Professor Tim Skerry

BVet, Med, FRCVS, Cert, SAO, PhD

Department of Oncology and Metabolism

Professor of Orthopaedic Biology

Tim Skerry
t.skerry@sheffield.ac.uk
+44 114 215 9026

Full contact details

Professor Tim Skerry
Department of Oncology and Metabolism
FU19, F Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
Profile
  • 2005 – Present: Professor of Orthopaedic Biology University of Sheffield;
  • 2003 - 2005: Vice Principal Research RVC;
  • 2001 – 2003: Head of Veterinary Basic Sciences; RVC
  • 1995 – 2001: Professor of Cellular and Molecular Biology University of York;
  • 1987 – 1995: Lecturer in Surgery, then Anatomy University of Bristol;
  • 1984 – 1987: PhD Functional adaptation in bone;
  • 1980 – 1986: Mixed practice, small animal practice, specialist orthopaedic practice;
  • 1980: Veterinary Graduate RVC London.
Research interests

After spending a considerable number of years researching the mechanisms behind the way that the skeleton responds to exercise, my interests have shifted substantially in recent years. Interest in the calcitonin family of hormones and receptors led to a project on understanding the roles of so-called receptor activity modifying proteins in bone (RAMPs). RAMPs are interesting accessory proteins that control the ligand selectivity of a small number of receptors. For example a calcitonin receptor (CTR) alone binds and responds primarily to the hormone calcitonin.

However, co-expression of the CTR with any of the 3 human RAMPs leads to the heteromeric receptor complex becoming a one of 3 distinct receptors for the hormone amylin. Similarly, the calcitonin like-receptor (CLR) which is an orphan becomes a CGRP receptor with RAMP1 and either an adrenomedullin 1 or 2 receptor with RAMPs 2 and 3 respectively.

We have studied the roles of the RAMPs in bone by assessing the skeletal phenotypes of RAMP KO mice and shown that there appears to be no overt phenotype in RAMP 1 KO mice, there is a haploid insufficiency phenotype in RAMP2 heterozygotes with delayed development and intracortical porosity. In RAMP3 mice though there is accelerated development and an increased response of the bones to mechanical loading.

Our work on RAMPs has taken us into other directions too. Exploration of the role of RAMPs with other receptors where there is no change in ligand selectivity but a role in trafficking the receptors to the cell surface resulted in a paper on the need for RAMP1 for trafficking of the calcium sensing-receptor in a cell line not engineered to overexpress the proteins.

However, the main focus of the lab is now on development of small molecule antagonists of the AM2 adrenomedullin receptor. AM is involved centrally in regulation of blood pressure but it is also a potent player in tumorigenesis, where it has innate tumour cell to tumour cell actions, and roles in which AM released by the tumour upregulates AM2R expression in host cells around the tumour.

As a broad spectrum AM antagonist would interfere with AM’s potent vasodilator effect, we cannot tractably use such an approach to block AM’s role in tumours. However, we have shown that the physiological roles of AM are maintained predominantly by the AM1 receptor (CLR+RAMP2) while the AM2 receptor (CLR+RAMP3) can be blocked without significant deleterious effects.

A graph on adrenomedullin functions

Our major research programme is now a Wellcome Trust funded drug discovery programme in which Dr Gareth Richards and I work with collaborators in Industry (Dr Karl Gibson, a modeller at Sandexis and Dr Matt Tozer formerly a medicinal chemist at Peakdale Molecular) and Professor Joe Harrity in the Department of Chemistry here in Sheffield to develop and optimise small molecule AM2R antagonists for cancer treatment. 

Publications

Books

Journal articles

Chapters

Conference proceedings papers

  • Balasubramanian M, Hurst J, DeVile C, Bishop N, Arundel P, Offiah A, Pollitt R, Hughes D, Longman D, Caceres J & Skerry T (2017) NBAS variants causing a novel form of inherited bone fragility. Bone Abstracts, Vol. 6(2017). Bristol, UK, 10 June 2017 - 13 June 2017. View this article in WRRO RIS download Bibtex download
  • Skerry TM, Samvelyan H & Mathers J (2017) TIMING OF EATING POTENTIATES THE EFFECT OF MECHANICAL LOADING ON BONE. OSTEOPOROSIS INTERNATIONAL, Vol. 28 (pp S466-S467) RIS download Bibtex download
  • Samvelyan H, Mathers J & Skerry T (2017) Feeding after overnight fast enhances bone’s response to mechanical loading in mice. Journal of Bone and Mineral Research, Vol. 31(S1) (pp S403-S403). USA, 16 September 2016 - 19 September 2016. View this article in WRRO RIS download Bibtex download
  • Notomi T, Kuno N, Amano H & Skerry TM (2008) The Pacemaker Channel, HCN, Controls Functions of Osteoclasts.. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 23 (pp S267-S267) RIS download Bibtex download
  • Martinez-Bautista S, Wang N, Richards Q & Skerry TM (2008) Mice Lacking NMDA Receptor Expression in Osteoblasts Have Pronounced Vertebral Bone Abnormalities. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 23 (pp S87-S87) RIS download Bibtex download
  • Roberts DJ & Skerry T (2007) The cognition enhancer aniracetam increases the number of osteoblastic colonies in MSC cultures when combined with fluid shear stress. CALCIFIED TISSUE INT, Vol. 80 (pp S85-S85) RIS download Bibtex download
  • Skerry TM & Dastjerdi AM (2006) Microarray analysis of bones from Myod Myf5 null mice to identify genes regulated in bone by disuse.. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 21 (pp S373-S373) RIS download Bibtex download
  • Lanham SA, Roberts C, Burford J, Skerry TM, Taylor P, Green LR, Hanson MA, Cooper C & Oreffo ROC (2005) Intrauterine programming of skeletal development. PEDIATRIC RESEARCH, Vol. 58(5) (pp 1045-1045) RIS download Bibtex download
  • Notomi T, Ludwig A, Reilly G, Hofmann FB & Skerry TM (2005) HCN2 ion channels regulate bone development, mass and strength.. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 20(9) (pp S62-S62) RIS download Bibtex download
  • Bowe EA & Skerry TM (2005) Repetitions of mechanical loading potentiate bone cellular responses by a mechanism involving NMDA type glutamate receptors. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 20(9) (pp S25-S25) RIS download Bibtex download
  • MOLLOY T, WANG Y, HORNER A, SKERRY T & MURRELL G (2005) Microarray analysis of healing rat Achilles tendon: Evidence for glutamate signalling mechanisms and embryonic gene expression in healing tendon tissue. Journal of Orthopaedic Research RIS download Bibtex download
  • Lanham SA, Roberts C, Burford J, Skerry TM, Taylor P, Green LR, Hanson MA, Cooper C & Oreffo ROC (2005) Intrauterine programming of skeletal development. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 20(7) (pp 1299-1299) RIS download Bibtex download
  • Burford JH, Perrien DS, Horner A, Bowe EA, Notomi T, Suva LJ & Skerry TM (2004) Glutamate signalling regulates skeletogenesis and bone growth.. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 19 (pp S212-S213) RIS download Bibtex download
  • Chenu CC, De Souza RL, Pitsillides AA, Lanyon LE & Skerry TM (2004) Sciatic denervation increases load-induced cortical new bone formation independently of the sympathetic nervous system.. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 19 (pp S38-S38) RIS download Bibtex download
  • Odoi S, Burford JH, Souza RL, Parry LK & Skerry TM (2004) Increased osteoblastic differentiation in cultured marrow cells after blood loss or surgery. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 19(6) (pp 1048-1048) RIS download Bibtex download
  • Skerry TM (2004) Neurotransmitters in bone: New players in bone physiology. OSTEOPOROSIS INTERNATIONAL, Vol. 15 (pp S2-S2) RIS download Bibtex download
  • Horner A, Bowe E, Burford J, Bailey R & Skerry T (2004) Glutamate signalling via AMPA receptors regulates cell survival during embryonic mesenchymal cell differentiation. Bone, Vol. 34 (pp S5-S6) RIS download Bibtex download
  • Bowe EA, Notomi T, Horner A & Skerry T (2004) Glutamate signalling and LTP-like mechanisms account for loading memory in osteoblasts.. Journal of Bone and Mineral Research, Vol. 19 (pp S10-S10) RIS download Bibtex download
  • Parry LK, Burton VJ, Perry MJ & Skerry TM (2004) Anaesthetics Effect the Osteogenic Response to Mechanical Loading. Calcified tissue international, Vol. 74 (pp S54-S55) RIS download Bibtex download
  • Whitehouse C, Horner A, Stewart A, Cobourne M, McGowan N, Burford J, Grigoriadis A, Sharpe P, Skerry T & Solomon E (2004) Nbr1 mutant mice exhibit age dependent increases in bone volume and mass. Bone, Vol. 34 (pp S15-S16) RIS download Bibtex download
  • Skerry TM & Suva LJ (2003) Investigation of the regulation of bone mass by mechanical loading: from quantitative cytochemistry to gene array. CELL BIOCHEMISTRY AND FUNCTION, Vol. 21(3) (pp 223-229) RIS download Bibtex download
  • Parry LK, Burton VJ, Gheduzzi S, Beresford J, Perry MJ, Skerry TM & Humphrey VF (2003) Ultrasound mimics the effect of mechanical loading in vivo on rat ulnae and bone marrow cells.. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 18 (pp S217-S217) RIS download Bibtex download
  • Dallas-Skerry DJ, Murphy G & Skerry TM (2003) Regulation of bone resorption and formation through the cell-surface processing of RANKL and Jagged-1. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 18(7) (pp 1361-1361) RIS download Bibtex download
  • Skerry TM & Peet NM (2002) MyoD/Myf5 null mice cannot move actively in utero and have thin weak long bones and no rib development.. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 17 (pp S170-S170) RIS download Bibtex download
  • Taylor AF, Odoi SO, Nokes CJ & Skerry TM (2002) AMPA type glutamate receptors regulate osteoblast/adipocyte plasticity and bone formation. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 17(7) (pp 1327-1327) RIS download Bibtex download
  • Odoi SO, Taylor AF, Lee K, Lanyon LE & Skerry TM (2002) Interactions between estrogen and glutamate signalling pathways. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 17(7) (pp 1331-1331) RIS download Bibtex download
  • Skerry TM & Peet NM (2002) Mechanical influences on skeletal development in utero. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 17(7) (pp 1324-1324) RIS download Bibtex download
  • Lacey JE, Skerry TM & Grabowski PS (1997) Differences in nitric oxide modulated matrix metalloproteinase activity in chondrocytes and synoviocytes. J BONE MINER RES, Vol. 12(9) (pp P18-P18) RIS download Bibtex download
  • Peet N, Grabowski P, Birch M, Patton A, Haman G & Skerry T (1997) Inhibition of bone resorption by the glutamate receptor antagonist MK-801 through suppression of osteoclast differentiation.. J BONE MINER RES, Vol. 12 (pp T379-T379) RIS download Bibtex download
  • Skerry TM, Genever PG, Patton AJ, Grabowski PS, Stueckle S & Suva LJ (1996) Glutamate receptors in bone cells suggest a paracrine role for excitatory amino acids in regulation of the skeleton?. J BONE MINER RES, Vol. 11 (pp P202-P202) RIS download Bibtex download
Research group

Members of research group

  • Dr Gareth Richards (Co-Investigator)
  • Dr Ning Wang

PhD students

  • Jasmine Samvelyan
  • Jess Warrington
  • Paris Avgoustou
  • Ameera Jailani
  • Hind Naffadi
  • Jo Holmes
  • Kamilla Bigos
  • Ewan Lilley
Grants

Principal funding sources

Professional activities

External UK Research-Related Activities

  • Member of MRC industrial studentships committee