined. Using an AdvSca1-SM cell lineage tracing model, scRNA-Seq, flow cytometry, histological approaches, we confirmed AdvSca1-SM-derived localized throughout vessel wall atherosclerotic plaques, where they primarily...
ABSTRACT Cardiac fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) material resulting in cardiac tissue scarring and dysfunction. While it commonly accepted that myofibroblasts are major contributors to ECM deposition fibrosis, their origin remains debated. By combining lineage tracing RNA sequencing, our group made paradigm-shifting discovery a subpopulation resident vascular stem cells residing within aortic, carotid artery, femoral aartery adventitia (termed...
Vascular smooth muscle cells (SMCs) play a critical role in intimal hyperplasia atherosclerosis and restenosis. SMCs diseased arteries exhibit modulated phenotype with reduced contractile gene expression, elevated proliferation, proinflammatory/profibrotic phenotype. Metabolic reprogramming accompanies is essential for SMC phenotypic modulation. Our group previously demonstrated that the tumor suppressor gene, PTEN, contributes to maintenance of Analysis human GTEx project data established...
Cardiac fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) material resulting in cardiac tissue scarring and dysfunction. While it commonly accepted that myofibroblasts are major contributors to ECM deposition fibrosis, their origin remains debated. By combining lineage tracing RNA sequencing, our group made paradigm-shifting discovery a subpopulation resident vascular stem cells residing within adventitia (termed AdvSca1-SM cells) originate from mature smooth...
Purpose: Atherosclerosis is a major cause of morbidity and mortality worldwide, but current therapies fail to adequately meet clinical needs. Emerging evidence implicates the outer layer blood vessel, adventitia, in pathogenesis atherosclerosis. Specifically, it has been suggested that expansion adventitial microvessels, vasa vasorum (VV), drives atherosclerosis by facilitating inflammatory cell infiltration. Our group previously identified unique population multipotent resident vascular...
We previously established that vascular smooth muscle-derived adventitial progenitor cells (AdvSca1-SM) preferentially differentiate into myofibroblasts and contribute to fibrosis in response acute injury. However, the role of these chronic atherosclerosis has not been defined. Using an AdvSca1-SM lineage tracing model, scRNA-Seq, flow cytometry, histological approaches, we confirmed localize throughout vessel wall atherosclerotic plaques, where they primarily fibroblasts, SMCs, or remain a...
Cardiac myofibroblasts are the major contributors to ECM deposition in pathological cardiovascular fibrosis, which is characteristic feature of diseases. However, due potential heterogeneity myofibroblasts, origin these cells remains controversial. Using highly specific smooth muscle cell lineage-tracing mouse models, we discovered a subpopulation resident vascular adventitial progenitor cells, defined by expression stem marker Sca1 (AdvSca1-SM cells), rapidly proliferate and adopt...
Cardiovascular diseases lead to stiffening of blood vessels. We identified a population smooth muscle-derived progenitor cells that reside in the adventitial layer (AdvSca1-SM cells) drive vascular fibrosis after acute injury. AdvSca1-SM can differentiate into myofibroblasts and secrete pro-remodeling factors including extracellular matrix proteins pro-inflammatory cytokines. While response injury has been studied, epigenetic changes influence their differentiation towards is poorly...
Purpose: Atherosclerosis is a major cause of morbidity and mortality worldwide, but current therapies fail to adequately meet clinical needs. Our group discovered unique population adventitial multipotent resident vascular stem cells (AdvSca1-SM cells) that derive from mature smooth muscle (SMCs) are poised respond injury. The goal this project was determine the role AdvSca1-SM in setting atherosclerosis. We hypothesized contribute plaque growth or neovascularization drive disease...
Vascular smooth muscle cells (SMCs) play a critical role in intimal hyperplasia atherosclerosis and restenosis. SMCs diseased arteries exhibit modulated phenotype with reduced contractile gene expression, elevated proliferation, proinflammatory/profibrotic phenotype. Metabolic reprogramming accompanies is essential for SMC phenotypic modulation. Our group previously demonstrated that the tumor suppressor gene, PTEN, contributes to maintenance of Analysis GTEx project data established...
OBJECTIVES/GOALS: Our lab previously identified a population of vascular smooth muscle (SMC)-derived progenitor cells (AdvSca1-SM) which expand robustly in response to disease and can differentiate into multiple cell types. We now aim define the role these AdvSca1-SM atherosclerotic plaque progression. METHODS/STUDY POPULATION: Goal one uses SMC lineage tracing mice model atherosclerosis track reprogramming SMCs setting disease. Arteries are analyzed using flow cytometry immunofluorescence...
Cardiovascular diseases lead to long-term stiffening of arteries and small vessels. The vascular wall contains several cellular populations that coordinate maintain vessel homeostasis induce remodeling in disease states. We identified a population smooth muscle-derived progenitor cells reside the adventitial layer (AdvSca1-SM cells) drive fibrosis after acute injury. AdvSca1-SM can differentiate into myofibroblasts secrete numerous pro-remodeling factors including extracellular matrix...
Cardiovascular diseases lead to long-term stiffening of arteries and small vessels. The vascular wall contains several cellular populations that coordinate maintain vessel homeostasis induce remodeling in disease states. We identified a population smooth muscle-derived progenitor cells reside the adventitial layer (AdvSca1-SM cells) drive fibrosis after acute injury. AdvSca1-SM can differentiate into myofibroblasts secrete numerous pro-remodeling factors including extracellular matrix...
Purpose: Atherosclerosis is a major cause of morbidity and mortality worldwide, but current therapies fail to adequately meet clinical needs. Emerging evidence implicates the outer layer blood vessel, adventitia, in pathogenesis atherosclerosis. Specifically, it has been suggested that expansion adventitial microvessels, vasa vasorum (VV), drives atherosclerosis progression by facilitating inflammatory cell infiltration. Our group previously identified unique population multipotent resident...
Activated cardiac myofibroblasts are the major contributors to ECM deposition in pathological cardiovascular fibrosis, which is characteristic feature of diseases. However, due potential heterogeneity myofibroblasts, origin these cells remains controversial. Using highly specific smooth muscle cell lineage-tracing mouse models, we discovered a subpopulation resident vascular adventitial progenitor cells, defined by expression stem marker Sca1 (AdvSca1-SM cells), rapidly proliferate and adopt...
The primary aim of this work was to identify compounds that upregulate phosphatase and tensin homolog (PTEN) expression in smooth muscle cells (SMCs), with the expectation PTEN upregulation would inhibit pathological vascular remodeling by promoting SMC homeostasis. Our recent demonstrated is an important regulator phenotype. SMC-specific deletion promotes spontaneous loss correlates increased atherosclerotic lesion severity human coronary arteries. In mice, overexpression reduces plaque...