Antoniades Group: Cross-talk between adipose tissue and the cardiovascular system in humans: Using Artificial Intelligence to design precision Imaging diagnostics and discover novel therapeutic targets

About the Research

We undertake translational cardiovascular research by moving from bench to bedside and vice versa; our main focus is the cross-talk between adipose tissue (AT) and the cardiovascular system. Using a translational approach, we bring the knowledge of how AT implicates in the redox-sensitive inflammatory mechanisms into developing imaging biomarker that can be used in clinical practice to predict cardiovascular outcomes (Carena et al, J Am Coll Cardiol, 2023; Kotanidis et al, Lancet Digit Health, 2022; Kondo et al, Eur Heart J, 2021; Akawi, et al, J Am Coll Cardiol 2021; Akoumianakis et al, Science Transl Med, 2019 and 2020; Oikonomou et al, The Lancet, 2018). The overall goal is to tailor prompt treatments for vulnerable patients at risk of cardiovascular disease. We have employed a wide range of novel approaches, such as radiotranscriptomics by linking transcriptomics (e.g. RNA sequencing of human tissues) with radiomics in cardiac computed tomography (CTCA) imaging, to delineate the biological mechanisms underpinning the radiomic changes (Oikonomou, Eur Heart J, 2019). This involves the application of artificial intelligence and machine learning approaches to develop radiotranscriptomic fingerprints of the human coronary arteries and adipose tissue. We offer projects within both the basic science team and the clinical imaging team of the laboratory, focused on understanding the cellular and molecular mechanisms that affect the cross-talk between AT and the cardiovascular system and on developing new diagnostic tool for early detection of cardiovascular disease and enhanced risk prediction.

The basic science project that we are offering aims to investigate the molecular mechanisms underlying the cross talk between perivascular adipose tissue (PVAT) and the vascular wall. The candidate will take advantage of recently generated transcriptomic data from hundreds of human samples obtained from different AT depots and from the vessels and of Mendelian randomisation approach to discover novel key player and possibly therapeutic target in the bidirectional communication between AT and the vascular wall that may mediate the development of cardiovascular disease. To validate the molecules found during the multi-omics discovery phase and to unveil the mechanisms though which they act the candidate will perform ex vivo experiments in human arteries and saphenous veins, as well as mechanistic experiments in primary vascular cells and adipocytes. The causal role of druggable molecular target may be further investigated in small clinical trials.

The clinical imaging project will focus on understanding the role of coronary inflammation, using AT imaging biomarkers, in the development of vulnerable atherosclerotic plaque that are prone to rupture, causing acute myocardial infarction. This will build on the exciting body of work from the Oxford Risk Factors and Non Invasive Imaging (ORFAN) study, which includes a retrospective clinical cohort of 200,000+ CTCAs from across the UK, Europe, Asia, and United States. This cohort is a rich source of pseudonymiased data including the CTCA scans, patient risk factor data, pathology and long term clinical outcomes (2010-current). In addition, >3000 patients undergoing clinical CTCA are being recruited that form a large prospective clinical cohort to investigate serum biomarkers in association with CTCA imaging data. Candidates will be actively involved in recruitment, data analysis and clinical governance of the ORFAN study. The lab has unfettered access to the Oxford Acute Multidisciplinary Imaging and Interventional Centre (AMIIC) under the direction of Professor Antoniades.  To support the image analysis of the cohort, the core lab has its own state of art GPU server infractructure. For imaging analysis automation and developing machine learning algorithms. AMIIC has also recently been equipped a photon-counting detector CT scanner, which is the most advanced CT imaging technology available yet, for high resolution tissue phenotyping. This will enable novel research into the pathobiology of coronary plaque and peri-vascular tissues.

Training Opportunities

If necessary to the project, the successful candidate will receive training in several techniques relevant to the execution of the project that are already available in the lab, such as isolation and culturing of primary cells from human vessels, myocardial and fat biopsies; co-culture bioassays; vasomotor studies on human vessels; superoxide measurements on human tissues/cells; pertinent techniques of biochemistry and cellular and molecular biology. The student will be also encouraged to undertake any training outside the lab that is necessary for a successful execution of the project.

Clinical students will receive training on the analysis of CTCA images and clinical reporting of CTCA. Training opportunities will also be available on image processing, machine learning techniques, and big-data analysis of clinical outcomes. The candidate will be well supported by a team of senior post-doctoral researchers in deep-learning, bioinformatics, and clinical research fellows experienced in the application of radiomic techniques.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

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