A5011624588- Congenital heart defects research
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Tissue Engineering and Regenerative Medicine
- RNA Interference and Gene Delivery
- Cardiac Fibrosis and Remodeling
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Signaling Pathways in Disease
- Autophagy in Disease and Therapy
- Virus-based gene therapy research
- Cardiac Structural Anomalies and Repair
- Lysosomal Storage Disorders Research
- MicroRNA in disease regulation
- Acute Lymphoblastic Leukemia research
- Collagen: Extraction and Characterization
- Cancer Cells and Metastasis
- Viral-associated cancers and disorders
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Cytomegalovirus and herpesvirus research
- RNA Research and Splicing
- Down syndrome and intellectual disability research
University of Colorado Anschutz Medical Campus
2018-2023
The Medical Center of Aurora
2023
Horizon Discovery Group (United States)
2022
University of Colorado Boulder
2022
University of Wisconsin–Madison
2014
Rationale: Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in preclinical models heart failure (HF). However, since target ubiquitously, it is unclear whether this chromatin reader functions cell type-specific manner control pathological myocardial fibrosis. Furthermore, molecular mechanisms by which stimulates transcriptional program for remain unknown. Objective: We sought test hypothesis that a cell-autonomous and...
Congenital heart defects (CHDs) are frequent in children with Down syndrome (DS), caused by trisomy of chromosome 21. However, the underlying mechanisms poorly understood. Here, using a human-induced pluripotent stem cell (iPSC)-based model and Dp(16)1Yey/+ (Dp16) mouse DS, we identified downregulation canonical Wnt signaling downstream increased dosage interferon (IFN) receptors (IFNRs) genes on 21 as causative factor cardiogenic dysregulation DS. We differentiated human iPSCs derived from...
Abnormalities in Ca2+ homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role cardiomyocytes. Alternative splicing of a single triadin gene produces multiple isoforms. The cardiac-predominant isoform, mouse MT-1 or human Trisk32, is encoded by exons 1 to 8. In humans, mutations the that lead reduction Trisk32 levels can cause dysfunction arrhythmias. Decreased also common patients However, mechanisms maintain isoform composition remain...
ABSTRACT Ikaros is a zinc finger DNA-binding protein that regulates chromatin remodeling and the expression of genes involved in cell cycle, apoptosis, Notch signaling. It master regulator lymphocyte differentiation functions as tumor suppressor acute lymphoblastic leukemia. Nevertheless, no previous reports described effects on life cycle any human lymphotropic virus. Here, we demonstrate full-length (IK-1) major factor maintenance viral latency Epstein-Barr virus (EBV)-positive Burkitt's...
While CRISPR interference (CRISPRi) systems have been widely implemented in pooled lentiviral screening, there has limited use with synthetic guide RNAs for the complex phenotypic readouts enabled by experiments arrayed format. Here we describe a novel deactivated Cas9 fusion protein, dCas9-SALL1-SDS3, which produces greater target gene repression than first or second generation CRISPRi when used chemically modified single (sgRNAs), while exhibiting high specificity. We show that...
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 Cell culture has long been essential for preclinical modeling of human development and disease. However, conventional two‐dimensional (2D) cell fails to faithfully model the complexity found in vivo, novel drug candidates that show promising results 2D models often do not translate clinic. More recently, three‐dimensional (3D) have gained popularity owing their greater physiological relevance vivo biology. In particular, 3D spheroid are becoming widely used due ability mimic solid...
Abstract Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in pre-clinical models heart failure (HF). However, mechanisms by which promotes pathological myocardial remain unclear. Here, we demonstrate that functions as an effector TGF-β signaling stimulate conversion quiescent fibroblasts into Periostin ( Postn )-positive cells express high levels extracellular matrix. undergoes stimulus-dependent, genome-wide redistribution...
Summary Direct reprogramming of fibroblasts into cardiomyocytes (CMs) represents a promising strategy to regenerate CMs lost after ischemic heart injury. Overexpression G ATA4, H AND2, M EF2C, T BX5, miR-1, and miR-133 (GHMT2m) along with transforming growth factor beta (TGF-β) inhibition efficiently promotes reprogramming. However, the mechanisms by which TGF-β blockade cardiac remain unknown. Here, we identify interactions between histone H3 lysine 27 trimethylation (H3K27me3) –...