Cancer Genetics and Functional Genomics

Cancer Genetics and Functional Genomics Research group led by Professor Ron Firestein
Research Group

Prof Ron Firestein leads both the Cancer Genetics and Functional Genomics lab, and the Next Generation Precision Medicine program at Hudson Institute.

The work of the Cancer Genetics and Functional genomics research group, directed by Professor Ron Firestein, is focused on using functional and integrated genomic approaches to understanding the basic underpinnings of cancer.  Major themes in the lab are listed below:

  1. Integrative genomic approaches to identify new oncogenic drivers in cancer. Our lab has undertaken sophisticated integrative genomic analyses of colorectal, lung and breast cancers. Using innovative functional genomic screens (CRISPR, shRNA/siRNA) we have uncovered a number of novel oncogenic drivers and dissected their mechanistic input into cancer signalling pathways.  Importantly, two of these targets have led to novel small molecule programs that are currently in drug development (CDK8 and LDHB).
  2. Identification and characterisation of Wnt pathway regulators in colon cancer. While a post-doc at Dana Farber Cancer Institute, we identified CDK8 as a colon cancer oncogene that regulates the Wnt/b-catenin pathway (Firestein R. et al Nature 2008). Since then, my group has developed mouse models and in vivo systems to characterise the function of CDK8 and its paralog, CDK19, in normal homeostasis, development and cancer progression.  We have also collaborated with other groups to develop targeted therapies to upstream regulators of the Wnt pathway.
  3. Elucidation of novel cancer therapeutic biomarkers in preclinical models and clinical samples. Our recent work has identified an important role for enhancer mediated transcripts, i.e. eRNAs, as biomarkers for distinct cancer states and predicting therapeutic response. We are now working to systematically characterise eRNA function and expression in tumours using state of the art genomic editing technologies.

Research Group