Margarita Dzama, PhD, Postdoctoral Fellow in the laboratory of Dr. Jesse Raab, has been awarded a Fellowship grant from the American Cancer Society, for her project titled “Identification of Epigenetic Therapies for Liver Cancer”.
The proposed work will focus on mutations in chromatin regulators, which are found in ~50% of liver cancer, specifically two novel targets, MEN1 and ASH2L, which are the core subunits of the H3K4 methyltransferase menin-MLL complex. Dr. Dzama aims to establish the mechanism of how menin and ASH2L regulate HCC on the molecular level by performing a comprehensive analysis of changes in gene expression (RNA-seq), chromatin accessibility (ATAC-seq), and distribution of active (H3K4me1/2/3) and repressive (H3K27me3) chromatin marks as well as binding patterns of menin and ASH2L to chromatin (CUT&RUN). She will characterize the importance of menin and ASH2L in vivo by using xenograft and genetically-modified mouse models. Using CRISPR/Cas9 screen, the project will evaluate the most critical genes of epigenetic regulators that sensitize with menin and ASH2L inhibition in HCC cell lines in 3D culture settings. Based on these data, she will establish a brand-new combinatorial therapeutic approach against HCC that will be functionally evaluated in vitro and in vivo.