A/Professor Shireen Lamande

Biography:

Dr Shireen Lamandé obtained her PhD at the University of Melbourne, studying the collagen mutations that cause osteogenesis imperfecta (brittle bone disease). Her research continues to focus on the molecular genetics of inherited disorders of the musculoskeletal system, including muscular dystrophy and bone and cartilage disorders.

She is a National Health and Medical Research Council Senior Research Fellow and an Honorary Senior Fellow in the Department of Paediatrics, University of Melbourne. She is the current president of the International Society for Matrix Biology and on the Editorial Board of the journal Matrix Biology.

Other Affiliations:

Honorary Senior Fellow, Department of Paediatrics, University of Melbourne

Awards:

Solander Fellowship, University of Melbourne and Lund University, 2006
Senior Research Fellow, NHMRC, 2007-2012
Senior Research Fellow, NHMRC, 2013-

Research:

Dr Lamandé's research goal is to understand the causes of inherited musculoskeletal disease and identify pathogenic pathways, modifying genes and potential therapies. A major focus has been characterising new human musculoskeletal disease genes and unravelling the functional consequences of the mutations - how the mutations cause disease. This requires applying range of techniques including cell culture (including iPS cells) and animal models of disease, mRNA expression profiling, proteomic profiling, and microscopic imaging to identify pathogenic pathways that could be targeted with therapies.

Inflammation is a major contributor to muscle degeneration in muscular dystrophy and Dr Lamandé's team are studying the role of extracellular matrix proteins and protease generated matrix fragments in signalling inflammation and the possibility that this can lessen muscle damage by inhibiting extracellular matrix turnover. The team are also exploring nutraceutical and other novel therapies for muscular dystrophy.

Projects:

Improving muscular dystrophy by targeting the ADAMTS5 metalloproteinase
TRPV4 in skeletal development and disease
Upregulating Akt signalling and utrophin expression to treat Duchenne muscular dystrophy
Stop codon read through to treat genetic disorders

Bateman, J.F., Boot-Handford, R.P. and Lamandé, S.R. (2009) Genetic diseases of connective tissues: Cellular and extracellular effects of ECM mutations Nature Reviews Genetics. 10(3):173-83 PMID: 19204719

Tooley, LD, Zamurs, LK, Beecher, N, Baker, NL, Peat, RA, Adams, NE, Bateman, JF, North, KN, Baldock, C, Lamandé, SR (2010) Collagen VI microfibril formation is abolished by an a2(VI) von Willebrand factor type A domain mutation in a patient with Ullrich congenital muscular dystrophy. J Biol Chem 285, 33567-33576

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. (2011) Mutationsin TRPV4 cause an inherited arthropathy of hands and feet.Nature Genetics. 2011 Oct 2;43(11):1142-6. doi: 10.1038/ng.945. PMID: 21964574

Andreucci, D, 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, Lamandé, SR, Savarirayan, R. (2011) TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted by clinical, radiographic, and molecular studies in 21 new families. Orph. J. Rare Diseases 6, 37-44

Fang Y, Bateman JF, Mercer JF, Lamandé SR (2013) Nonsense-mediated mRNA decay of collagen – emerging complexity in RNA surveillance mechanisms. J Cell Science 126, 2551-2560

Lamandé SR, North KN (2014) Activating internal ribosome entry to treat Duchenne muscular dystrophy. Nature Medicine 20, 987-988

Funding: