skeletal biology & disease

summary

Genetic and acquired disorders of the skeleton involving bone, cartilage and joints are a major health problem.  We aim to understand the causes of these disorders by unravelling the key genetic and biological mechanisms of skeletal disease and development.  Our research underpins the development of new diagnostic tests and better treatments such as tissue engineering; to ultimately improve the quality of life of children affected by these debilitating conditions.

group leader(s)

  Professor John Bateman
  Skeletal Biology & Diseases
  Murdoch Childrens Research Institute
  Royal Children's Hospital
  Flemington Road
  Parkville Victoria 3052
 
  T +61 3 8341 6422 (Bateman)
     +61 3 8341 6423 (Shirley D'Cruz - PA)
  F +61 3 8341 6429
  E john.bateman@mcri.edu.au
     shirley.dcruz@mcri.edu.au

  group leader biography

  Professor Ravi Savarirayan
  Skeletal Biology & Disease
  Murdoch Childrens Research Institute
  Royal Children's Hospital
  Flemington Road
  Parkville Victoria 3052

  T +61 3 9936 6541
  F +61 3 8341 6390
  E ravi.savarirayan@ghsv.org.au

  group leader biography

current research projects

Formation of the human skeleton and the proper functioning of the bone and cartilaginous elements are determined by complex interactions of extracellular, cell surface and intracellular regulatory molecules.  The extracellular matrix is an intricate network providing a structural scaffolding and regulatory signals for growth and development.  A major component of our research is directed at understanding the synthesis, regulation, structure and function of these complex matrices in development and in inherited and acquired diseases of bone and cartilage.  Our studies over many years have defined mutations leading to osteogenesis imperfecta and a range of inherited cartilage diseases (chondrodysplasias). 

These studies have explored protein structure, assembly and interactions to provide an important platform for the development of new therapeutic approaches and biomaterial development for tissue repair and regeneration.  Our current research program continues to explore the functional genomics of skeletal disease.  In addition, we are using comprehensive proteomic and RNA expression profiling approaches for the study of cartilage and bone development and degenerative joint disease.  Other studies are directed at examining the mechanisms of how cells monitor and respond to the production of mutant RNA and protein, processes that are critical to the clinical outcome of all genetic diseases. 

team members

• Constanza Angelucci - Research Officer
• Andrea Aspinall - VOLUNTEER
• Naomi Baker - Research Officer
• Trevor Cameron - Research Officer
• Melanie Cottee - VOLUNTEER
• Stacey Cuscadden - VOLUNTEER
• Yiwen Fang - PhD Student (Deakin Life&EnvirSci)
• Jamie Fitzgerald - HONORARY RESEARCH FELLOW
• Irma Gresshoff - Research Officer
• Louise Heavey - VOLUNTEER
• Michael Hubbard - HONORARY RESEARCH FELLOW
• Melita Irving - HONORARY RESEARCH FELLOW
• Nicky Kilpatrick - Honorary Research Fellow
• Jasmine Kumar - VOLUNTEER
• Shireen Lamande - GROUP LEADER / SENIOR RESEARCH FELLOW

• Christopher Little - HONORARY RESEARCH FELLOW
• Kristin Nour - Visitor
• Kate Pope - Clinical Research Coordinator
• Audrey Price - VOLUNTEER
• Supriya Raj - Research Coordinator
• Lochana Ramalingham - RESEARCH AFFILIATE
• Julie Reid - HONORARY RESEARCH FELLOW
• Elisha Riggs - RESEARCH AFFILIATE
• Lynn Rowley - Research Assistant
• Emma Sanford - PhD Student (UoM Paeds)
• Andrea Verhoeven - VOLUNTEER
• Elizabeth Waters - HONORARY RESEARCH FELLOW
• Richard Wilson - Honorary Research Fellow
• Laura Zamurs - Research Officer

publications

• Andreucci E., Aftimos S., Alcausin M., Haan E., Hunter W., Kannu P., Kerr B., McGillivray G., Gardner RJM., Patricelli MG., Sillence D., Thompson E., Zacharin M., Zankl A., Lamande SR., Savarirayan R. TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families. ORPHANET JOURNAL OF RARE DISEASES 6 (2011) PubMed
• Bernardo BC., Belluoccio D., Rowley L., Little CB., Hansen U., Bateman JF. Cartilage Intermediate Layer Protein 2 (CILP-2) Is Expressed in Articular and Meniscal Cartilage and Down-regulated in Experimental Osteoarthritis. Journal of Biological Chemistry 286 (43) : 37758 - 37767(2011) PubMed
• Bowen ME., Boyden ED., Holm IA., Campos-Xavier B., Bonafe L., Superti-Furga A., Ikegawa S., Cormier-Daire V., Bovee JV., Pansuriya TC., de Sousa SB., Savarirayan R., Andreucci E., Vikkula M., Garavelli L., Pottinger C., Ogino T., Sakai A., Regazzoni BM., Wuyts W., Sangiorgi L., Pedrini E., Zhu M., Kozakewich HP., Kasser JR., Seidman JG., Kurek KC., Warman ML. Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome. PLOS GENETICS 7 (4) (2011) PubMed
• Boyden ED., Campos-Xavier AB., Kalamajski S., Cameron TL., Suarez P., Tanackovich G., Andria G., Ballhausen D., Briggs MD., Hartley C., Cohn DH., Davidson HR., Hall C., Ikegawa S., Jouk P-S., Konig R., Megarbane A., Nishimura G., Lachman RS., Mortier G., Rimoin DL., Rogers RC., Rossi M., Sawada H., Scott R., Unger S., Valadares ER., Bateman JF., Warman ML., Superti-Furga A., Bonafe L. Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity. American Journal of Human Genetics 89 (6) : 767 - 772(2011)
• Bruno DL., Stark Z., Amor DJ., Burgess T., Butler K., Corrie S., Francis D., Ganesamoorthy D., Hills L., James PA., O'Rielly D., Oertel R., Savarirayan R., Prabhakara K., Salce N., Slater HR. Extending the scope of diagnostic chromosome analysis: Detection of single gene defects using high-resolution SNP microarrays. HUMAN MUTATION 32 (12) : 1500 - 1506(2011) PubMed
• Cameron TL., Bell KM., Tatarczuch L., Mackie EJ., Rajpar MH., McDermott BT., Boot-Handford RP., Bateman JF. Transcriptional profiling of chondrodysplasia growth plate cartilage reveals adaptive ER-stress networks that allow survival but disrupt hypertrophy. PLOS ONE 6 (9) (2011) PubMed
• Chan BY., Fuller ES., Russell AK., Smith SM., Smith MM., Jackson MT., Cake MA., Read RA., Bateman JF., Sambrook PN., Little CB. Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis. OSTEOARTHRITIS AND CARTILAGE 19 (7) : 874 - 885(2011) PubMed
• Holloway TP., Rowley SM., Delatycki MB., Sarsero JP. Detection of interruptions in the GAA trinucleotide repeat expansion in the FXN gene of Friedreich ataxia. BIOTECHNIQUES 50 (3) : 182 (2011) PubMed
• Jackson GC., Mittaz-Crettol L., Taylor JA., Mortier GR., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall CM., Offiah A., Wright MJ., Savarirayan R., Nishimura G., Ramsden SC., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs MD. Pseudoachondroplasia and multiple epiphyseal dysplasia: a 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution. HUMAN MUTATION (2011) PubMed
• Kannu P., Bateman J., Savarirayan R. Clinical phenotypes associated with type II collagen mutations. JOURNAL OF PAEDIATRICS AND CHILD HEALTH (2011) PubMed
• Kannu P., Irving M., Aftimos S., Savarirayan R. Two Novel COL2A1 Mutations Associated with a Legg-Calv,-Perthes Disease-like Presentation. CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 469 (6) : 1785 - 1790(2011) PubMed
• Lamandé SR., Yuan Y., Gresshoff IL., Rowley L., Belluoccio D., Kaluarachchi K., Little CB., Botzenhart E., Zerres K., Amor DJ., Cole WG., Savarirayan R., McIntyre P., Bateman JF. Mutations in TRPV4 cause an inherited arthropathy of hands and feet. NATURE GENETICS 43 (11) : 1142 - 1146(2011)
• Lucas N., Neumann A., Kilpatrick N., Nicholson JM. State-level differences in the oral health of Australian preschool and early primary school-age children. AUSTRALIAN DENTAL JOURNAL 56 (1) : 56 - 62(2011) PubMed
• Mill P., Lockhart PJ., Fitzpatrick E., Mountford HS., Hall EA., Reijns MAM., Keighren M., Bahlo M., Bromhead CJ., Budd P., Aftimos S., Delatycki MB., Savarirayan R., Jackson IJ., Amor DJ. Human and Mouse Mutations in WDR35 Cause Short-Rib Polydactyly Syndromes Due to Abnormal Ciliogenesis. American Journal of Human Genetics 88 (4) : 508 - 515(2011) PubMed
• Neumann AS., Lee KJ., Gussy MG., Waters EB., Carlin JB., Riggs E., Kilpatrick NM. Impact of an oral health intervention on pre-school children < 3 years of age in a rural setting in Australia. JOURNAL OF PAEDIATRICS AND CHILD HEALTH 47 (6) : 367 - 372(2011) PubMed
• Puspasari N., Rowley SM., Gordon L., Lockhart PJ., Ioannou PA., Delatycki MB., Sarsero JP. Long Range Regulation of Human FXN Gene Expression. PLOS ONE 6 (7) (2011) PubMed
• Slack-Smith LM., Read AW., Colvin LJ., Leonard H., Kilpatrick N., McAullay D., Messer LB. Total population investigation of dental hospitalizations in Indigenous children under five years in Western Australia using linked data. AUSTRALIAN DENTAL JOURNAL 56 (4) : 358 - 364(2011)
• Stark Z., Gillessen-Kaesbach G., Ryan MM., Cirstea IC., Gremer L., Ahmadian MR., Savarirayan R., Zenker M. Two novel germline KRAS mutations: expanding the molecular and clinical phenotype. Clinical genetics (2011) PubMed
• Stark Z., Storen R., Bennetts B., Savarirayan R., Jamieson RV. Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring. EUROPEAN JOURNAL OF HUMAN GENETICS 19 (7) : 753 - 756(2011) PubMed
• Warman ML., Cormier-Daire V., Hall C., Krakow D., Lachman R., LeMerrer M., Mortier G., Mundlos S., Nishimura G., Rimoin DL., Robertson S., Savarirayan R., Sillence D., Spranger J., Unger S., Zabel B., Superti-Furga A. Nosology and Classification of Genetic Skeletal Disorders: 2010 Revision. AMERICAN JOURNAL OF MEDICAL GENETICS PART A (5) : 943 - 968(2011) PubMed
• Wilson R., Norris EL., Brachvogel B., Angelucci C., Zivkovic S., Gordon L., Bernardo BC., Stermann J., Sekiguchi K., Gorman JJ., Bateman JF. Changes in the Chondrocyte and Extracellular Matrix Proteome during Post-natal Mouse Cartilage Development. Molecular and cellular proteomics (2011) PubMed