A5059520372- Hippo pathway signaling and YAP/TAZ
- Pancreatic function and diabetes
- Dietary Effects on Health
- Circadian rhythm and melatonin
- Congenital Heart Disease Studies
- Transplantation: Methods and Outcomes
- Congenital heart defects research
- Viral Infections and Immunology Research
- Parvovirus B19 Infection Studies
- Cardiovascular Function and Risk Factors
- Cardiovascular Effects of Exercise
- Mitochondrial Function and Pathology
- Protein Degradation and Inhibitors
- Diet, Metabolism, and Disease
- Smart Agriculture and AI
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Congenital Anomalies and Fetal Surgery
- Cardiovascular Issues in Pregnancy
- Adipose Tissue and Metabolism
- Cardiac Structural Anomalies and Repair
- Mechanical Circulatory Support Devices
- Pulmonary Hypertension Research and Treatments
- Cytomegalovirus and herpesvirus research
- Cardiomyopathy and Myosin Studies
University of Pittsburgh
2018-2024
Children's Hospital of Pittsburgh
2018-2024
UPMC Health System
2024
University of Pittsburgh Medical Center
2024
KPR Institute of Engineering and Technology
2023
The University of Texas Health Science Center at Houston
2013-2019
University of Utah
2013
The University of Texas at Austin
2010-2012
Texas Children's Hospital
2007
Baylor College of Medicine
2007
Circadian disruption has deleterious effects on metabolism. Global deletion of Bmal1, a core clock gene, results in β-cell dysfunction and diabetes. However, it is unknown if this due to loss cell-autonomous function Bmal1 β cells. To address this, we generated mice with by deleting cells (β-Bmal1(-/-)). β-Bmal1(-/-) develop diabetes glucose-stimulated insulin secretion (GSIS). This GSIS the accumulation reactive oxygen species (ROS) consequent mitochondrial uncoupling, as fully rescued...
Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating the established number cardiomyocytes.
TEAD1 and the mammalian Hippo pathway regulate cellular proliferation function, though their regulatory function in β cells remains poorly characterized. In this study, we demonstrate that while cell-specific deletion results a cell-autonomous increase of cell proliferation, its canonical coactivators, YAP TAZ, does not affect suggesting involvement other cofactors. Using an improved split-GFP system yeast two-hybrid platform, identify VGLL4 MENIN as corepressors cells. We show bind to...
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, requirement Tead1, transcriptional effector this pathway, adult heart unknown. Here, we show tamoxifen-inducible CM-specific Tead1 ablation led lethal acute-onset dilated cardiomyopathy,...
Abstract The Hippo-TEAD pathway regulates cellular proliferation and function. existing paradigm is that TEAD co-activators, YAP TAZ, co-repressor, VGLL4, bind to the pocket region of TEAD1 enable transcriptional activation or repressive Here we demonstrate a pocket-independent transcription repression mechanism whereby controls cell in both non-malignant mature differentiated cells malignant models. overexpression can repress tumor distinct cancer lines. In pancreatic β cells, conditional...
Adult heart size is determined predominantly by the cardiomyocyte number and size. The primarily in embryonic perinatal period, as adult proliferation restricted comparison to that seen during period. Recent evidence has implicated mammalian Hippo kinase pathway being critical proliferation. Though transcription factor, Tead1, canonical downstream transcriptional factor of hippo cardiomyocytes, specific role Tead1 period not been determined. Here, we report generation a deletion using...
This study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation. Viral myocardial causes heart failure, but its role transplantation is unclear. We hypothesized that allograft reduces graft survival. Between June 1999 November 2004, 94 pediatric transplant patients were screened for presence genome in serial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced coronary artery disease (TCAD), acute...
Abstract Background: Complete atrioventricular canal defects (CAVC) are a common heart defect, but few epidemiologic studies have evaluated non‐syndromic CAVC. Risk factors for CAVC not been well established. Methods: To assess the relationship between risk in offspring and several sociodemographic reproductive parental factors, including maternal diabetes obesity, we conducted Poisson regression analyses, using data ascertained through Texas Birth Defects Registry, large, population‐based...
Mitochondrial dysfunction occurs in most forms of heart failure. We have previously reported that Tead1, the transcriptional effector Hippo pathway, is critical for maintaining adult cardiomyocyte function, and its deletion results lethal acute dilated cardiomyopathy. Growing lines evidence indicate pathway plays a role regulating mitochondrial although cardiomyocytes unknown. Here, we show Tead1 OXPHOS cardiomyocytes. Assessment bioenergetics isolated mitochondria from hearts showed loss...
BACKGROUND: TEAD1, the mammalian Hippo pathway regulated transcription factor, plays a critical and non-redundant role in maintaining cardiomyocyte (CM) homeostasis. However, specific cellular pathways by TEAD1 CMs remain poorly defined. We hypothesized that has an essential, cell autonomous CM oxidative stress response directly regulating of NRF2, master regulator response. METHODS AND RESULTS: Tamoxifen induced conditional CM-specific deletion adult mice leads to acute heart failure (HF)...
A breakdown in self-tolerance underlies autoimmune destruction of β-cells and type 1 diabetes. cure by restoring β-cell mass is limited the availability transplantable need for chronic immunosuppression. Evidence indicates that inhibiting costimulation through PD-1/PD-L1 pathway central to immune tolerance. We therefore tested whether induction islet neogenesis liver, protected PD-L1-driven tolerance, reverses diabetes NOD mice. demonstrated a robust neo-islets liver diabetic mice gene...
Plant diseases are regarded as one of the major variables affecting food production and reducing losses. Early identification disease diagnosis fruit crops essential for industry to increase production. The development healthy sector is highly dependent on plant diseases. Guava a good source fiber, calcium, pectins, vitamin C. has become issue guava production, which negative impact farmers' socioeconomic growth. Infections that harm plants fruits pose greatest obstacles, although they can...
Background Despite compelling epidemiological evidence that circadian disruption inherent to long‐term shift work enhances atherosclerosis progression and vascular events, the underlying mechanisms remain poorly understood. A challenge use of mouse models for mechanistic interventional studies involving light‐dark patterns is spectral absolute sensitivities murine human systems are very different, light stimuli in nocturnal mice should be scaled represent system. Methods Results We used...
The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of heme protein myoglobin increases by over 50% during differentiation, a role for in regulating has not been tested. Here, we show deletion models decreases gene markers stimulates cellular proliferation, consistent with de-differentiation. Mechanistically, prosthetic group catalyzes oxidation Hippo pathway kinase LATS1, resulting phosphorylation...
Proliferative quiescence in β-cells is required to maintain functional competence. While this presents a significant hurdle regenerative therapy for diabetes, the molecular underpinnings of reciprocal relationship remain unclear. Here, we demonstrate that TEAD1, transcription effector mammalian-Hippo pathway, drives developmental stage-specific β-cell proliferative capacity conjunction with its maturation. TEAD1 promotes adult mature identity by direct transcriptional control network...
Cytokine-induced β-cell apoptosis is a major pathogenic mechanism in type 1 diabetes (T1D). Despite significant advances understanding its underlying mechanisms, few drugs have been translated to protect β-cells T1D. Epigenetic modulators such as bromodomain-containing BET (bromo- and extra-terminal) proteins are important regulators of immune responses. Pre-clinical studies demonstrated protective effect inhibitors an NOD (non-obese diabetes) mouse model However, the protein inhibition on...
Summary Proliferative quiescence in β-cells is required to maintain functional competence. While this presents a significant hurdle regenerative therapy for diabetes, the molecular underpinnings of reciprocal relationship remain unclear. Here, we demonstrate that TEAD1, transcription effector mammalian-Hippo pathway, drives developmental stage-specific β-cell proliferative capacity conjunction with its maturation. TEAD1 promotes adult mature identity by direct transcriptional control network...