A5012590158- Heat shock proteins research
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- thermodynamics and calorimetric analyses
- Endoplasmic Reticulum Stress and Disease
- Genomics, phytochemicals, and oxidative stress
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Inflammation biomarkers and pathways
- Genetics, Aging, and Longevity in Model Organisms
- Liver Disease Diagnosis and Treatment
- Effects of Radiation Exposure
- Apelin-related biomedical research
- Viral Infectious Diseases and Gene Expression in Insects
- Physiological and biochemical adaptations
- Spaceflight effects on biology
- Protein Structure and Dynamics
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- Amoebic Infections and Treatments
- Complement system in diseases
- Adipose Tissue and Metabolism
Augusta University Health
2011-2024
Augusta University
2015-2024
Charlie Norwood VA Medical Center
2010-2017
Georgia Regents Medical Center
2013-2015
Cancer Research Center
2015
Nashville VA Medical Center
2014
Frederick National Laboratory for Cancer Research
2012
National Cancer Institute
2012
Center for Cancer Research
2012
Science Applications International Corporation (United States)
2012
Chronic inflammation drives liver cancer pathogenesis, invasion, and metastasis. Liver Kupffer cells have crucial roles in mediating the inflammatory processes that promote cancer, but mechanistic basis for their contributions are not fully understood. Here we show expression of proinflammatory myeloid cell surface receptor TREM-1 expressed by is a factor development progression cancer. Deletion murine homolog Trem1 mice attenuated hepatocellular carcinogenesis triggered diethylnitrosamine...
Heat shock transcription factor 1 (HSF-1) activates the of heat genes in eukaryotes. Under normal physiological growth conditions, HSF-1 is a monomer. Its transcriptional activity repressed by constitutive phosphorylation. Upon activation, forms trimers, acquires DNA binding activity, increases and appears as punctate granules nucleus. In this study, using bromouridine incorporation confocal laser microscopy, we demonstrated that newly synthesized pre-mRNAs colocalize to after shock,...
Abstract The rapid synthesis of heat shock proteins (Hsps) in cells subjected to environmental challenge is controlled by transcription factor‐1 (Hsf1). Regulation Hsps Hsf1 highly complex and, the whole organism, remains largely unexplored. In this study, we have used mouse embryo fibroblasts and bone marrow progenitor from hsf1 −/− mice as well hsp70.3 ‐ lacZ knock‐in bred on deficient genetic background ( +/− ), further elucidate function its participation a transcriptional activator...
Abstract Summary: Heat shock transcription factors (Hsfs) are major transactivators of heat protein (Hsp) genes in the response to stress stimuli, but also thought be involved embryonic development and spermatogenesis. Among three known mammalian Hsfs, Hsf1 is recognized as most effective transactivator Hsps thermal challenge, role Hsf2 regulation under normal or increased conditions vivo remains elusive. To study its physiological function vivo, we generated mice deficient hsf2 by gene...
The mammalian heat shock transcription factor HSF-1 regulates the expression of proteins, molecular chaperones that are involved in cellular processes from higher order assembly to protein degradation. is a phosphorylated monomer under physiological growth conditions and located mainly cytoplasm. Upon activation by variety environmental stresses, translocated into nucleus, forms trimers, acquires DNA binding activity, hyperphosphorylated, appears as punctate granules, increases...
The murine hsp70 gene family includes the evolutionarily conserved hsp70.1 andhsp70.3 genes, which are major proteins induced by heat and other stress stimuli.hsp70.1 encode identical protect cells facilitate their recovery from stress-induced damage. While has been widely studied roles of it encodes as molecular chaperones in a range human pathologies appreciated, little is known about developmental regulation expression vivo biological function products. To directly study physiological...
Controlling macrophage responses to pathogenic stimuli is critical for prevention of and recovery from the inflammatory state associated with pathogenesis many diseases. The adhesion receptor αVβ3 integrin thought be an important that regulates differentiation external signaling, but it has not been previously identified as a contributor macrophage-related inflammation. Using in vitro model human blood monocytes (Mo) monocyte-derived macrophages (MDMs) we demonstrate ligation results...
ErbB2/Neu oncogene is overexpressed in 25% of invasive/metastatic breast cancers. We have found that deletion heat shock factor Hsf1 mice overexpressing significantly reduces mammary tumorigenesis and metastasis. Hsf1(+/-)ErbB2/Neu(+) tumors exhibit reduced cellular proliferative invasive properties associated with activated ERK1/2 epithelial-mesenchymal transition (EMT). Hsf1(+/+)Neu(+) epithelial cells exposed to TGFβ show high levels activity EMT; this expression E-cadherin increased Slug...
Estrogen receptor positive (ER + ) breast cancer is the most common diagnosed annually in US with endocrine-based therapy as standard-of-care for this subtype. Endocrine includes treatment antiestrogens, such selective estrogen modulators (SERMs), downregulators (SERDs), and aromatase inhibitors (AIs). Despite appreciable remission achievable these treatments, a substantial cohort of women will experience primary tumor recurrence, subsequent metastasis, eventual death due to their disease....
Abstract Heat shock factors (Hsfs) are major transactivators of heat proteins but also involved in regulation other genes active embryonic development. High expression levels Hsfs mouse testis during development suggest a role for these spermatogenesis, cyclic process spermatogonia cell‐differentiation into mature spermatozoa. In contrast to hsf1 −/− mice, which exhibit normal targeted disruption hsf2 results reduced testicular size only small impairment male fertility. We show here that...
Abstract Mammalian ocular lens development results via a differentiation program that is highly regulated by tissue‐specific transcription factors. Central to this the terminal of fiber cells, which develop from epithelial cells on anterior surface lens, accompanied change in cell shape and expression structural proteins (such as membrane MP19, MIP26, connexin 43, 46, 50, cytoskeletal CP49, CP115, α, β, γ crystallins), creating transparent, refractive index gradient lens. Mutations genes...
Abstract The mammalian small heat shock protein (sHSPs) family is comprised of 10 members and includes HSPB1, which proposed to play an essential role in cellular physiology, acting as a molecular chaperone regulate diverse processes. Whilst differential roles for sHSPs are suggested specific tissues, the relative contribution individual sHSP organ physiology remains unclear. To address function HSPB1 vivo determine its tissue‐specific expression during development adult, we generated...
The heat shock transcription factors (Hsfs) are responsible for the response, an evolutionarily conserved process clearance of damaged and aggregated proteins. In organisms such as Caenorhabditis elegans , which contain a single Hsf, reduction in level Hsf is associated with appearance age-related phenotypes increased accumulation protein aggregates. Mammalian cells express three hsfs ( hsf1 hsf2 hsf4 ) their role CNS homeostasis remains unclear. this study, we examined effects deletion or...
Accumulation of tau into neurofibrillary tangles is a pathological consequence Alzheimer's disease and other tauopathies. Failures the quality control mechanisms by heat shock proteins (Hsps) positively correlate with appearance such neurodegenerative diseases. However, in vivo genetic evidence for roles Hsps neurodegeneration remains elusive. Hsp110 nucleotide exchange factor Hsp70, direct substrate binding to may facilitate folding. Hsp70 complexes have been implicated phosphorylation...
Deciphering the molecular basis of stem cell pluripotency is fundamental to understanding biology, early embryonic development, and clinical application regenerative medicine. We report here that chaperone heat shock protein 90 (Hsp90) essential for mouse (ESC) through regulating multiple factors, including Oct4, Nanog, signal transducer activator transcription 3. Inhibition Hsp90 by either 17-N-Allylamino-17-demethoxygeldanamycin or miRNA led ESC differentiation. Overexpression Hsp90β...
Metabolic energy reprogramming facilitates adaptations to a variety of stress conditions and cellular dysfunction, but how the energetic demands are monitored met in response physiological stimuli remains elusive. Our data support model demonstrating that heat shock factor 1 (HSF1), master transcriptional regulator chaperone response, has been coopted from its role as critical protein quality-control having central systemic sensing for metabolic adaptation nutrient availability. We found...
The activation of heat shock transcription factor-1 (HSF-1) after treatment mammalian cells with stresses such as shock, heavy metals, or ethanol induces the synthesis proteins. HSF-1 is phosphorylated at normal growth temperature and hyperphosphorylated upon stress. We recently presented evidence that can be by mitogen activated protein kinase, ERK1, phosphorylation appears to negatively regulate activity HSF-1. In this report, we have tested ability ERK1 phosphorylate various deletion...
Pretreatment by a sublethal insult is associated with induction of stress proteins and protection from subsequent injury. Heat pretreatment protects the brain ischemia, shown here to protect primary astrocyte cultures oxygen-glucose deprivation. To determine whether expression single protein, HSP-70, could account for much this protection, we expressed HSP-70 or β-galactosidase in astrocytes using retroviral vectors. Only 12% expressing died after 7 hours deprivation compared 65% 82% normal...