Ruth Wang

A series of derivatives of the known thromboxane A2 prostanoid receptor antagonists, 3-sulfonamido)-5,6,7,8-tetrahydronaphthalen-1-yl)propanoic acid and 3-sulfonamido)ethyl)phenyl) propanoic acid, were synthesized in which the carboxylic acid functional group was replaced with substituted cyclopentane-1,3-dione bioisosteres. Characterization of these molecules led to the discovery of remarkably potent new analogues, some of which were considerably more active than the corresponding parent carboxylic acid compounds. Depending on the choice of the C2 substituent of the CPD unit, these new derivatives can produce either a reversible or an apparent irreversible inhibition of the human TP receptor. Given the potency and the long-lasting inhibition of TP receptor signaling, these novel antagonists may comprise promising leads for the development of antithromboxane therapies.

© 2016 Optical Society of America.We propose an all-solid-state tunable Bragg filter with a phase transition material as the defect layer. Bragg filters based on a vanadium dioxide defect layer sandwiched between silicon dioxide/titanium dioxide Bragg gratings are experimentally demonstrated. Temperature dependent reflection spectroscopy shows the dynamic tunability and hysteresis properties of the Bragg filter. Temperature dependent Raman spectroscopy reveals the connection between the tunability and the phase transition of the vanadium dioxide defect layer. This work paves a new avenue in tunable Bragg filter designs and promises more applications by combining phase transition materials and optical cavities.

© 2015 American Association for Cancer Research.Purpose: Myxopapillary ependymoma is a distinct histologic variant of ependymoma arising commonly in the spinal cord. Despite an overall favorable prognosis, distant metastases, subarachnoid dissemination, and late recurrences have been reported. Currently, the only effective treatment for MPE is gross-total resection. We characterized the genomic and transcriptional landscape of spinal ependymomas in an effort to delineate the genetic basis of this disease and identify new leads for therapy. Experimental Design: Gene expression profiling was performed on 35 spinal ependymomas, and copy number profiling was done on an overlapping cohort of 46 spinal ependymomas. Functional validation experiments were performed on tumor lysates consisting of assays measuring pyruvate kinase M activity, hexokinase activity, and lactate production. Results: At a gene expression level, we demonstrate that spinal grade II and MPE are molecularly and biologically distinct. These are supported by specific copy number alterations occurring in each histologic variant. Pathway analysis revealed that MPE are characterized by increased cellular metabolism, associated with upregulation of HIF1α. These findings were validated by Western blot analysis demonstrating increased protein expression of HIF1α, HK2, PDK1, and phosphorylation of PDHE1A. Functional assays were performed on MPE lysates, which demonstrated decreased PKM activity, increased HK activity, and elevated lactate production. Conclusions: Our findings suggest that MPE may be driven by a Warburg metabolic phenotype. The key enzymes promoting the Warburg phenotype: HK2, PKM2, and PDK are target-able by small-molecule inhibitors/activators, and should be considered for evaluation in future clinical trials for MPE.