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Staff Profile

Professor Brian Walker

Strategic Advisor, Executive Office

Background

Brian Walker joined Newcastle University in 2017 as Pro Vice Chancellor for Research Strategy & Resources. He led the design and implementation of the University’s Research Strategy, including the re-alignment of multi-disciplinary research into a portfolio of NUCoREs, the recruitment of additional academics through the NUAcT and NUFutures schemes, the expansion of the University’s innovation centres, and the development of our research culture roadmap and PGR delivery plan.


As Deputy Vice Chancellor from 2022 to 2024, Brian had a broader remit to support the implementation of the University’s Vision & Strategy, responsible for academic leadership of strategy, planning, budgeting and resources across all of our core missions in education and research. He also led on strategic projects that span the portfolios of other members of Executive Board.


As Strategic Advisor in the Executive Office since September 2024, Brian continues to contribute to strategic projects in Newcastle University with a particular focus on innovation and translation of research.


He was previously at the University of Edinburgh, where he was Head of the BHF Centre for Cardiovascular Science, Dean of Research for the College of Medicine & Veterinary Medicine, and an architect of the sector-leading Edinburgh Clinical Academic Track scheme. A clinical Endocrinologist, his research on steroid hormones in cardiovascular disease, supported principally by BHF and Wellcome Trust has led to >250 original research papers (h-index >100) and a new drug which has reached clinical trials in patients with dementia. He has also edited three editions of the iconic textbook Davidson’s Principles & Practice of Medicine and supervised >40 PhD students.


Brian is a Fellow of the Royal Society of Edinburgh and of the Academy of Medical Sciences, a former Chair of the Wellcome Trust Clinical Interview Committee, BHF Project Grants Committee, and MRC Population & Systems Medicine Board and was a member of the Clinical Medicine sub-panel for REF2021. Amongst a variety of national and international roles he is currently a BHF Trustee and Board Chair for the National Innovation Centre for Ageing.


See Brian Walker's LinkedIn profile here - https://www.linkedin.com/in/brian-walker-43a80289/

 

Research

Excessive activity of glucocorticoids (eg cortisol) causes Cushing's syndrome, with hypertension, obesity, glucose intolerance and accelerated cardiovascular disease. Brian Walker’s research using a wide range of translational tools (rodent models, detailed integrative physiology in humans, and epidemiology) has systematically documented that cortisol contributes to the association between multiple risk factors for cardiovascular disease (‘metabolic syndrome’) in the population, how glucocorticoids influence vascular lesions and their complications,and that manipulation of cortisol action offers novel therapeutic approaches in type 2 diabetes and cardiovascular disease.


With BHF support, in epidemiological studies Walker and colleagues showed that plasma cortisol levels are elevated in subjects with metabolic syndrome, in particular those born with low birth weight, and that hypercortisolaemia is an independent prospective cardiovascular risk factor. In parallel pharmaco-epidemiological studies involving >250,000 participants, Walker and colleagues also documented that exposure to exogenous glucocorticoids increases the risk of cardiovascular disease. He then established the CORtisol NETwork (CORNET) consortium, undertaking genome wide association metaanalysis in a sample of >20,000; this provided a genetic instrument with which to establish the causal relationship of hypercortisolaemia with cardiovascular disease; and identified novel biological determinants of tissue-specific cortisol action which his group have since dissected further under a Wellcome Trust Investigator award.


One of the determinants of cortisol action identified by Walker and colleagues has proven to be a tractable therapeutic target. In the mid-1990s the intracellular enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1)was thought to inactivate cortisol, and perhaps ‘protect’ liver, adipose tissue, and blood vessels from excessive exposure to cortisol. The Edinburgh group showed, initially in liver, that 11b-HSD1 in fact regenerates active cortisol from cortisone. In a seminal 1995 paper, Walker showed that inhibition of 11b-HSD1 reduces cortisol generation and enhances insulin sensitivity in human liver. His group developed novel stable isotope tracers and other tools to investigate this system comprehensively in vivo in humans, and found that 11b-HSD1 expression is increased selectively within adipose tissue in obesity. Walker also discovered 11b-HSD1 in vascular smooth muscle in the early 1990s and later showed that glucocorticoids generated within the vessel wall inhibit angiogenesis. By deleting 11b-HSD1 new vessel growth is enhanced, eg following myocardial infarction in mice. This offers the exciting prospect of 11b-HSD1 inhibitors enhancing revascularisation following ischaemia. These findings spawned intensive efforts in the pharmaceutical industry to make 11b-HSD1 inhibitors (>200 new chemical entity patents filed). Supported by a Wellcome Trust Seeding Drug Discovery award, Walker and colleagues discovered novel 11b-HSD1 inhibitors, developed these to clinical trials and in commercial partnership are exemplifying their efficacy in metabolic, cardiovascular and also cognitive disease.


Another mechanism dictating tissue-specific responsiveness to glucocorticoids is the local expression of ABC transporters. Walker's group showed that ABCC1 is expressed in the absence of ABCB1 in adipose tissue, resulting in excretion of corticosterone but not cortisol from adipose tissue. They have pursued the therapeutic implication of this result, that corticosterone might be as effective as cortisol (hydrocortisone) in steroid replacement therapy without inducing side effects mediated in adipose tissue, such as obesity.


Walker's group have applied their unique tools and expertise to explain alterations in steroid metabolism and action in clinical settings from sepsis to heart failure, and to dissect the cardiometabolic consequences of manipulating additional components of steroid signalling, including 5a-reductases (in prostate disease) and aromatase (in breast disease). Already, this work has identified steroids with selective anti-inflammatory rather than dysmetabolic properties, and novel tissue-specific determinants of intracellular steroid concentrations, that have important therapeutic potential.

 

Teaching

Brian Walker is best known in undergraduate medical education for his contribution to Davidson's Principles & Practice of Medicine, an iconic textbook that is read by >250 thousand students per edition, to which Brian contributed as an Endocrinology chapter author for 5 editions and editor for 3 editions. His role as editor led to discussions of curriculum and pedagogy with many international educators, including during tours in India and Russia.


In postgraduate education, Brian has led the development of an online MSc in Translational Medicine and was one of the team at Edinburgh who delivered a 4y PhD programme in Cardiovascular Science with serial awards from Wellcome and BHF. He has supervised more than 40 PhD students, of whom around half are clinicians and around two thirds were subsequently employed in research-active roles. In addition, Brian was an architect of the acclaimed Edinburgh Clinical Academic Track (ECAT) scheme, funded serially by Wellcome, which supports clinicians from pre-PhD through to Lectureship and Career Development Fellowship level. ECAT was the model for similar schemes in Wales (WCAT) and Ireland (ICAT).

Publications