||Dr Daniel McCulloch
||Lecturer in Medical Biology
||+61 3 522 72838
||Geelong at Waurn Ponds
Extracellular matrix in development and diseases
The ADAMTS (A Disintegrin And Metalloproteinase with Thrombospondin type-1 repeats) enzymes are highly specialised zinc-dependent metalloproteinases with emerging roles in biology of the extracellular matrix (connective tissue). Transgenic mouse models have recently identified ADAMTS enzymes as key mediators of important developmental processes including ovarian function and heart development. In addition, challenging ADAMTS transgenic mice with disease states has exemplified their importance in the underlying pathology of processes such as inflammatory arthritis and osteoarthritis. Our program focuses on gaining novel information regarding largely uncharacterised ADAMTS enzymes during development, as well as defining mechanisms underlying newly identified roles for well-characterised members of this evolutionary-conserved family of enzymes.
||Legend:Cultured muscle precursor cells (myoblasts) are stimulated to form multi-nucleated myotubes, which represents mature muscle in vitro. Using this assay we can understand the molecular mechanisms underlying muscle regeneration, and examine the role the ADAMTS enzymes have during this process.
- The role of ADAMTS enzymes in skeletal muscle regeneration and muscular dystrophy.
- Novel mechanisms of inhibiting ADAMTS enzymes to treat arthritis.
- ADAMTS enzymes in cancer.
- ADAMTS enzymes in infection and immunity.
- Biosynthesis, activation mechanisms and substrate recognition of ADAMTS enzymes.
- The expression and roles of ADAMTS enzymes during key developmental processes.
Ongoing recruitment of Honours and PhD students, please email curriculum vitae with an expression of interest to: firstname.lastname@example.org.
Dr McCulloch gained his PhD examining the roles of metalloproteinases in prostate cancer at the Queensland University of Technology, Brisbane. He continued his research in prostate cancer at the Bernard O'Brien Institute of Microsurgery, Melbourne before broadening his interests into diseases of the extracellular matrix with research carried out at the Murdoch Children's Research Institute, Melbourne. He completed an overseas fellowship at Lerner Research Institute in the Department of Biomedical Engineering, the Cleveland Clinic, Cleveland, Ohio where he carried out intensive research specifically focussing on ADAMTS biology during development and disease: www.lerner.ccf.org/bme/apte/adamts.
Work arising from his fellowship at the Cleveland Clinic was recently published in the prestigious Cell Press journal Developmental Cell.
Dr McCulloch's research is currently funded by the Financial Markets Foundation for Children.
Dr Daniel McCulloch's Publications
- Kintakas C, McCulloch DR. 2011. Emerging roles for ADAMTS5 during development and disease. Matrix Biol Jun; 30(5-6):311-7.
- Wiley JD, Ho J, McCulloch, DR, and Apte, SS. 2011. Adamts5 (aggrecanase-2) is widely expressed in the mouse musculoskeletal system and is induced in specific regions of knee joint explants by inflammatory cytokines. J Orthop Res doi; 10.1002/jor.21508.
- Dupuis LE, McCulloch DR, McGarity JD, Bahan A, Wessels A, Weber D, Diminich AM, Nelson CM, Apte SS, Kern CB. 2011. Altered versican cleavage in ADAMTS5 deficient mice; A novel etiology of myxomatous valve disease. Dev Biol; 357(1):152-64.
- McCulloch DR, Wylie JD, Longpre JM, Leduc R, Apte SS. 2010. 10mM glucosamine prevents activation of proADAMTS5 (aggrecanase-2) in transfected cells by interference with post-translational modification of furin. Osteoarthritis Cartilage; 18(3):455-63.
- McCulloch DR, Nelson CM, Dixon LJ, Silver DL, Wylie JD, Lindner V, Sasaki T, Cooley MA, Argraves WS, Apte SS. 2009. ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Dev Cell; 17(5):687-98.Cell Press.
- Longpre JM, McCulloch DR, Koo BH, Alexander JP, Apte SS, Leduc R. 2009. Characterization of proADAMTS5 processing by proprotein convertases. Int J Biochem Cell Biol; 41(5):1116-26.
- McCulloch DR, Le Goff C, Bhatt S, Dixon LJ, Sandy JD, Apte SS. 2009. Adamts5, the gene encoding a proteoglycan-degrading metalloprotease, is expressed by specific cell lineages during mouse embryonic development and in adult tissues. Gene Expr Patterns; 9(5):314-23. Most cited article: 2008-2010.