Mariann Bienz's group at the MRC LMB studies the molecular mechanisms of Wn/beta-catenin signalling and how the aberrant activation of this important cancer pathway drives colorectal cancer. They focus on the functions and molecular interactions of newly-discovered components of this pathway, aiming to understand how these control the transcriptional activity of beta-catenin and to develop their potential as cancer drug targets.
Simon Buczacki's lab is interested primarily in the role sub-clonal interactions play on colorectal cancer cell identity and behaviour. We believe that the behaviour of normal intestinal cells is often analogous to that seen in oncogenically transformed cells and thus, we also study the behaviour of progenitor and differentiated cells from normal intestinal tissues to provide insights into cancer cell behaviour. We are particularly interested in understanding the mechanisms and links behind cancer plasticity and identity switching. The lab is also interested in understanding the fundamental biology of small intestinal neuro-endocrine tumours through organoid biology and mouse modelling.
Pietro Cicuta is a Professor of Biological Physics in the Physics Department, Cambridge University. His team combines: (a) experience in single cell measuring on micro-organisms, including studies of cell size, adhesion, gene regulation; (b) microfluidic fabrication and automation of imaging and optical measurements; (c) quantitative mechanistic/physical modelling. Developing new experimental techniques to study the mechanics and dynamics of soft and biological systems is the heart of his research. Recent work includes studies of model bacteria and pathogens in host/pathogen interactions, physiology of ciliated epithelia and mechanics/lipidomics of cell membranes.
Matthew Hoare’s group studies the profound effects that senescent cells have on the microenvironment, particularly within the liver. They focus on how senescent cells recruit and activate components of the immune system to prevent tumorigenesis. Currently much of their work investigates how senescent cells regulate endothelial-dependent immune cell recruitment and whether this can be therapeutically targeted to prevent cancer development.
What are the regulatory mechanisms that control homeostatic turnover, and how do their perturbation contribute to disease progression? The lung is a very slow cycling organ that is composed of diverse epithelial and stromal cell types, but has capacity to rapidly regenerate new cells after injury. Lee group is trying to understand how stem cells respond to different signals from their local environment and orchestrate the changes in chromatin, transcription, translation, and cellular dynamics in homeostasis and injury repair. We investigate the regulatory networks that need to be turned on and off at the right time and place for stem cells to become activated and generate specialised cell types during regeneration. We are also interested in defining cellular heterogeneity and plasticity during this process. Elucidating the normal process of lung dynamics will provide us a foundation to understand lung diseases and cancer. We couple ex vivo 3D organoid cultures of human and mouse lungs with genetic tools, in vivo transgenic mouse models with lineage tracing techniques, quantitative mathematic modelling of clonal dynamics, and bioinformatics at the single cell level.
The main aim of Carla Martin's programme is to define the molecular and functional alterations that enable lung tumour progression from benign stages to high-grade adenocarcinoma. While their immediate goal is to improve the targeting of tumours harbouring particular sets of mutations, their ultimate goal is to identify broader and targetable signatures associated with benign and advanced disease. They are currently focused on the evolution of lung tumours expressing mutant versions of Kras and p53.
Emma Rawlins' lab - based at the Gurdon Institute, works on the roles of stem cells in lung development and homeostasis with the dual aims of understanding how the normal homeostatic control mechanisms are subverted in cancer and whether mechanisms of differentiation can be exploited as possible therapies. They investigate these questions using both in vivo mouse models and human organoids.
Kourosh Saeb-Parsy's lab, in the University of Cambridge's Department of Surgery, is focused on collaborative, multidisciplinary and translational research in experimental and clinical transplantation. Experimental research themes include: function and immunogenicity of transplanted regenerative cellular therapies; ischaemia-reperfusion injury in transplantation; safety and efficacy of cancer immunotherapies in humanised mouse models; and cryopreservation of multicellular aggregates and bioengineered tissues.
Jacqui Shields' Lab take a multidisciplinary approach, integrating experimental cancer models, complex in vitro and in silico systems, high throughput genomics and bioinformatics to understand how the tumour stroma regulates immune activity from early stages of disease to promote carcinogenesis.
Cancers of the colon, like other cancers, arise from the abnormal growth of cells containing oncogenic mutations. This provides the motivation to understand in detail the molecular changes accompanying such mutations. In contrast the impact of mutations on cell fates within affected tissues receives relatively little attention. Yet cancers are comprised of expanded clones of cells. Every mutated clone has a natural history involving discrete steps that establishes the fate of the founding cell and of its clonal descendants to dictate their contribution to, and availability for, neoplastic transformation. Doug Winton's group investigate the origin of clones in the intestinal epithelium to understand the probability of their survival and expansion at each stage and how this varies with different mutations. By defining when during their natural history clones predisposed to cancer become permanently fixed and how much they subsequently grow we can tailor interventions appropriately: aiming either to promote their extinction or limit their growth.