A5047293673- Cardiac Fibrosis and Remodeling
- Congenital heart defects research
- Tissue Engineering and Regenerative Medicine
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Cardiomyopathy and Myosin Studies
- Cardiac Ischemia and Reperfusion
- Pluripotent Stem Cells Research
- Angiogenesis and VEGF in Cancer
- Cancer-related cognitive impairment studies
- Cardiac Structural Anomalies and Repair
- Microbial Metabolic Engineering and Bioproduction
- Mitochondrial Function and Pathology
- GDF15 and Related Biomarkers
- Functional Brain Connectivity Studies
- T-cell and B-cell Immunology
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiovascular Function and Risk Factors
- Spaceflight effects on biology
- Molecular Biology Techniques and Applications
- Kruppel-like factors research
- Electrospun Nanofibers in Biomedical Applications
- Advanced Electron Microscopy Techniques and Applications
University of Minnesota System
2024
Boston Children's Hospital
2024
University of Minnesota
2017-2023
University of Amsterdam
2023
Amsterdam University Medical Centers
2023
Minneapolis Heart Institute Foundation
2020-2023
University of Minnesota Medical Center
2022
The initial hypertrophy response to cardiac pressure overload is considered compensatory, but with sustained stress, it eventually leads heart failure. Recently, a role for recruited macrophages in determining the transition from compensated decompensated has been established. However, whether resident immune cells influence early phase of development not established.To assess induced by transverse aortic constriction (TAC).We performed cytometry time-of-flight determine identity and...
Human iPSC-derived cardiomyocytes (hiPSC-CMs) have proven invaluable for cardiac disease modeling and regeneration. Challenges with quality, inter-batch consistency, cryopreservation scale remain, reducing experimental reproducibility clinical translation. Here, we report a robust stirred suspension differentiation protocol, perform extensive morphological functional characterization of the resulting bioreactor-differentiated iPSC-CMs (bCMs). Across multiple different iPSC lines, protocol...
Background: c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Objective: Targeting modulators HSC quiescence could lead to cycle entry with concomitant expansion. Methods Results: Here we show that inhibitor 10074-G5 treatment leads 2-fold increase murine LSKCD34low compartment post 7 days. In addition, inhibition increases CD34+ CD133+ human number. downregulation cyclindependent kinase (CDKI) gene expression ex vivo vivo....
Meis1, which belongs to TALE-type class of homeobox gene family, appeared as one the key regulators hematopoietic stem cell (HSC) self-renewal and a potential therapeutical target. However, small molecule inhibitors MEIS1 remained unknown. This led us develop that could modulate HSC activity. To this end, we have established library relevant family developed high-throughput in silico screening strategy against homeodomain MEIS proteins using AutoDock Vina PaDEL-ADV platform. We screened over...
ABSTRACT Inflammation is a significant risk factor and contributes to cardiovascular disease by driving both adaptive maladaptive processes. Macrophages are the most abundant immune cells in heart play an important role remodeling of cardiac tissue. We have previously shown overall protective function resident macrophages after pressure-overloaded injury. However, subpopulation also expresses high levels profibrotic CC motif chemokine ligand 24 (CCL24), suggesting dichotomous pressure...
Hypertension is the most significant risk factor for heart failure in doxorubicin (DOX)-treated childhood cancer survivors. We previously developed a two-hit mouse model of juvenile DOX-induced latent cardiotoxicity that exacerbated by adult-onset angiotensin II (ANGII)-induced hypertension. It still not known how would predispose to pathologic stimuli do cause Our main objective determine cardiac effects ANGII (a hypertensive stimulus) and isoproterenol (ISO, non-hypertensive adult mice...
The heart is one of the least regenerative organs. This in large part due to inability adult mammalian cardiomyocytes proliferate and divide. In recent years, a number small molecules molecular targets have been identified stimulate cardiomyocyte proliferation, including p38 inhibition, YAP-Tead activation, fibroblast growth factor 1 Neuregulin 1. Despite these exciting initial findings, therapeutic approach enhance proliferation vivo still lacking. We hypothesized that more comprehensive...
The adult mammalian heart is composed of various cell types including cardiomyocytes, endothelial cells and fibroblasts. Since it difficult to reliably identify nuclei cardiomyocytes on histological sections, many groups rely isolating viable prior fixation perform immunostaining. However, these live cardiomyocyte isolation techniques require optimization maximize the yield, viability quality samples, with inherent fluctuations from sample despite maximum optimization. Here, we report a...
Background: In response to cardiac injury, the heart undergoes a remodeling process, which may be defined by complex set of genomic, expression, molecular, cellular and interstitial changes, can become maladaptive contribute development failure (HF). One most important components in is fibrosis, characterized excessive deposition extracellular matrix (ECM) proteins fibroblasts, disrupts myocardial architecture function, thus predisposing progression diseases HF. The small GTPase Septin4...
The mammalian heart loses almost all its regenerative potential in the first week of life due to cessation ability cardiomyocytes proliferate. In recent years, a number regulators cardiomyocyte proliferation have been identified. Despite this, clear understanding regulatory pathways that control and cardiac regeneration is lacking, there are likely additional be discovered. Here, we performed genome-wide screen on fetal murine identify novel proliferation. Endoglin was identified as an...
Abstract Meis1 , which belongs to TALE-type class of homeobox gene family, appeared as one the key regulators hematopoietic stem cell (HSC) self-renewal and a potential therapeutical target. However, small molecule inhibitors MEIS1 remained unknown. This led us develop that could modulate HSC activity. To this end, we have established library relevant family developed high-throughput in silico screening strategy against homeodomain MEIS proteins using AutoDock Vina PaDEL-ADV platform. We...
c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Targeting modulators HSC quiescence could lead to cycle entry with concomitant expansion. Here we show that inhibitor 10074-G5 treatment leads 2-fold increase murine LSKCD34low compartment post 7 days. In addition, inhibition increases CD34+ CD133+ human number. downregulation cyclin-dependent kinase (CDKI) gene expression ex vivo vivo. upregulates HDR modulator Rad51 cells....
The adult mammalian heart is composed of various cell types including cardiomyocytes, endothelial cells and fibroblasts. Since it difficult to reliably identify nuclei cardiomyocytes on histological sections, many groups rely isolating viable prior fixation perform immunostaining. However, these live cardiomyocyte isolation techniques require optimization maximize the yield, viability quality samples, with inherent fluctuations from sample despite maximum optimization. Here, we report a...
In response to cardiac injury or increased workload, the mammalian heart undergoes ventricular remodeling maintain function. Initally, these changes are compensatory, although ultimately, they can lead death of cardiomyocytes, dilation, and progression failure. It is critical understand underlying mechanisms that regulate this transition, since it could identify new therapeutic targets. The role small GTPase Septin4 in heart, regulating stress unknown. Previous research has implicated Septin...
Heart failure (HF) is the leading cause of death worldwide. Systemic inflammation associated with HF and considered an independent predictor adverse cardiac outcomes. Macrophages are most abundant immune cells in heart have integral roles homeostasis remodeling. Despite their unique identity homeostatic functions, precise role macrophages during remodeling poorly understood. We previously reported that resident expand early response to pressure overload injury provide cardioprotection. Using...