Accepting PhD Students

PhD projects

PhD projects will depend on being able to secure funding.

If you made any changes in Pure these will be visible here soon.

Personal profile

My research in a nutshell

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:

  1. 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).
  2. 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.
  3. 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).
  4. 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:

  1. Discovered that, unexpectedly, adiponectin KO enhances the metabolic benefits of CR (Sulston PhD Thesis) and alters CR’s immunological effects (Mattiucci PhD thesis).
  2. 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.

 

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.

More information can be found elsewhere on the Centre for Cardiovascular Science website, and via my profile on Edinburgh Research Explorer (which includes further details of my research, publications, funding and other activities).

Research Interests

White adipose tissue (WAT) is a key regulator of metabolic homeostasis, both as a site for energy storage and as an endocrine organ. The past generation has seen extensive research into WAT biology, fuelled largely by the public health burden posed by obesity and associated diseases. As such, WAT formation and function is now relatively well understood. Adipocytes also exist in bone marrow, yet in contrast to WAT, our understanding of such bone marrow adipose tissue (BMAT) is extremely limited. This ignorance is surprising: BMAT accounts for up to 70% of bone marrow volume in healthy adult humans, which suggests that BMAT has a role in normal human physiology. BMAT further increases in conditions of altered bone formation or metabolic health. For example, increased BMAT occurs in osteoporosis, suggesting that BMAT might contribute to the bone fragility that defines this disease. Perhaps most bizarrely, BMAT formation increases in starvation states, such as during caloric restriction (CR) in animals or in human patients with anorexia nervosa. This is in stark contrast to WAT, which is broken down during starvation to be used as fuel. CR has numerous health benefits, including increased lifespan, decreased risk of cancer and cardiovascular disease, and metabolic benefits such as enhanced fat breakdown and insulin sensitivity. BMAT also increases in response to treatment with anti-diabetic drugs such as thiazolidinediones or fibroblast growth factor-21, which, like CR, enhance insulin sensitivity. These clinical observations raise the possibility that BMAT directly promotes insulin sensitivity and metabolic health. However, whether BMAT impacts metabolic homeostasis remains unknown. Such knowledge could reveal new approaches to treat metabolic diseases. Thus, there is a critical need to understand the functions of BMAT.

 

My postdoctoral research revealed that, during CR, BMAT is a key source of adiponectin, a hormone that helps to maintain insulin sensitivity and fat breakdown, and which is linked to decreased risk of obesity-associated cancers, cardiovascular disease and diabetes. My postdoctoral work further revealed that BMAT expansion is required for skeletal muscle to adequately adapt to CR. This suggests that, as an endocrine organ, BMAT can exert systemic effects in metabolically relevant peripheral tissues.

My lab is now building on these observations by addressing the following questions (and their broader implications):

  1. What factors regulate BMAT formation in normal development, and aberrant BMAT expansion in disease states? Can we manipulate BMAT formation to achieve improved health outcomes?
  2. Does BMAT contribute to the impact of CR on metabolic homeostasis, cardiovascular risk, skeletal remodelling, haematopoiesis and/or immune function? What is the evolutionary function of BMAT, and how might this impact human health and disease?
  3. Does adiponectin contribute to the above effects of CR? What is the evolutionary function of adiponectin?
  4. We have found striking sex differences in the effects of CR on metabolic and immune function: What are the mechanisms underlying these sex differences? Can these be targeted to develop improved strategies to prevent and treat chronic disease?
  5. BMAT in humans can be measured non-invasively using magnetic resonance imaging (MRI) or spectroscopy (MRS). Can this be done at a population-level to reveal new insights into BMAT formation and function?

By pursuing the above questions, my research aims to reveal fundamental new knowledge about how BMAT, adiponectin and CR impact normal physiology and diverse disease states.

Current Research Interests

My current research addresses why BMAT expands during CR, and investigating if BMAT impacts metabolic health. Our previous publications in Cell Metabolism (PMID 24998914), Endocrinology (PMID 26696121), Frontiers in Endocrinology (PMC5030308) and Nature Communications (PMID 32555194) provide several insights toward these questions. Building on this, my lab is exploring the impact of BMAT on skeletal remodelling and immunological function.

I am also interested in sex differences in the metabolic and other effects of CR, based on our findings in mice which show that females, unlike males, do not lose fat mass or improve glucose tolerance in response to CR. Notably, in collaboration with other groups, we have found similar differences in humans. Finally, we have shown that BMAT is a major source of increased circulating adiponectin during CR. Therefore, we are now investigating the function of this hormone during CR.

Finally, my lab is investigating if BMAT and BMAT-derived factors, such as adiponectin, influence the metabolic, skeletal and immunological effects of ageing.

Improving our knowledge of BMAT formation and function might shed new light not only on normal human physiology, but also on diseases such as diabetes, osteoporosis, and cardiovascular disease. Similarly, by better understanding the mechanisms through which CR exerts diverse effects, we may be able to identify fundamental evolutionary pathways, as well as improved CR-related strategies to treat chronic diseases. Such knowledge will be vital if we are to reduce the public health impact of globally relevant health problems.

Websites

Research students

Current students:

  • Kuan-Chan Chen (PhD student funded by Taiwanese government)
  • Benjamin Thomas (BHF-funded PhD student)
  • Worachet (Bew) Promruk (PhD student)

Previous students:

  • Andrea Lovdel (CMVM-funded PhD student). Now Clinical Trial manager at Novo Nordisk.
  • Lisa Ivatt (MScR student, as part of her 4-year BHF PhD)
  • Richard Sulston (BHF-funded PhD student, 2015-2019). Currently pursuing a career in patent law in London.
  • Domenico Mattiucci (visiting PhD student from Italy; went on to a postdoc at the University of Edinburgh Centre for Regenerative Medicine; now at Novo Nordisk)
  • Yige Sun (Master's student on the Neuroscience MSc programme).
  • Iris Pruñonosa (visiting Erasmus student, now a student in CVS on the BHF 4-year PhD programme)
  • Alexandre Lafond, Diana Said, Matthew Sinton, Xuan Han, Holly Woodward (Previous MScR students). Matthew and Holly completed their PhDs in our department.
  • Fiona Roberts, Rachel Bell, Eleanor Brain, Kim Crane, Lucius Lo and Wendy Workman (previous BSc Hons students. Fiona has since completed her PhD at Edinburgh and is now a postdoc in Copenhagen. Rachel is now doing her PhD in Edinburgh. Eleanor and Kim are at Medical School, and Wendy is exploring PhD opportunities).
  • Caitlin Jones, Catherine Redshaw and Richard West (previous summer undergraduate students)

Administrative Roles

  • LERU (League of European Research Universities) Open Science Ambassador for the University of Edinburgh. (Since 2021)
  • Member of CVS Student Experience Committee (Since 2021)
  • Co-founder, Edinburgh Open Research Initiative (@edinburgh_open)
  • Lead for University of Edinburgh arm of the UKRN (UK Reproducibility Network) (Since 2021)
  • Secretary and founding member of the International Bone Marrow Adiposity Society (BMAS; http://bma-society.org/). (Since 2017)
  • Member of the Editorial Board for Diabetes
  • Member of the University of Edinburgh working group on Research Metrics (2020-2021)
  • Member of the CVS Seminars and Symposium Committee (2015-2019)
  • Member of the CVS Social and Communications Committee (2015-2019)
  • Creator and first coordinator of the CVS Twitter account (@EdinUniCVS) (2016-2018)
  • Coordinator (with Prof Nik Morton, Dr James Minchin and Dr Ruth Morgan) of the CVS Metabolism, Obesity and Diabetes (MOD) theme Twitter account (@EdinUniMetabol)
  • Coordinator of the BMAS Twitter account (@BMA_Society)

Teaching

Since moving to the University of Edinburgh in January 2015 I have supported students and postdoctoral trainees in the following ways:

  • Lecturer for the MScR in Cardiovascular Science and undergraduate Endocrine Physiology and Pharmacology Honours course.
  • Currently supervising one four-year BHF-funded PhD student (Ben Thomas); co-supervisor for PhD student at the Roslin Institute (Worachet Promruk)
  • Previous superviser for two PhD students (Richard Sulston and Andrea Lovdel), seven Master's students (Alex Lafond, Diana Said, Matthew Sinton, Xuan Han, Holly Woodward, Lisa Ivatt and Yige Sun), one ECAT researcher (Tyler Morrison), one visiting Erasmus+ student (Iris Pruñonosa) and eleven University of Edinburgh undergraduates during their Honours Projects or summer studentships in my lab.
  • Co-supervisor for a previous college-funded PhD student (Rebecca Wafer).
  • Previous superviser for one MRC-funded postdoctoral research fellow (Karla Suchacki; 2015-2020) and one visiting postdoctoral researcher (Juilia Münzker) who has since obtained a permanent position in Germany.
  • Currently mentoring one postdoctoral researcher at the University of Edinburgh. Previously served as a mentor to two postdoctoral researchers who have since obtained a positions at other universities in the UK and USA.

Positions available

I am interested in hearing from enthusiastic candidates for PhD or Postdoctoral research projects. Please get in touch by email if you're interested. For students based outside of the EU, please first contact the CMVM Graduate School office to discuss your eligibility and funding options available.

Collaborative Activity

I am the Interim President and a founding member of the International Bone Marrow Adiposity Society (BMAS, http://www.bma-society.org/). From 2017-2022 I served as BMAS Secretary. BMAS was established through my membership of an EU consortium called BoneAHEAD (Bone Adiposity in HEalth and Disease; http://www.boneahead.com/). The aim of BoneAHEAD is to apply for EU funding to advance our knowledge of BMAT, to train PhD students, to forge new collaborations within and beyond academia, and to translate understanding of BMAT to yield economic and public health benefits.

I am the lead PI on a collaborative MRC proposal that aims to establish methods for population-level imaging of BMAT. This includes Co-Investigators from the Universities of Edinburgh, Dundee and Westminster, as well as collaborators from the University of Lille, spanning diverse fields of imaging, genomics and adipose biology. 

My lab has forged other collaborations around the UK and internationally, based on our expertise in BMAT analysis.

Education/Academic qualification

Doctor of Philosophy (PhD), University of Cambridge

Award Date: 1 Jan 2008

Bachelor of Arts, University of Cambridge

Award Date: 1 Jan 2004

Master of Natural Science at Cambridge University, University of Cambridge

Award Date: 1 Jan 2004

Keywords

  • QP Physiology

Fingerprint

Dive into the research topics where William Cawthorn is active. These topic labels come from the works of this person. Together they form a unique fingerprint.
  • 1 Similar Profiles

Network

Recent external collaboration on country/territory level. Dive into details by clicking on the dots or