Professor Tim Skerry BVet Med FRCVS Cert SAO PhD
Academic Unit of Bone Biology
School of Medicine & Biomedical Sciences
D Floor, Medical School
Beech Hill Road
Telephone: +44 (0)114 271 2414
Fax: +44 (0)114 271 2475
Secretary: Gillian Griffiths
Telephone: 0114 271 3518
Professor of Orthopaedic Biology & Head of Department of Human Metabolism
- 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.
My research falls into 2 areas. First, I have a long standing interest in bone biology, particularly the way that the skeleton responds to exercise and specifically the cellular and molecular mechanisms behind that response. My second area of interest is in the development of a new therapeutic target for cancer and other diseases targeting a receptor mechanism with novel chemical and biological agents.
The function of our skeleton is to support our bodies, protect vital tissues and provide attachment for muscles. However when we are born, we do not know what activities we will undertake in life. Theoretically everyone could be inactive or athletic. That means either we all have bones strong enough for us to be successful weightlifters, or they can respond to activity to become strong enough for what we do.
As nature avoids carrying around unwanted mass, bones adapt to loads, so they get stronger when we exercise but weaker with inactivity. This means that we usually have bones with a safety margin to cope with occasional high loads. However with age, and after the menopause, control of the adaptive response is turned down, as though the bones have a "mechanical thermostat".
Part of the work is aimed at understanding how cells in bone perceive and respond to exercise. One remarkable finding is that they use a system to communicate similar to communication on the brain. Regulation of this system may provide ways to prevent and treat diseases so drugs could increase effect of loading on bone cells, or allow them to remember exercise stimuli longer. As everyone in the population will suffer from bone diseases of some sort in their life, this work has potential impacts of all of us.
These studies have led to discoveries of roles in bone for signalling systems known to function in other tissues. For several years we have worked on glutamate signalling in the skeleton, and more recently we have focused on the role of HCN channels, known to function in the brain and heart.
Other work includes studies on the nature of the response of the skeleton to movement/exercise. One surprising finding is how early the response of the skeleton to loading begins. In fetal life, it appears that movements exert a strong influence on bone development. In humans with so-called fetal akinaesias, conditions characterised by poor or abnormal muscle function, babies are born with weak thin bones. We have shown even more clearly that in mice that do not move during development the bones are grossly affected. This suggests that brief periods of activity in babies are highly beneficial in the acquisition of normal skeletal mass and architecture. With the current upsurge of work on the fetal origins of adult disease, this may suggest that our likelihood of bone disease in old age is at least in part determined by how active we were as fetuses!
Forelimb bones from normal mouse pup at birth (left) and a pup unable to move during development (right) Note the curved shape of the humerus in the normal bones and the relative straightness in the non-moving bones (A) , and the large sites of muscle origin and insertion the Deltoid tuberosity and olecranon (B&C respectivel;y) that are absent or reduced in the non-moving mice.
In general, the example above illustrates our approach to research, using translational approaches to understand integrative physiology and the function of genes in vivo. We use molecular and cellular biology models where appropriate, but tissue specific gene knockout technologies are an increasing feature of the research.
Much of our work on commercial therapeutics is confidential as it is in commercial development, through our University of Sheffield spinout company Medella Therapeutics, formed in partnership with Biofusion. The basis of the technology is that many important hormones interact not with sole specific cell surface receptors, but with more "general purpose" receptors which are made specific for the hormone in question by a Receptor Activity Modifying Protein or RAMP. For example, the calcitonin receptor (CTR) binds the hormone calcitonin, which suppresses osteoclastic bone resorption. However, When a RAMP associates with the CTR, the complex becomes a receptor for amylin, a hormone that causes new bone formation. Medella exists to exploit the therapeutic potential of targeting RAMPs either in disease for treatment or as preventive therapy.
Principal Funding Sources
- Medella Therapeutics
- Other industry and commercialisation funding sources
External UK Research-Related Activities
Member of BBSRC Healthy Organism strategy panel (vice chair), integrative physiology and ageing working groups, and review group for capacity building awards in integrative mammalian biology.
Member of ARC Scientific Strategy and programme grants committees.
Member of Research into Ageing advisory committee (vice chair).
Member of Horserace Betting Levy Board Veterinary Advisory Committee (vice chair) and chair of education sub-committee.
Members of Research Group
- Dr Dave Roberts
- Mr Gareth Richards
- Ms Susana Martinez-Bautista
- Mr Ning Wang
- Miss Brindha Ashok Kumar
- Mr Aditya Desai
Representative Publications (last 5 years)
Gomez C, David, V.,Peet N.M.,Vico, L,Chenu C., Malaval L, Skerry TM. Absence of mechanical loading in utero influences bone mass and architecture but not innervation in Myod-Myf5 deficient mice. J.Anat (2007) 210, pp259–271
Skerry TM. One mechanostat or many? Modifications of the site-specific response of bone to mechanical loading by nature and nurture. J Musculoskelet Neuronal Interact. 2006 6(2):122-7.
Gomez C, David, V.,PeetN.M.,Vico, L,Chenu C., Malaval L, Skerry TM. Absence of mechanical loading in utero influences bone mass and architecture but not innervation in Myod-Myf5 deficient mice. J.Anat (in press)Skerry TM One mechanostat or many? Modifications of the site-specific response of bone to mechanical loading by nature and nurture. J Musculoskelet Neuronal Interact. 2006 6(2):122-7.
Gomez C, Burt-Pichat B, Mallein-Gerin F, Merle B, Delmas PD, Skerry TM, Vico L, Malaval L, Chenu C. Expression of Semaphorin-3A and its receptors in endochondral ossification: potential role in skeletal development and innervation. Dev Dyn. 2005 Oct;234(2):393-403. Abstract.
Molloy TJ, Wang Y, Horner A, Skerry TM, Murrell GA. Microarray analysis of healing rat Achilles tendon: Evidence for glutamate signaling mechanisms and embryonic gene expression in healing tendon tissue. J Orthop Res. 2006 Mar 2;24(4):842-855. Abstract.
De Souza R, Pitsillides AA, Lanyon LE, Skerry TM, Chenu C. The sympathetic nervous system does not mediate load-induced cortical new bone formation. 2005, J Bone Miner Res Volume 20, Number 12; p. 2159.
Pead MJ, Skerry TM, Lanyon LE Direct transformation from quiescence to bone formation in the adult periosteum following a single brief period of bone loading. (Reprinted "Seminal paper" from J Bone Miner Res, vol 3, pg 647-656, 1988) J Bone Miner Res 20 (1): 161-171 Jan 2005.
Inkson CA, Brabbs AC, Grewal TS, Skerry TM, Genever PG. Characterization of acetylcholinesterase expression and secretion during osteoblast differentiation. Bone. 2004 Oct;35(4):819-27.
Skerry TM, Suva LJ. Investigation of the regulation of bone mass by mechanical loading: from quantitative cytochemistry to gene array. Cell Biochem Funct. 2003 223-9, Abstract.
Hitchcock IS, Skerry TM, Howard MR, Genever PG.NMDA receptor-mediated regulation of human megakaryocytopoiesis. Blood. 2003 Aug 15;102(4):1254-9. Epub 2003 Mar 20, Abstract.
Noble BS, Peet NM, Stevens HY, Brabbs AC, Mosley JR, Reilly GC, Reeve J, Skerry TM, Lanyon LE. Mechanical Loading: Biphasic Osteocyte Survival and the Targeting of Osteoclasts for Bone Destruction in Rat Cortical Bone. Am.J.Physiol 2003 Apr;284(4):C934-43. Epub 2002 Dec 11, Abstract.
Gu Y, Genever PG, Skerry TM, Publicover SJ. The NMDA type glutamate receptors expressed by primary rat osteoblasts have the same electrophysiological characteristics as neuronal receptors. Calcif Tissue Int 2002; 70(3): 194-203, Abstract.
Croucher PI, Shipman CM, Lippitt J, Perry M, Asosingh K, Hijzen A, Brabbs AC, van Beek EJ, Holen I, Skerry TM, Dunstan CR, Russell GR, Van Camp B, Vanderkerken K. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 2001; 98(13): 3534-40, Abstract.
Lanyon LE, Skerry TM. Postmenopausal Osteoporosis as a Failure of Bone's Adaptation to Functional Loading: an Hypothesis. J.Bone Miner Res 2001; 11.
Bhangu PS, Genever PG, Spencer G, Grewal TS, Skerry TM. Evidence for targeted vesicular glutamate exocytosis in osteoblasts. Bone 2001; 29 (1): 16-23, Abstract.
Genever PG, Skerry TM. Regulation of spontaneous glutamate release activity in osteoblastic cells and its role in differentiation and survival: evidence for intrinsic glutamatergic signalling in bone. FASEB J 2001; 15(9) 1586-8.
Skerry TM, Genever PG Glutamate signalling in non-neuronal tissues Trends Pharmacol Sci 22 (4): 174-181 2001.