A5085462852- Cardiomyopathy and Myosin Studies
- Circadian rhythm and melatonin
- Light effects on plants
- Cardiovascular Effects of Exercise
- Congenital heart defects research
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Genetics, Aging, and Longevity in Model Organisms
- Cellular transport and secretion
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Protease and Inhibitor Mechanisms
- Protein Tyrosine Phosphatases
- Endoplasmic Reticulum Stress and Disease
- Connective tissue disorders research
- Receptor Mechanisms and Signaling
- Neurobiology and Insect Physiology Research
- Mitochondrial Function and Pathology
- Spaceflight effects on biology
- Cardiac Valve Diseases and Treatments
- Cardiovascular Issues in Pregnancy
- Viral Infections and Immunology Research
- Cancer, Hypoxia, and Metabolism
- Histone Deacetylase Inhibitors Research
- Autophagy in Disease and Therapy
Northwestern University
2015-2024
Northwestern Memorial Hospital
2022-2024
Renal Research Institute
2018-2024
Northwestern Medicine
2022
Cardiovascular Institute Hospital
2015-2017
University of Chicago
2017
University of California, San Francisco
2010-2016
Howard Hughes Medical Institute
1998-2006
University of Toronto
2006
University of Wisconsin–Madison
2006
The mouse Clock gene encodes a bHLH-PAS protein that regulates circadian rhythms and is related to transcription factors act as heterodimers. Potential partners of CLOCK were isolated in two-hybrid screen, one, BMAL1, was coexpressed with PER1 at known clock sites brain retina. CLOCK-BMAL1 heterodimers activated from E-box elements, type factor–binding site, found adjacent the per1 an identical be important for per expression Drosophila. Mutant dominant-negative allele BMAL1 formed bound DNA...
Background: Mutations in desmoplakin ( DSP ), the primary force transducer between cardiac desmosomes and intermediate filaments, cause an arrhythmogenic form of cardiomyopathy that has been variably associated with right ventricular cardiomyopathy. Clinical correlates have limited to small case series. Methods: genetic data were collected on 107 patients pathogenic mutations 81 plakophilin 2 PKP2 ) as a comparison cohort. A composite outcome severe arrhythmia was assessed. Results: cohorts...
The basic helix-loop-helix (bHLH)–Per-Arnt-Sim (PAS) domain transcription factor BMAL1 is an essential component of the mammalian circadian pacemaker. Bmal1 –/– mice lose rhythmicity but also display tendon calcification and decreased activity, body weight, longevity. To investigate whether these diverse functions are tissue-specific, we produced transgenic that constitutively express in brain or muscle examined effects rescued gene expression mice. Circadian rhythms wheel-running activity...
SIRT2 is a cytoplasmic sirtuin that plays role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized directly regulates iron homeostasis. Here, have demonstrated depletion results decrease levels both vitro vivo. Mechanistically, determined maintains by binding to deacetylating nuclear factor erythroid-derived 2-related 2 (NRF2) on lysines 506 508, leading reduction total NRF2 levels. The leads reduced...
Truncating mutations in the giant sarcomeric protein Titin result dilated cardiomyopathy and skeletal myopathy. The most severely affected patients harbor truncations C-terminal two-thirds of protein, suggesting that mutation position might influence disease mechanism. Using CRISPR/Cas9 technology, we generated six zebrafish lines with N-terminal regions. Although all exons were constitutive, caused severe myopathy whereas demonstrated mild phenotypes. Surprisingly, neither type acted as a...
Tyro3, AXL, and MerTK (TAM) receptors are activated in macrophages response to tissue injury as such have been proposed therapeutic targets promote inflammation resolution during sterile wound healing, including myocardial infarction. Although the role of cardioprotection is well characterized, unique other structurally similar TAMs, particularly clinically relevant models ischemia/reperfusion infarction (IRI) comparatively unknown. Utilizing complementary approaches, validated by flow...
A conserved transcription-translation negative feedback loop forms the molecular basis of circadian oscillator in animals. Molecular interactions within this have been relatively well characterized vitro and cell culture; however, vivo approaches are required to assess functional significance these interactions. Here, regulation gene expression was studied by using transgenic reporter mouse lines which 6.75 kb Period1 ( mPer1 ) promoter drives luciferase luc expression. Six - were created,...
// Asish K. Ghosh 1 , Rahul Rai Kitae E. Park Mesut Eren Toshio Miyata 2 Lisa D. Wilsbacher and Douglas Vaughan Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, Illinois, USA United Centers for Advanced Translational Tohoku University, Miyagi, Japan Correspondence to: Vaughan, email: Ghosh, Keywords : cellular senescence, doxorubicin, cardiomyocytes, fibroblasts, endothelial cells, Gerotarget Received June 15, 2016 Accepted September 29,...
Hypoxia-inducible factors (HIFs) are activated in parenchymal cells response to low oxygen and as such have been proposed therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs also within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics development for cardiac ischemic injury, surprisingly, unique role of myeloid HIFs, particularly HIF-2α, is unknown. Using a murine model mice with conditional genetic loss gain...
Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure early death. We have previously shown that FATp300-p300 with intrinsic factor acetyltransferase activity-is an essential epigenetic regulator fibrogenesis, is elevated in several fibrotic tissues. In this report, we investigate therapeutic efficacy a novel FATp300 inhibitor,...
Cardiovascular aging underpins the development of age-related diseases, including heart failure and vascular dysfunction, is driven by molecular cellular mechanisms described in hallmarks aging. Plasminogen activator inhibitor-1 (PAI-1), a key regulator fibrinolysis, also mediates processes like stiffness, senescence, immune evasion. This review highlights PAI-1’s role cardiovascular with special emphasis on hallmark It further explores therapeutic potential, focus its contribution to ECM...
Toward understanding their redundancies and interactions in hemostasis thrombosis, we examined the roles of thrombin receptors (protease-activated receptors, PARs) ADP receptor P2RY12 (purinergic P2Y G protein-coupled 12) human mouse platelets ex vivo models. Par3 −/− Par4 +/− showed partially decreased responses to thrombin, resembling those PAR1 antagonist-treated platelets. P2ry12 ADP, clopidogrel-treated mice nearly complete protection against carotid artery thrombosis caused by low FeCl...
Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing.Whole-genome sequencing induced pluripotent stem cells were used to examine atrial ventricular arrhythmias. We also characterized mouse model heterozygous homozygous deletion of Mybphl.Whole-genome identified premature stop codon, R255X, the MYBPHL encoding MyBP-HL...
Many cardiomyopathy-associated
A broad array of stressors induce ACTH release from the anterior pituitary, with consequent stimulation adrenal cortex and glucocorticoids critical for survival animal. stimulates adrenocortical gene expression in vivo inhibits cell proliferation. Binding to its G-protein-coupled receptor production cAMP activation protein kinase pathway. The stress-activated kinases (SAPKs) (or c-Jun N-terminal kinases) extracellular signal-regulated (ERKs) are members mitogen-activated family...