Biology subjects

Hachim, M. Y.

Publications and source records attributed to Hachim, M. Y..

3 recordsLinked to original sources

bioRxiv2023

Nischarin negatively impacts ShcD-mediated tumor cell migration

ShcD was previously found to promote cell motility in melanoma cells. Screening of a yeast two hybrid mouse embryo cDNA library identified Nischarin, a negative regulator to cell motility, as an interacting partner to the ShcD-CH2 domain. Therefore, we aimed to investigate the interaction between Nischarin and ShcD in mammalian cells and to determine their functional impact on cell migration. The Nischarin/ShcD interaction was confirmed by transfection and co-immunoprecipitation assays using full-length constructs in HEK293, MCF7 and MM253 cell lines. Deletion of the first 93 amino acids of ShcD abrogated the interaction indicating the importance of these residues for Nischarin binding. Co-expression of Nischarin and ShcD demonstrated an inhibitory effect on the levels of phospho-ERK and phospho-LIMK. In support of this, Nischarin was found to block the migratory activities of ShcD. A brief in silico analysis of publicly available breast cancer patient data was performed to elucidate the effect of Nischarin/ShcD co-expression on the patients overall survival. Patients with high expression of both proteins had better survival than those with only ShcD overexpression. Our results reveal that the novel protein Nischarin is an interacting partner to ShcD. In addition, we report that the tumour suppressive abilities of Nischarin can overcome ShcD-mediated cell migration when both proteins are concomitantly expressed. *This abstract was presented in the National Cancer Research Institute (NCRI)-2019

molecular biology↗

bioRxiv2020

Cellular exocytosis gene (EXOC6/6B): a potential molecular link for the susceptibility and mortality of COVID-19 in diabetic patients

Diabetes is one of the most critical comorbidities linked to an increased risk of severe complications in the current coronavirus disease 2019 (COVID-19) pandemic. A better molecular understanding of COVID-19 in people with type diabetes mellitus (T2D) is mandatory, especially in countries with a high rate of T2D, such as the United Arab Emirates (UAE). Identification of the cellular and molecular mechanisms that make T2D patients prone to aggressive course of the disease can help in the discovery of novel biomarkers and therapeutic targets to improve our response to the disease pandemic. Herein, we employed a system genetics approach to explore potential genomic, transcriptomic alterations in genes specific to lung and pancreas tissues, affected by SARS-CoV-2 infection, and study their association with susceptibility to T2D in Emirati patients. Our results identified the Exocyst complex component, 6 (EXOC6/6B) gene (a component for docks insulin granules to the plasma membrane) with documented INDEL in 3 of 4 whole genome sequenced Emirati diabetic patients. Publically available transcriptomic data showed that lung infected with SARS-CoV-2 showed significantly lower expression of EXOC6/6B compared to healthy lungs. In conclusion, our data suggest that EXOC6/6B might be an important molecular link between dysfunctional pancreatic islets and ciliated lung epithelium that makes diabetic patients more susceptible to severe SARS-COV-2 complication.

bioinformatics↗

bioRxiv2020

Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19

The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene which is involved in regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow completion of their viral replication cycles. Furthermore, a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs which negatively correlated with the expression of genes that code for sterol response element binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Together our results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.

immunology↗