Understanding the biology of triple negative breast cancer (TNBC)
Our primary research interest lies at the interface between basic developmental biology and cancer development. We are particularly interested in the transcriptional control of cell fate in the mammary epithelium and how we can use these unique transcription factors to specifically target the different subtypes of breast cancer. We utilise both candidate and high throughput approaches for the identification and characterisation cell fate regulators with the ultimate aim of developing therapeutics.
One of the major challenges in the treatment of breast cancer is the heterogeneous nature of the disease. In the post-genomic era, detection of such heterogeneity is now possible. However, to develop more effective and targeted therapeutics better understanding of the cellular and molecular basis of breast cancer heterogeneity is required.
Therefore, our research focuses on deconstructing the molecular basis of breast cancer heterogeneity by studying mammary epithelial cell fate regulators hat drive tumour heterogeneity. By understanding how normal mammary epithelial cells develop one can understand the origins of tumour development and thus, develop more targeted therapies. To achieve this we will be focusing on two themes of research in the lab:
1) Cellular and molecular characterisation of a recently identified mammary epithelial cell fate regulator, BCL11A, using novel proteomics, genetics and genomics.
2) Perform genome-wide Crispr/Cas9 and piggybac genetic screens to comprehensively identify mammary epithelial cell fate regulators.
Naked mole-rat cancer resistance (in collaboration with Ewan Smith and Kosuke Yusa)
Naked mole-rats (NMR) are highly unusual mammals: eucosial, cold-blooded and with a remarkable resistance to hypercapnia and hypoxia. A further characteristic that sets NMR apart from many other mammals is their exceptional longevity: the maximum life span is 30 years, over 5 times longer than what would be predicted from body mass – mice are of a similar size and yet rarely live longer than 3.5 years. One likely factor underlying the extreme longevity of NMR is their resistance to cancer. In a retrospective pathology study of 138 NMR from a zoo population over a period of 15 years no malignant neoplasms were ever observed. This is a remarkable observation given the longevity of the NMR in comparison to other mammals. In humans, approximately one in three will develop cancer at some point in their lives, with numbers expected to rise as we are living longer. There have been only a handful of studies investigating the reasons behind the resistance of the NMR to cancer. Most recently it has been shown that NMR cells secrete a high molecular weight hyaluronan, which when removed renders NMR fibroblasts susceptible to transformation.
Dr Pentao Liu, Sanger Institute
Dr. Kosuke Yusa, Sanger Institute
Dr Jason Carroll, CRUK CI
Prof. Carlos Caldas, CRUK CI
Dr. David Adams, Sanger Institute
Dr. John Marioni, EBI/CRUK CI