Dr Lisa Ooms is a mid-career biomedical scientist in the Biomedicine Discovery Institute at Monash University. Her research focuses on how dysregulated PI3K signalling affects breast cancer progression.

Dr Ooms' research has primarily focused on investigating the function of inositol polyphosphate 5-phosphatases firstly in the yeast Saccharomyces cerevisiae and more recently in mammalian cells and animal models. Dr Ooms demonstrated a role for two of the yeast 5-phosphatases in regulating the actin cytoskeleton in response to hyperosmotic stress (PMID: 11094088). She was the first to demonstrate a key functional role for the 5-phosphatase PIPP in neuronal cells, demonstrating that PIPP negatively regulates phosphoinositide 3-kinase (PI3K) signalling in the growth cone and plays an important role in neuronal cell differentiation (PMID: 16280363). She also determined that PIPP regulates neuronal cell polarity and forms a complex with CRMP2 to oppose its function in regulating neurite outgrowth (PMID: 21550974). More recently she identified PIPP as a tumour suppressor in breast cancer, which was the first demonstration of a tumour suppressor role for an inositol polyphosphate 5-phosphatase in this malignancy. Pipp ablation accelerated oncogene-driven breast cancer growth in vivo, but paradoxically reduced metastasis by regulating AKT1-dependent tumour cell migration (PMID: 26267533). Her studies revealed PIPP expression is lost in triple negative human breast cancers and is associated with poorer prognosis.

            Dr Ooms was involved in characterising the tumour suppressor role of INPP4B in breast and prostate cancer via suppression of PI3K signalling (PMID: 21127264, 25284366). She was also involved in identifying that INPP4B expression is increased in acute myeloid leukemia and is associated with chemoresistance and worse outcome (PMID: 25736313). More recently, Dr Ooms was part of Prof Mitchell's team that identified INPP4B expression is increased in a subset of estrogen receptor positive breast cancers where it plays an oncogenic role via activation of Wnt signalling (PMID:34035258). Further studies by Dr Ooms, Prof Mitchell and team revealed that breast cancer cells with INPP4B overexpression are selectively sensitive to the FDA-approved drug pyrvinium and a 4-OHT-pyrvinium combination treatment. These findings suggest that repurposing pyrvinium as a Wnt inhibitor may be an effective therapeutic strategy for human ER+ breast cancers with high INPP4B levels (PMID: 36612130).

            Dr Ooms has also investigated the inactive 4-phosphatase family member P-Rex1. Although increased P-Rex1 expression promotes melanoma progression, its role in breast cancer is complex. Examination of PREX1 in human breast cancer databases and gene arrays revealed higher PREX1 expression was associated with poor outcome in Luminal B breast cancers. Prof Mitchell, Dr Ooms, and team generated the first murine and cell line models of gain or loss of function of P-Rex1 in breast cancer. These studies revealed P-Rex1 acts as an oncogene and co-operates with other oncogenes to promote Rac1 and ERK1/2 activation leading to enhanced breast cancer initiation and metastasis (PMID: 27358402, 26112412, 33097662).

• Breast Cancer - tumour initiation and progression
• Signal transduction - PI3K signalling pathways