Spotlight on Research and Covid-19 Research News
This page will collect links and research news to all the 'Spotlight on...' articles we have published into one place. The purpose of this page is to highlight some ongoing projects that will benefit patients in future and to give more visibility to BHF-funded group leaders and research Fellows. Please contact Denise Hatherly if you would like your own research to be featured or if you know of someone who we should interview!
Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance (April 2022)
Pellegrinelli V et al Nat Metabolism.
Our paper identifies Peptidase D (PEPD) as an essential protein for the development of adipose tissue dysfunction, fibro-inflammation, and insulin resistance in obesity. PEPD gene can explain the metabolically healthy obese and unhealthy non-obese paradox by providing a mechanism that uncouples fat mass expansion from its fibro-inflammatory complications. This is possible because PEPD has two functions: a) PEPD is an enzyme that controls collagen turnover and, consequently, fibrosis deposition, and also b) it is a secreted protein that signals through the EGF receptors exacerbating fibrosis and inflammation.
Our paper, led by Dr Pellegrinelli, shows that in human and murine obesity, the expression of PEPD and its enzymatic activity is decreased in adipose tissue macrophages facilitating the development of fibrosis and adipose tissue dysfunctions. On the other hand, in obesity, PEPD is secreted from macrophages and promotes inflammation and insulin resistance. We have used insights from human genetics, human cohorts, fibro-inflammatory cell and murine models, molecular profiling, and computing biology to show that PEPD produced by the macrophages in adipose tissue might serve as a biomarker of fibro-inflammation and insulin resistance and could represent a therapeutic target to prevent or reverse fibrosis and obesity-associated insulin resistance and type 2 diabetes.
This is a major effort from many laboratories through a broad international collaboration, including laboratories from Paris, Bielefeld, Nanjing, Girona, Valencia, Taiwan, Bari, Uppsala, London, New York, and Copenhagen. We are very thankful for the funding bodies that have supported this global collaboration, particularly MRC and British Heart Foundation supporting us here in Cambridge and the agencies supporting our collaborators.
LINK TO PAPER
https://www.nature.com/articles/s42255-022-00561-5
Pericoronary adipose tissue density is associated with inflammatory disease activity in Takayasu arteritis (September 2021)
Inflammation of the main arteries that supply blood to the heart is associated with changes in the density of surrounding fat, which can be detected using a CT scan. Research at the University of Cambridge led by Dr Christopher Wall and Dr Jason Tarkin found this method to be accurate for identifying active arterial inflammation in patients with a rare form of systemic vasculitis, called Takayasu arteritis. Coronary artery involvement is common in Takayasu arteritis, and there is a clinical need for a better method of identifying inflammation in these vessels than is currently available. For this work, Dr Wall received the Young Investigator Award at the British Society of Cardiovascular Imaging 2021 conference held in Oxford. This research published in the European Heart Journal Open was performed in collaboration with Dr James Rudd, Professor Justin Mason (Imperial College London) and Dr Damini Dey (Cedars-Sinai Medical Centre, Los Angeles), among others. It was funded by the Wellcome Trust and supported by the Cambridge BHF Centre of Research Excellence. LINK TO PAPER
(Representative images showing increased fat density surrounding the right coronary artery of a patient with Takayasu arteritis and bilateral coronary artery aneurysms) See link to paper for full image.
Radiomics in stroke medicine: assessing robustness and feasibility for stroke prevention
A cross-discipline group of researchers, led by MB PhD student Elizabeth Le and PI James Rudd, have published in Nature Scientific Reports the first attempt to determine whether radiomics might be useful for predicting stroke in patients with carotid artery disease. Radiomics refers to the harnessing of information 'hidden' within medical images for diagnostic and prognostic purposes, and is being increasingly used in oncology. Read more here
CRE Funded projects
A new online series of short personal interviews with Cambridge Stem Cell Institute researchers exploring how they are adapting their research to investigate Covid-19.
BHF CRE Pump Priming Funds - Multi-modality imaging and immunophenotyping of COVID-19 related myocardial injury project
The BHF CRE pump priming funds is being used to support a Multi-modality imaging and immunophenotyping of COVID-19 related myocardial injury project. This project run by Dr's Jason Tarkin, Meritxell Nus and Andrew Sage will work towards a better understanding of the mechanisms underlying the excess mortality risk attributable to myocardial injury in COVID-19 is urgently needed and may help to improve patient care. This project now has approval to move forward. For further information contact Dr Tammy Dougan.
Professor Toni Vidal-Puig, Reflecting on the Covid-19 pandemic and its impact on the research landscape
Professor Antonio Vidal-Puig is Professor of Molecular Nutrition and Metabolism at the University of Cambridge. Reflecting on the Covid-19 pandemic and its impact on the research landscape. Toni tells in an interview with the BHF how the BHF CRE have supported the research, about fundraising for PPE, testing the strength of global networks, and what we can learn from the crisis https://alumni.bhf.org.uk/news/286709
BHF CRE Funded Covid projects
Contact Dr Jane Sugars for further information.
Cambridge Investigation of Cardiac Complications of Severe COVID-19 (CICERO-19) - Dr Sanjay Sinha, Prof. Anthony Davenport (Clinical Pharmacology), Prof. Paul Lehner (Medicine), Dr Nick Matheson (Medicine).
Molecular mechanism underlying late-stage pathology in COVID19 – platelets and megakaryocytes- Cedric Ghevaert, Amie Waller
For any information or queries related to Covid-19 topics regarding Cambridge Infectious Diseases IRC, Cambridge Immunology Network SRN, and the Cambridge Cardiovascular IRC, please email covid-response@cam.ac.uk and include CINCID in the subject line or contact Dr Jane Sugars
The Naked Scientists: Covid-19
150 scientists from new institute join Cambridge fight against COVID-19
COG-UK captures SARS-CoV-2 samples from COVID-19 infections from across the UK
Past Articles
- SIRT6 Protects Smooth Muscle Cells from Senescence and Reduces Atherosclerosis Mandy Grootaert, Alison Finigan, Nichola Figg, Anna Katarzyna Uryga, and Martin Bennett
- Understanding the management of heart failure with preserved ejection fraction: a qualitative multiperspective study.
Dr Christi Deaton, Florence Nightingale Foundation Clinical Professor of Nursing, Department of Public Health & Primary Care. University of Cambridge School of Clinical Medicine
- Glycoprotein-VI: a stroke of luck in understanding blood clot formation Dr Isuru Induruwa is a BHF-funded clinical PhD Fellow (Dept Clinical Neurosciences) and an ST5 in Stroke Medicine (CUH).
- Next-generation materials for heart valve replacement Prof Geoff Moggridge is a Professor in Chemical Engineering Science (Dept Chemical Engineering & Biotechnology).
- Engineered platelets could meet demand and mend a broken heart Dr Cedric Ghevaert is a Senior Lecturer in Transfusion Medicine (Dept Haematology).
- Functional genomics: Shedding light on cardiovascular disease Dr Mattia Frontini is a BHF-funded Senior Research Fellow (Dept Haematology).
- Investigating CADASIL and CARASIL molecular mechanisms in young adult stroke Dr Alex Granata is a Medical Research Foundation Fellow and a Senior Research Associate (Dept Clinical Neurosciences)
- Understanding the management of heart failure with preserved ejection fraction: a qualitative multiperspective study.
