Gene Regulation Laboratory

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

Basic and pre-clinical characterisation of novel apoptosis-inducing therapeutic agents used alone and in combination.
Determining the effects of combining novel agents designed to specifically kill breast cancer cells with other agents that stimulate a host anti-tumor immune response
Development and use of genetically engineered mouse models of hematological malignancies and solid cancers for pre-clinical studies.
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 and the role of interferon signaling in tumor immune surveillance.

Research overview

A major focus of The Gene Regulation Laboratory is to determine the molecular events necessary for the apoptotic and therapeutic activities of novel small molecule and antibody-based anti-cancer agents. These agents target various molecular pathways and processes and we aim to determine exactly how these agents kill tumor cells and how the tumors can circumvent or prevent their activities. 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 tumor cell apoptosis and augmenting host immune responses greatly enhances anti-tumor 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 tumor 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-tumor immune response. We have also demonstrated that loss of type I interferon-induced cell signaling alters immune-mediated tumor surveillance and we are identifying the molecular and biological processes that underpin this effect.

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