Naresh Gupta

© 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.

Glacier mass variations have a direct impact on some of the key components of the global water cycle, including sea level rise and freshwater availability. Apart from being one of the largest Himalayan glaciers, Gangotri is one of the sources of water for the Ganges river, which has a considerable influence on the socioeconomic structure of a largely over-populated catchment area accounting for ~26% of India's landmass. In this study, we present the most recent assessment of the Gangotri glacier dynamics, combining the use of interferometric techniques on synthetic aperture radar data and sub-pixel offset tracking on Advanced Spaceborne Thermal Emission and Reflection Radiometer satellite imagery. Results show that on average, the Gangotri glacier snout has receded at a rate of 21.3 ± 3 m year-1 over a period of 6 years. While glacier surface velocity near the snout is estimated to be between 24.8 ± 2.3 and 28.9 ± 2.3 m year-1, interior portions of the glacier recorded velocities in the range of 13.9 ± 2.3 to 70.2 ± 2.3 m year-1. Further, the average glacier surface velocity in the northern portions is observed to be significantly lower than in the southern portions of the Gangotri glacier. These values are calculated with an uncertainty of less than 5 m year-1. Results also highlight a consistent retreat and non-uniform dynamics of the Gangotri glacier. © 2013 © Taylor & Francis.