Dr Peter Grabowski PhD
Lecturer in Bone Biology
Academic Unit of Child Health
University of Sheffield
Sheffield Children's NHS Trust,
Sheffield. S10 2TH UK
Tel: +44 (0)114 271 1798
Fax: +44 (0)114 275 5364
Laboratories and Office
School of Medicine & Biological Sciences,
Beech Hill Road,
Sheffield. S10 2RX UK
1979 B.Sc (Hons) Pharmacology, University of Liverpool; 1983 M.Sc., University of Liverpool; 1987 Ph.D., University of Liverpool; 1986-1987 Research Fellow, University of Kiel, Germany; 1987-1996 Research Fellow, University of Aberdeen; 1996-1999 Research Fellow, University of York; 1999 - present Lecturer in Bone Biology, University of Sheffield.
Osteopetrosis is a rare genetic disorder in which osteoclasts function poorly or fail to form. We have been developing approaches to characterise the cellular and molecular defects in osteoclast formation and function in infantile onset osteopetrosis.
Osteoclasts arise by the directed cell membrane fusion of monocyte/macrophage lineage precursors, producing multinucleated bone resorbing cells. We are combining molecular genetic and live cell imaging approaches to identify and characterise molecules participating in and mediating cell membrane fusion during osteoclastogenesis.
Tetracycline derivatives as modulators of bone formation and resorption
Novel chemically modified tetracycline derivatives (CMTs) were developed as inhibitors of matrix metalloproteinases, the enzymes responsible for breakdown of proteins in connective tissues. We have shown that they induce apoptosis in mature osteoclasts and potently inhibit the osteoclastogenesis at pharmacologically relevant concentrations through additional mechanisms.
The role of TRPV5 and TRPV6 calcium channels in osteoblasts and osteoclasts during ageing
TRPV5 and TRPV6 are closely related calcium selective ion channels that mediate calcium ion absorption from the intestine and reabsorption from the kidney. We are investigating the role and regulation of TRPV5 and TRPV6 in osteoblasts and osteoclasts in relation to ageing.
Principal Funding Sources
- Research into Ageing
- National Association for the Relief of Paget's Disease
- Sheffield Children's Appeal
- University of Sheffield
Members of Research Group
- Robert Little
- Susan Smith
Holmes S, Smith S, Borthwick L, Dunford J, Rogers M, Bishop N, Grabowski PS (2007) "CMT3 alters mitochondrial function in murine osteoclast lineage cells." Biochemical and Biophysical Research Communications accepted 14.11.08
Afifi A, Olpin S, Dalton A, Bishop N, Grabowski PS (2007) "Failure to repair the c.338C>T mutation in carnitine palmitoyl transferase 2 deficient skin fibroblasts using chimeraplasty." Mol. Genet. Metab. in press, doi:10.1016/j.ymgme.2007.10.005
Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A, Susani L, Bredius R, Mancini G, Cant A, Bishop N, Grabowski P, Del Fattore A, Messina C, Errigo G, Coxon FP, Scott DI, Teti A, Rogers MJ, Vezzoni P, Villa A, Helfrich MH. (2007) "Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL." Nature Genetics 39:960-2. Epub 2007 Jul 15
Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A, Longo M, Fortunati D, Ballanti P, Iacobini M, Luciani M, Devito R, Pinto R, Caniglia M, Lanino E, Messina C, Cesaro S, Letizia C, Bianchini G, Fryssira H, Grabowski P, Shaw N, Bishop N, Hughes D, Kapur RP, Datta HK, Taranta A, Fornari R, Migliaccio S, Teti A (2006) "Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment." Journal of Medical Genetics 43:315-25.
Holmes SG, Still K, Buttle DJ, Bishop NJ, Grabowski PS (2004) "Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors." Bone. 2004 35:471-8.
Helfrich MH, Hobson RP, Grabowski PS, Zurbriggen A, Cosby SL, Dickson GR, Fraser WD, Ooi CG, Selby PL, Crisp AJ, Wallace RGH, Kahn S, Ralston SH (2000) "A negative search for a paramyxoviral etiology of Paget's disease of bone: Molecular, immunological, and ultrastructural studies in UK patients." Journal of Bone and Mineral Research 15:2315-2329.
Bettany JT, Peet NM, Wolowacz RG, Skerry TM, Grabowski PS (2000) "Tetracyclines induce apoptosis in osteoclasts." Bone 27:75-80.
Peet NM, Grabowski PS, Laketic-Ljubojevic I, Skerry TM (1999) "The glutamate receptor antagonist MK801 modulates bone resorption in vitro by a mechanism predominantly involving osteoclast differentiation." FASEB Journal 13:2179-2185.
Armour KE, Van't Hof RJ, Grabowski PS, Reid DM, Ralston SH (1999) "Evidence for a pathogenic role of nitric oxide in inflammation- induced osteoporosis." Journal of Bone and Mineral Research 14:2137-2142.
Grabowski PS, Wright PK, VanThof RJ, Helfrich MH, Ohshima H, Ralston SH (1997) "Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumatoid arthritis and osteoarthritis." British Journal of Rheumatology 36:651-655.
Ralston SH, Grabowski PS (1996) "Mechanisms of cytokine induced bone resorption: Role of nitric oxide, cyclic guanosine monophosphate, and prostaglandins." Bone 19:29-33.
Grabowski PS, Macpherson H, Ralston SH (1996) "Nitric oxide production in cells derived from the human joint." British Journal of Rheumatology 35:207-212.
Grabowski PS, England AJ, Dykhuizen R, Copland M, Benjamin N, Reid DM, Ralston SH (1996) "Elevated nitric oxide production in rheumatoid arthritis - Detection using the fasting urinary nitrate:creatinine ratio." Arthritis and Rheumatism 39:643-647.