Professor Gareth G Lavery PhD

Professor Gareth G Lavery

Institute of Metabolism and Systems Research
Professor of Molecular Metabolism
Wellcome Trust Senior Research Fellow

Contact details

Address
Institute of Metabolism and Systems Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Gareth is a Wellcome Trust Senior Research Fellow and leads the Molecular Metabolism Research Group (MMRG).

 Metabolism plays a critical role in all cellular processes, and metabolic plasticity permits both transient and long-term adaptations to changes in nutritional status and energetic demand.

 The Molecular Metabolism Research Group seeks to understand the mechanisms by which hormones, nutrients and exercise interact and impact metabolic pathways that influence basal and adaptive physiology in health and disease. We focus on metabolically important tissues to decode these signals and processes, defining their molecular and metabolic properties. The MMRG has developed extensive capacity for cell and animal bioenergetic analysis through the Mouse Metabolic Phenotyping facility and Metabolic Tracer Analysis Core.

 Aims of the MMRG

- Define the underpinning mechanisms by which nutrients, exercise, and hormones integrate to control whole- body and tissue-specific metabolism.

- Identify therapeutic strategies that can support and improve the adaptive capacity and flexibility of metabolism to maintain metabolic health.

 Ultimately we hope that our research creates opportunities to develop human benefit, in order to decrease the incidence of age-related metabolic disease.

Qualifications

  • PhD Medicine 2003
  • BSc (Hons) Genetics 1998

Biography

Gareth is a proud Cumbrian who completed his PhD training at the University of Birmingham with Prof. Paul Stewart studying genetic and molecular aspects of glucocorticoid metabolism and it relationship with blood pressure. He then moved to the University of Texas Southwestern Medical Centre, Dallas in 2002 with Prof. Keith Parker and identified a novel mechanism for redox regulated glucocorticoid action, generating a series of animal models that have gone on to define the tissue-specific properties of glucocorticoid regulated metabolism. In 2009 Gareth was awarded a BBSRC David Philips Career Development Fellowship and joined the Centre for Endocrinology Diabetes and Metabolism in Birmingham and furthered his work of understanding how redox regulated glucocorticoid action impacts metabolic energy homeostasis. During this period he consolidated his research and helped define how enzymes involved in steroid metabolism can modulate the ageing process and defined the genetic basis of the syndromes of ‘apparent’ and ‘true’ cortisone reductase deficiency. Also during this period he defined a mechanism by which glucocorticoids exert their activity when in patho-physiological excess, leading to increased potential for patients with this problem to receive novel therapies. In 2014 Gareth became a Wellcome Trust Senior Research Fellow and established The Molecular Metabolism Research Group. Gareth is working to consolidate Metabolism and Systems Research at the forefront of translational research efforts, while fostering a vibrant and enabling working environment at the University of Birmingham.

Teaching

Teaching Programmes

  • BMedSci
  • MBChB
  • Mres

Research

Research in the MMRG

 The Molecular Metabolism Research Group seeks an understanding of systemic and tissue-specific nutrient and energy metabolism, defining signals and processes that mediate homeostasis and using this information to better understand health and disease. We focus on hormonal and nutritional mediators of metabolism in the context of exercise and ageing, with particular focus on skeletal muscle. The aim is to define the properties of these processes and target them in ways that may stave off the increasing incidence of metabolic and age-related decline. Identifying ways to retain healthy, functional skeletal muscle that can maximally benefit from exercise and nutritional interventions will be important to support ageing societies. The MMRG have developed a range of technologies to decipher metabolic process using in vitro and in vivo metabolic tracing (MTAC), mitochondrial analysis and rodent genetic models assessed in the Mouse Metabolic Profiling Facility, extending in to human experimental medicine approaches. The group is comprised of technicians and PhD students working alongside clinical and postdoctoral fellows. The MMRG is currently supported by the Wellcome Trust, MRC, DUK and the EU.  

Projects:

  • Regulation of NAD+ metabolism in skeletal muscle during ageing and exercise
  • Glucocorticoid regulation of Muscle metabolism and function
  • NAD+ therapy in human ageing and disease.

 

Group:

Stuart Morgan (Seconded to Toronto)- Marie Curie Global Fellow

Antje Garten- Marie Curie Individual Fellow

Craig Doig- Senior Post Doctoral fellow

Rachel Fletcher- Post-Doctoral fellow

Yasir Elhassan- Clinical Fellow

Kathi Lang- Clinical fellow

Silke Heising- Senior technician

Lucy Oakey- PhD student

David Cartwright- PhD student

Alpesh Thakker- MTAC Post-doctoral fellow

Other activities

  • IMSR Executive and Research Committee member
  •  Wellcome Trust ISSF management group member
  • Editorial board of ‘Endocrinology’
  •  Active member of Society for Endocrinology (Career support, Programme organising and Science Committee)

Publications

Selected Publications since 2010

 Fine NH, Doig CL, Elhassan YS, Vierra NC, Marchetti P, Bugliani M, Nano R, Piemonti L, Rutter GA, Jacobson DA, Lavery GG, Hodson DJ. Glucocorticoids Reprogram Beta Cell Signaling to Preserve Insulin Secretion. Diabetes. 2018 Feb;67(2):278-290.

 Diguet N, Trammell SA, Tannous C, Deloux R, Piquereau J, Mougenot N, Decaux JF, Lavery GG, Zoll J, Garnier A, Li Z, Brenner C, Mericskay M. Nicotinamide riboside preserves cardiac function in a mouse model of dilated cardiomyopathy. Circulation. 2017 Dec Accepted.

 Doig CL, Fletcher RS, Morgan SA, McCabe EL, Larner DP, Tomlinson JW, Stewart PM, Philp A, Lavery GG. 11β-HSD1 Modulates the Set Point of Brown Adipose Tissue Response to Glucocorticoids in Male Mice. Endocrinology. 2017 Jun 1;158(6):1964-1976.

 Bird AD, Greatorex S, Reser D, Lavery GG, Cole TJ. Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary-gonadal axis of primates. Endocr Connect. 2017 Oct;6(7)

 Fletcher RS, Ratajczak J, Doig CL, Oakey LA, Callingham R, Da Silva Xavier G, Garten A, Elhassan YS, Redpath P, Migaud ME, Philp A, Brenner C, Canto C, Lavery GG. Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells. Mol Metab. 2017 May 29;6(8):819-832.

 Zielinska AE, Fletcher RS, Sherlock M, Doig CL, Lavery GG. Cellular and genetic models of H6PDH and 11β-HSD1 function in skeletal muscle. Cell Biochem Funct. 2017 Jul;35(5):269-277

 Hardy RS, Doig CL, Hussain Z, O'Leary M, Morgan SA, Pearson MJ, Naylor A, Jones SW, Filer A, Stewart PM, Buckley CD, Lavery GG, Cooper MS, Raza K. 11β-Hydroxysteroid dehydrogenase type 1 within muscle protects against the adverse effects of local inflammation. J Pathol. 2016 Dec;240(4):472-483.

 Zeng X, Jedrychowski MP, Chen Y, Serag S, Lavery GG, Gygi SP, Spiegelman BM. Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation. Genes Dev. 2016 Aug 15;30(16):1822-36.

 Larner DP, Morgan SA, Gathercole LL, Doig CL, Guest P, Weston C, Hazeldine J, Tomlinson JW, Stewart PM and Lavery GG. Male 11β-HSD1 knockout mice fed trans-fats and fructose are not protected from metabolic syndrome or non-alcoholic fatty liver disease. Endocrinology. 2016 Jul 6:en20161357.

 Morgan SA, Hassan-Smith Z, Doig CL, Sherlock M, Stewart PM, Lavery GG. Glucocorticoids and 11β-HSD1 are major regulators of intramyocellular protein metabolism. J Endocrinol. 2016 Jun;229(3):277-86.

 Hassan-Smith ZK, Morgan SA, Sherlock M, Hughes B, Taylor AE, Lavery GG, Tomlinson JW, Stewart PM. Gender-Specific Differences in Skeletal Muscle 11β-HSD1 Expression Across Healthy Aging. J Clin Endocrinol Metab. 2015, Jul;100(7):2673-81.

 Morgan SA, McCabe EL, Gathercole , Hassan-Smith ZK, Larner DP, Bujalska IJ, Stewart PM, Tomlinson  JW*, Lavery GG*. 11β-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess. PNAS. 2014 Jun 17;111(24):E2482-91. *Joint senior Authors.

 Penno CA, Morgan SA, Rose AJ, Herzig S, Lavery GG, Odermatt A. 11β-hydroxysteroid dehydrogenase 1 is involved in bile acid homeostasis by modulating fatty acid transport protein 5 in the liver of mice. Mol Metab. 2014, May 2;3(5):554-64.

 Doig CL, Bashir J, Zielinska AE, Cooper MS, Stewart PM, Lavery GG. TNFα mediated HSD11B1 binding of NF-κB p65 is associated with suppression of 11β-HSD1 in muscle. J Endocrinol. 2014, Feb 10;220(3):389-96.

 Dowman JK, Hopkins LJ, Reynolds GM, Armstrong MJ, Lavery GG, Oprescu A, Hübscher SG, Newsome PN, Tomlinson JW. Loss of 5α-reductase type 1 Accelerates the Development of Hepatic Steatosis but Protects Against Hepatocellular Carcinoma in Male Mice. Endocrinology. 2013, Dec;154(12):4536-47.

 Penno CA, Morgan SA, Lavery GG and Odermatt A. Impaired oxoreduction by 11β-hydroxysteroid dehydrogenase 1 results in the accumulation of 7-oxolithocholic acid. J Lipid Res. 2013, Oct;54(10):2874-83.

 Morgan SA, Gathercole LL, Simonet C, Hassan-Smith Z, Bujalska I, Guest P, Abrahams L, Smith D Stewart PM, Lavery GG and Tomlinson JW .Regulation of Lipid Metabolism by Glucocorticoids and 11β-HSD1 in Skeletal Muscle. Endocrinology. 2013, Jul;154(7):2374-84.

 Tiganescu A, Tahrani A, Morgan SA, Otranto M, Desmoulière A, Abrahams L, Hassan-Smith Z, Walker EA, Rabbitt EH, Cooper MS, Amrein K, Stewart PM* and Lavery GG*. 11ß-hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects. J Clin Invest. 2013 Jul 1;123(7):3051-60. *Joint senior Authors.

 Lavery GG, Rabbitt EH, Zielinska AE, Hughes B, Semjonous N, Guest P, Saqib K, M Sherlock,  Gathercole LL, Morgan S, Walker EA, Stewart PM. Liver-specific disruption of 11β-hydroxysteroid dehydrogenase type 1 implies extra-hepatic glucocorticoid metabolism contributes significantly to the cardio-protective phenotype observed in global KO mice. Endocrinology. 2012, Jul;153(7):3236-48.

 Lawson AJ, Walker EA, Lavery GG, Bujalska IJ, Hughes BA, Arlt W, Stewart PM, Ride JP. Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1. PNAS. 2011, Mar 8;108(10):4111-6.

 Semjonous NM, Sherlock M, Jeyasuria P, Parker KL, Walker EA, Stewart PM, Lavery GG. Hexose-6-phosphate dehydrogenase contributes to skeletal muscle homeostasis independent of 11β-hydroxysteroid dehydrogenase type 1. Endocrinology.  2011 Jan;152(1):93-102.

 

 

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