Western Australian Institute for Medical Research (WAIMR)


http://www.waimr.uwa.edu.au

Dr Bryan Ward

Bryan Ward

After obtaining his PhD in Microbiology in 1994 from the University of Western Australia, Dr Ward joined Tom Ratajczak's group in the Laboratory for Molecular Endocrinology (located in the Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital). Research interests in this laboratory have focused on the role of co-chaperone proteins in the modulation of steroid receptor function, the role of the calcium-sensing receptor (CaR) in disorders of calcium metabolism and, more recently, the genetic mechanisms underlying Paget's disease of bone.

In 2003, Dr Ward obtained a Raine Medical Research Foundation Priming Grant to further develop research related to the CaR. In conjunction with Tom Ratajczak he now leads a group examining various aspects of the receptor, most notably those centred around the CaR tail and its role in cell signalling. In particular, the 'CaR signalling group' is conducting studies to elucidate the functional role of various partner binding proteins (identified in a recent yeast two-hybrid analysis of the tail) in mediating CaR signalling. In conjunction with Tom Ratajczak and clinicians within the Department of Endocrinology and Diabetes, Dr Ward also participates in an ongoing screening programme which aims to identify and functionally characterize mutations in the CaR from patients with inherited diseases of calcium homeostasis.

Dr Ward has developed expertise in a number of areas, in particular: molecular cloning and tissue culture techniques, yeast two-hybrid analysis, MAPK and inositol phosphate assays, GST pulldown techniques, site-directed mutagenesis/mutational analysis and cell surface expression assays. He has published widely, both in the immunophilin/steroid receptor and CaR fields and has collaborative links with Associate Professor Arthur Conigrave (School of Molecular and Microbial Biosciences, Univesity of Sydney), Karin Eidne (7-Transmembrane Laboratory, WAIMR) and Evan Ingley (Laboratory for Cancer Medicine, WAIMR).

Qualifications

1973DipHortSc - University of Melbourne, Australia
1978BSc (Hons) - Microbiology, University of Melbourne, Australia
1994PhD - Microbiology, University of Western Australia, Australia
Thesis Title: "Identification, cloning and characterization of papillomavirus-like sequences from the goat"

Research Interests

  • The calcium-sensing receptor as a signalling module; understanding how signalling events mediated by the receptor relate to disease states in which the CaR plays a pivotal role.
  • Identification and functional characterization of mutations in the CaR from families presenting with various disorders of calcium homeostasis.
  • The role of immunophilin co-chaperones in modulating steroid receptor function; implications for hormonally controlled cancers.
  • Understanding the role of sequestosome 1 (p62) in the NF-κB signalling pathway as it relates to Paget's disease of bone; identification and functional assessment of mutations in the p62 gene in patients with Paget's disease of bone.

Scientific Involvement

  • Endocrine Society of Australia - Associate Member.
  • Australian and New Zealand Bone and Mineral Society - Associate Member.
  • Endocrine and Reproductive Biology Society of Western Australia (ERBSWA) - Member and Treasurer.

Major Grants Awarded

  • UWA Medical Faculty Research Fund: 1991 ($8,910)
  • Cancer Foundation of Western Australia (with T Ratajczak): 1998 ($45,000); 2000 ($49,214); 2003-06 ($55,000)
  • Sir Charles Gairdner Hospital Research Fund (with T Ratajczak and/or BGA Stuckey): 1999 ($3,000); 2002 ($10,000); 2003 ($10,000); 2006 ($10,000)
  • Menopause Society of Australia (with T Ratajczak): 2000 ($44,221)
  • Raine Medical Research Foundation (with AH Franks): 2003-2004 ($152,422)
  • UWA Research Grants Scheme (with T Ratajczak): 2004 ($11,500); 2007 ($21,000)

Top Publications

  1. Ward BK, Mark PJ, Ingram DM, Minchin RF, Ratajczak T. 1999. Expression of the estrogen receptor-associated immunophilins, cyclophilin 40 and FKBP52, in breast cancer. Breast Cancer Research and Treatment 58(3):267-80. [NCBI PubMed Entry]
  2. Ward BK, Kumar P, Turbett GR, Edmondston JE, Papadimitriou JM, Laing NG, Ingram DM, Minchin RF, Ratajczak T. 2001. Allelic loss of cyclophilin 40, an estrogen receptor-associated immunophilin, in breast carcinomas. Journal of Cancer Research and Clinical Oncology 127(2):109-15. [NCBI PubMed Entry]
  3. Kumar P, Ward BK, Minchin RF, Ratajczak T. 2001. Regulation of the Hsp90-binding immunophilin, cyclophilin 40, is mediated by multiple sites for GA-binding protein (GABP). Cell Stress & Chaperones 6(1):78-91. [NCBI PubMed Entry]
  4. Mark PJ, Ward BK, Kumar P, Lahooti H, Minchin RF, Ratajczak T. 2001. Human cyclophilin 40 is a heat shock protein that exhibits altered intracellular localization following heat shock. Cell Stress & Chaperones 6(1):59-70. [NCBI PubMed Entry]
  5. Ward BK, Allan RK, Mok D, Temple SE, Taylor P, Dornan J, Mark PJ, Shaw DJ, Kumar P, Walkinshaw MD, Ratajczak T. 2002. A structure-based mutational analysis of cyclophilin 40 identifies key residues in the core tetratricopeptide repeat domain that mediate binding to Hsp90. The Journal of Biological Chemistry 277(43):40799-809. [NCBI PubMed Entry]
  6. Ward BK, Magno AL, Davis EA, Hanyaloglu AC, Stuckey BG, Burrows M, Eidne KA, Charles AK, Ratajczak T. 2004. Functional deletion of the calcium-sensing receptor in a case of neonatal severe hyperparathyroidism. The Journal of Clinical Endocrinology and Metabolism 89(8):3721-30. [NCBI PubMed Entry]
  7. Ward BK, Cameron FJ, Magno AL, McDonnell CM, Stuckey BG, Ratajczak T. 2006. A novel homozygous deletion in the calcium-sensing receptor ligand-binding domain associated with neonatal severe hyperparathyroidism. Journal of Pediatric Endocrinology & Metabolism 19(1):93-100. [NCBI PubMed Entry]
  8. Allan RK, Mok D, Ward BK, Ratajczak T. 2006. Modulation of chaperone function and cochaperone interaction by novobiocin in the C-terminal domain of Hsp90: evidence that coumarin antibiotics disrupt Hsp90 dimerization. The Journal of Biological Chemistry 281(11):7161-71. [NCBI PubMed Entry]
  9. Ward BK, Magno AL, Blitvich BJ, Rea AJ, Stuckey BG, Walsh JP, Ratajczak T. 2006. Novel mutations in the calcium-sensing receptor gene associated with biochemical and functional differences in familial hypocalciuric hypercalcaemia. Clinical Endocrinology 64(5):580-7. [NCBI PubMed Entry]
  10. Rea SL, Walsh JP, Ward L, Yip K, Ward BK, Kent GN, Steer JH, Xu J, Ratajczak T. 2006. A novel mutation (K378X) in the sequestosome 1 gene associated with increased NF-kappaB signaling and Paget's disease of bone with a severe phenotype. Journal of Bone and Mineral Research 21(7):1136-45. [NCBI PubMed Entry]