Miranda Brun, B.Sc.,  Graduate Student

                           

Research Project: Malignant gliomas are the most common type of human adult brain tumour, and comprise grades III and IV astrocytomas. Our lab has found that brain fatty-acid binding protein (B-FABP) and glial fibrillary acidic protein (GFAP) are co-expressed in a subset of malignant glioma cell lines. This is of note because B-FABP is a marker of radial glial cells (a neuronal precursor cell type), whereas GFAP is an intermediate filament protein specifically expressed in astrocytes (a differentiated glial cell type). Co-expression of these two genes in malignant glioma cells suggests that they may be regulated by the same transcription factors. Previous work from our laboratory has demonstrated that B-FABP and GFAP transcription in malignant glioma is regulated by Nuclear Factor I (NFI). NFI is a transcription factor family which consists of NFI-A, NFI-B, NFI-C and NFI-X. These transcription factors can act as both activators and repressors. Both the B-FABP and GFAP genes have three NFI binding sites upstream of their respective transcription start sites. We have shown that different members of the NFI family bind with different affinities to these NFI binding sites. My research focuses on determining how specific NFIs regulate the expression of the B-FABP and GFAP genes in malignant glioma. As well, I am studying additional mechanisms of B-FABP regulation in malignant glioma. Techniques: RNA isolation, qRT-PCR, confocal microscopy, immunoprecipitation, western blot analysis, DNase I footprintings

Presentations:

Brun, M., Coles, J.E., Glubrecht, D.D., Monckton, E.A. and Godbout, R. Regulation of brain fatty acid-binding protein genes in malignant glioma by nuclear factor I. The 39th Summer Students’ Research Day, University of Alberta (October 21, 2006).

Brun, M., Coles, J.E., Glubrecht, D.D., Monckton, E.A. and Godbout, R. Regulation of brain fatty acid-binding protein and glial fibrillary acidic protein genes in malignant glioma by nuclear factor I. ACB Annual Research Meeting, Banff (November 7-9, 2006).

Brun, M., Coles, J.E., Glubrecht, D.D., Monckton, E.A. and Godbout, R. Regulation of brain fatty acid-binding protein and glial fibrillary acidic protein in malignant glioma by nuclear factor I. 33rd FEBS Congress and 11th IUBMB Conference, Athens, Greece (June 28 – July 2, 2008). Published in the FEBS J 275 (Supplement 1): 119 (PP2A-9) June 2008.

Brun, M., Coles, J.E., Glubrecht, D.D., Monckton, E.A. and Godbout, R. Regulation of gene expression in malignant glioma by nuclear factor I. Alberta Cancer Research Institute Research Meeting, Banff, Alberta (November 25-27, 2008).

Brun, M., Coles, J.E., Monckton, E.A., Bisgrove, D.A. and Godbout, R. Nuclear Factor I Regulation of Brain Fatty Acid-binding Protein and Glial Fibrillary Acidic Protein Genes in Malignant Glioma. 2nd Annual Canadian Human Genetics Conference, Harrison Hot Springs, BC (May 24-27, 2009).

Brun, M., Coles, J.E., Monckton, E.A., Glubrecht, D.D., Bisgrove, D.A. and Godbout R. Role of Nuclear Factor I in the Regulation of the Brain Fatty-Acid Binding Protein and Glila Fibrillary Acidic Protein Genes. Mechanisms of Eukaryotic Transcription. Cold Spring Harbor Laboratory Meeting, Cold Spring Harbor, New York (August 25-29, 2009).

Brun, M., Coles, J.E., Glubrecht, D., Monckton, E.A. and Godbout, R. Nuclear Factor I regulation of gene expression in malignant glioma. 2009 Alberta Cancer Institute Research Meeting, Banff, Alberta (November 24-26, 2009).

Brun, M., Bisgrove, D.A. and Godbout, R. PP2B regulates Nuclear Factor I transcriptional activity in malignant glioma. 2010 FASEB Summer Research Conference on Protein Phosphatases, Steamboat Springs, Colorado (July 18-23, 2010).

Brun, M., Bisgrove, D. and Godbout, R. Calcineurin regulates Nuclear Factor I in malignant glioma. 2010 Alberta Cancer Foundation Research Conference, Banff, Alberta (November 8-10, 2010).

Publications:

Brun, M.¹, Coles, J.E.¹, Monckton, E.A., Glubrecht, D.D., Bisgrove, D.A. and Godbout, R. Nuclear Factor I Regulates Brain Fatty Acid-binding Protein and Glial Fibrillary Acidic Protein Gene Expression in Malignant Glioma Cell Lines.  J. Mol. Biol. 391: 282-300 (2009). ¹co-first authors

Awards

 Department of Oncology endowed studentship
Provost Doctoral Entrance Award
Alberta Cancer Foundation – Cyril Kay award
Alberta Heritage Foundation for Medical Research
Marie Arnold Cancer Research Graduate Scholarship