Discipline: Biological Sciences
Subcategory: Cancer Research
Joseph Michael Fields - Langston University
Co-Author(s): Sheri Holmen, Gemma Robinson, and Beatrice Philip, Huntsman Cancer Institute, Salt Lake City, UT
Malignant gliomas are aggressive brain tumors that carry a grim prognosis to over 10,000 patients a year in the United States. The highest grade tumor, glioblastoma, has an average survival of one year with the current standard of care, which includes surgical resection, radiotherapy, and temozolomide chemotherapy. Gliomas are also the most common primary central nervous system tumor but the molecular mechanisms responsible for the development and progression of these tumors are far from being completely understood. Also, mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) were recently found in ~80% of WHO grade II-III gliomas and secondary glioblastomas. These mutations inhibit the enzyme’s ability to convert isocitrate to a-ketoglutarate and, instead, confer a novel gain-of-function resulting in the conversion of a-ketoglutarate to 2-hydroxglutarate. However, the fundamental mechanism(s) by which these mutations affect glioma cell growth remain unclear. Our goal is to further our understanding of the function of mutant IDH using an established brain tumor mouse model. In this model we injected our mutant IDH inter cranially into our mouse pups and waited for tumor development. Also we isolated primary astrocytes from our mice and combined that with the supernatant of the infected avian cells and then looked for tumor development. This resulted in no tumor growth. Therefore, we ran some assays and mass spectrometer samples to verify the IDH importance. The results of those procedures supported our belief that IDH is a driver mutation in the process of tumorigenesis. Therefore, our next step will be to analyze what other metabolic genes could be participants in this process. Together, these approaches will lead to a better understanding of the biology of mutant IDH gliomas and will help guide the development of new therapies to improve survival and reduce morbidity in these patients.
Funder Acknowledgement(s): National Science Foundation (NSF) & National Institute of Health (NIH)
Faculty Advisor: Sharon Lewis,