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 Tower, Rm 225
University of Birmingham
Edgbaston
Birmingham
B15 2TT UK

Prof. 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 Prof. 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

Prof. 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 neighboring UCLA at the end of 2007 as Professor-in-Residence. In September 2014 Prof. Hewison returned to The University of Birmingham to join the newly-established IMSR as Deputy Director. Prof. 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

  • B Med Sc 3rd Year (Molecular Medicine)
  • MB ChB 1st Year (Endocrinology)

Postgraduate supervision

  • Four PhD students and one Biological Sciences Integrated Masters student 

Research

 

Research

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

Basic Biology of Vitamin D
Prof. Hewison has published more than 130 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
Prof. 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. Prof. 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. Prof. 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). Prof. 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

  • Nature Scientific Reports – Editorial Board
  • Endocrinology – Editorial Board
  • Journal of Bone and Mineral Research – Editorial Board
  • Cell Biochemistry and Function – Reviews Editor
  • Cell Biochemistry and Function – Editorial Board
  • Data and Safety Monitoring Committee, Medical University of South Carolina
  • NIH Study Group (Special Emphasis Panel) Ad-hoc reviewer
  • NIH Study Group (Skeletal Biology Development and Disease Section) Ad-hoc reviewer
  • Category Chair ASBMR Annual Meeting
  • Membership Development Committee – ASBMR
  • Program Organizing Committee - 14th International Congress of Hormonal Steroids and Hormones & Cancer
  • Workshop on Vitamin D Executive Committee
  • European Congress of Endocrinology Organizing Committee

Publications

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.

 Jeffery LE, Raza K, Hewison M (2016) Vitamin D in rheumatoid arthritis-towards clinical application. Nat Rev Rheumatol. 12(4):201-10.

 Nielson CM, Jones KS, Chun RF, Jacobs JM, Wang Y, Hewison M, Adams JS, Swanson CM, Lee CG, Vanderschueren D, Pauwels S, Prentice A, Smith RD, Shi T, Gao Y, Schepmoes AA, Zmuda JM, Lapidus J, Cauley JA, Bouillon R, Schoenmakers I, Orwoll ES (2016) Osteoporotic Fractures in Men (MrOS) Research Group. Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial-Genotypic Associations. J Clin Endocrinol Metab. 101(5):2226-34.

 Nielson CM, Jones KS, Bouillon R; Osteoporotic Fractures in Men (MrOS) Research Group, Chun RF, Jacobs J, Wang Y, Hewison M, Adams JS, Swanson CM, Lee CG, Vanderschueren D, Pauwels S, Prentice A, Smith RD, Shi T, Gao Y, Zmuda JM, Lapidus J, Cauley JA, Schoenmakers I, Orwoll ES (2016). Role of Assay Type in Determining Free 25-Hydroxyvitamin D Levels in Diverse Populations. N Engl J Med. 28;374(17):1695-6.

 Jenkinson C, Taylor AE, Hassan-Smith ZK, Adams JS, Stewart PM, Hewison M, Keevil BG (2016) High throughput LC-MS/MS method for the simultaneous analysis of multiple vitamin D analytes in serum. J Chromatogr B Analyt Technol Biomed Life Sci. 1;1014:56-63.

 Sarkar S, Hewison M, Studzinski GP, Li YC, Kalia V (2016) Role of vitamin D in cytotoxic T lymphocyte immunity to pathogens and cancer. Crit Rev Clin Lab Sci. 53(2):132-45.

 Chun RF, Liu NQ, Lee T, Schall JI, Denburg MR, Rutstein RM, Adams JS, Zemel BS, Stallings VA, Hewison M (2015) Vitamin D supplementation and antibacterial immune responses in adolescents and young adults with HIV/AIDS. J Steroid Biochem Mol Biol. 148:290-7.

 Zhou R, Chun RF, Lisse TS, Garcia AJ, Xu J, Adams JS, Hewison M (2015) Vitamin D and alternative splicing of RNA. J Steroid Biochem Mol Biol. 148:310-7.

 Tamblyn JA, Hewison M, Wagner CL, Bulmer JN, Kilby MD (2015) Immunological role of vitamin D at the maternal-fetal interface. J Endocrinol. 224(3):R107-21.

 Chan SY, Susarla R, Canovas D, Vasilopoulou E, Ohizua O, McCabe CJ, Hewison M, Kilby MD (2015) Vitamin D promotes human extravillous trophoblast invasion in vitro. Placenta 36(4):403-9.

 Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M (2014) Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol. 144 Pt A:132-7.

 Chun RF, Liu PT, Modlin RL, Adams JS, Hewison M (2014) Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol. 21;5:151.

 Chun RF, Blatter E, Elliott S, Fitz-Gibbon S, Rieger S, Sagasti A, Adams JS, Hewison M (2014). Cloning of a functional 25-hydroxyvitamin D-1α-hydroxylase in zebrafish (Danio rerio). Cell Biochem Funct. 32(8):675-82.

 Montoya D, Inkeles MS, Liu PT, Realegeno S, Teles RM, Vaidya P, Munoz MA, Schenk M, Swindell WR, Chun R, Zavala K, Hewison M, Adams JS, Horvath S, Pellegrini M, Bloom BR, Modlin RL (2014) IL-32 is a molecular marker of a host defense network in human tuberculosis. Sci Transl Med. 20;6(250):250ra114.

 Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, Nayak A, Wesseling-Perry K, Westerman M, Hollis BW, Salusky IB, Hewison M (2014) Suppression of iron-regulatory hepcidin by vitamin D. J Am Soc Nephrol. 25(3):564-72.

 Lisse TS, Vadivel K, Bajaj SP, Chun RF, Hewison M, Adams JS (2014) The heterodimeric structure of heterogeneous nuclear ribonucleoprotein C1/C2 dictates 1,25-dihydroxyvitamin D-directed transcriptional events in osteoblasts. Bone Res. 2. pii: 14011.

 Bacchetta J, Chun RF, Gales B, Zaritsky JJ, Leroy S, Wesseling-Perry K, Boregaard N, Rastogi A, Salusky IB, Hewison M (2014) Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation. PLoS One 30;9(12):e116530.

 Bacchetta J, Sea JL, Chun RF, Lisse TS, Wesseling-Perry K, Gales B, Adams JS, Salusky IB and Hewison M (2013) Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytesJ Bone Miner Res 28(1):46-55

 Lisse TS, Chun FR, Rieger S, Adams JS and Hewison M (2013) Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts. J Bone Miner Res 28(6):1478-88

 Teles RM, Graeber TG, Krutzik SR, Montoya D, Schenk M, Lee DJ, Komisopoulou E, Kelly-Scumpia K, Chun R, Iyer SS, Sarno EN, Rea TH, Hewison M, Adams JS, Popper SJ, Relman DA, Stenger S, Bloom BR, Cheng G and Modlin RL (2013) Type I interferon suppresses Type II interferon-triggered human anti-mycobacterial responsesScience 339(6126):1448-53

 Liu NQ, Ouyang Y, Bulut Y, Lagishetty V, Chan SY, Hollis BW, Wagner C, Equils O and Hewison M (2013) Dietary vitamin D restriction in pregnant female mice is associated with maternal hypertension and altered placental and fetal development. Endocrinology 154(7):2270-80