A5017190138- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Ubiquitin and proteasome pathways
- Axon Guidance and Neuronal Signaling
- Protein Kinase Regulation and GTPase Signaling
- Peroxisome Proliferator-Activated Receptors
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Nuclear Receptors and Signaling
- Atherosclerosis and Cardiovascular Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Protein Tyrosine Phosphatases
- Renin-Angiotensin System Studies
- Redox biology and oxidative stress
- HER2/EGFR in Cancer Research
- Pancreatic function and diabetes
- Cancer, Lipids, and Metabolism
- Advanced Antenna and Metasurface Technologies
- Metamaterials and Metasurfaces Applications
- Monoclonal and Polyclonal Antibodies Research
- Melanoma and MAPK Pathways
- PI3K/AKT/mTOR signaling in cancer
Center For Advanced Meta-Materials
2017-2024
Augusta University
2013-2023
University of Rochester Medical Center
2010-2014
University of Rochester
2005-2013
Gojo (France)
2009-2013
Augusta University Health
2012-2013
Montclair State University
2012
University of Manchester
2012
Howard Hughes Medical Institute
2012
University of North Carolina at Chapel Hill
2012
The Nogo-66 receptor (NgR1) is a promiscuous for the myelin inhibitory proteins Nogo/Nogo-66, myelin-associated glycoprotein (MAG), and oligodendrocyte (OMgp). NgR1, an axonal glycoprotein, founding member of protein family composed structurally related molecules NgR2, NgR3. Here we show that NgR2 novel MAG acts selectively to mediate responses. binds directly with greater affinity than NgR1. In neurons NgR1 support binding in sialic acid-dependent Vibrio cholerae neuraminidase-sensitive...
In the mature nervous system, changes in synaptic strength correlate with neuronal structure. Members of Nogo-66 receptor family have been implicated regulating morphology. 1 (NgR1) supports binding myelin inhibitors Nogo-A, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte is important for growth cone collapse response to acutely presented vitro. After injury corticospinal tract, NgR1 limits axon collateral sprouting but not blocking long-distance regenerative vivo. Here, we...
The protein optic atrophy 1 (OPA1) is a dynamin-related associated with the inner mitochondrial membrane and functions in fusion cristae maintenance. Inner membrane-anchored long OPA1 (L-OPA1) undergoes proteolytic cleavage resulting short (S-OPA1). It often thought that S-OPA1 functionally insignificant product of L-OPA1 because accumulation due to observed fragmentation dysfunction. However, cells contain mixture both L- normal conditions, suggesting functional significance maintaining...
In the adult mammalian CNS, growth inhibitors oligodendrocyte-myelin glycoprotein (OMgp) and reticulon RTN4 (Nogo) are broadly expressed in oligodendrocytes neurons. Nogo OMgp complex with neuronal cell surface receptors receptor-1 (NgR1) paired Ig-like receptor-B (PirB) to regulate morphology. healthy NgR1 regulates dendritic spine shape attenuates activity-driven synaptic plasticity at Schaffer collateral–CA1 synapses. Here, we examine whether influence functional plasticity, efficacy by...
Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology recently suggested as an important contributor in controlling mitochondrial bioenergetics. divide fuse continuously, which affected environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered reported tissues patients animal models dysfunction. In this study, we found that fission...
Vascular smooth muscle cell (VSMC) migration in response to arterial wall injury is a critical process the development of intimal hyperplasia. Cell an energy-demanding that predicted require mitochondrial function. Mitochondria are morphologically dynamic, undergoing continuous shape change through fission and fusion. However, role morphology VSMC not well understood. The aim study understand how contributes provides its vivo relevance mouse model In primary VSMCs, chemoattractant PDGF...
Background— Diabetes mellitus is a major risk factor for cardiovascular mortality by increasing endothelial cell (EC) dysfunction and subsequently accelerating atherosclerosis. Extracellular-signal regulated kinase 5 (ERK5) activated steady laminar flow regulates EC function nitric oxide synthase expression inhibiting inflammation. However, the role regulatory mechanisms of ERK5 in atherosclerosis are poorly understood. Here, we report critical p90 ribosomal S6 (p90RSK)/ERK5 complex diabetes...
Atherosclerosis is readily observed in regions of blood vessels where disturbed flow (d-flow) known to occur. A positive correlation between protein kinase C ζ (PKCζ) activation and d-flow has been reported, but the exact role d-flow–mediated PKCζ atherosclerosis remains unclear. We tested hypothesis that by induces endothelial cell (EC) apoptosis regulating p53. found peroxynitrite (ONOO−) increased activation, which subsequently induced p53 SUMOylation, p53–Bcl-2 binding, EC apoptosis....
Mitochondria are the essential eukaryotic organelles that produce most cellular energy. The energy production and supply by mitochondria appear closely associated with continuous shape change of mediated fission fusion, as evidenced not only hereditary diseases caused mutations in fission/fusion genes but also aberrant mitochondrial morphologies numerous pathologic insults. However, how morphological is linked to their energy-producing activity poorly understood. In this study, we found...
Abstract Mitochondria are critical for metabolic homeostasis of the liver, and their dysfunction is a major cause liver diseases. Optic atrophy 1 (OPA1) mitochondrial fusion protein with role in cristae shaping. Disruption OPA1 causes dysfunction. However, function poorly understood. In this study, we delete fully developed male mice. Unexpectedly, knockout (LKO) mice healthy unaffected respiration, despite disrupted morphology. LKO induces stress response that establishes new homeostatic...
Following injury to the adult mammalian central nervous system, regenerative growth of severed axons is very limited. The lack neuronal repair often associated with significant functional deficits, and depending on severity injury, may result in permanent paralysis distal site injury. A detailed understanding molecular mechanisms that limit injured spinal cord an important step toward development specific strategies aimed at restoring connectivity lost as a consequence While rapid progress...
Because ERK5 inhibits endothelial inflammation and dysfunction, activating might be a novel approach to protecting vascular cells (ECs) against various pathological conditions of the blood vessel. We have identified small molecules that protect ECs via activation determined their contribution preventing cardiac allograft rejection. Using high-throughput screening, we certain statins antimalarial agents including chloroquine, hydroxychloroquine, quinacrine as strong activators. Pitavastatin...
The maintenance of mitochondrial energetics requires the proper regulation morphology, and vice versa. Mitochondrial dynamins control morphology by mediating fission fusion. One them, optic atrophy 1 (OPA1), is inner membrane remodeling protein. OPA1 has a dual role in maintaining through fusion cristae structure. expressed multiple variant forms alternative splicing post-translational proteolytic cleavage, but functional differences between these variants have not been completely...
Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 also necessary for maintaining cristae and thus essential supporting cellular energetics. exists as membrane-anchored long form (L-OPA1) short (S-OPA1) lacks transmembrane region generated by cleavage of L-OPA1. Mitochondrial dysfunction stresses activate membrane-associated zinc metallopeptidase OMA1 cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been L-OPA1...
Myelin-associated glycoprotein (MAG) is a sialic acid-binding Ig-family lectin that functions in neuronal growth inhibition and stabilization of axon–glia interactions. The ectodomain MAG comprised five Ig-like domains uses cell-type-specific mechanisms to signal inhibition. We show the first three bind with high affinity acid-dependent manner Nogo-66 receptor-1 (NgR1) its homolog NgR2. Domains Ig3–Ig5 are sufficient inhibit neurite outgrowth but fail associate NgR1 or Nogo receptors...
Cardiomyocyte apoptosis is one of the key events in development and progression heart failure, a crucial role for ICER (inducible cAMP early repressor) this process has been previously reported. ERK5 known to inhibit cardiac after myocardial infarction (MI), especially hyperglycemic states, via association with CHIP ubiquitin (Ub) ligase subsequent upregulation activity, which induces ubiquitination protein degradation. The regulatory mechanism governing ERK5/CHIP interaction unknown.
Dynamin-related membrane remodeling proteins regulate mitochondrial morphology by mediating fission and fusion. Although is considered an important factor in maintaining function, a direct mechanistic link between function has not been defined. We report here previously unrecognized cellular process of transient contraction the matrix. Importantly, we found that this morphological mitochondria accompanied reversible loss or decrease inner potential. Fission deficiency greatly amplified...
Fission and fusion of mitochondrial tubules are the major processes regulating morphology. However, physiological significance shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires ATP production which evokes Ca2+ influx through plasma membrane depolarization, triggering vesicle exocytosis. Therefore, GSIS reflects function can be used for evaluating functional changes associated with morphological alterations mitochondria. Using...
Growing evidence indicates a critical role of ubiquitin-proteosome system in apoptosis regulation. A cardioprotective effect ubiquitin (Ub) ligase the C terminus Hsc70-interacting protein (CHIP) on myocytes has been reported. In current study, we found that insulin growth factor-1 (IGF-1) was mediated by ERK5-CHIP signal module via inducible cAMP early repressor (ICER) destabilization. vitro runoff assay and Ub showed ICER as substrate CHIP ligase. Both disruption binding with inhibitory...