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Cancer systems biology
The Cancer Systems Biology Group (Miller lab) at CRUK Cambridge Institute uses experimental and computational approaches to characterise cancer signalling and cell-cell interactions.
We are a cancer systems biology group that uses experimental and computational approaches to investigate the tumour microenvironment. To decipher intercellular communication in cancer, we develop and apply technologies that can decompose the transcriptome or label the proteome of specific cell populations in multicellular settings. Our long-term research goal is to better understand how immune cells and stromal cells are involved in oncogenesis and how this can be exploited in cancer therapy.
Pan-cancer analysis of the TME
To investigate the tumour microenvironment across human cancer types, we take an integrative approach combining data from publicly available clinical data with data from cancer genomics (TCGA) and proteomics studies (CPTAC). We perform functional analyses of associations between clinical features, cell infiltrations, and somatic mutations in signaling pathways and protein domains (see e.g. Ciriello et al 2013, Nat Gen; Miller et al 2015, Cell Syst; Gauthier et al 2016, NAR). Through our on-going collaborations with clinician-scientists, we will also characterise the tumour-immune microenvironment of primary and metastatic tumour samples.
Figure 1: Cell-cell interactions in the tumour microenvironment
Cell-cell communication in the TME
In many human cancer types, stromal cells in the tumour microenvironment are causally involved in cancer development and resistance to therapy. We have recently developed a new proteomic method (CTAP) to globally interrogate the cell-of-origin of proteins in cells in coculture, greatly facilitating studies of cell-to-cell communication in models of the tumour microenvironment (Gauthier et al 2013, Nat Methods). We will use CTAP and quantitative mass spectrometry to systematically characterise tumour-stroma interactions in order to identify effective drug treatments that overcome both tumour intrinsic and -extrinsic mechanisms of drug resistance. Combining cell-selective proteomic methods with pathway analysis and perturbation-based network modeling (Molinelli et al 2013, PLOS Comp Biol; Miller et al 2013, Sci Sig), our research will pioneer modelling of cell-cell communication in the tumor microenvironment of cancers such as pancreatic ductal adenocarcinoma (PDAC).