William Cawthorn Research Group
Information on the research interests, projects, and members of William Cawthorn's Research Group.
Dr William Cawthorn
My research addresses the interplay between metabolism, immunological function and skeletal health in the context of both fundamental biology and chronic diseases. To do so I combine preclinical animal models, human clinical studies and data science approaches using the UK Biobank. Methods include the development of new biomedical imaging techniques and artificial intelligence to open new avenues for population-level studies. My key research interests are as follows:
A) Bone marrow adipose tissue (BMAT):
My overarching research goal is to determine the function of BMAT and its impact on human health. BMAT comprises >10% of total adipose mass in lean, healthy humans, and further increases in diverse clinical contexts. In striking contrast to white adipose tissue (WAT) and brown adipose tissue (BAT), BMAT accumulates during caloric restriction (CR), a condition that promotes healthy ageing by preventing and treating chronic diseases. Thus, altered BMAT formation and/or function might impact numerous human diseases. However, the physiological and pathological functions of BMAT were previously almost completely unknown.
In 2015 I was awarded an MRC Career Development Award to investigate the metabolic and endocrine functions of BMAT. One barrier to understanding BMAT formation and function has been the inability to measure BMAT on a population-level. To address this, in 2019 I was awarded an MRC Research Grant to develop new deep-learning methods for high-throughput, automated analysis of BMAT in the UK Biobank imaging study. My key achievements are as follows:
- Discovered that, during states of caloric restriction (CR), BMAT is a key source of adiponectin, a hormone implicated with improved cardiometabolic health (Cawthorn et al, Cell Metabolism 2014).
- Identified glucocorticoids as drivers of BMAT accumulation during CR (Cawthorn et al, Endocrinology 2016 and Lovdel et al, Endocrine Abstracts 2018), highlighting mechanisms through which nutritional status regulates BMAT formation.
- Developed new biomedical imaging methods to investigate BMAT function in vivo, both preclinically and in humans. This research, which has yielded new research datasets (GSE138690) and software code (ROCPerPixel), revealed that BMAT has high basal glucose uptake and is metabolically distinct from WAT and BAT; thus, BMAT represents a third major, distinct adipose tissue subtype(Suchacki et al, Nature Communications 2020).
- Developed deep learning to automate BMAT analysis from MRI data in the UK Biobank (presented at ISMRM 2021).
Moreover, in 2017 I worked as key member of an international, multidisciplinary team of researchers to co-found The International Bone Marrow Adiposity Society (BMAS; http://bma-society.org/), of which I am the inaugural Secretary and am currently acting as interim President. I edited the first special issue on BMAT for Frontiers in Endocrinology; lead the BMAS Nomenclature Working Group, with corresponding authorship on our first BMAS position paper (Bravenboer et al, Frontiers in Endocrinology 2020; and serve on of the BMAS Biobanking Working Group, co-authoring our recently published biobanking guidelines for BMAT research (Lucas et al, Frontiers in Endocrinology 2021).
Since 2015 my BMAT research has contributed to 24 peer-reviewed journal articles, 29 invited seminars, 29 conference abstracts, 2 PhD theses and 1 book chapter.
B) Adiponectin function in caloric restriction
My finding that BMAT is a key source of adiponectin raises a key question: what is adiponectin’s function during CR? Thus, another of my major research interests is to elucidate adiponectin’s contribution to the metabolic and immunological benefits of CR. I have pursued this goal through preclinical studies in adiponectin knockout (KO) mice, and through Mendelian Randomisation using the UK Biobank. Key advances are as follows:
- Discovered that, unexpectedly, adiponectin KO enhances the metabolic benefits of CR (Sulston PhD Thesis) and alters CR’s immunological effects (Mattiucci PhD thesis).
- Mendelian Randomisation revealed that decreased circulating adiponectin may influence immunological function in humans, including the risk of adverse COVID-19 outcomes (unpublished studies in progress).
Since 2015 my adiponectin research has contributed to 24 invited seminars, three abstracts at major international meetings, two PhD theses, and are the basis for one manuscript in preparation.
C) Sex differences in the effects of caloric restriction
My BMAT and adiponectin research has identified age-dependent sex differences in the CR response, with young females resisting many of CR’s health benefits. For example, in male mice CR decreases fat mass, improves glucose tolerance and suppresses haematopoiesis, whereas females resist these effects. These differences no longer occur in aged mice, in which CR elicits similar metabolic benefits in both sexes. Notably, my research has revealed similar age-dependent sex differences during CR in humans. These data are the basis of a preprint in bioRxiv that is now under peer review.
To further investigate the basis and extent of these sex differences I have been awarded two research grants (one as PI, one as Co-Investigator) and am the principal supervisor for a final-year PhD student who is contributing to this research. Since 2015 this research has contributed to 21 invited seminars and 18 abstracts at local, national and international meetings. These findings are the main subject of one manuscript under review and the basis for ongoing collaborative funding proposals.
Open Research and Research Integrity
Finally, I am a strong advocate for open research and research integrity, including serving as the University of Edinburgh's representative for the UK Reproducibility Network (UKRN) and Open Science Ambassador for the League of European Research Universities (LERU). In the latter role I aim to advance the University of Edinburgh's progress along it's Open Research Roadmap, which will help to improve research culture and reproducibility.