Marian Grade Post-Doctoral Fellow Phone: (301) 435-4041 (office) (301) 402-2008 (lab) (301) 402-1204 (FAX) e-mail: mgrade@mail.nih.gov   Bibliography Curriculum Vitae

Colorectal cancer is the second leading cause of cancer death in Europe and the United States, with about 300,000 new cases and 200,000 deaths each year. But despite the stage-dependent application of effective (neo-) adjuvant therapeutic modalities, many patients die due to disease recurrence or metastatic spread. Thus, understanding colorectal cancer progression and establishing novel therapeutic strategies remains of considerable clinical interest.

We have recently analyzed a series of primary rectal and colon cancers and matched normal mucosa biopsies. For instance, 12 genes were found to always have a more than two-fold separation in expression between a rectal cancer and its matched mucosa in addition to significant differential expression measured by the t-statistic (p < 1.0e-7), and a greater than five-fold difference in average expression between the mucosa and tumor groups. For the colon cancers, 17 genes had a greater than five-fold average expression difference between normal colon mucosa and the tumors, including up-regulation of MYC and HMGA1. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of transcriptional deregulation, including activation of the Wnt/ß-catenin signaling cascade, suggesting similar pathogenic pathways.

The major objective of my project is to functionally validate a subset of these differentially regulated genes using RNA interference (in collaboration with Dr. Natasha Caplen), and expression constructs. For functional validation, we will focus on cell lines that have been extensively characterized in our lab by means of SKY, expression microarrays, and array-CGH.