Browsing by Author "Najm, Rania"

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Divulging a Pleiotropic Role of Succinate Receptor SUCNR1 in Renal Cell Carcinoma Microenvironment
(2022-12) Najm, Rania; Hachim, Mahmood Yaseen
Abstract: The succinate receptor, SUCNR1, has been attributed to tumor progression, metastasis, and immune response modulation upon its activation via the oncometabolite succinate. Nonetheless, little is known about the prognostic relevance of SUCNR1 and its association with tumor immune infiltrates and microbiota in renal cell carcinoma (RCC). Herein, publicly available platforms including Human Protein Atlas, cBioPortal, TIMER2.0, and TISIDB were utilized to depict a divergent implication of SUCNR1 in the immune microenvironment of clear cell RCC (KIRC) and papillary RCC (KIRP); the two major subtypes of RCC. Our results showed that the SUCNR1 expression level was augmented in RCC compared to other solid cancers, yet with opposite survival rate predictions in RCC subtypes. Consequently, a higher expression level of SUCNR1 was associated with a good disease-specific survival rate (p = 5.797 × 10-5) in KIRC patients albeit a poor prognostic prediction in KIRP patients (p = 1.9282 × 10-3). Intriguingly, SUCNR1 was mainly correlated to immunomodulators and diverse immune infiltrates in KIRP. Additionally, the SUCNR1 was mostly associated with a repertoire of microbes including beneficial bacteria that likely influenced a better disease-specific survival rate in KIRC. Our findings illustrate a significant novel subtype-specific role of SUCNR1 in RCC which potentially modulates tumor immune infiltration and microbiome signature, hence altering the prognosis of cancer patients.
HAS 1: A natural product from soil-isolated Streptomyces species with potent activity against cutaneous leishmaniasis caused by Leishmania tropica
(2022) Najm, Rania
Abstract: Cutaneous Leishmaniasis (CL) is a neglected tropical disease, classified by the World Health Organization (WHO) as one of the most unrestrained diseases. The Syrian war and the significant displacement of refugees aggravated the spread of this ailment into several neighboring countries in the Eastern Mediterranean Region (EMR). In Syria, Leishmania tropica is identified as one of the most aggressive and endemic identified species, causing localized or generalized lesions, often chronic or relapsing. Pentavalent antimonial drugs are currently used as first line treatment against CL. Nonetheless, these drugs exhibit several limitations, including the repetitive painful injections, high cost, poor availability, and mainly systemic toxicity. Besides, the emergence of acquired parasitic resistance hinders their potency, stressing the need for new therapies to combat CL. Natural products (NPs) epitomize a valuable source in drug discovery. NPs are secondary metabolites (SMs) produced by plants, sponges, or a wide variety of organisms, including environmental microorganisms. The EMR is characterized by its immense biodiversity, yet it remains a relatively untapped area in drug discovery. NPs of the region were explored over the last 2 decades, but their discoveries lack biogeographical diversity and are limited to the Red Sea. Here, we isolated previously uncultured environmental soil-dwelling Streptomyces sp. HAS1, from Hasbaya region in southeast Lebanon. When fermented in one of our production media named INA, HAS1 produced a crude extract with significant potency against a clinical Leishmania tropica isolate. Using bio-guided fractionation, the bioactive compound was purified and the structure was elucidated by NMR and LC-HRMS. Our findings establish NPs as strong candidates for treating Leishmania tropica and further dwells on the importance of these natural sources to combat microbial infections.
Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence
(2022) Najm, Rania
Abstract: Toxoplasma gondii is a single-celled parasitic eukaryote that evolved to successfully propagate in any nucleated cell. As with any other eukaryote, its life cycle is regulated by signaling pathways controlled by kinases and phosphatases. T. gondii encodes an atypical bacterial-like phosphatase absent from mammalian genomes, named Shelph, after its first identification in the psychrophilic bacterium Schewanella sp. Here, we demonstrate that Toxoplasma Shelph is an active phosphatase localized in the parasite endoplasmic reticulum. The phenotyping of a shelph knockout (KO) line showed a minor impairment in invasion on human fibroblasts, while the other steps of the parasite lytic cycle were not affected. In contrast with Plasmodium ortholog Shelph1, this invasion deficiency was not correlated with any default in the biogenesis of secretory organelles. However, Shelph-KO parasites displayed a much-pronounced defect in virulence in vivo. These phenotypes could be rescued by genetic complementation, thus supporting an important function for Shelph in the context of a natural infection.