Gene Regulation Laboratory

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Gene Regulation Laboratory - Research at Peter Mac

The Gene Regulation laboratory performs basic and pre-clinical research aimed at defining the molecular processes required for anti-cancer drug action and drug resistance, and the mechanisms of interferon signal transduction.

Research Focus

Collaborative basic, translational and clinical research into the anti-cancer activities of histone deacetylase inhibitors. Basic and pre-clinical characterisation of novel apoptosis-inducing therapeutic agents used alone and in combination. Use of functional genomics-based screens to identify novel tumour suppressor genes and genes that regulate the apoptotic response to new anti-cancer agents. Characterisation of novel signal transduction pathways stimulated by type I and II interferons.

Research Overview

A major focus of the Gene Regulation Laboratory is to determine the molecular events necessary for the apoptotic and therapeutic activities of histone deacetylase inhibitors (HDACi) used alone and in combination with small molecule or antibody-based anti-cancer agents. In most instances, we use genetically engineered, immunocompetent mouse models of cancer that reflect the genetics, biology and pathology of human disease. We have evidence demonstrating the combined approach of inducing tumour cell apoptosis and augmenting host immune responses greatly enhances anti-tumour efficacy. We are therefore testing this therapeutic regimen in various mouse models of haematological malignancies and solid cancers to identify the molecular mechanisms of these combination strategies. We have recently initiated a series of “discovery-based” projects using functional genomics to identify novel genes involved in tumour onset and progression, and genes that are necessary for the induction of HDACi-mediated apoptosis. Another important aspect of the laboratory has been the study of interferon-induced signal transduction pathways and we have recently identified a novel mechanism of crosstalk between type I and II interferons that we predict will result in a shift in paradigm regarding the molecular events that are necessary for a full and robust interferon-mediated anti-tumour immune response.