A5016540407- Receptor Mechanisms and Signaling
- Mitochondrial Function and Pathology
- Cardiac electrophysiology and arrhythmias
- Protein Kinase Regulation and GTPase Signaling
- Adipose Tissue and Metabolism
- Cardiac Ischemia and Reperfusion
- Trauma Management and Diagnosis
- Neuropeptides and Animal Physiology
- Circadian rhythm and melatonin
- Psychosomatic Disorders and Their Treatments
- Genomics and Chromatin Dynamics
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cardiovascular Disease and Adiposity
- Adipokines, Inflammation, and Metabolic Diseases
- Tryptophan and brain disorders
- HIV Research and Treatment
- Phosphodiesterase function and regulation
- Genetic Neurodegenerative Diseases
- Urinary Bladder and Prostate Research
- Nitric Oxide and Endothelin Effects
- Cardiovascular Effects of Exercise
- Cardiac Arrest and Resuscitation
- Mass Spectrometry Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Glycation End Products research
Johns Hopkins Medicine
2023
Johns Hopkins University
2023
Temple University
2017-2022
University of Pittsburgh Medical Center
2014
Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits CaMKII inhibition in numerous preclinical models heart disease, translation antagonists into humans has been stymied by low potency, toxicity, an enduring concern for adverse effects on cognition due to established role learning memory. To address these challenges, we asked whether any clinically approved drugs,...
Toll-like receptor 4 (TLR4) is ubiquitously expressed on parenchymal and immune cells of the liver most studied TLR responsible for activation proinflammatory signaling cascades in ischemia reperfusion (I/R). Since pharmacological inhibition TLR4 during sterile inflammatory response I/R has not been studied, we sought to determine whether eritoran, a antagonist trialed sepsis, could block hepatic TLR4-mediated inflammation end organ damage. When C57BL/6 mice were pretreated with eritoran...
Cholesterol synthesis and clearance by astrocytes are tightly regulated to maintain constant levels within the brain. In this context, liver X receptors (LXRs) master regulators of cholesterol homeostasis in central nervous system (CNS). Increasing trigger LXR activation leading transcription target genes involved trafficking efflux, including apolipoprotein E, cytochrome P450 enzymes, sterol regulatory binding protein, several ATP-binding cassette transporter proteins. The disturbance...
Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain, depression, weakness, mood disturbances, and neuropsychological impairment. In this mini review case report, we address central nervous system (CNS) involvement CFS present neuropathological autopsy findings patient who died prior diagnosis CFS. Among the most remarkable...
G protein-coupled receptor (GPCR) kinase 2 (GRK2) is highly expressed in the heart, where during injury or heart failure (HF), both its levels and activity increase. GRK2 canonically studied context of GPCR phosphorylation; however, noncanonical activities have emerged it now appreciated that has a large non-GPCR interactome. For example, cardiac myocytes, translocates from cytosol to mitochondria (mtGRK2) following oxidative stress ischemia injury, this pool mtGRK2 associated with negative...
The GPCR kinase GRK2 is highly expressed the heart; importantly, during cardiac injury or heart failure (HF) both levels and activity of increase. role HF canonically studied upstream β-adrenergic desensitization. However, has a large interactome noncanonical functions for this are being uncovered. We have discovered that in heart, translocates to mitochondria ( mtGRK2 ) following associated with negative effects on metabolism. Thus, we sought identify mechanism(s) by which can regulate...
<b>Abstract ID 54365</b> <b>Poster Board 159</b> <b>Background and Significance:</b> Heart failure (HF) is characterized by aberrant cardiac beta-adrenergic receptor (β-AR) signaling, leading to upregulation of GPCR kinase 2 (GRK2) subsequent phosphorylation desensitization β-ARs. A peptide inhibitor GRK2, comprised the last 194 carboxyl-terminal amino acids GRK2 (βARKct), has been shown bind G protein beta-gamma subunits, preventing binding β-AR desensitization. Overexpression βARKct...
<b>Abstract ID 29057</b> <b>Poster Board 155</b> Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII) is an established negative regulator of cardiac injury. Both the expression and activity levels CaMKII are elevated in models heart failure such as ischemia-reperfusion (I/R) injury myocardial infarction (MI). This due part to CaMKII's role regulation excitation-contraction coupling, apoptosis, activation hypertrophic programming, arrhythmias pro-inflammatory signaling. We have...
Background: Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is an established negative regulator of cardiac injury. Both the expression and activity levels CaMKII delta, primary isoform this kinase, are elevated in models heart failure (HF) such as ischemia-reperfusion (I/R) injury following myocardial infarction (MI). This upregulation due part to CaMKII’s role regulation excitation-contraction coupling, apoptosis, activation hypertrophic programming, arrhythmias pro-inflammatory...
Background: Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII) hyperactivity is an established driver of cardiac arrhythmias. Despite proven benefits CaMKII inhibition in numerous preclinical arrhythmia models, translation antagonists into humans has remained unsuccessful, and today, there are no clinically approved inhibitors. Our ability to identify potent inhibitors been hamstrung by a lack biosensor with sufficient sensitivity for high throughput drug discovery. Research question: We...
G Protein-Coupled Receptor Kinase 2 (GRK2) is a culprit in the loss of cardiac contractile function heart failure due to β-Adrenoceptor (AR) desensitization after its upregulation. Indeed, inhibition has been demonstrated improve and increased GRK2 leads larger injury an ischemic insult. Nitric oxide (NO) via S-nitrosothiol (SNO) at residue Cys340 reported endogenous inhibitor activity. ß3ARs, on other hand, are known be resistant by they upregulated pathologies. Activation ß3ARs can...
Introduction: During heart failure, levels and activity of G protein-coupled receptor kinase 2 (GRK2) increase. GRK2 is canonically studied in the phosphorylation GPCRs β-adrenergic desensitization. Noncanonical activities are being uncovered, however. Our lab has recently discovered that cardiac myocytes, translocates to mitochondria ( mtGRK2 ) following injury associated with negative effects on metabolism cell survival. Hypothesis: plays a role regulating mitochondrial function stress...
Introduction: The GPCR kinase GRK2 is highly expressed the heart; during cardiac injury or heart failure (HF) levels and activity of increase. While GRKs are canonically studied upstream β-adrenergic desensitization, has a large non-GPCR interactome novel, noncanonical functions. We have discovered that in heart, translocates to mitochondria ( mtGRK2 ) following negatively affects cellular metabolism substrate utilization. Thus, we sought identify mechanism(s) by which regulates...