JOSEPH COSTELLO, Ph.D.
University of California, San Francisco (UCSF)
“Evolution of a Hypomethylated and Hyperproliferative Phenotype in Glioblastoma Multiforme (GBM) and its Reversal by a High Methyl-donor Regimen”
Dr. Costello’s study is an in vivo exploration of how replenishing DNA methylation (the normal enzyme-mediated addition of methyl-groups to DNA), managed through diet can affect GBM tumor growth. If successful, Dr. Costello hopes this investigation could lead to a novel and quickly available dietary approach for replenishing global DNA methylation in order to control tumor growth.
Tumor cell growth is believed to be due to deregulation of genes through genetic and epigenetic mechanisms. Epigenetic mechanisms of gene regulation include DNA methylation. Dr. Costello and his team have discovered a novel connection between severe loss of DNA methylation and excessive cell proliferation in human glioblastomas. The connection appears to involve the abnormal activation of a small set of genes that are normally kept silent by methylation, and when activated might cause increased growth. To evaluate this connection, and to make use of it therapeutically, he will determine whether the abnormal methylation actually causes the gene activation which, in turn, causes the cell proliferation.
To determine if loss of methylation causes increased cell proliferation and tumor growth, Dr. Costello will use a GBM xenograft model in which the live human GBM tissue is obtained from the patient during surgery. It is believed that diets high in methyl-contributors can increase DNA methylation levels. This study will determine if replenishing methylation can help control tumor growth.