A5009398649- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Congenital heart defects research
- Congenital Heart Disease Studies
- Developmental Biology and Gene Regulation
- Chemical Synthesis and Analysis
- Tracheal and airway disorders
- Genomic variations and chromosomal abnormalities
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Tissue Engineering and Regenerative Medicine
- Computational Drug Discovery Methods
- Marine Ecology and Invasive Species
- Acute Myeloid Leukemia Research
- Genetics and Neurodevelopmental Disorders
- Signaling Pathways in Disease
- Chromatin Remodeling and Cancer
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Thyroid Disorders and Treatments
- Folate and B Vitamins Research
- Coronary Artery Anomalies
- Electric Motor Design and Analysis
Institute of Genetics and Biophysics
2009-2024
National Research Council
2009-2024
National Research Council
2024
University of Lahore
2017
Pir Mehr Ali Shah Arid Agriculture University
2017
Telethon Institute Of Genetics And Medicine
2009
Stazione Zoologica Anton Dohrn
2003
Hammersmith Hospital
1993
Purpose: Histone deacetylase inhibitors (HDACi) are promising anticancer drugs. Although some HDACi have entered the clinic, mechanism(s) underlying their tumor selectivity poorly understood.Experimental Design and Results: Using gene expression analysis, we define a core set of six genes commonly regulated in acute myeloid leukemia (AML) blasts cell lines. MYC, most prominently modulated, is preferentially altered leukemia. Upon treatment, c-Myc acetylated at lysine 323 its decreases,...
Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation survival normal hematopoietic progenitors. In acute myeloid leukemias this is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression...
Pathological conditions caused by reduced dosage of a gene, such as gene haploinsufficiency, can potentially be reverted enhancing the expression functional allele. In practice, low specificity therapeutic agents, or their toxicity reduces clinical applicability. Here, we have used high throughput screening (HTS) approach to identify molecules capable increasing Tbx1, which is involved in one most common haploinsufficiency syndromes, 22q11.2 deletion syndrome. Surprisingly, found that two...
The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and gene is haploinsufficient DiGeorge syndrome, a typical developmental anomaly of pharyngeal apparatus. Despite almost two decades research, if how function triggers chromatin remodeling not known. Here, we explored genome-wide expression independent cellular models Tbx1 loss function, mouse embryonic carcinoma cells P19Cl6, stem (mESCs). results our study revealed that or knockdown caused extensive...
The Ezh2 gene encodes a histone methyltransferase of the polycomb repressive complex 2 that methylates H3 lysine 27. In this study, we investigated whether EZH2 has role in development pharyngeal apparatus and it regulates expression Tbx1 gene, which key transcription factor required development. To these ends, performed genetic vivo experiments with mouse embryos used embryonic stem cell (ESC)-based protocols to probe endoderm cardiogenic mesoderm differentiation. Results showed occupies...
The T-box transcription factor TBX1 has critical roles in maintaining proliferation and inhibiting differentiation of cardiac progenitor cells the second heart field (SHF). Haploinsufficiency gene that encodes it is a cause congenital disease. Here, we developed an embryonic stem (ES) cell-based model which Tbx1 expression can be modulated by tetracycline. Using this model, found down regulates VEGFR2, confirmed finding vivo during development. In addition, Vegfr2 domain expression, not...
Endothelial cells (EC) differentiate from multiple sources, including the cardiopharyngeal mesoderm, which gives rise also to cardiac and branchiomeric muscles. The enhancers activated during endothelial differentiation within mesoderm are not completely known. Here, we use a cardiogenic model that activates an transcription program identify regulatory elements in early mesoderm. Integrating chromatin remodeling gene expression data with available single-cell RNA-seq mouse embryos, 101...
TBX1 is a key regulator of pharyngeal apparatus (PhAp) development. Vitamin B12 (vB12) treatment partially rescues aortic arch patterning defects Tbx1+/- embryos. Here, we show that it also improves cardiac outflow tract septation and branchiomeric muscle anomalies Tbx1 hypomorphic mutants. At the molecular level, in vivo vB12 enabled us to identify genes were dysregulated by haploinsufficiency rescued treatment. We found SNAI2, known as SLUG, encoded gene Snai2, identified population...
Tbx1 mutant mice are a widely used model of 22q11.2 deletion syndrome (22q11.2DS) because they manifest broad spectrum physical and behavioral abnormalities that is similar to found in 22q11.2DS patients. In mutants, brain include changes cortical cytoarchitecture, hypothesized be caused by the precocious differentiation progenitors. The objectives this research identify drugs have efficacy against phenotype, through phenotypic rescue approach, gain insights into pathogenetic mechanisms...
Abstract Introduction The brain-related phenotypes observed in 22q11.2 deletion syndrome (22q11.2DS) are highly variable and their origin is poorly understood. Changes brain metabolism may cause or contribute to the phenotypes, given that many of deleted genes (approx. 10%) implicated metabolic processes, but this currently unknown. It clearly important address knowledge gap, humans, primary material required for studying inaccessible. For reason, we sought issue using two mouse models...
The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes brain metabolism might contribute to these phenotypes, as many of the deleted genes involved metabolic processes, but this unknown. This study shows for first time that Tbx1 haploinsufficiency causes imbalance. We studied two mouse models 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, transcriptomics. found +/− mice...
ABSTRACT The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and gene is haploinsufficient DiGeorge syndrome, a typical developmental anomaly of pharyngeal apparatus. Despite almost two decades research, if how function triggers chromatin remodeling not known. Here, we explored genome-wide expression independent cellular models Tbx1 loss function, mouse embryonic carcinoma cells P19Cl6, stem (mESCs). results our study revealed that or knockdown caused...
# 266 Metoprolol induces cardiac beta-3 adrenergic receptor and Sphingosine 1 phosphate signals to prevent adverse Left-ventricle remodeling dysfunction after myocardial infarction {#article-title-2} Background: β-adrenergic (AR)-blockers are fore-front therapies against (MI)-induced other forms of heart failure (HF). Mechanisms accounting for these beneficial effects remain however only partially understood. In particular, due the difference in targeting great variability human HF-patients...
<p>Epigenetic status of the TRAIL promoter region after HDACi exposure.</p>
<p>SAHA effects in normal cells.</p>
<p>Suppl. Methods</p>
<p>The down-regulation of c-Myc by SAHA.</p>