Daniel Schramek, Assistant Professor at the University of Toronto
Date & Time
May 26, 2021, 2PM EST
Finding the genes that are on the one hand responsible for tumor development and on the other hand those genes essential for a tumor cell to survive is one of the oldest goals of cancer research. Genes that are essential and fall into classes, which allow drug development to suppress their function, lie at the heart of finding novel therapies to combat cancer. Conventional experiments use cells grown in a plastic dish and switch off one gene at a time followed by analysis of a cell’s ability to divide and grow. While we have learned a great deal from those studies, cells grown on a plastic dish do not mimic the situation of a tumor within a patient where dozens of cell types interact in a very intricate and sophisticated way. As such, the genes that might be necessary for a tumor cell to grow on plastic might be very different than the genes required for growth in an organ within a living organism. Our first proof-of-concept experiments shows that cancer cells grown on plastic behave very differently compared to the same cells grown in an organism such as an experimental mouse. This experiment has taught us that the mouse experiment indeed appears to be physiologically more relevant. As such, we are using several physiologically-relevant models of various cancers in mice and test every gene, for which drugs and therapeutic strategies can conceivably be generated with the goal of finding novel and more potent drug targets to combat Head and Neck, breast and brain cancer.
My overall research objective is to identify molecular and cellular mechanisms that regulate tissue growth in development, adult homeostasis and are corrupted during cancer development. My graduate training in Australia and Austria was rich and diverse as I performed genome-wide RNAi screens in Drosophila melanogaster and also conducted multiple gene ablation studies in the mouse. My most important findings are that Gab2 functions as a proto-oncogene in human breast epithelial cells, that hedgehog functions as cell fate determinant in brown versus white adipocytes, that the osteoclast differentiation factor RANKL functions as key transforming agent in hormone-driven breast cancer and that the stress kinase MKK7 couples oncogenic stress to p53 stability and tumor suppression. I soon realized that faster models are needed to evaluate all potential cancer genes and that RNAi or transposon screens would be the only way to do so. I therefore joined Prof. Elaine Fuchs’ lab at the Rockefeller University in New York, which has developed a novel in utero delivery system to target RNAi to the skin. I combined my experience in mouse cancer models and Drosophila RNAi screening with Prof. Fuchs’ technique to rapidly test hundreds of candidate cancer genes using as my model skin and Head&Neck squamous cell carcinoma (HNSCCs). My current research program focus is to explore which genetic and epigenetic alterations associated with various carcinomas trigger tumorigenesis, malignant transformation and metastasis by establishing in vivo screening platforms, which also allow me to devise and test novel therapeutic intervention. We specifically focus on HNSCCs, gliomas and breast cancers.