The QBI Seminar Series is presenting Diako Ebrahimi on March 21  at 11 am in room BH-215. Dr. Ebrahimi will talk about the quantitative biology approaches he uses to discover important hidden patterns in the fields of virus-host interactions and cancer. His recent quantitative biology studies have unveiled hidden dysregulated processes in cancer and have also helped reveal novel host-pathogen interaction mechanisms. The purpose of Ebrahmimi's visit is to share these new findings with the Krogan Lab and discuss collaboration opportunities. 

Abstract: 

Molecular processes involved in cancer and viral immunity are complex and interrelated. These processes are often characterized by changes in the genome, transcriptome, and proteome of host cells and viruses. Quantitative biology approaches are needed to deconvolute these complex molecular signatures and identify their sources.

APOBEC3 enzymes are DNA editing proteins with roles in cancer and viral mutagenesis. Using a quantitative gene expression deconvolution approach, we discovered that, in tumor tissue biopsies, only <20% of APOBEC3 gene expression variations are due to tumor-specific dysregulated processes. The remaining >80% arises, mostly, from infiltrating immune cells. This analysis also revealed multiple hidden patterns of APOBEC3 dysregulation in cancers such as prostate and uterine tumors.

Additionally, using combined bioinformatic/experimental approaches we found that HIV-1 uses different strategies to counteract APOBEC3H in different human populations. The underlying mechanism is differential mRNA splicing induced by a genomic deletion, which has an archaic origin. Importantly, our studies indicate that population-specific mRNA splicing of immune-related genes is not an uncommon phenomenon and may play a role in differential antiviral immunity.