13 results on '"Al-Sayegh, Mohamed"'
Search Results
2. Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function
- Author
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Palanikumar, L., Karpauskaite, Laura, Al-Sayegh, Mohamed, Chehade, Ibrahim, Alam, Maheen, Hassan, Sarah, Maity, Debabrata, Ali, Liaqat, Kalmouni, Mona, Hunashal, Yamanappa, Ahmed, Jemil, Houhou, Tatiana, Karapetyan, Shake, Falls, Zackary, Samudrala, Ram, Pasricha, Renu, Esposito, Gennaro, Afzal, Ahmed J., Hamilton, Andrew D., Kumar, Sunil, and Magzoub, Mazin
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- 2021
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3. The role of SRF coactivators MRTF-A and MRTF-B in adipogenesis in vitro
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Al-Sayegh, Mohamed
- Subjects
571.65072 - Abstract
This thesis comprises the work undertaken to investigate the role of the family of myocardin- related transcription factors, MRTF-A and MRTF-B, at regulating adipogenesis using the well- established in vitro model of 3T3-LI preadipocyte cells. Serum response factor (SRF) is an essential transcription factor that activates the expression of early immediate genes via recruitment of the family ternary complex factors or the transcription of cytoskeleton and muscle-specific genes via MRTF-A and MRTF-B recruitment. It has been shown that SRF depletion is sufficient to promote adipocyte differentiation in the absence of adipogenic stimuli though the mechanisms responsible for this are unknown. The work presented in this thesis shows that MRTF activity is abrogated at the onset of adipogenesis by two mechanisms: relocation of MRTF protiens to the cytoplasm and downregulation of both MRTF-A and MRTF- B protein and mRNA expression levels. These results suggest that inhibition of MRTF activity might be a pre-requisite for adipogenesis to proceed. In agreement with this, depletion of MRTF- A and MRTF-B protein levels via lentiviral mediated RNA interference was shown to promote adipogenesis in the absence of adipogenic cues where overexpression of a dominant positive MRTF-A form inhibited adipocyte differentiation. Several potential endogenous MRTF target genes that could mediate the effects of MR TFs on adipogenesis were identified using a combination of genome-wide RNA expression analysis of MRTF-depleted cells, quantitative PCR and chromatin immunoprecipitation assays. •
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- 2012
4. Mouse Embryonic Fibroblast Adipogenic Potential: A Comprehensive Transcriptome Analysis.
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Al-Sayegh, Mohamed, Ali, Hamad, Jamal, Mohammad H, ElGindi, Mei, Chanyong, Tina, Al-Awadi, Khulood, and Abu-Farha, Mohamed
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ADIPOKINES , *FIBROBLASTS , *TRANSCRIPTOMES , *ADIPOSE tissues , *ADIPOGENESIS , *MICE - Abstract
Our understanding of adipose tissue has progressed from an inert tissue for energy storage to be one of the largest endocrine organs regulating metabolic homoeostasis through its ability to synthesize and release various adipokines that regulate a myriad of pathways. The field of adipose tissue biology is growing due to this association with various chronic metabolic diseases. An important process in the regulation of adipose tissue biology is adipogenesis, which is the formation of new adipocytes. Investigating adipogenesis in vitro is currently a focus for identifying factors that might be utilized in clinically. A powerful tool for such work is high-throughput sequencing which can rapidly identify changes at gene expression level. Various cell models exist for studying adipogenesis and has been used in high-throughput studies, yet little is known about transcriptome profile that underlies adipogenesis in mouse embryonic fibroblasts. This study utilizes RNA-sequencing and computational analysis with DESeq2, gene ontology, protein–protein networks, and robust rank analysis to understand adipogenesis in mouse embryonic fibroblasts in-depth. Our analyses confirmed the requirement of mitotic clonal expansion prior to adipogenesis in this cell model and highlight the role of Cebpa and Cebpb in regulating adipogenesis through interactions of large numbers of genes. [ABSTRACT FROM AUTHOR]
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- 2021
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5. Oligopyridylamide-based protein mimetic inhibits cancer-associated mutant p53 amyloid-like aggregation and restores its tumor suppressor function
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Loganathan, Palanikumar, Karpauskaite, Laura, Al-Sayegh, Mohamed, Chehade, Ibrahim, Ali, Maheen, Hassan, Sarah, Maity, Debabrata, Ali, Liaqat, Kalmouni, Mona, Houhou, Tatiana, Esposito, Gennaro, Afzal, Ahmed J., Hamilton, Andrew D., Kumar, Sunil, and Magzoub, Mazin
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- 2022
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6. Tumor Microenvironment in Prostate Cancer: Toward Identification of Novel Molecular Biomarkers for Diagnosis, Prognosis, and Therapy Development.
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Bahmad, Hisham F., Jalloul, Mohammad, Azar, Joseph, Moubarak, Maya M., Samad, Tamara Abdul, Mukherji, Deborah, Al-Sayegh, Mohamed, and Abou-Kheir, Wassim
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PROSTATE cancer prognosis ,TUMOR microenvironment ,CASTRATION-resistant prostate cancer ,CONNECTIVE tissue growth factor ,PROSTATE cancer ,MOLECULAR diagnosis ,PROSTATE-specific antigen ,ANDROGEN receptors - Abstract
Prostate cancer (PCa) is by far the most commonly diagnosed cancer in men worldwide. Despite sensitivity to androgen deprivation, patients with advanced disease eventually develop resistance to therapy and may die of metastatic castration-resistant prostate cancer (mCRPC). A key challenge in the management of PCa is the clinical heterogeneity that is hard to predict using existing biomarkers. Defining molecular biomarkers for PCa that can reliably aid in diagnosis and distinguishing patients who require aggressive therapy from those who should avoid overtreatment is a significant unmet need. Mechanisms underlying the development of PCa are not confined to cancer epithelial cells, but also involve the tumor microenvironment. The crosstalk between epithelial cells and stroma in PCa has been shown to play an integral role in disease progression and metastasis. A number of key markers of reactive stroma has been identified including stem/progenitor cell markers, stromal-derived mediators of inflammation, regulators of angiogenesis, connective tissue growth factors, wingless homologs (Wnts), and integrins. Here, we provide a synopsis of the stromal-epithelial crosstalk in PCa focusing on the relevant molecular biomarkers pertaining to the tumor microenvironment and their role in diagnosis, prognosis, and therapy development. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Establishment and characterization of prostate organoids from treatment-naïve patients with prostate cancer.
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Cheaito, Katia, Bahmad, Hisham F., Hadadeh, Ola, Msheik, Hiba, Monzer, Alissar, Ballout, Farah, Dagher, Christelle, Telvizian, Talar, Saheb, Nour, Tawil, Ayman, El-Sabban, Marwan, El-Hajj, Albert, Mukherji, Deborah, Al-Sayegh, Mohamed, and Abou-Kheir, Wassim
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PROSTATE cancer patients ,PROSTATE cancer ,ORGANOIDS ,RADICAL prostatectomy ,PROSTATE ,CELL suspensions - Abstract
Three-dimensional (3D) organoid culture systems are emerging as potential reliable tools to investigate basic developmental processes of human disease, especially cancer. The present study used established and modified culture conditions to report successful generation and characterization of patient-derived organoids from fresh primary tissue specimens of patients with treatment-naïve prostate cancer (PCa). Fresh tissue specimens were collected, digested enzymatically and the resulting cell suspensions were plated in a 3D environment using Matrigel as an extracellular matrix. Previously established 12-factor medium for organoid culturing was modified to create a minimal 5-factor medium. Organoids and corresponding tissue specimens were characterized using transcriptomic analysis, immunofluorescent analysis, and immunohistochemistry. Furthermore, patient-derived organoids were used to assess the drug response. Treatment-naïve patient-derived PCa organoids were obtained from fresh radical prostatectomy specimens. These PCa organoids mimicked the heterogeneity of corresponding parental tumor tissue. Histopathological analysis demonstrated similar tissue architecture and cellular morphology, as well as consistent immunohistochemical marker expression. Also, the results confirmed the potential of organoids as an in vitro model to assess potential personalized treatment responses as there was a differential drug response between different patient samples. In conclusion, the present study investigated patient-derived organoids from a cohort of treatment-naïve patients. Derived organoids mimicked the histological features and prostate lineage profiles of their corresponding parental tissue and may present a potential model to predict patient-specific treatment response in a pre-clinical setting. [ABSTRACT FROM AUTHOR]
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- 2022
8. May the Force Be with You (Or Not): The Immune System under Microgravity.
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ElGindi, Mei, Sapudom, Jiranuwat, Ibrahim, Ibrahim Hamed, Al-Sayegh, Mohamed, Chen, Weiqiang, Garcia-Sabaté, Anna, and Teo, Jeremy C. M.
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REDUCED gravity environments ,HUMAN space flight ,IMMUNE system ,GRAVITATION ,KNOWLEDGE gap theory - Abstract
All terrestrial organisms have evolved and adapted to thrive under Earth's gravitational force. Due to the increase of crewed space flights in recent years, it is vital to understand how the lack of gravitational forces affects organisms. It is known that astronauts who have been exposed to microgravity suffer from an array of pathological conditions including an impaired immune system, which is one of the most negatively affected by microgravity. However, at the cellular level a gap in knowledge exists, limiting our ability to understand immune impairment in space. This review highlights the most significant work done over the past 10 years detailing the effects of microgravity on cellular aspects of the immune system. [ABSTRACT FROM AUTHOR]
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- 2021
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9. The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update.
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Azar, Joseph, Bahmad, Hisham F., Daher, Darine, Moubarak, Maya M., Hadadeh, Ola, Monzer, Alissar, Al Bitar, Samar, Jamal, Mohamed, Al-Sayegh, Mohamed, and Abou-Kheir, Wassim
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ORGANOIDS ,ORGANS (Anatomy) ,STEM cells ,EMBRYONIC stem cells ,MEDICAL research ,PLURIPOTENT stem cells - Abstract
Organoids represent one of the most important advancements in the field of stem cells during the past decade. They are three-dimensional in vitro culturing models that originate from self-organizing stem cells and can mimic the in vivo structural and functional specificities of body organs. Organoids have been established from multiple adult tissues as well as pluripotent stem cells and have recently become a powerful tool for studying development and diseases in vitro, drug screening, and host–microbe interaction. The use of stem cells—that have self-renewal capacity to proliferate and differentiate into specialized cell types—for organoids culturing represents a major advancement in biomedical research. Indeed, this new technology has a great potential to be used in a multitude of fields, including cancer research, hereditary and infectious diseases. Nevertheless, organoid culturing is still rife with many challenges, not limited to being costly and time consuming, having variable rates of efficiency in generation and maintenance, genetic stability, and clinical applications. In this review, we aim to provide a synopsis of pluripotent stem cell-derived organoids and their use for disease modeling and other clinical applications. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Modeling Adipogenesis: Current and Future Perspective.
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Bahmad, Hisham F., Daouk, Reem, Azar, Joseph, Sapudom, Jiranuwat, Teo, Jeremy C. M., Abou-Kheir, Wassim, and Al-Sayegh, Mohamed
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CELL differentiation ,ADIPOGENESIS ,STEM cells ,HUMAN body ,FAT cells ,REGENERATIVE medicine ,ADIPOSE tissues - Abstract
Adipose tissue is contemplated as a dynamic organ that plays key roles in the human body. Adipogenesis is the process by which adipocytes develop from adipose-derived stem cells to form the adipose tissue. Adipose-derived stem cells' differentiation serves well beyond the simple goal of producing new adipocytes. Indeed, with the current immense biotechnological advances, the most critical role of adipose-derived stem cells remains their tremendous potential in the field of regenerative medicine. This review focuses on examining the physiological importance of adipogenesis, the current approaches that are employed to model this tightly controlled phenomenon, and the crucial role of adipogenesis in elucidating the pathophysiology and potential treatment modalities of human diseases. The future of adipogenesis is centered around its crucial role in regenerative and personalized medicine. [ABSTRACT FROM AUTHOR]
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- 2020
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11. MicroRNAs as clinical tools for diagnosis, prognosis, and therapy in prostate cancer.
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Ghamlouche F, Yehya A, Zeid Y, Fakhereddine H, Fawaz J, Liu YN, Al-Sayegh M, and Abou-Kheir W
- Abstract
Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men worldwide. Despite the presence of accumulated clinical strategies for PCa management, limited prognostic/sensitive biomarkers are available to follow up on disease occurrence and progression. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression through post-transcriptional regulation of their complementary target messenger RNA (mRNA). MiRNAs modulate fundamental biological processes and play crucial roles in the pathology of various diseases, including PCa. Multiple evidence proved an aberrant miRNA expression profile in PCa, which is actively involved in the carcinogenic process. The robust and pleiotropic impact of miRNAs on PCa suggests them as potential candidates to help more understand the molecular landscape of the disease, which is likely to provide tools for early diagnosis and prognosis as well as additional therapeutic strategies to manage prostate tumors. Here, we emphasize the most consistently reported dysregulated miRNAs and highlight the contribution of their altered downstream targets with PCa hallmarks. Also, we report the potential effectiveness of using miRNAs as diagnostic/prognostic biomarkers in PCa and the high-throughput profiling technologies that are being used in their detection. Another key aspect to be discussed in this review is the promising implication of miRNAs molecules as therapeutic tools and targets for fighting PCa., Competing Interests: Declaration of Competing Interest All authors declared that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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12. Epidermal Growth Factor Is Essential for the Maintenance of Novel Prostate Epithelial Cells Isolated From Patient-Derived Organoids.
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Cheaito K, Bahmad HF, Jalloul H, Hadadeh O, Msheik H, El-Hajj A, Mukherji D, Al-Sayegh M, and Abou-Kheir W
- Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related mortality and morbidity among males worldwide. Deciphering the biological mechanisms and molecular pathways involved in PCa pathogenesis and progression has been hindered by numerous technical limitations mainly attributed to the limited number of cell lines available, which do not recapitulate the diverse phenotypes of clinical disease. Indeed, PCa has proven problematic to establish as cell lines in culture due to its heterogeneity which remains a challenge, despite the various in vitro and in vivo model systems available. Growth factors have been shown to play a central role in the complex regulation of cell proliferation among hormone sensitive tumors, such as PCa. Here, we report the isolation and characterization of novel patient-derived prostate epithelial (which we named as AUB-PrC) cells from organoids culture system. We also assessed the role of epidermal growth factor (EGF) in culturing those cells. We profiled the AUB-PrC cells isolated from unaffected and tumor patient samples via depicting their molecular and epithelial lineage features through immunofluorescence staining and quantitative real-time PCR (qRT-PCR), as well as through functional assays and transcriptomic profiling through RNA sequencing. In addition, by optimizing a previously established prostate organoids culture system, we were able to grow human prostate epithelial cells using growth medium and EGF only. With these data collected, we were able to gain insight at the molecular architecture of novel human AUB-PrC cells, which might pave the way for deciphering the mechanisms that lead to PCa development and progression, and ultimately improving prognostic abilities and treatments., (Copyright © 2020 Cheaito, Bahmad, Jalloul, Hadadeh, Msheik, El-Hajj, Mukherji, Al-Sayegh and Abou-Kheir.)
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- 2020
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13. A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.
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Velasco S, Ibrahim MM, Kakumanu A, Garipler G, Aydin B, Al-Sayegh MA, Hirsekorn A, Abdul-Rahman F, Satija R, Ohler U, Mahony S, and Mazzoni EO
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- Animals, DNA metabolism, Embryonic Stem Cells metabolism, Enhancer Elements, Genetic genetics, Genetic Loci, Mice, Models, Biological, Motor Neurons metabolism, Nucleotide Motifs genetics, Promoter Regions, Genetic genetics, Protein Binding genetics, Sequence Analysis, RNA, Single-Cell Analysis, Time Factors, Transcription Factors metabolism, Cellular Reprogramming genetics, Chromatin metabolism, Embryonic Stem Cells cytology, Motor Neurons cytology, Transcription, Genetic
- Abstract
Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions. Subsequently, Isl1/Lhx3 binding shifts from one set of targets to another, controlling regulatory region activity and gene expression as cell differentiation progresses. Binding of Isl1/Lhx3 to later motor neuron enhancers depends on the Ebf and Onecut TFs, which are induced by Ngn2 during the programming process. Thus, motor neuron programming is the product of two initially independent transcriptional modules that converge with a feedforward transcriptional logic., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2017
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