A5034147286- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Mechanisms of cancer metastasis
- Tissue Engineering and Regenerative Medicine
- Macrophage Migration Inhibitory Factor
- Telomeres, Telomerase, and Senescence
- Pluripotent Stem Cells Research
- Phytochemical compounds biological activities
- Receptor Mechanisms and Signaling
- RNA Interference and Gene Delivery
- Enzyme function and inhibition
- Cell death mechanisms and regulation
- Developmental Biology and Gene Regulation
- Neonatal Respiratory Health Research
- Microplastics and Plastic Pollution
- Mesenchymal stem cell research
- Cardiac Structural Anomalies and Repair
- Cardiovascular Issues in Pregnancy
- GDF15 and Related Biomarkers
- Cardiac electrophysiology and arrhythmias
- interferon and immune responses
- MXene and MAX Phase Materials
- NF-κB Signaling Pathways
- Galectins and Cancer Biology
AstraZeneca (United States)
2019-2022
San Diego State University
2007-2020
Optimum Therapeutics (United States)
2014
University of California, San Diego
2010
United BioSource Corporation (United Kingdom)
2008
Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing regenerative potential adoptively transferred cardiac progenitor (CPCs) via genetic engineering overexpress Pim-1, a cardioprotective kinase that enhances cell survival proliferation.Intramyocardial injections CPCs...
The Notch network regulates multiple cellular processes, including cell fate determination, development, differentiation, proliferation, apoptosis, and regeneration. These processes are regulated via Notch-mediated activity that involves hepatocyte growth factor (HGF)/c-Met receptor phosphatidylinositol 3-kinase/Akt signaling cascades. impact of HGF on was assessed following myocardial infarction as well in cultured cardiomyocytes. Notch1 is activated border zone cardiomyocytes coincident...
Mitochondrial morphological dynamics affect the outcome of ischemic heart damage and pathogenesis. Recently, mitochondrial fission protein dynamin-related 1 (Drp1) has been identified as a mediator changes cell death during cardiac injury. In this study, we report unique relationship between Pim-1 activity Drp1 regulation morphology in cardiomyocytes challenged by stress. Transgenic hearts overexpressing display reduction total levels, increased phosphorylation Drp1- S637 , inhibition...
Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unmet medical need. It characterized by formation scar tissue leading to progressive and irreversible decline in lung function. IPF associated with repeated injury, which may alter the composition extracellular matrix (ECM). Here, we demonstrate that patient–derived ECM drives profibrotic response normal human fibroblasts (NHLF) 3D spheroid assay. Next, reveal distinct alterations diseased ECM, identifying potentially novel...
Cumulative evidence indicates that myocardium responds to growth or injury by recruitment of stem and/or progenitor cells participate in repair and regenerative processes. Unequivocal identification this population has been hampered lack reagents markers specific the recruited population, leading controversies regarding nature these cells. Use a transgenic mouse expressing green fluorescent protein driven c-kit promoter allows for unambiguous cell population. Green (GFP) labels fraction...
Cardioprotective signaling mediates antiapoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector AKT-mediated cardioprotection but the mechanistic basis for integrity by remains unexplored. This study details responsible enhanced cell survival in cardiomyocytes with elevated activity.
Cardioprotective effects of Pim-1 kinase have been previously reported but the underlying mechanistic basis may involve a combination cellular and molecular mechanisms that remain unresolved. The elucidation for mediated cardioprotection provides important insights designing therapeutic interventional strategies to treat heart disease.Effects cardiac-specific expression on cardiac progenitor cell (CPC) population were examined determine whether mediates beneficial through augmenting CPC...
Nucleolar stress, characterized by loss of nucleolar integrity, has not been described in the cardiac context. In addition to ribosome biogenesis, nucleoli are critical for control cell proliferation and stress responses. Our group previously demonstrated induction protein nucleostemin (NS) response pathological insult. NS interacts with nucleophosmin (NPM), a marker cytoprotective properties. The dynamic behavior NPM reveal that disruption is an early event associated cells. Rapid...
Abstract Senescence is a mechanism associated with aging that alters tissue regeneration by depleting the stem cell pool. Chronic obstructive pulmonary disease (COPD) displays hallmarks of senescence, including diminished population. DNA damage from cigarette smoke (CS) induces senescence via p16 pathway. This study evaluated contribution to CS-associated lung pathologies. expression was prominent in human COPD lungs compared normal subjects. CS impaired function, emphysema, and increased...
Pim-1 kinase exerts potent cardioprotective effects in the myocardium downstream of AKT, but participation cardiac hypertrophy requires investigation. Cardiac-specific expression (Pim-WT) or dominant-negative mutant (Pim-DN) transgenic mice together with adenoviral-mediated overexpression these constructs was used to delineate role hypertrophy. Transgenic protects from pressure-overload-induced relative wild-type controls as evidenced by improved hemodynamic function, decreased apoptosis,...
Aims: Cardiac stem cells (CSCs) show potential as a cellular therapeutic approach to blunt tissue damage and facilitate reparative regenerative processes after myocardial infarction. Despite multiple published reports of improvement, functional benefits remain modest using normal delivered by adoptive transfer into damaged myocardium. The goal this study is enhance survival proliferation CSCs that have undergone lineage commitment in early phases evidenced expression proteins driven the...
Cardiac regeneration following myocardial infarction rests with the potential of c-kit+ cardiac progenitor cells (CPCs) to repopulate damaged myocardium. The ability CPCs reconstitute heart is restricted by patient age and disease progression. Increasing CPC proliferation, telomere length, survival will improve autologous be successful in regeneration. Prior studies have demonstrated enhancement engineering express Pim-1 kinase, but cellular molecular mechanisms for Pim-1-mediated effects on...
Cardiac progenitor cells (CPCs) in the adult heart are used for cell-based treatment of myocardial damage, but factors determining stemness, self-renewal, and lineage commitment poorly understood. Immortal DNA strands inherited through asymmetric chromatid segregation correlate with self-renewal stem cells, capacity CPCs to retain immortal is unknown. Cardioprotective kinase Pim-1 increases cell division vivo, ability enhance unknown.We aimed demonstrate strand enhancement distribution by...
Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 a cardioprotective kinase that antagonizes the aging phenotype delays senescence by maintaining telomere length, but mechanism remains unknown. Another pathway responsible for regulating length transforming growth factor beta (TGFβ) signalling where inhibiting TGFβ maintains length. The relationship between has not been explored....
Rationale: A cell has DNA strands of different replication ages because is semi-conservative. Double-stranded molecules possess one strand that generation older than the other. Non-sister chromatids containing newly synthesized and ‘old’ are non-randomly partitioned between mother daughter cells. Stem cells presumed to segregate determine fate cells, although experimental evidence lacking. Resident cardiac progenitor (CPC) present in adult heart have been used for cell-based treatment...