Dr Merino received her PhD at the University of Burgundy (France) studying the molecular mechanism involved in the extrinsic pathway of apoptosis, in particular TRAIL-mediated cell death. In 2008 she joined the Molecular Genetics of Cancer Division at WEHI as an ARC postdoc fellow to study the role of the intrinsic pathway of apoptosis in immune homeostasis and cancer progression.
Her work was extended to the study of BH3 mimetics, small molecules inhibiting pro-survival proteins. In collaboration with the pharmaceutical companies Genentech and AbbVie (US), Dr Merino and colleagues showed that the new BH3 mimetic ABT-199 was highly toxic to malignant cells such as CLL (Chronic lymphocytic leukaemia), but not to immature lymphoid and myeloid cells, in mouse models and patient biopsies. In 2012, Dr Merino joined the Stem Cells and Cancer Division (WEHI), to study the effect of ABT-199 on breast cancer. She found that BH3 mimetics have a great synergy with Tamoxifen and mTOR inhibitors in the treatment of oestrogen positive breast cancer. Altogether these pre-clinical models have contributed to the clinical development of ABT-199 for the treatment of both leukaemia and breast cancer.
Cell death is also an important obstacle for metastasis development. Using in vivo models, Dr Merino and colleagues found that the deletion of pro-apoptotic genes can significantly promote metastatic spread. She characterized the ability of PDXs (Patient Derived Xenografts) to metastasize in immunodeficient mice, and perform RNAseq analysis in circulating tumour cells. More recently, she has developed new models of patient derived xenografts using cellular barcoding to track the clonal origin of metastases in different organs. These models are useful not only to understand how the tumour spreads, but also how current therapies influence the clonality of metastases. Therefore her study provides exciting new insights into cancer heterogeneity, and promising new models for drug discovery.
Abstracts this author is presenting: