个人简介

Prof Hardeman received her doctorate from the Department of Biological Sciences, Stanford University and then took up a postdoctoral fellowship in the Department of Pharmacology, Stanford Medical School. She established her laboratory, the Muscle Development Unit at the Children’s Medical Research Institute in Sydney, and has built an international reputation defining mechanisms of muscle gene regulation, and generating mouse models for human skeletal muscle diseases and trialling therapies as part of an international consortium of the European Neuromuscular Centre. In 2009 she moved to the University of New South Wales to take up a Research Chair in Anatomy and establish the Neuromuscular and Regenerative Medicine Unit. Notable achievements include: developing the human skeletal alpha-actin promoter for skeletal muscle-specific expression in animal models of human disease and for gene therapy, the identification of a novel pulsatory, stochastic mode of gene transcription that contributed a new mechanism to the field of gene regulation, the generation of mouse models for nemaline myopathy and identification of therapies, member of collaborative team that identified tropomyosins as the gatekeepers of actin filament function, and the discovery of the gene Gtf2ird1 which is implicated in aspects of human cognition and behaviour.

研究领域

Biochemistry and Cell Biology

The Neuromuscular and Regenerative Medicine Unit (NRMU) is engaged in a range of research activities that span basic mechanisms in cell biology to cell-based therapies to the cellular basis for aspects of human cognition and behaviour. Our disease foci are neuromuscular disorders, regenerative medicine, childhood cancer, cancer metabolic syndrome, and the neurodevelomental disorder William Beurens Syndrome. In particular, our research aims to understand muscle cytoarchitecture, muscle regeneration and develop stem cell-based therapy, to understand how radiation therapy for childhood cancers impacts the epigenome of muscle stem cells, to analyse anti-cytoarchitecture/anti-cancer drugs, and to understand how one gene, discovered by us, GTF2IRD1, can profoundly affect skeletal muscle and yet also play a role in human cognition and behaviour. Current research projects are: Development of anti-tropomyosin drugs, anti-cancer drugs Regulation of glucose uptake by tropomyosins and myosins Regulation of cell proliferation by the actin cytoskeleton The role of epigenetic modifications in longterm memory of irradiation in childhood cancer survivors

近期论文

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Corley SM; Canales CP; Carmona-Mora P; Mendoza-Reinosa V; Beverdam A; Hardeman EC; Wilkins MR; Palmer SJ, 2016, 'RNA-Seq analysis of Gtf2ird1 knockout epidermal tissue provides potential insights into molecular mechanisms underpinning Williams-Beuren syndrome', BMC Genomics, vol. 17, no. 1, http://dx.doi.org/10.1186/s12864-016-2801-4 Tinklenberg J; Meng H; Yang L; Liu F; Hoffmann RG; Dasgupta M; Allen KP; Beggs AH; Hardeman EC; Pearsall RS; Fitts RH; Lawlor MW, 2016, 'Treatment with ActRIIB-mFc Produces Myofiber Growth and Improves Lifespan in the Acta1 H40Y Murine Model of Nemaline Myopathy', American Journal of Pathology, vol. 186, no. 6, pp. 1568 - 1581, http://dx.doi.org/10.1016/j.ajpath.2016.02.008 Lindqvist J; Levy Y; Pati-Alam A; Hardeman EC; Gregorevic P; Ochala J, 2016, 'Modulating myosin restores muscle function in a mouse model of nemaline myopathy', Annals of Neurology, vol. 79, no. 5, pp. 717 - 725, http://dx.doi.org/10.1002/ana.24619 Brayford S; Bryce NS; Schevzov G; Haynes EM; Bear JE; Hardeman EC; Gunning PW, 2016, 'Tropomyosin promotes lamellipodial persistence by collaborating with Arp2/3 at the leading edge', Current Biology, vol. 26, no. 10, pp. 1312 - 1318, http://dx.doi.org/10.1016/j.cub.2016.03.028 Bonello TT; Janco M; Hook J; Byun A; Appaduray M; Dedova I; Hitchcock-DeGregori S; Hardeman EC; Stehn JR; Böcking T; Gunning PW, 2016, 'A small molecule inhibitor of tropomyosin dissociates actin binding from tropomyosin-directed regulation of actin dynamics', Scientific Reports, vol. 6, http://dx.doi.org/10.1038/srep19816 Kee AJ; Yang L; Lucas CA; Greenberg MJ; Martel N; Leong GM; Hughes WE; Cooney GJ; James DE; Ostap EM; Han W; Gunning PW; Hardeman EC, 2016, 'Corrigendum to An Actin Filament Population Defined by the Tropomyosin Tpm3.1 Regulates Glucose Uptake [Traic, (2015), 16, 7, 691-711]', Traffic, vol. 17, no. 1, pp. 80 - 81, http://dx.doi.org/10.1111/tra.12342 Erami Z; Herrmann D; Warren SC; Nobis M; McGhee EJ; Lucas MC; Leung W; Reischmann N; Mrowinska A; Schwarz JP; Kadir S; Conway JRW; Vennin C; Karim SA; Campbell AD; Gallego-Ortega D; Magenau A; Murphy KJ; Ridgway RA; Law AM; Walters SN; Grey ST; Croucher DR; Zhang L; Herzog H; Hardeman EC; Gunning PW; Ormandy CJ; Evans TRJ; Strathdee D; Sansom OJ; Morton JP; Anderson KI; Timpson P, 2015, 'Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue', Cell Reports, http://dx.doi.org/10.1016/j.celrep.2015.12.020 Gunning PW; Hardeman EC; Lappalainen P; Mulvihill DP, 2015, 'Tropomyosin - master regulator of actin filament function in the cytoskeleton', Journal of Cell Science, vol. 128, no. 15, pp. 2965 - 2974, http://dx.doi.org/10.1242/jcs.172502 Carmona-Mora P; Widagdo J; Tomasetig F; Canales CP; Cha Y; Lee W; Alshawaf A; Dottori M; Whan RM; Hardeman EC; Palmer SJ, 2015, 'The nuclear localization pattern and interaction partners of GTF2IRD1 demonstrate a role in chromatin regulation', Human Genetics, http://dx.doi.org/10.1007/s00439-015-1591-0 Schevzov G; Kee AJ; Wang B; Sequeira VB; Hook J; Coombes JD; Lucas CA; Stehn JR; Musgrove EA; Cretu A; Assoian R; Fath T; Hanoch T; Seger R; Pleines I; Kile BT; Hardeman EC; Gunning PW, 2015, 'Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments', Molecular Biology of the Cell, vol. 26, no. 13, pp. 2475 - 2490, http://dx.doi.org/10.1091/mbc.E14-10-1453 Jalilian I; Heu C; Cheng H; Freittag H; Desouza M; Stehn JR; Bryce NS; Whan RM; Hardeman EC; Fath T; Schevzov G; Gunning PW, 2015, 'Cell elasticity is regulated by the tropomyosin isoform composition of the actin cytoskeleton', PLoS One, vol. 10, no. 5, http://dx.doi.org/10.1371/journal.pone.0126214 Kee AJ; Yang L; Lucas CA; Greenberg MJ; Martel N; Leong GM; Hughes WE; Cooney GJ; James DE; Michael Ostap E; Han W; Gunning PW; Hardeman EC, 2015, 'An Actin Filament Population Defined by the Tropomyosin Tpm3.1 Regulates Glucose Uptake', Traffic, http://dx.doi.org/10.1111/tra.12282 Caldwell BJ; Lucas C; Kee AJ; Gaus K; Gunning PW; Hardeman EC; Yap AS; Gomez GA, 2015, 'Tropomyosin isoforms support actomyosin biogenesis to generate contractile tension at the epithelial zonula adherens', Cytoskeleton, http://dx.doi.org/10.1002/cm.21202 Canales CP; Wong ACY; Gunning PW; Housley GD; Hardeman EC; Palmer SJ, 2015, 'The role of GTF2IRD1 in the auditory pathology of Williams–Beuren Syndrome', European Journal of Human Genetics, vol. 23, no. 6, pp. 774 - 780, http://dx.doi.org/10.1038/ejhg.2014.188 Lindqvist J; Hardeman EC; Ochala J, 2014, 'Sexually dimorphic myofilament function in a mouse model of nemaline myopathy', Archives of Biochemistry and Biophysics, vol. 564, pp. 37 - 42, http://dx.doi.org/10.1016/j.abb.2014.09.011 Gineste C; Ottenheijm C; Fur YL; Banzet S; Pecchi E; Vilmen C; Cozzone PJ; Koulmann N; Hardeman EC; Bendahan D; Gondin J, 2014, 'Alterations at the cross-bridge level are associated with a paradoxical gain of muscle function in vivo in a mouse model of Nemaline myopathy', PLoS One, vol. 9, no. 9, http://dx.doi.org/10.1371/journal.pone.0109066 Head SI; Chan S; Chen G; Hardeman EC; Houweling PJ, 2014, 'Properties of regenerated mouse extensor digitorum longus muscle following notexin injury', Experimental Physiology, http://dx.doi.org/10.1113/expphysiol.2013.077289 Curthoys NM; Freittag H; Connor A; Desouza M; Brettle M; Poljak A; Hall A; Hardeman E; Schevzov G; Gunning PW; Fath T, 2014, 'Tropomyosins induce neuritogenesis and determine neurite branching patterns in B35 neuroblastoma cells', Molecular and Cellular Neuroscience, vol. 58, pp. 11 - 21, http://dx.doi.org/10.1016/j.mcn.2013.10.011 Wang B; Schevzov G; Coombes J; Hook J; Kee A; Lucas C; Stehn J; Sequeira V; Seger R; Hardeman E; Gunning P, 2013, 'Regulation of cell proliferation mediated by the actin filament regulator Tropomyosin 5NM1', Molecular Biology of the Cell, vol. 24, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000209348702025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a Suchowerska A; Chen B; Mueller J; Ittner A; Hardeman E; Ittner L; Janitz M; Gunning P; Fath T, 2013, 'Increased levels of actin filaments containing the tropomyosin Tm5NM1 regulate excitotoxicity in the mouse', Molecular Biology of the Cell, vol. 24, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000209348702020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a