Profiles

Our lab is focused on the development of biomarkers for the prognosis of prostate and breast cancer through novel application of analytic and bioinformatic tools. We were the first to show that the microenvironment of prostate cancer exhibited gene expression changes that could be used to form a prognostic classifier. More recently novel applications of eQTL (Expression Quantitative Trait Loci) to test the hypothesis that SNPs of noncoding DNA, that were identified by application of lab-collected and curated tissues to Illumina Inc. DNA SNP arrays, were associated with the regulation of specific coding genes (Chen et al., 2015). We observed 47 significant associations between eight risk variants and the expression patterns of 46 genes (Chen et al., 2015). This is the first study to identify associations between multiple SNPs and multiple in-trans gene expression differences in cancer stroma. In an analysis of HER2 positive breast cancer, an aggressive form of breast cancer, we used expression analysis of cells and over 800 publicly available tissues combined with chip-on-chip, using a method patented by our lab, of RNA polymerase II to identify genes specifically expressed in HER2 positive tissues but not in cell lines indicating that the breast cancer microenvironment plays a role in the activation of HER2 receptors (Rahmatpanah et al., 2015). We have applied our bioinformatic experience to analysis of the immune system, a major constituent of the tumor microenvironment, by collection of human blood and analysis by RNAseq data of young and old donors. These methods revealed over 4000 significant gene expression changes of aged dendritic cells (Rahmatpanah et al., 2018). The differences reveal that DC from aged subjects display an activated state coupled with reduced antigen presentation which may be responsible for age-associated immune dysfunction. Current studies utilize a unique resource organized by our lab for the development of prostate cancer stroma primary cell lines of dozens a European American and African American prostate cancer patients. RNAseq analysis of the stroma cell lines revealed deficiencies in the immunological mechanisms of African American stroma which correlates with the more aggressive nature of prostate cancer in Africa Americans. These studies are continuing including use in a in vivo mouse model in collaboration with Dr. Xiaolin Zi.