ساره باسل أبو جلبوش

ASUجامعة العلوم التطبيقية الخاصة - الصفحة الرئيسيةكلية العلوم الطبية المساندةساره باسل أبو جلبوشالأبحاث

الأبحاث

Research Title : Improving the performance of selective solid-state nanopore sensing using a polyhistidine-tagged monovalent streptavidin.

Authors : Sara Abu Jalboush, Ian D. Wadsworth, Komal Sethi, LeAnn C. Rogers, Thomas Hollis, Adam R. Hall

Abstract :Solid-state (SS-) nanopore sensing has gained tremendous attention in recent years, but it has been constrained by its intrinsic lack of selectivity. To address this, we previously established a novel SS-nanopore assay that produces translocation signals only when a target biotinylated nucleic acid fragment binds to monovalent streptavidin (MS), a protein variant with a single high-affinity biotin-binding domain. While this approach has enabled selective quantification of diverse nucleic acid biomarkers, sensitivity enhancements are needed to improve the detection of low-abundance translational targets. Because the translocation dynamics that determine assay efficacy are largely governed by constituent charge characteristics, we here incorporate a polyhistidine-tagged MS (hMS) to alter the component detectability. We investigate the effects of buffer pH, salt concentration, and SS-nanopore diameter on the performance with the alternate reagent, achieve significant improvements in measurement sensitivity and selectivity, and expand the range of device dimensions viable for the assay. We used this improvement to detect as little as 1 nM miRNA spiked into human plasma. Overall, our findings improve the potential for broader applications of SS-nanopores in the quantitative analyses of molecular biomarkers.

Keywords : solid-state nanopores, nucleic acid, monovalent streptavidin, amplification-free detection, selective detection, biomarkers

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Research Title :Book Chapter : Quantitative detection of cancer nucleic acid biomarkers with a selective solid-state nanopore assay.

Authors : Adam R. Hall, Sara Abu Jalboush, Ian D. Wadsworth, Mohamed Amin Elaguech, Komal Sethi

Abstract :Solid-state nanopores enable the electrical detection and characterization of biomolecules on an individual basis. Conventionally, any charged molecule can yield a signal in the system, necessitating advanced analyses and interpretation for any but the simplest mixtures. This has limited the translational utility of the platform. In this chapter, we describe a selective nanopore assay designed to produce a signal only for target molecules of interest. We discuss applications of the approach to diverse nucleic acid biomarkers related to cancer including DNA base modifications, microRNAs, and specific sequence motifs within large nucleic acid constructs.

Keywords :

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Research Title :TrkA interacts with and phosphorylates STAT3 to enhance gene transcription and promote breast cancer stem cells in triple-negative and HER2-enriched breast cancers

Authors : Angelina T. Regua, Noah R. Aguayo, Sara Abu Jalboush, Daniel L. Doheny, Sara G. Manore, Dongqin Zhu, Grace L. Wong, Austin Arrigo, Calvin J. Wagner, Yang Yu, Alexandra Thomas, Michael D. Chan, Jimmy Ruiz, Guangxu Jin, Roy Strowd, Peiqing Sun, Jiayuh Lin, and Hui-Wen Lo

Abstract :: JAK2–STAT3 and TrkA signaling pathways have been separately implicated in aggressive breast cancers; however, whether they are co-activated or undergo functional interaction has not been thoroughly investigated. Herein we report, for the first time that STAT3 and TrkA are significantly co-overexpressed and co-activated in triple-negative breast cancer (TNBC) and HER2-enriched breast cancer, as shown by immunohistochemical staining and data mining. Through immunofluorescence staining–confocal microscopy and immunoprecipitation–Western blotting, we found that TrkA and STAT3 co-localize and physically interact in the cytoplasm, and the interaction is dependent on STAT3-Y705 phosphorylation. TrkA–STAT3 interaction leads to STAT3 phosphorylation at Y705 by TrkA in breast cancer cells and cell-free kinase assays, indicating that STAT3 is a novel substrate of TrkA. β-NGF-mediated TrkA activation induces TrkA–STAT3 interaction, STAT3 nuclear transport and transcriptional activity, and the expression of STAT3 target genes, SOX2 and MYC. The co-activation of both pathways promotes breast cancer stem cells. Finally, we found that TNBC and HER2-enriched breast cancer with JAK2–STAT3 and TrkA co-activation are positively associated with poor overall metastasis-free and organ-specific metastasis-free survival. Collectively, our study uncovered that TrkA is a novel activating kinase of STAT3, and their co-activation enhances gene transcription and promotes breast cancer stem cells in TNBC and HER2-enriched breast cancer.

Keywords : breast cancer; TrkA; STAT3; cancer stem cells; SOX2; MYC

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Research Title :Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Authors : Grace L. Wong, Sara Abu Jalboush, Hui-Wen Lo

Abstract :: Breast cancer is the most frequent malignancy for women in which one in eight women will be diagnosed with the disease in their lifetime. Despite advances made in treating primary breast cancer, there is still no effective treatment for metastatic breast cancer. Consequently, metastatic breast cancer is responsible for 90% of breast cancer-related deaths while only accounting for approximately one third of all breast cancer cases. To help develop effective treatments for metastatic breast cancer, it is important to gain a deeper understanding of the mechanisms by which breast cancer metastasizes, particularly, those underlying organotropism towards brain, bone, and lungs. In this review, we will primarily focus on the roles that circulating exosomal microRNAs (miRNAs) play in organotropism of breast cancer metastasis. Exosomes are extracellular vesicles that play critical roles in intercellular communication. MicroRNAs can be encapsulated in exosomes; cargo-loaded exosomes can be secreted by tumor cells into the tumor microenvironment to facilitate tumor–stroma interactions or released to circulation to prime distant organs for subsequent metastasis. Here, we will summarize our current knowledge on the biogenesis of exosomes and miRNAs, mechanisms of cargo sorting into exosomes, the exosomal miRNAs implicated in breast cancer metastasis, and therapeutic exosomal miRNAs.

Keywords : breast cancer; metastasis; exosomes; microRNAs; organotropism

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Research Title :Heat Shock Protein Association with Clinico-Pathological Characteristics of Gastric Cancer in Jordan HSP70 is Predictive of Poor Prognosis

Authors :Khaldon Bodoor, Sara Abu Jalboush, Ismail Matalka, Aya Abu-Sheikha, Rofieda Al Waq, Hanadi Ebwaini, Aymen Abu-Awad, Luma Fayyad, Jamal Al-Arjat, Yazan Haddad

Abstract :Gastric cancer (GC) is a major health problem worldwide and is one of the ten most commonly diagnosed cancers in Jordan. GC is usually diagnosed at late aggressive stages in which treatment options are limited. Recently, heat shock proteins (HSPs) were found to be overexpressed in a wide range of malignancies have been considered as promising candidate biomarkers for GC. The aim of this study was to investigate pathogenic roles of a panel of cytosolic HSPs including HSP90, HSP70, HSP60 and HSP27 in GC. Immunohistochemistry was used to assess the level of expression of these proteins in archived tumor samples (N87) representing various pathological characteristics of GC. HSP90, HSP60 and HSP27 were expressed abundantly in gastric tumors. On the other hand, HSP70 was reduced signi cantly and also found to be associated with Helicobacter pylori infection in tissues collected from GC patients. Furthermore, HSP27 was found to be associated with the level of differentiation. Our ndings indicate a role of HSP70 as a potential prognostic biomarker, patients harboring positive HSP70 expression displaying worse disease free survival than those with negative HSP70 expression. Differential expression of HSPs may play crucial roles in the initiation and progression of GC, and could be exploited as future therapeutic targets.

Keywords : Gastric cancer - heat shock proteins - immunohistochemistry - prognosis

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