Walid Khaled

Epithelial cell fate and tumour development

Laboratory Location: Department of Pharmacology

Departmental Affiliation: Department of Pharmacology

Biography

Walid Khaled obtained his undergraduate degree in Genetics at the University of Edinburgh followed by a MSc at Imperial College, London working with Prof. Eric Lam on the PI3K pathway and cell cycle regulation. He did his PhD training with Prof. Christine Watson, Department of Pathology, University of Cambridge where he characterised the role of STAT6 in controlling mammary epithelial cell fate. In 2008 he was awarded a junior research fellowship at King's College, Cambridge and in 2009 he joined the Sanger Institute to work with Dr. Pentao Liu. During his time at Sanger he worked on the connection between cell fate regulation and breast cancer development particularly focusing on the transcription regulator BCL11A. In October 2013, he was appointed as a University Lecturer at the Department of Pharmacology, University of Cambridge. In May 2014 he was awarded a CRUK Career Establishment Award to investigate the cellular and molecular drivers of breast cancer heterogeneity with a particular focus on the development of novel therapies for triple negative breast cancer (TNBC).

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The use of scRNAseq to identify the different mammary epithelial cell types and how that can help in our understanding of the earliest events required for tumours to develop.

Research

The overall objective of my laboratory is the study and development of more effective therapeutics for aggressive epithelial tumours, namely, triple negative breast cancer (TNBC) and lung squamous carcinoma (LUSC). We have developed several interconnected workstreams focusing on the identification of key drivers of TNBC/LUSC and studying their function in normal development and tumorigenesis. In collaboration with Dr. John Marioni (CRUK CI & EBI) we have recently used single cell RNA sequencing (scRNAseq) to identify the differentiation dynamics of mammary epithelial cells across 4 adult developmental stages (Bach K. et al. Nature Comm. 2017). This new dataset provides novel insights into how mammary epithelial cells organise and develop during adulthood improving our understanding of how breast cancer develops. We are currently applying the same technology to identify the earliest gene expression changes in epithelial and non-epithelial cells in mouse models of breast cancer. These novel scRNAseq efforts are running alongside the lab’s main focus of characterising the transcription factor BCL11A as a TNBC and LUSC oncogene (Khaled W.T. et al. Nature Comm 2015 and Lazarus K et al. bioAxiv 2017). We have developed multiple mouse models to assess the involvement of BCL11A in initiating TNBC and also identified novel BCL11A protein interactions found only in cancer cells (Pensa S. Lazarus K., Bach K, Santolla M.F. et al unpublished). We recently secured funding from CRUK (Drug Discovery SMERP) to investigate the therapeutic potential of disrupting these cancer specific protein-protein interactions in TNBC and LUSC.