Professor Colin Farquharson

The Roslin Institute

Research Interests

Overview

My research programme is focused on the fundamental/translational mechanisms underpinning bone growth and development with a specific focus on the genetic and endocrine control of skeletal growth, development and mineralisation.  This work is/has been supported by grants from BBSRC, MRC, Medical Research Scotland, Arthritis Research UK and Industry. My research interests are inter-related  and whilst mostly fundamental in nature translate into the medical and veterinary arena. To complete my studies I have created novel mouse models and organ culture techniques to address my research questions.

Examples of ongoing research interests

  • Defining the mechanisms of skeletal biomineralisation has been a long standing interest.  I discovered a bone-specific phosphatase, PHOSPHO1, and together with colleagues at the Sanford Burnham Prebys Medical Discovery Institute, San Diego (Professor Jose Luis Millan) we substantiated its non-redundant functional role in bone mineralisation; genetic PHOSPHO1 ablation results in hypomineralised, functionally impaired skeletons with bowing of bones and spontaneous fracture.  Co-ablation of alkaline phosphatase (ALP) produces complete lack of skeletal mineralisation. This work is actively ongoing producing novel insights into the ability of phosphatases (PHOSPHO1 and ALP) to regulate skeletal mineralisation.
  • In another project, my group has proven a critical role for SOCS2 in regulating epiphyseal (growth plate) chondrocyte and osteoblast responses to growth hormone. SOCS2 suppresses STAT phosphorylation to inhibit linear growth and bone accretion and the absence of SOCS2 protects against bone loss typical of inflammatory bowel disease. These data are consistent with the premise that increased osteoblast SOCS2 expression represents a critical mediator through which pro-inflammatory cytokines inhibit GH signalling and decrease osteoblast function and bone accrual. This work is done in collaboration with colleagues at the University of Glasgow (Professor Faisal Ahmed).
  • Other joint studies with Professor Ahmed, funded by the MRC are investigating the bone and growth phenotype of various mouse models of Duchenes Muscular Dystrophy (DMD).  The study will further determine how bone anabolic agents (GH and IGF-1) can prevent the osteopenia and growth disorders that is prevalent in this condition.
  • In collaboration with colleagues at the RVC (Professor Andy Pitsillides) and the University of Sheffield (Dr Dave Buttle), we have shown that matrix mineralisation drives osteocyte formation and E11 (podoplanin) expression and that stabilisation of E11 protein (by cysteine protease inhibitors) is essential for the acquisition of the osteocyte morphology. Further work funded by Arthritis Research UK has allowed us to generate bone specific E11 deficient mice and extend these studies to investigate the role of E11 during subchondral bone thickening and the pathogenesis of osteoarthritis.
  • In collaboration with colleagues at the University of Oxford (Professor Kim Midwood) and Axis-Shield Diagnostics, Dundee (Dr Jeff Brady) and funded by Medical Research Scotland we are developing assays to assess the clinical utility of tenascin-C in inflammatory diseases. 

 

 

 

Selected Publications

  • Ahmed Al-Jazzar , Behzad Javaheri , Matt Prideaux, Alan Boyde , Cheryl Scudamore , Chahrazad Cherifi , Eric Hay, Mark Hopkinson , Michael Boyd, Martine Cohen-Solal , Colin Farquharson, Andrew Pitsillides. 2017. Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues. International Journal of Molecular Sciences Vol: 18. More»
  • Dean Houston, Katherine Myers, Victoria MacRae, Katherine Staines, Colin Farquharson. 2016. The expression of PHOSPHO1, nSMase2 and TNAP is coordinately regulated by continuous PTH exposure in mineralising osteoblast cultures. Calcified Tissue International Vol: 99 Pages: 510-524. More»
  • Katherine Staines, Matt Prideaux, David Buttle, Andrew Anthony Pitsillides, Colin Farquharson. 2016. E11/podoplanin protein stabilization through inhibition of the proteasome promotes osteocyte differentiation in murine in vitro models. Journal of Cellular Physiology Vol: 231 Pages: 1392-1404. More»
  • Manisha C. Yadav, Ana Maria Sper Simao, Sonoko Narisawa, Carmen Huesa, Marc D. McKee, Colin Farquharson, Jose Luis Millan. 2011. Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: A unified model of the mechanisms of initiation of skeletal calcification. Journal of Bone and Mineral Research Vol: 26 Pages: 286-297. More»
  • C. Pass, V.E. Macrae, C. Huesa, S.F. Ahmed, C. Farquharson. 2012. SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis. Journal of Bone and Mineral Research Vol: 27 Pages: 1055-1066. More»
  • H. C. Owen, S. J. Roberts, S. F. Ahmed, C. Farquharson. 2008. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. American Journal of Physiology - Endocrinology and Metabolism Vol: 294 Pages: E1023-E1034. More»