Sameer Agnihotri

Summary

The lab has a focus on several topics:

1) It is now appreciated that HGG glioma comprises of several molecular subgroups and that the genetics of pediatric and adult HGG are distinct. Therefore, a one size that fits all approach to therapy will not be successful. The Agnihotri Laboratory interests include using next-generation sequencing technology to identify and validate driver alterations of various HGG with a focus on DIPG and non-histone mutated RTK Glioblastoma (GBM).

2) The lab also has an interest in NF1, which encodes neurofibromin, plays a critical role in negatively regulating the RAS-MAPK pathway. Current research on NF1 is centered on developing novel genome engineering tools to enhance gene therapy strategies and uncover the link between NF1 and metabolism.

3) A defining hallmark of glioblastoma and DIPG is altered tumor metabolism. The metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation, regardless of oxygen availability, is a phenomenon known as the Warburg effect. In addition to the Warburg effect, glioblastoma tumor cells also utilize the tricarboxylic acid cycle/oxidative phosphorylation in a different capacity than normal tissue. The Agnihotri Laboratory investigates the metabolic dependencies of brain tumors and if they can provide therapeutic vulnerabilities.

4) The lab uses the genomic and metabolic information to build better representative brain tumor pre-clinical models for testing of novel therapies. Working closely with a clinical team , the use of these accurate models is essential to start early phase clinical trials.