Overview
The Cancer Origins group is dedicated to understanding how cancer begins, specifically, how oncogenic cells overcome normal tissue restraints, gain malignant potential, and initiate tumour formation.
We are interested in how environmental exposures, such as air pollutants, shape the tissue microenvironment to support the expansion of latent oncogenic cells and promote lung cancer.
Lung cancer remains the leading cause of cancer-related death in both men and women, responsible for over 1.8 million deaths globally each year. While smoking has long been recognized as a primary risk factor, a growing body of evidence highlights air pollution as an increasingly significant driver of lung cancer. As smoking rates decline and global pollution levels rise, the number of lung cancer deaths linked to air pollution has increased, rising by nearly 30% since 2007.
To address these questions, we utilise genetically engineered mouse models, multiple real world and source-specific environmental exposures, single cell approaches, advanced imaging techniques and 3D in vitro culture systems. By working with exceptional collaborators, we aim to translate these findings clinical samples.
Featured Publications
Lung adenocarcinoma promotion by air pollutants
5th April 2023
The authors propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue.
Impact of risk factors on early cancer evolution
13th April 2023
This review discusses how early initiated cells are protected from further tumorigenesis and the non-mutagenic pathways by which cancer risk factors promote tumor growth, and considers existing strategies for early cancer interception with perspectives on the next steps for molecular cancer prevention.
EPHA2-dependent outcompetition of KRASG12D mutant cells by wild-type neighbors in the adult pancreas
21st June 2021
This study provides evidence to support a conserved functional role of EphA2 in Ras-driven cell competition in epithelial tissues and suggests that EphA2 is a novel tumor suppressor in pancreatic cancer.
Group Goals
Our goal is to uncover the cellular and molecular pathways required for cancer promotion by carcinogens. By understanding these mechanisms, we aim to inform new strategies for cancer prevention, improve early detection efforts, and support evidence-based public health policies.
Research projects
Research projects
Defining the molecular mechanisms of lung cancer initiation
Lung cancer is the leading cause of cancer-related death worldwide. The lung is challenged throughout life by environmental exposures which may promote cancer but precisely how is unclear.
Recent studies have demonstrated that over time histologically normal tissues become replete with somatic mutations, with no evidence of cancer. This suggests that pre-cancerous cells are present in the body without forming a cancer. We have previously identified that air pollutants can act on these pre-cancerous cells to drive cancer. This project will build on this work exploring how environmental exposures act on dormant mutant cells at the molecular, cellular and tissue level to drive cancer. Specifically, it will define oncogenic cell signalling networks induced by exposures and determine the impact on mutant cell selection and lung cancer. The project involves in vivo animal models and 3D ex vivo models which will be analysed by single cell analysis (RNA-seq/CyTOF), immunofluorescence imaging and functional assays. A deeper understanding of early lung carcinogenesis will help guide cancer screening, promote public health policy and is critical for developing therapies to inhibit the impact of environmental exposures and prevent lung cancer.
Get in touch
Institute life in Manchester
We strive to make our community a welcoming, caring and enthusiastic one, fuelling ambition with opportunities for training and mentoring to help us all achieve our personal and professional goals.
“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow
“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow
Our vision for world leading cancer research in the heart of Manchester
We are a leading cancer research institute within The University of Manchester, spanning the whole spectrum of cancer research – from investigating the molecular and cellular basis of cancer, to translational research and the development of therapeutics.
Our collaborations
Bringing together internationally renowned scientists and clinicians
Scientific Advisory Board
Supported by an international Scientific Advisory Board
Careers that have a lasting impact on cancer research and patient care
We are always on the lookout for talented and motivated people to join us. Whether your background is in biological or chemical sciences, mathematics or finance, computer science or logistics, use the links below to see roles across the Institute in our core facilities, operations teams, research groups, and studentships within our exceptional graduate programme.
A note from the Group Leader – William Hill
I’m excited to integrate across from the incredible local scientific community, the medical oncologists from The Christie NHS Foundation Trust and Wythenshawe hospital all the way through to the experts in atmospheric science in the Department of Earth and Environmental Sciences.