Professor Martin Hewison

Image of Martin Hewison

Institute of Metabolism and Systems Research
Professor of Molecular Endocrinology
Deputy Director of the Institute of Metabolism and Systems Research

Contact details

Address
Institute of Metabolism and Systems Research
IBR Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT UK

Professor Hewison’s work focuses on different facets of vitamin D physiology, including classical skeletal effects and non-classical extra-skeletal effects. He has a particular interest in the interaction between vitamin D and the immune system, where antigen-presenting cells such as dendritic cells and macrophages synthesize active vitamin D (calcitriol) and also express the nuclear receptor for calcitriol (VDR). Vitamin D can therefore act as an endogenous regulator of both innate and adaptive immunity by enhancing antibacterial activity, and modulating antigen presentation and T lymphocyte function. Crucially these responses are highly dependent on the bioavailability of vitamin D, and Professor Hewison has hypothesized that immune function is influenced by vitamin D status in humans. His group is using a variety of models to test this hypothesis including basic molecular and cell analyses, and vitamin D supplementation trials in human cohorts. A key objective of his work is to increase awareness of vitamin D-deficiency in the UK population.

Qualifications

  • PhD (1987)
  • BSc (Hons) (1982)

Biography

Professor Hewison is currently Professor of Molecular Endocrinology in the Institute of Metabolism and Systems Research (IMSR) at The University of Birmingham. He gained his PhD in Biochemistry from Guy’s Hospital Medical School London and then spent nine years at University College London. He then moved to the University of Birmingham where he established the UK’s major vitamin D research group, leading to an appointment as Professor of Molecular Endocrinology in 2004. In 2005 he joined Cedars-Sinai Medical Center Los Angeles but was then recruited to neighbouring UCLA at the end of 2007 as Professor-in-Residence.In September 2014 Professor Hewison returned to The University of Birmingham to join the newly-established IMSR as Deputy Director.

Professor Hewison has published over 200 peer-reviewed manuscripts focused on various facets of steroid hormone endocrinology, and he is Chair of the Vitamin D Workshop (http://www.vitamindworkshop.org/). He currently has a team of two postdocs, four PhD students and a clinical fellow who are funded by US and UK research grants.

Teaching

  • BMedSc 3rd Year (Molecular Medicine)
  • MBChB 1st Year (Endocrinology)

Postgraduate supervision

  • Four PhD students and one Biological Sciences Integrated Masters student 

Research

Research

Professor Hewison’s main research interest is vitamin D and its importance to human health.

Basic Biology of Vitamin D
Professor Hewison has published more than 200 research papers on classical (skeletal) and non-classical (extra-skeletal) actions of vitamin D. Prominent amongst these are newly published studies describing the impact of vitamin D binding protein (DBP) on vitamin D bioavailability and tissue-specific responses to vitamin D.

Vitamin D and the immune system
Professor Hewison’s group is at the forefront of research linking vitamin D and the immune system. This has implications for a wide range of clinical disorders including inflammatory and autoimmune disease, but more recently has been expanded to include studies of infection. Current studies include analysis of vitamin D insensitivity in T lymphocytes from the inflamed joints of patients with rheumatoid arthritis, and characterisation of the role of non-coding microRNAs in mediating the anti-inflammatory effects of vitamin D.  

Vitamin D and inflammatory bowel disease
Inflammatory bowel diseases (IBD) such as Crohn’s disease have been shown to be associated with vitamin D-insufficiency. Professor Hewison’s group have shown that abnormal vitamin D metabolism in IBD is key factor in the osteoporotic bone disease commonly associated with these patients. Conversely, studies using mouse models have shown that vitamin D-deficiency predisposes to IBD. Recent projects have explored the relationship between the gut microbiota, vitamin D and IBD. Current experiments are focused on the role of DBP as a determinant of vitamin D bioavailability and how this impacts IBD.

Vitamin D and pregnancy
Pregnant women are at high risk of vitamin D-insufficiency. Professor Hewison has shown that vitamin D plays a key role in several aspects of placental physiology, notably adequate immune activity, control of vascular/trophoblastic architecture and fetal programming of the skeleton. Studies are currently assessing the impact of vitamin D-deficiency on pre-term birth, as well as infection and inflammation during pregnancy, and how this may affect fetal development.

Vitamin D metabolism
Studies of the health impact of vitamin D-deficiency and vitamin D-supplementation are a prominent feature of modern vitamin D research. However, almost all of this work is dependent on the measurement of a single vitamin D metabolite, 25-hydroxyvitamin D (25OHD). Professor Hewison’s group has pioneered a range of studies to explore other markers of vitamin D ‘status’. This includes development of novel high throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology to measure multiple metabolites of vitamin D – the vitamin D metabolome. The aim of this work is to provide a more accurate measurement of optimal vitamin D for current and future clinical trials.

Other activities

  • Endocrinology – Editorial Board
  • Journal of Bone and Mineral Research – Editorial Board
  • Cell Biochemistry and Function – Reviews Editor
  • Cell Biochemistry and Function – Editorial Board
  • NIH Study Group (Special Emphasis Panel) Ad-hoc reviewer
  • NIH Study Group (Skeletal Biology Development and Disease Section) Ad-hoc reviewer
  • Workshop on Vitamin D Executive Committee
  • Secretary Vitamin D Workshop
  • REF Output Lead IMSR

Publications

JenkinsonC, BradburyJ, TaylorA, HeS, DunnWB, ViantMR, Hewison M (2017) Automated development of an LC-MS/MS method for measuring multiple vitamin D metabolites using MUSCLE software. Analytical and Bioanalytical Chemistry (Epub ahead of print)

LiuNQ, LarnerDP, YaoQ, ChunRF, Yuxin O, ZhouR, TamblynJA, WagnerCL, Hewison M (2017) Vitamin D-deficiency and sex-specific dysregulation of placental inflammation. Journal of Steroid Biochemistry and Molecular Biology (Epub ahead of print).

Hassan-Smith ZK, Jenkinson C, Smith DJ, Hernandez I, Morgan SA, Crabtree NJ, Gittoes NJ, Keevil BG, Stewart PM, Hewison M (2017) 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression. PLoS One. 12(2):e0170665.

Shieh A, Ma C, Chun RF, Witzel S, Rafison B, Contreras HT, Wittwer-Schegg J, Swinkels L, Huijs T, Hewison M, et al. (2017) Effects of cholecalciferol vs. calcifediol on total and free 25-hydroxyvitamin D and parathyroid hormone. J Clin Endocrinol Metab. 102(4):1133-1140.

Tamblyn JA, Susarla R, Jenkinson C, Jeffery LE, Ohizua O, Chun RF, Chan SY, Kilby MD, Hewison M (2017) Dysregulation of maternal and placental vitamin D metabolism in preeclampsia. Placenta 50:70-77.

Zhou R, Park JW, Chun RF, Lisse TS, Garcia AJ, Zavala K, Sea JL, Lu ZX, Xu J, Adams JS, Xing Y, Hewison M (2017) Concerted effects of heterogeneous nuclear ribonucleoprotein C1/C2 to control vitamin D-directed gene transcription and RNA splicing in human bone cells. Nucleic Acids Res. 25;45(2):606-618.

Zhao H, Rieger S, Abe K, Hewison M, Lisse TS (2016) DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization. Int J Mol Sci. 26;17(12). pii: E1984. 

Chun RF, Hernandez I, Pereira R, Swinkles L, Huijs T, Zhou R, Liu NQ, Shieh A, Guemes M, Mallya SM, Adams JS, Hewison M (2016) Differential Responses to Vitamin D2 and Vitamin D3 Are Associated With Variations in Free 25-Hydroxyvitamin D. Endocrinology. 157(9):3420-30.

Srikanth P, Chun RF, Hewison M, Adams JS, Bouillon R, Vanderschueren D, Lane N, Cawthon PM, Dam T, Barrett-Connor E, Daniels LB, Shikany JM, Stefanick ML, Cauley JA, Orwoll ES, Nielson CM (2016) Osteoporotic Fractures in Men (MrOS) Study Research Group. Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men. Osteoporos Int. 27(7):2291-300.

Shieh A, Chun RF, Ma C, Witzel S, Meyer B, Rafison B, Swinkels L, Huijs T, Pepkowitz S, Holmquist B, Hewison M, Adams JS (2016) Effects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance. J Clin Endocrinol Metab. 101(8):3070-8.

For a full list of Professor Hewison's publications