Papers by Hisham Mohammed
Most invasive lobular breast cancers (ILC) are of the luminal A subtype and strongly hormone rece... more Most invasive lobular breast cancers (ILC) are of the luminal A subtype and strongly hormone receptor positive. Yet, they are relatively resistant to tamoxifen and are associated with inferior long-term outcomes compared to invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. Through a comprehensive analysis of the epigenome of ILC in pre-clinical models and clinical samples we found that compared to IDC, ILC has a distinct chromatin state that is linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This results in an ILC-unique FOXA1-estrogen receptor (ER) axis that promotes the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis leads to retained ER chromatin binding after tamoxifen treatment thereby facilitating tamoxifen re...
Supplemental material, sj-docx-1-joo-10.1177_1465312520984166 for Are developmentally missing tee... more Supplemental material, sj-docx-1-joo-10.1177_1465312520984166 for Are developmentally missing teeth a predictive risk marker of malignant diseases in non-syndromic individuals? A systematic review by Lubna Al-Muzian, Mohammed Almuzian, Hisham Mohammed, Aman Ulhaq and Alexander J Keightley in Journal of Orthodontics
Figure S1. Sensitivity analyses. (PDF 530 kb)
Table S2. List of communications. (PDF 137 kb)
MeSH terms and keywords used for the electronic database search. (DOCX 12Â kb)
Michael Chiang, Davide Michieletto, Chris A. Brackley, Nattaphon Rattanavirotkul, Hisham Mohammed... more Michael Chiang, Davide Michieletto, Chris A. Brackley, Nattaphon Rattanavirotkul, Hisham Mohammed, Davide Marenduzzo, Tamir Chandra 1 SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK, 2 MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK 3 Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA
Cancers, 2021
Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castra... more Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance can occur when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or through the expression of constitutively active splice variants lacking the androgen binding domain entirely (e.g., ARV7). In this study, we are reporting the discovery of a novel AR-NTD covalent inhibitor 1-chloro-3-[(5-([(2S)-3-chloro-2-hydroxypropyl]amino)naphthalen-1-yl)amino]propan-2-ol (VPC-220010) targeting the AR-N-terminal Domain (AR-NTD). VPC-220010 inhibits AR-mediated transcription of full length and truncated variant ARV7, downregulates AR response genes, and selectively reduces the growth of both full-length AR- and truncated AR-dependent prostate cancer cell lines. We show that VPC-220010 disrupts interactions between AR and known coactivators and coregulatory proteins, such as CHD4, FOXA1, ZMIZ1, and several SWI/SNF complex proteins. ...
Nowadays, Mobile Network Operators are confronted with many challenges to operate and maintain th... more Nowadays, Mobile Network Operators are confronted with many challenges to operate and maintain their network. Subscribers expect stable and perpetual services. Repeated interruptions of services will result in the dissatisfaction of users and may lead to losing the end user. One of the major issues facing a Radio Access Network (RAN) mobile operator is coping with the uplink interference in their RAN, such as the Receive Total Wideband Power (RTWP) in the Universal Mobile Telecommunications System (UMTS) band. A frequently occurring issue in such networks is the RTWP alarm. This alarm is reported in the Network Operation Centre (NOC) and contribute to poor quality in the network. Such an alarm may occur daily, thus impacting the network's Key Point Indicator (KPI). The mobile network I also thank my caring and supportive family, especially my wife, Hiba Eisa, and my daughter, Mayar, for always uplifting my spirit and cheering me on to work as hard as I could. Finally, I thank the Almighty God for giving me strength and courage to never fear my weaknesses, but learn from them to grow personally and professionally. v
Journal of Orthodontics, 2021
Background: Different genes and loci that are associated with non-syndromic developmental tooth a... more Background: Different genes and loci that are associated with non-syndromic developmental tooth agenesis (TA) have the same causation pathway in the development of tumours including breast cancer (BC), epithelial ovarian cancer (EOC), colorectal cancer (CRC) and lung cancer (LC). Objectives: To assess the link between TA and the development of cancer. Search sources: This registered review included a comprehensive search of electronic databases (Cochrane Central Register of Controlled Trials [CENTRAL], LILACS, Scopus, Web of Science and Medline via Ovid) until 1 April 2020, supplemented by manual, grey literature and reference lists search. There was no restriction in term of date of publication, gender, race or type of hypodontia. Data selection: The primary outcome was the relationship between TA and cancer. The secondary outcome was to identify the genetic correlation between TA and cancer. Data extraction: Study selection, data extraction and risk of bias assessment were perform...
Nature, 2019
Recent technological advances have enabled the profiling of multiple molecular layers at single-c... more Recent technological advances have enabled the profiling of multiple molecular layers at single-cell resolution 9-13 , providing novel opportunities to study the relationship between the transcriptome and epigenome during cell-fate decisions. We applied single-cell nucleosome, methylome and transcriptome sequencing 12 (scNMT-seq) to profile 1,105 single cells isolated from mouse embryos at four developmental stages (embryonic day (E)4.5, E5.5, E6.5 and E7.5) representing the exit from pluripotency and primary germ-layer specification (Fig. 1a-d, Extended Data Fig. 1). Cells were assigned to a specific lineage by mapping their RNA-expression profiles to a comprehensive single-cell atlas 4 from the same stages when available or using marker genes (Extended Data Fig. 2). Using dimensionality reduction, we show that all three molecular layers contain sufficient information to separate cells by stage (Fig. 1b-d) and lineage identity (Extended Data Figs. 2, 3). Epigenome dynamics at pluripotency exit We characterized the changes in DNA methylation and chromatin accessibility during each stage transition. Globally, methylation levels increase from approximately 25% to approximately 75% in embryonic tissues and to about 50% in extra-embryonic tissues, driven mainly by a wave of de novo methylation from E4.5 to E5.5 that preferentially targets CpG-poor genomic loci 6,8,14 (Fig. 1e, Extended Data Fig. 3). By contrast, we observed a more gradual decline in global chromatin accessibility from around 38% at E4.5 to around 30% at E7.5 (Fig. 1f), with no differences between embryonic and extra-embryonic tissues (Extended Data Fig. 3). To relate epigenetic changes to the transcriptional dynamics across stages, we calculated-for each gene and across all embryonic cells-the correlation between RNA expression and the corresponding DNA methylation or chromatin accessibility at the promoter. Out of
The Angle Orthodontist, 2019
Objectives: To evaluate systematically the effectiveness of miniscrew-supported maxillary incisor... more Objectives: To evaluate systematically the effectiveness of miniscrew-supported maxillary incisor intrusion compared with other nonsurgical intrusive mechanics for deep-bite correction. Materials and Methods: Unrestricted electronic searches in Embase, Web of Science, MEDLINE, LILACS, and Cochrane's CENTRAL as well as manual searches were conducted up to August 2019. Only randomized clinical trials (RCTs) were included. Study selection, data extraction, and bias assessment were done by two independent reviewers. The Cochrane risk-of-bias tool was used, and the quality of evidence was graded using the GRADE approach. A random-effects meta-analysis of continuous data, with its 95% confidence intervals (CIs), was used. Results: Seven RCTs were included in the quantitative synthesis, and the overall quality of evidence was very low to low. When compared with intrusion arches, miniscrews resulted in a more efficient deep-bite reduction with a standardized mean difference (SMD) of −0....
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Papers by Hisham Mohammed