A5083151274- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
- Cancer-related gene regulation
- Lung Cancer Research Studies
- Cardiac electrophysiology and arrhythmias
- Neuroendocrine Tumor Research Advances
- Autophagy in Disease and Therapy
- Cardiac Fibrosis and Remodeling
- Bone Tumor Diagnosis and Treatments
- Sarcoma Diagnosis and Treatment
- Head and Neck Surgical Oncology
- Salivary Gland Tumors Diagnosis and Treatment
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Receptor Mechanisms and Signaling
- Neuroblastoma Research and Treatments
- Lung Cancer Treatments and Mutations
- Tumors and Oncological Cases
- Tissue Engineering and Regenerative Medicine
- Head and Neck Cancer Studies
- Peptidase Inhibition and Analysis
- Medical Imaging and Pathology Studies
- Liver Disease Diagnosis and Treatment
- Signaling Pathways in Disease
The University of Texas Health Science Center at San Antonio
2022-2025
University of Minnesota
2015-2024
St.John's Medical College Hospital
2024
Audie L. Murphy Memorial VA Hospital
2023
Foundation Medicine (United States)
2022
Yale University
2011-2022
University of Alabama at Birmingham
2017-2022
University of Minnesota Medical Center
2017-2022
University of Minnesota Rochester
2022
Universidad Libre de Colombia
2022
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...
The presence of increased ubiquitinated proteins and amyloid oligomers in failing human hearts strikingly resembles the characteristic pathology brain many neurodegenerative diseases. ubiquitin–proteasome system (UPS) is responsible for degradation most cellular plays essential roles virtually all processes. UPS impairment by aberrant protein aggregation was previously shown cell culture but remains to be demonstrated intact animals. Mechanisms underlying are poorly understood. We report...
Background— Autophagy is essential to intracellular homeostasis and involved in the pathophysiology of a variety diseases. Mechanisms regulating selective autophagy remain poorly understood. The COP9 signalosome (CSN) conserved protein complex consisting 8 subunits (CSN1 through CSN8), known regulate ubiquitin-proteasome system. However, it unknown whether CSN plays role autophagy. Methods Results— Marked increases LC3-II p62 proteins were observed on Csn8 depletion cardiomyocytes mouse...
Differentiation of primary from metastatic adenocarcinoma in the lung can be challenging, and it demands sensitive specific biomarkers, especially when tissue for diagnosis is limited. Thyroid transcription factor-1 (TTF-1) has been considered a reliable marker origin. However, several recent studies have shown that TTF-1 immunostaining also positive adenocarcinomas arising different organs including colon, endometrium, endocervix, ovary. In addition, approximately 20% are negative...
Neointimal hyperplasia characterized by abnormal accumulation of vascular smooth muscle cells (SMCs) is a hallmark occlusive disorders such as atherosclerosis, postangioplasty restenosis, vein graft stenosis, and allograft vasculopathy. Cyclic nucleotides are vital in SMC proliferation migration, which regulated cyclic nucleotide phosphodiesterases (PDEs).Our goal to understand the regulation function PDEs pathogenesis diseases.We performed screening for genes differentially expressed normal...
Abstract Cytotoxic chemotherapy agents (e.g., cisplatin) are the first-line drugs to treat non-small cell lung cancer (NSCLC) but NSCLC develops resistance agent, limiting therapeutic efficacy. Despite many approaches identifying underlying mechanism for cisplatin resistance, there remains a lack of effective targets in population that resist treatment. In this study, we sought investigate role cytoplasmic RAP1, previously identified positive regulator NF- κ B signaling, development cells....
How canonical Wnt/β-catenin signals in adult hearts, especially different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It not clear whether c-Myc activated or how it regulated heart failure.We investigated signaling expression failing hearts of human ischemic disease, idiopathic dilated cardiomyopathy, murine desmin-related cardiomyopathy. Our data demonstrated that was through nuclear accumulation β-catenin...
Abstract Translational control is crucial for protein production in various biological contexts. Here, we use Ribo-seq and RNA-seq to show that genes related oxidative phosphorylation are translationally downregulated during heart regeneration. We find Nat10 regulates the expression of Uqcr11 Uqcrb mRNAs mouse human cardiomyocytes. In mice, overexpression cardiomyocytes promotes cardiac regeneration improves function after injury. Conversely, treating neonatal mice with Remodelin—a...
αB-crystallin (CryAB) is the most abundant small heat shock protein in heart. Upregulation of CryAB desmin-related myopathy and its downregulation end-stage congestive heart failure have both been reported. We previously demonstrated via cardiac-specific transgenesis that modest increases normal are not detrimental to heart, whereas expression R120G mutation caused a desminopathy. It generally believed plays an important role protecting intermediate filaments, but underlying mechanism...
The COP9 signalosome (CSN) is an evolutionarily conserved protein complex composed of 8 unique subunits (CSN1 through CSN8). We have recently discovered in perinatal mouse hearts that CSN regulates not only proteasome-mediated proteolysis but also macroautophagy. However, the physiological significance a post-mitotic organ adult vertebrates has been determined. sought to study role CSN8/CSN hearts.Csn8 was conditionally ablated cardiomyocytes mice (CSN8(CKO)) using temporally controlled...
Androgen receptor (AR) signals have been implicated in bladder carcinogenesis and tumor progression. Activation of Wnt/β-catenin signaling has also reported to correlate with cancer progression poor patients' outcomes. However, cross talk between AR β-catenin pathways remains uncharacterized. In radical cystectomy specimens, we immunohistochemically confirmed aberrant expression especially aggressive tumors. There was a strong association nuclear expressions tumors ( P =0.0215). Kaplan–Meier...
Background Lysosomal dysfunction is implicated in human heart failure for which ischemic disease the leading cause. Altered myocardial expression of CTSD (cathepsin D), a major lysosomal protease, was observed failure, but its pathophysiological significance has not been determined. Methods and Results Western blot analyses revealed an increase precursor mature form samples from explanted failing hearts with disease, recapitulated chronic infarction produced via coronary artery ligation Ctsd...
G protein–coupled receptor kinases (GRKs) are known to be involved in the development of cardiac hypertrophy. Their exact role and subcellular distribution during hypertrophy failure remain elucidated. We examined expression GRK2 GRK5 left ventricle female spontaneously hypertensive heart (SHHF) rats at 6 months age using Western blots fluorescent confocal microscopy. was expressed mainly Triton X-100 soluble fraction with similar levels between SHHF age-matched Wistar-Kyoto (WKY) rats. had...
Recent progresses in signal transduction have revealed that β-catenin signaling controls embryonic development, tumorigenesis, cell shape, and polarity. The role of this pathway myocyte shape regulation during cardiac hypertrophy failure is, however, not clearly defined. Since homozygous knockout is embryonically lethal, we deleted genes specifically the heart adult mice by crossing loxP-flanked with transgenic expressing tamoxifen-activated MerCreMer protein (MCM) driven α-myosin heavy...
The ubiquitin-proteasome system (UPS) degrades a protein molecule via 2 main steps: ubiquitination and proteasomal degradation. Extraproteasomal ubiquitin receptors are thought to couple the steps, but this proposition has not been tested in vivo with vertebrates. More importantly, impaired UPS performance plays major role cardiac pathogenesis, including myocardial ischemia-reperfusion injury (IRI), molecular basis of impairment remains poorly understood. Ubiquilin1 is bona fide...
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions with excessive inflammation in the lung. Glucocorticoids had been widely used for ALI/ARDS, but their clinical benefit remains unclear. Here, we tackled problem by conjugating prednisolone (PSL) a targeting peptide termed CRV. Systemically administered CRV selectively homes to inflamed of murine ALI model, not healthy organs or mice. The expression receptor, retinoid X receptor β, was...