A5060362085- Pluripotent Stem Cells Research
- Congenital heart defects research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Tissue Engineering and Regenerative Medicine
- Adipose Tissue and Metabolism
- Histone Deacetylase Inhibitors Research
- Immune Cell Function and Interaction
- Sirtuins and Resveratrol in Medicine
- Diabetes and associated disorders
- Medical Imaging and Pathology Studies
- CRISPR and Genetic Engineering
- Pulmonary Hypertension Research and Treatments
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Autophagy in Disease and Therapy
- Respiratory Support and Mechanisms
- Spondyloarthritis Studies and Treatments
- Aldose Reductase and Taurine
- Endoplasmic Reticulum Stress and Disease
- Alzheimer's disease research and treatments
- Renin-Angiotensin System Studies
- Cancer, Hypoxia, and Metabolism
- Neonatal Respiratory Health Research
- Cardiac Fibrosis and Remodeling
University of Colorado Anschutz Medical Campus
2010-2025
University of Colorado Denver
2015-2023
University of Colorado Boulder
2010
Hospital Militar Central
2009
Direct reprogramming of fibroblasts into cardiomyocytes by forced expression cardiomyogenic factors, GMT (GATA4, Mef2C, Tbx5) or GHMT Hand2, Tbx5), has recently been demonstrated, suggesting a novel therapeutic strategy for cardiac repair. However, current approaches are inefficient. Here we demonstrate that pro-fibrotic signalling potently antagonizes reprogramming. Remarkably, inhibition using small molecules target the transforming growth factor-β Rho-associated kinase pathways converts...
Mutations in lysosomal-associated membrane protein 2 (LAMP-2) gene are associated with Danon disease, which often leads to cardiomyopathy/heart failure through poorly defined mechanisms. Here, we identify the LAMP-2 isoform B (LAMP-2B) as required for autophagosome-lysosome fusion human cardiomyocytes (CMs). Remarkably, LAMP-2B functions independently of syntaxin 17 (STX17), a that is essential non-CMs. Instead, interacts autophagy related 14 (ATG14) and vesicle-associated 8 (VAMP8) its...
Little is known about the biological function of histone deacetylase 11 (HDAC11), which lone class IV HDAC. Here, we demonstrate that deletion HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging white (WAT). Consequently, HDAC11-deficient exhibit enhanced thermogenic potential and, response to high-fat feeding, attenuated obesity, improved insulin sensitivity, reduced hepatic steatosis. Ex vivo cell-based assays revealed catalytic activity suppresses BAT...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they immature, which is barrier to modeling adult-onset cardiovascular disease. Here, we sought develop simple method that could drive cultured hiPSC-CMs toward maturity across number of phenotypes, with the aim utilizing mature model human were in fatty acid-based medium and plated on micropatterned surfaces. These cells display many characteristics adult...
Mitochondrial dysfunction has been associated with age-related diseases, including idiopathic pulmonary fibrosis (IPF). We provide evidence that implicates chronic elevation of the mitochondrial anion carrier protein, uncoupling protein-2 (UCP2), in increased generation reactive oxygen species, altered redox state and cellular bioenergetics, impaired fatty acid oxidation, induction myofibroblast senescence. This pro-oxidant senescence reprogramming occurs concert conventional actions UCP2 as...
MAS-1, a nanoparticular, emulsion-based adjuvant, was evaluated for its ability to promote Th2 and regulatory immune responses prevent type 1 diabetes progression when given alone or as antigen-specific immunotherapy (ASI) using insulin B chain (IBC; MER3101) analog B:9-23(19Ala) (MER3102). MAS-1 formulations were administered NOD mice at age 9 13 weeks followed through 52 weeks. MER3101 MER3102 provided long-term protection with 60% 73% of remaining diabetes-free week 35, 47% 52. adjuvant...
Trans-differentiation of one somatic cell type into another has enormous potential to model and treat human diseases. Previous studies have shown that mouse embryonic, dermal, cardiac fibroblasts can be reprogrammed functional induced-cardiomyocyte-like cells (iCMs) through overexpression cardiogenic transcription factors including GATA4, Hand2, Mef2c, Tbx5 both in vitro vivo. However, these previous relatively low efficiency. In order restore heart function following injury, mechanisms...
Abstract Little is known about the biological function of histone deacetylase 11 (HDAC11), which lone class IV HDAC. Here, we demonstrate that deletion HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging white (WAT). Consequently, HDAC11-deficient exhibit dramatically enhanced thermogenic potential and, response to high fat feeding, attenuated obesity, insulin resistance, hepatic steatosis. Ex vivo cell-based assays revealed catalytic activity suppresses BAT...
Abstract Rationale Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they immature, which is barrier to modeling adult-onset cardiovascular disease. Objective We sought develop simple method could drive cultured hiPSC-CMs towards maturity across number of phenotypes. Methods and results Cells were in fatty acid-based media plated on micropatterned surfaces promote alignment elongation. These cells display many...
The mammalian heart is composed of ~30% cardiomyocytes which have limited capacity to regenerate and ~70% non-cardiomyocytes including endothelial cells cardiac fibroblasts. Direct reprogramming fibroblasts into by forced expression cardiomyogenic transcription factors, GMT (GATA4, Mef2C, Tbx5) or GHMT Hand2, Tbx5), has recently been demonstrated, suggesting a novel therapeutic strategy for repair. Despite extensive efforts, the efficiency direct embryonic adult yet exceed 20%, 0.1%...