We talk to DPhil student Becky Im about her investigations into oesophageal cancer risks in Asian populations
The Royal Society, the UK’s distinguished academy of science, has announced the election of 62 new Fellows and Foreign Members, which include Professor Xin Lu FMedSci FRS. Xin is the current co-director of the CRUK Oxford Centre and Director of the Oxford branch of the Ludwig Institute for Cancer Research. It has been Xin’s distinguished career as a cancer biologist and her contributions to the understanding of cellular pathways that control cell fate in development and disease, particularly cancer, has earnt her this accolade.
She has a long-standing interest in how to selectively kill cancer cells, and her major research advances have provided insights into how p53, the most mutated or inactivated tumour suppressor in human cancers, can make life or death decisions for a cell. Xin’s early work showed how p53 responds to activation of cancer-causing genes and DNA damage. She has since discovered the ASPP family of proteins as molecular switches that control p53-mediated cell killing. Find out more about Xin’s research here.
Xin’s impact on the cancer landscape in Oxford
Of equal importance is the impact that Xin has had on the cancer research community here at Oxford. Her ability and desire to bring researchers together across traditional thematic boundaries was one of the many reasons she was appointed to the Cancer Research UK Oxford Centre Management Group in 2016 and as co-Director in 2018. During this time, her ability to identify new opportunities for collaboration and galvanise research teams from multiple corners of both the University and Hospital, has impacted both Oxford’s Oesophageal Cancer and Early Cancer Detection communities.
“It’s fantastic that Xin’s academic work has been recognised in this way” said Professor Mark Middleton, co-Director of the Cancer Research UK Oxford Centre.
“We are fortunate in Oxford to have a scientist of Xin’s calibre who is so committed to making sure that our world class science improves patient care. Many of the achievements of the Oxford Centre in recent years would not have been possible without her drive and leadership. Her ability to engage and energise research teams has had a profound impact on the cancer research community at the University and Trust, that will be felt for years to come.”
The fruits of these efforts are numerous and include Oxford being selected to host the inaugural CRUK International Symposium on Oesophageal Cancer; engaging with local clinicians to drive the opening of numerous innovative clinical and experimental medicine studies in upper GI cancers (including LUD2015-005 to test novel combinations of radiation-, chemo- and immune- therapy in this setting), the launch of the Oxford Centre for Early Cancer Detection and the external funding of numerous Oxford-ed project and programme awards in these fields.
“I am humbled to receive this honour from the Royal Society” said Professor Lu.
“As someone who barely spoke English at the beginning of my scientific career, I am hugely grateful for all the support I have received from my supervisors and mentors. My appreciation also goes to the Ludwig Institute for Cancer Research for its long-term research funding and to the Department, College and University for a supportive and creative environment. Most important of all, my deep gratitude goes to the fantastic scientists in my laboratory, and colleagues I’ve had the privilege to work with throughout my career to date, without whom this recognition would not have been possible.”
About the Fellowship
The Royal Society is a self-governing Fellowship dating back to the 1660s that is dedicated to promoting excellence in science for the benefit of humanity. The Fellowship comprises the most eminent scientists, engineers and technologists from the UK and the Commonwealth. Former members include Sir Isaac Newton, Charles Darwin, Albert Einstein, Dorothy Hodgkin and Stephen Hawking. This year, 51 Fellows, 10 Foreign Members and one Honorary Fellow have been elected for life through a peer review process on the basis of scientific excellence. There are approximately 1,700 Fellows and Foreign Members in total, including around 70 Nobel Laureates. These include Ludwig Oxford’s Professor Sir Peter Ratcliffe, a co-recipient of the 2019 Nobel Prize in Physiology or Medicine.
Venki Ramakrishnan, President of the Royal Society, said
“At this time of global crisis, the importance of scientific thinking, and the medicines, technologies and insights it delivers, has never been clearer. Our Fellows and Foreign Members are central to the mission of the Royal Society, to use science for the benefit of humanity. While election to the Fellowship is a recognition of exceptional individual contributions to the sciences, it is also a network of expertise that can be drawn on to address issues of societal, and global significance.
“This year’s Fellows and Foreign Members have helped shape the 21st century through their work at the cutting-edge of fields from human genomics, to climate science and machine learning. It gives me great pleasure to celebrate these achievements, and those yet to come, and welcome them into the ranks of the Royal Society.”
Six academics from Oxford have been honoured in this year’s round of Royal Society Fellowship elections. Find out more on the Royal Society website.
Researchers from the Nuffield Department of Surgical Sciences, Nuffield Department of Medicine and Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, have been investigating microRNA sequences and their influence on the migration and wider metastasis of prostate cancer cells around the body.
Prostate cancer is the second most fatal cancer in males, due in part to its slow growth and difficulties in early diagnosis before it spreads. Once spread, standard treatments are less effective and the disease is often incurable. Understanding mechanisms that modulate and cause the process of cancer metastasis is important in order for us to better understand how to detect, prevent and treat it.
Led by Claire Edwards, postdoctoral researcher Srinivasa Rao Rao devised a series of transcriptomic and functional screening strategies. This novel combination of migrational and morphological analysis allowed the team to focus on the wider biological relevance of microRNA in the development of prostate cancer.
After studying the entire microRNA genome, the team focused on overexpressing microRNAs belonging to specific families, specifically, those known as miR-372 and miR-302 clusters, which emerged as interesting candidates in the regulation of prostate cancer. 16% of microRNAs screened in this novel method, were found to decrease the rate of cell migration when dysregulated. Similarly, 19% of microRNAs were found to alter the morphology and shape of cancer cells.
This publication demonstrates an application using a series of integrated screening approaches to enhance the specificity and accuracy of screens. By using a variety of screening strategies in succession, the team were able to narrow down the microRNA candidates to those more likely to be directly involved in prostate cancer progression. There are additional applications of this work through the use of these relatively stable microRNAs as diagnostics markers for the earlier detection and diagnosis of prostate cancer.
Claire Edwards, Associate Professor at the Nuffield Department of Surgical Sciences, says;
“Through our collaboration with Daniel Ebner, we have been able to develop a screen to rapidly discover those microRNAs that could reduce migration and so deduce which of them may play a role in prostate cancer metastasis.”
To read the publication in full, see here.
Claire Edwards is an Associate Professor of Bone Oncology. Her main focuses are on obesity and adipokines in cancer-induced bone disease, metabolism and miRNA in prostate cancer bone metastases and bone marrow stromal cells in the pathogenesis of cancer-induced bone disease.
Daniel Ebner is a Principle investigator at the Nuffield Department of Medicine. He worked with the Target Discovery Institute to develop new target screening methodologies, investigate disease pathways as a means for identifying ‘drug targets’ and advance therapeutically relevant targets for drug development.
Freddie Hamdy is a Nuffield Professor of Surgery with a research focus on management of urological malignancies, in particular prostate and bladder cancer He is the Chief Investigator of many studies including the ProtecT (Prostate testing for cancer and Treatment) study of case-finding and randomised controlled trial of treatment effectiveness in prostate cancer – the largest of its kind worldwide.
This work was supported by the FP7 Marie Curie Initial Training Network PRO-NEST, Cancer Research UK, through the Cancer Research UK Oxford Centre Development Fund and through the University of Oxford Medical Research Fund.
Cancer imaging is an umbrella term that defines diagnostic procedures to identify cancer through imaging – such as scans via x-rays, CT scans and ultrasounds. There is no single imaging test that can accurately diagnose cancer, but a variety of imaging tests can be used in the monitoring of cancer and planning of its treatments.
What is NCITA?
NCITA – the UK National Cancer Imaging Translational Accelerator – is a new consortium that brings together world leading medical imaging experts to create an infrastructure for standardising the cancer imaging process, in order to improve its application in clinical cancer treatment.
Research and medical experts from the University of Oxford have come together with UCL, University of Manchester, the Institute of Cancer Research, Imperial, Cambridge University and many more to create this open access platform.
How will NCITA help cancer research?
On top of bringing together leading experts in cancer imaging to share their knowledge, the NCITA consortium will create a variety of systems, software and facilities to help localise and distribute new research and create a centralised location for cancer-image data to be analysed.
NCITA will in include a data repository for imaging, artificial intelligence (AI) tools and training opportunities – all of which will contributing to a revolution in the speed and accuracy of cancer diagnosis, tumour classification and patient response to treatment.
The NCITA network is led by Prof Shonit Punwani, Prof James O’Connor, Prof Eric Aboagye, Prof Geoff Higgins, Prof Evis Sala, Prof Dow Mu Koh, Prof Tony Ng, Prof Hing Leung and Prof Ruth Plummer with up to 49 co-investigators supporting the NCITA initiative. NCITA is keen to expand and bring in new academic and industrial partnerships as it develops.
Go to the NCITA website to stay up to date of news about cancer imaging research.
For more information on this exciting new initiative, see the media release about the NCITA launch here.
Research from Dr Heba Sailem, recently published in Molecular Systems Biology, showed that patients with specific smell-sensing genes ‘turned on’ are more likely to have worse colon cancer outcomes.
Through the development of a machine-learning approach to analyse the perturbation of over 18,000 genes, Dr Sailem and her team found that olfactory receptor gene expression may have some effect on the way that colon cancer cells are structured.
Dr Sailem used layers of Artificial Intelligence (AI), including computer algorithms, to detect the changes of cancer cell appearance and organisation when the genes are turned down using siRNA technology. AI played a crucial part of this research, as it allowed for speed and efficient analysis and mapping of cell image data to various gene functions that were studied, which greatly increase the amount of information that can be extracted and reduced human error.
Dr Sailem surveyed over 18,000 genes and found that specific smell-sensing genes called olfactory receptor genes are strongly associated with how colon cancer cells spread and align with each other akin to the changes induced by turning down key colon cancer genes.
The practical patient implications of this research include how we might approach patients with colon cancer, depending on their genetic makeup. In the long run, Dr Sailem hopes that these findings will allow clinicians to survey patient genes, create specific predictions based on their genetics and create tailored treatments to best treat their cancer.
There is already a large body of research into the genes that influence the structure of cancer tissues, but studies such as this might help to find new target genes. For example, by reducing the expression of olfactory genes, we could potentially inhibit cancer cells from spreading and eventually invading other tissues which is the major cause of cancer death
About the Author
Dr Heba Sailem is a Sir Henry Wellcome Research Fellow at the Big Data Institute and Institute of Biomedical Engineering at the University of Oxford. Her research is focused on developing intelligent systems that help further biological discoveries in the field of cancer.
This paper is a result of three years of work, focusing on identifying the role of genetic expression on the spread and management of colon cancer.
Following this research Dr Sailem hopes to apply this AI approach to a wider range of cancer, to see what genes are associated with and influence cancer tissue structure, proliferation and motility.
For more information about this research, see Dr Heba Sailem’s paper here.