Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies

Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein-Barr virus and malaria-associated aberrant B-cell activation and MYC chromosomal translocation. Survival rates hover at 50% after conventional chemotherapies; therefore, clinically relevant models are necessary to test additional therapies. Hence, we established five patient-derived BL tumor cell lines and corresponding NSG-BL avatar mouse models. Transcriptomics confirmed that our BL lines maintained fidelity from patient tumors to NSG-BL tumors. However, we found significant variation in tumor growth and survival among NSG-BL avatars and in Epstein-Barr virus protein expression patterns. We tested rituximab responsiveness and found one NSG-BL model exhibiting direct sensitivity, characterized by apoptotic gene expression counterbalanced by unfolded protein response and mTOR pro-survival pathways. In rituximab-unresponsive tumors, we observed an IFN-α signature confirmed by the expression of IRF7 and ISG15. Our results demonstrate significant inter-patient tumor variation and heterogeneity, and that contemporary patient-derived BL cell lines and NSG-BL avatars are feasible tools to guide new therapeutic strategies and improve outcomes for these children

The Large UV/Optical/Infrared Surveyor (LUVOIR): Decadal Mission Concept Design Update

In preparation for the 2020 Astrophysics Decadal Survey, NASA has commissioned the study of four large mission concepts, including the Large Ultraviolet / Optical / Infrared (LUVOIR) Surveyor. The LUVOIR Science and Technology Definition Team (STDT) has identified a broad range of science objectives including the direct imaging and spectral characterization of habitable exoplanets around sun-like stars, the study of galaxy formation and evolution, the epoch of reionization, star and planet formation, and the remote sensing of Solar System bodies. NASAs Goddard Space Flight Center (GSFC) is providing the design and engineering support to develop executable and feasible mission concepts that are capable of the identified science objectives. We present an update on the first of two architectures being studied: a 15-meter-diameter segmented-aperture telescope with a suite of serviceable instruments operating over a range of wavelengths between 100 nm to 2.5 microns. Four instruments are being developed for this architecture: an optical / near-infrared coronagraph capable of 10(exp -10) contrast at inner working angles as small as 2 lambda/D; the LUVOIR UV Multi-object Spectrograph (LUMOS), which will provide low- and medium-resolution UV (100 400 nm) multi-object imaging spectroscopy in addition to far-UV imaging; the High Definition Imager (HDI), a high-resolution wide-field-of-view NUV-Optical-IR imager; and a UV spectro-polarimeter being contributed by Centre National dEtudes Spatiales (CNES). A fifth instrument, a multi-resolution optical-NIR spectrograph, is planned as part of a second architecture to be studied in late 2017