Frédéric Hollande

Frederic obtained his PhD in 1994 from the University of Montpellier, France. He then worked as a post-doctoral research fellow at the Ludwig Institute for Cancer Research and the University of Melbourne, and he was recruited as a CNRS Research Fellow in 1996 to study molecular mechanisms that underlie the progression of colon cancer. Frederic has been a Group Leader (2000-2010) and Headed of the Oncology Research Department (2011-2012) at the Institute of Functional Genomics (IGF) of Montpellier. During that period his research projects aimed to study the impact of autocrine peptide regulators and of cell/cell adhesion in the progression of colon cancer. 

In 2007 he co-founded a small biotech company developing therapeutic monoclonal antibodies. He was the joint-scientific director of this company and designed its Intellectual Property portfolio. The company was acquired by the French Pharmaceutical company Servier in June 2011.

Frederic moved to Melbourne in September 2012 to take up a position as Associate Professor in the Department of Pathology at the University of Melbourne. He has developed a strong network of collaborations with researchers within Melbourne, across Australia, as well as in Europe and the USA. His laboratory is located at the new purpose-built Victorian Comprehensive Cancer Centre in Melbourne.

His research interests include the analysis of colorectal cancer stem cell regulation by their surrounding environment, as well as the study of the impact of inter and intra-tumour heterogeneity on metastatic progression and treatment response.

Optical barcoding highlights novel characteristics of treatment resistant cells in metastatic colorectal cancer

Treatment of metastatic colorectal cancer is frequently unsuccessful, as metastatic tumours within the liver and other organs often recur after treatment has ceased. Preventing recurrence of metastatic tumours would dramatically improve patient survival. Heterogeneous drug sensitivity among cell subpopulations within individual tumours has emerged as a key driver of recurrence. Yet, our poor understanding of cellular heterogeneity within metastases severely hampers the development of efficient treatments to target them. To gain further insight into the phenotypic and molecular heterogeneity of metastatic tumours, we transduced liver metastasis cells, isolated from chemo-naïve stage IV colorectal cancer patients and grown ex-vivo as tumour organoids, with a suite of lentiviral gene ontology (LeGO) vectors. Longitudinal monitoring of these optically barcoded cells during exposure to chemotherapeutics and targeted compounds led to the identification of small tumour cell subpopulations that exhibit markedly higher drug resistance abilities. Additionally, we found that growth interactions between individual cell subpopulations significantly changed upon exposure to increasing concentration of drugs, with enhanced collaboration between subsets likely to contribute to their enhanced resistance. Finally, purification and molecular analysis of individual cell subpopulations allowed the identification of differentially expressed pathways that characterise resistant cells prior to drug exposure, including differential lipid metabolism. Collectively these results suggest possible strategies to account for intra-metastatic heterogeneity in the clinical setting, by targeting small cell subsets with high recurrence potential in combination with current classes of therapeutic compounds.  


Keywords: Tumour heterogeneity – metastasis – colorectal cancer – self-renewal

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