Wei Wang

Email Address
phcwei@nus.edu.sg


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MEDICINE
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Now showing 1 - 4 of 4
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    Sphingosine 1-phosphate receptor 2 induces otoprotective responses to cisplatin treatment
    (MDPI AG, 2020) Wang, W.; Shanmugam, M.K.; Xiang, P.; Yam, T.Y.A.; Kumar, V.; Chew, W.S.; Chang, J.K.; Ali, M.Z.B.; Reolo, M.J.Y.; Peh, Y.X.; Karim, S.N.B.A.; Tan, A.Y.Y.; Sanda, T.; Sethi, G.; Herr, D.R.; PHARMACOLOGY; MEDICINE; PHYSIOLOGY; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); CANCER SCIENCE INSTITUTE OF SINGAPORE; PAEDIATRICS
    Ototoxicity is a major adverse effect of platinum-based chemotherapeutics and currently, there remains a lack of United States Food and Drug Administration-approved therapies to prevent or treat this problem. In our study, we examined the role of the sphingosine 1-phosphate receptor 2 (S1P2) in attenuating cisplatin-induced ototoxicity in several different animal models and cell lines. We found that ototoxicity in S1P2 knockout mice is dependent on reactive oxygen species (ROS) production and that S1P2 receptor activation with a specific agonist, CYM-5478, significantly attenuates cisplatin-induced defects, including hair cell degeneration in zebrafish and prolonged auditory brainstem response latency in rats. We also evaluated the cytoprotective effect of CYM-5478 across different cell lines and showed that CYM-5478 protects neural-derived cell lines but not breast cancer cells against cisplatin toxicity. We show that this selective protection of CYM-5478 is due to its differential effects on key regulators of apoptosis between neural cells and breast cancer cells. Overall, our study suggests that targeting the S1P2 receptor represents a promising therapeutic approach for the treatment of cisplatin-induced ototoxicity in cancer patients. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Sphingolipidomics analysis of large clinical cohorts. Part 2: Potential impact and applications
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018-10-07) Chong, Joyce R; Xiang, Ping; Wang, Wei; Hind, Tatsuma; Chew, Wee Siong; Ong, Wei-Yi; Lai, Mitchell KP; Herr, Deron R; Dr Kim Peng Mitchell Lai; PHARMACOLOGY; ANATOMY
    It has been known for decades that the regulation of sphingolipids (SLs) is essential for the proper function of many cellular processes. However, a complete understanding of these processes has been complicated by the structural diversity of these lipids. A well-characterized metabolic pathway is responsible for homeostatic maintenance of hundreds of distinct SL species. This pathway is perturbed in a number of pathological processes, resulting in derangement of the “sphingolipidome.” Recently, advances in mass spectrometry (MS) techniques have made it possible to characterize the sphingolipidome in large-scale clinical studies, allowing for the identification of specific SL molecules that mediate pathological processes and/or may serve as biomarkers. This manuscript provides an overview of the functions of SLs, and reviews previous studies that have used MS techniques to identify changes to the sphingolipidome in non-metabolic diseases.
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    Chronic voluntary ethanol consumption induces favorable ceramide profiles in selectively bred alcohol-preferring (P) rats
    (Public Library of Science, 2015) Godfrey J.; Jeanguenin L.; Castro N.; Olney J.J.; Dudley J.; Pipkin J.; Walls S.M.; Wang W.; Herr D.R.; Harris G.L.; Brasser S.M.; PHARMACOLOGY
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    Sphingosine 1-phosphate receptor 2 (S1P2) attenuates reactive oxygen species formation and inhibits cell death: Implications for otoprotective therapy
    (Nature Publishing Group, 2016) Herr, D.R; Reolo, M.J.Y; Peh, Y.X; Wang, W; Lee, C.-W; Rivera, R; Paterson, I.C; Chun, J; PHARMACOLOGY; DUKE-NUS MEDICAL SCHOOL; PAEDIATRICS
    Ototoxic drugs, such as platinum-based chemotherapeutics, often lead to permanent hearing loss through apoptosis of neuroepithelial hair cells and afferent neurons of the cochlea. There is no approved therapy for preventing or reversing this process. Our previous studies identified a G protein-coupled receptor (GPCR), S1P2, as a potential mediator of otoprotection. We therefore sought to identify a pharmacological approach to prevent cochlear degeneration via activation of S1P2. The cochleae of S1pr2-/- knockout mice were evaluated for accumulation of reactive oxygen species (ROS) with a nitro blue tetrazolium (NBT) assay. This showed that loss of S1P2 results in accumulation of ROS that precedes progressive cochlear degeneration as previously reported. These findings were supported by in vitro cell-based assays to evaluate cell viability, induction of apoptosis, and accumulation of ROS following activation of S1P2 in the presence of cisplatin. We show for the first time, that activation of S1P2 with a selective receptor agonist increases cell viability and reduces cisplatin-mediated cell death by reducing ROS. Cumulatively, these results suggest that S1P2 may serve as a therapeutic target for attenuating cisplatin-mediated ototoxicity.