A5033362734- Cardiac Fibrosis and Remodeling
- Peptidase Inhibition and Analysis
- Tissue Engineering and Regenerative Medicine
- Cardiac Structural Anomalies and Repair
- Wnt/β-catenin signaling in development and cancer
- Pancreatic function and diabetes
- Cytokine Signaling Pathways and Interactions
- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Chemotherapy-induced cardiotoxicity and mitigation
- Signaling Pathways in Disease
- S100 Proteins and Annexins
- Hippo pathway signaling and YAP/TAZ
- Click Chemistry and Applications
- Mitochondrial Function and Pathology
- PI3K/AKT/mTOR signaling in cancer
- Computational Drug Discovery Methods
- Cardiovascular Disease and Adiposity
- Congenital heart defects research
- Adenosine and Purinergic Signaling
- Parkinson's Disease Mechanisms and Treatments
- Chronic Myeloid Leukemia Treatments
- Immune cells in cancer
- Cell Adhesion Molecules Research
University of Alabama at Birmingham
2020-2025
University of Alabama
2022-2024
Vanderbilt University Medical Center
2017-2020
Vanderbilt University
2017-2019
National Centre for Cell Science
2016
Savitribai Phule Pune University
2015
Background: Heart failure is the leading cause of mortality, morbidity, and health care expenditures worldwide. Numerous studies have implicated GSK-3 (glycogen synthase kinase-3) as a promising therapeutic target for cardiovascular diseases. isoforms seem to play overlapping, unique even opposing functions in heart. Previously, we shown that 2 GSK-3, cardiac fibroblast GSK-3β acts negative regulator myocardial fibrosis ischemic However, role fibroblast-GSK-3α pathogenesis diseases...
The tyrosine kinase inhibitor ponatinib is the only treatment option for chronic myelogenous leukemia patients with T315I (gatekeeper) mutation. Pharmacovigilance analysis of Food and Drug Administration World Health Organization datasets has revealed that most cardiotoxic agent among all Administration-approved inhibitors in a real-world scenario. However, mechanism ponatinib-induced cardiotoxicity unknown.
Oxidative stress is closely associated with the pathophysiology of diabetic cardiomyopathy (DCM). The mitochondrial flavoenzyme monoamine oxidase A (MAO-A) an important source oxidative in myocardium. We sought to determine whether MAO-A plays a major role modulating DCM. Diabetes was induced Wistar rats by single intraperitoneal injection streptozotocin (STZ). To investigate development pathophysiological features DCM, hyperglycemic and age-matched control were treated or without...
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myelogenous leukaemia (CML). However, cardiotoxicity these agents remains a serious concern. The underlying mechanism adverse cardiac effects is largely unknown. Delineation mechanisms TKIs associated dysfunction could guide potential prevention strategies, rescue approaches, and future drug design. This study aimed to determine cardiotoxic approved CML TKIs, define signalling identify alternatives.In this study,...
Background: Myocardial infarction (MI) induces an intense injury response that ultimately generates a collagen-dominated scar. Although required to prevent ventricular rupture, the fibrotic process is often sustained in manner detrimental optimal recovery. Cardiac myofibroblasts are cells tasked with depositing and remodeling collagen prime target limit after MI. Serotonin 2B receptor (5-HT ) signaling has been shown be harmful variety of cardiopulmonary pathologies could play important role...
The role of the transforming growth factor (TGF)-β pathway in myocardial fibrosis is well recognized. However, precise this signaling axis cardiomyocyte (CM) biology not defined. In TGF-β signaling, SMAD4 acts as central intracellular mediator. To investigate CM biology, authors deleted adult mouse CMs. We demonstrate that CM-SMAD4–dependent critical for maintaining cardiac function, sarcomere kinetics, ion-channel gene expression, and survival. Thus, our findings raise a significant concern...
In light of the favorable outcomes few small, non-randomized clinical studies, Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to Hydroxychloroquine (HCQ) for hospitalized coronavirus disease 2019 (COVID-19) patients. fact, subsequent studies with COVID-19 HCQ have reported limited efficacy poor benefits. Unfortunately, a robust trial its effectiveness is not feasible at this emergency. Additionally, was suspected causing cardiovascular adverse reactions...
Background Lifestyle and metabolic diseases influence the severity pathogenesis of cardiovascular disease through numerous mechanisms, including regulation via posttranslational modifications. A specific modification, addition O ‐linked β‐ N acetylglucosamine ( ‐GlcNAcylation), has been implicated in molecular mechanisms both physiological pathologic adaptations. The current study aimed to test hypothesis that cardiomyocytes, sustained protein ‐GlcNAcylation contributes cardiac adaptations,...
Cardiac fibrosis can be mitigated by limiting fibroblast-to-myofibroblast differentiation and proliferation. Human antigen R (HuR) modulates messenger RNA stability expression of multiple genes. However, the direct role cardiac myofibroblast HuR is unknown. Myofibroblast-specific deletion limited preserved functions in pressure overload injury. Knockdown transforming growth factor-β1–treated fibroblasts suppressed abrogated cyclins D1 A2, suggesting a potential mechanism which promotes...
Obesity-associated metabolic disorders are rising to pandemic proportions; hence, there is an urgent need identify underlying molecular mechanisms. Glycogen synthase kinase-3 (GSK-3) signaling highly implicated in diseases. Furthermore, GSK-3 expression and activity increased Type 2 diabetes patients. However, the isoform-specific role of obesity glucose intolerance unclear. Pharmacological inhibitors not isoform-specific, tissue-specific genetic models limited value predict clinical outcome...
Glycogen synthase kinase 3 (GSK-3), a serine-threonine with two isoforms (α and β) is implicated in the pathogenesis of Type 2 diabetes mellitus (T2D). Recently, we reported isoform-specific role GSK-3 T2D using homozygous GSK-3α/β Knock-Out mice. While inhibition models are idealistic preclinical setting, they do not mimic seen pharmacological agents. Hence, this study, sought to investigate dose-response effect obesity-induced T2D. Specifically, gain insight into T2D, generated...
Obesity is an independent risk factor for cardiovascular diseases (CVD), including heart failure. Thus, there urgent need to understand the molecular mechanism of obesity-associated cardiac dysfunction. We recently reported critical role cardiomyocyte (CM) Glycogen Synthase Kinase-3 beta (GSK-3β) in dysfunction associated with a developing obesity model (deletion CM-GSK-3β prior obesity). In present study, we investigated clinically more relevant established after knockout...
Brain-derived neurotrophic factor (BDNF) is a neuronal growth and survival that harbors cardioprotective qualities may attenuate dilated cardiomyopathy. In ~30% of the population, BDNF has common, nonsynonymous single nucleotide polymorphism rs6265 (Val66Met), which might be correlated with increased risk cardiovascular events. We previously showed correlates better cardiac function in Duchenne muscular dystrophy (DMD) patients. However, effect Val66Met on not been determined. The goal...
Background: Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine that belongs to an evolutionary conserved HIPK family of kinases. HIPK2-mediated regulation the inflammation axis signaling comparatively new concept. Purinergic critical myocardial and function. However, there no literature on HIPK2 regulating purinergic signaling. Methods Results: Herein, we identified HIPK2, as novel regulator Cardiomyocyte-specific knockout (CM-HIPK2-KO) hearts exhibited reduced expression...