- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- Chromatin Remodeling and Cancer
- Protein Tyrosine Phosphatases
- Chromosomal and Genetic Variations
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Bioactive natural compounds
- Berberine and alkaloids research
- Congenital heart defects research
- Plant Micronutrient Interactions and Effects
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Estrogen and related hormone effects
- BRCA gene mutations in cancer
- Ocular Disorders and Treatments
- Glutathione Transferases and Polymorphisms
- Genomics, phytochemicals, and oxidative stress
- HER2/EGFR in Cancer Research
- HIV/AIDS drug development and treatment
- Cell Adhesion Molecules Research
United Arab Emirates University
2006-2024
Ain Shams University
2023
Nova Southeastern University
2023
South University
2023
Alexandria University
2018-2022
King Faisal Specialist Hospital & Research Centre
2013-2021
Al-Salam Hospital
2016-2019
University of Southern California
2013
Cardiovascular Research Center
2013
University of Dundee
2011
Embryonic lethality is a recognized phenotypic expression of individual gene mutations in model organisms. However, identifying embryonic lethal genes humans challenging, especially when the phenotype manifested at preimplantation stage. In an ongoing effort to exploit highly consanguineous nature Saudi population catalog recessively acting humans, we have identified two families with female-limited infertility phenotype. Using autozygosity mapping and whole exome sequencing, map this single...
Primary microcephaly (PM) is a developmental disorder of early neuroprogenitors that results in reduction the brain mass, particularly cortex. To gain fresh insight into pathogenesis PM, we describe consanguineous family with novel genetic variant responsible for disease. We performed autozygosity mapping followed by exome sequencing to detect causal variant. Several functional assays cells expressing wild-type or mutant gene were understand identified mutation. identify mutation PHC1, human...
The Saccharomyces cerevisiae Fun30 (Function unknown now 30) protein shares homology with an extended family of Snf2-related ATPases. Here we report the purification principally as a homodimer molecular mass about 250 kDa. Biochemical characterization this complex reveals that it has ATPase activity stimulated by both DNA and chromatin. Consistent this, also binds to exhibits in ATP-dependent chromatin remodeling assays. Interestingly, its histone dimer exchange is high relative ability...
Bromodomains are present in many chromatin-associated proteins such as the SWI/SNF and RSC chromatin remodelling SAGA HAT (histone acetyltransferase) complexes, can bind to acetylated lysine residues N-terminal tails of histones. Lysine acetylation is a histone modification that forms stable epigenetic mark on for bromodomain-containing dock turn regulate gene expression. In order better understand how bromodomains read ‘histone code’ interact with histones, we have tested interactions...
Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in pathological cardiac hypertrophy, but the mechanisms by which it modulates gene activity nucleus to mediate hypertrophic signaling remain unclear. Here, we report that nuclear CaMKII activates transcription directly binding chromatin and regulating phosphorylation of histone H3 at serine-10. These specific activities are demonstrated both vitro primary neonatal rat cardiomyocytes. Activation agonists increases...
Up to 10% of patients with severe early-onset obesity carry pathogenic variants in known obesity-related genes, mostly affecting the leptin-melanocortin pathway. Studying children from consanguineous populations provides a unique opportunity uncover novel molecular mechanisms. Using whole-exome sequencing, followed by rigorous analytical and filtration strategy, we identified three different homozygous missense SREK1 (encoding Splicing Regulatory glutamic acid lysine rich protein) Pakistani...
The SWI/SNF and SAGA chromatin-modifying complexes contain bromodomains that help anchor these to acetylated promoter nucleosomes. To study the importance of in complexes, we have compared chromatin-remodeling octamer-transfer activity complex a mutant lacks Swi2/Snf2 bromodomain. Here show can remodel or transfer SAGA-acetylated nucleosomes more efficiently than bromodomain-deleted complex. These results demonstrate bromodomain is important for remodeling as well on H3-acetylated Moreover,...
Dilated cardiomyopathy (DCM) is a common form of causing systolic dysfunction and heart failure. Rare variants in more than 30 genes, mostly encoding sarcomeric proteins the cytoskeleton, have been implicated familial DCM to date. Yet, majority remain be identified. The goal study identify novel mutations dilated cardiomyopathy. We FBXO32 (ATROGIN 1), member F-Box protein family, as DCM-causing locus. missense mutation affects highly conserved amino acid predicted severely impair binding SCF...
Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become hallmark hypertrophy and maladaptive ventricular remodelling, yet mechanisms regulate this transcriptional reprogramming are not fully understood. Using mice genetic ablation calcium/calmodulin-dependent protein kinase II δ (CaMKIIδ), which resistant to pathological stress, we show CaMKIIδ regulates phosphorylation histone H3 at serine-10 during pressure overload hypertrophy. S10 strongly...
Abstract Endoplasmic reticulum (ER) stress induction of cell death is implicated in cardiovascular diseases. Sustained activation ER-stress induces the unfolded protein response (UPR) pathways, which turn activate three major effector proteins. We previously reported a missense homozygous mutation FBXO32 ( MAFbx, Atrogin-1 ) causing advanced heart failure by impairing autophagy. In present study, we performed transcriptional profiling and biochemical assays, unexpectedly revealed reduced UPR...
The SWI/SNF chromatin‐remodeling complex contains a bromodomain in its Swi2/Snf2 subunit that helps tether it to acetylated promoter nucleosomes. To study the importance of this complex, we have compared nucleosome‐binding and activities mutant lacks bromodomain. Here show deleted cannot bind SAGA‐ or NuA4‐acetylated nucleosomes as well wild‐type complex. Moreover, reduced binding leads partial remodeling these nucleosome templates by Δbromodomain These results demonstrate is required for...
The liver is the main organ involved in lipid metabolism process and it helps drug detoxification. Insulin resistance considered one of risk reasons which lead to several metabolic diseases. Currently, berberine (BER) occupies a huge challenge against multiple diseases with no toxic effect. present work was aimed identify, does BER-chloride has poisonous influence on liver? investigating outcome PI3K/Akt-p/SIRT-1/PTEN pathway during insulin syndrome. model achieved experimental female rats...
Genetic alterations of the proto-oncogene human epidermal growth factor receptor (HER-2/neu) have been shown to induce malignant transformation and metastasis. Genotyping studies addressed association codon 655 isoleucine valine polymorphism located in transmembrane coding region risk breast cancer, but results are inconsistent. In this study, we investigated HER-2/neu Ile655Val cancer a Sudanese population. addition, joint effects variants our previously reported ESR1C325G were tested for...
Abstract The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed whose in vivo function heart and cardiac diseases remains unknown. To investigate role of LMPTP function, we generated mice with genetic inactivation Acp1 locus studied their response to long‐term pressure overload. −/− develop normally ageing do not show pathology major tissues under basal conditions. However, are strikingly resistant overload hypertrophy failure....
Estrogen and estrogen receptors play important roles in the proliferation development of breast cancer. Several genetic alterations identified receptor α gene (ESR1) are thought to influence expression or function this protein, many have been evaluated for their role cancer predisposition. The aim study was evaluate C325G single nucleotide polymorphism (SNP) ESR1 predisposition candidate SNP ESR1, exon 4 genotyped patients healthy controls that were age sex matched. Genotyping performed...
Abstract Insulin resistance is one of dangerous factors as it leads to numerous metabolic disorders such non-insulin dependent diabetes mellitus. It affects most tissues mainly adipose tissue, liver and muscle. Nowadays, berberine has several medical applications against diseases. The current study was carried out identify the effect chloride (BER-chloride) on phosphatidyl inositol-3-kinase/ phosphorylated protein kinase B/ sirtuin type 1/ phosphatase tension homologue...
The recent paradoxical dual citizenships of Runt-related transcription factor 3 (Runx3) in tumorigenesis remains poorly characterized. Here, we report the oncogenic capacity Runx3 as chromatin modulator metastatic gastric cancer model. exists homodimer and binds cooperatively to modified nucleosomes. Additionally, detected a synergistic functional enhancement octamer transfer, nucleosome sliding stochiometric integrity SWI/SNF by Runx3. We found that depletion increased nucleosomes occupancy...
T HE AIM of this study was to determine how cerium dioxide nanoparticles (CeO 2 NPs) affect the growth and physiology Brassica napus plants.CeO NPs were biosynthesized using Aloe Vera extract characterized a UV-visible spectrophotometer, X-ray diffraction, Fourier transform infrared spectroscopy, Zeta potential, particle size (DLS) as well transmission electron microscopy.Following foliar treatment with 250, 500, 1000ppm CeO NPs, growth, metabolism evaluated.Exposure 500ppm significantly...