Dr Justine Stehn

Fields of research: Cancer Cell Biology, Molecular Targets, Cell Development, Proliferation and Death, Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)

Contact Details

Phone: +61 2 9385 8591
Email: j.stehn@unsw.edu.au

Supervision

PHD
Masters
Honours

Tabs

Main

Dr Justine Stehn is the Drug Development Coordinator and group leader of the Anti-tropomyosin Drug Development Group which is part of the Cellular and Genetic Medicine Unit (CGMU) in the School of Medical Sciences. Research projects in the Drug Development Group centre on the development of compounds which target an essential protein component of the actin cytoskeleton in tumour cells. By targeting an actin binding protein, tropomyosin, it is possible to break down the the cellular architecture of cancer cells and initiate cell death. Research is now focussed on the nature of the drug target interaction and the how this interaction causes tumour cell death. The primary objective is to take these anti-tropomyosin compounds through to the clinic for the treatment of childhood cancers such as neuroblastoma.

Biography

Justine Stehn received her PhD from the Garvan Institute of Medical Research in 2000. She was awarded a prestigious National Health and Medical Research Council (NHMRC), CJ Martin Fellowship to support her post doctoral positions at Harvard University and the Centre for Cancer Research at the Massachusetts Institute of Technology (MIT), Boston, USA. The fellowship also supported two years further research in Australia and upon her return in 2003 Dr Stehn took up a position in the Oncology Research Unit at the Children’s Hospital at Westmead. Her main research focus for the past 9 years has been investigating the biological function of the actin cytoskeleton in cancer cells. The Oncology Research Unit relocated to the University of New South Wales in 2008 and Dr Stehn is currently the group leader of the Drug Development Project in the Cellular and Genetic Medicine Unit in the School of Medical Sciences. In 2009 Dr Stehn was awarded an Oncology Children’s Foundation Research Fellowship supported by The Kids Cancer Project.

Honours and Awards

Oncology Children’s Foundation –Cytoskeletal Cancer Consortium (C4 Research Fellow (2009-2012).
Translational Research Award by Stiftung Dermatologikum Hamburg at the XXXIX Annual Meeting of the Arbeitsgemeinschaft Dermatologische Forschung (ADF) (2012).
Ian Potter Foundation Travel award (2009).
National Health and Medical Research Council CJ Martin Postdoctoral Fellowship (2001-2006).
MIT Anna Fuller Fund Fellowship in Molecular Oncology (2000)
Juvenile Diabetes Foundation travel award (1999).
"Excellence In Research"- award, St Vincents' Campus Research Symposium (1999).
American Society of Cell Biology predoctoral travel award (1999).
European Association for the Study of Diabetes travel grant (1998).
American Society of Cell Biology predoctoral travel award (1998).

University role:

Conjoint Senior Lecturer

Groups:

Oncology Research Unit

Research

Socio-economic Objective (SEO) tags:

Cancer and Related Disorders

Publications related to this Person

Book Chapters

Bonello T; Coombes J; Schevzov G; Gunning P; Stehn J, 2012, 'Therapeutic targeting of the actin cytoskeleton in cancer', in Cytoskeleton and Human Disease, pp. 181 - 200, http://dx.doi.org/10.1007/978-1-61779-788-0_10

Journal articles

Bonello TT; Janco M; Hook J; Byun A; Appaduray M; Dedova I; Hitchcock-DeGregori S; Hardeman EC; Stehn JR; Böcking T, 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

Bryce NS; De Laurentiis A; Failes T; Arndt GM; Stehn JR; Hardeman EC; Gunning PW, 2015, 'Identification of the possible states of organisation of the actin cytoskeleton using high content image screening of a high diversity chemical library.', MOLECULAR BIOLOGY OF THE CELL, vol. 26, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000209928400229&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Glass JJ; Phillips PA; Gunning PW; Stehn JR, 2015, 'Hypoxia alters the recruitment of tropomyosins into the actin stress fibres of neuroblastoma cells', BMC Cancer, vol. 15, http://dx.doi.org/10.1186/s12885-015-1741-8

Schevzov G; Kee AJ; Wang B; Sequeira VB; Hook J; Coombes JD; Lucas CA; Stehn JR; Musgrove EA; Cretu A, 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, 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, 2015, 'Cell elasticity is regulated by the tropomyosin isoform composition of the actin cytoskeleton', PLoS ONE, vol. 10, http://dx.doi.org/10.1371/journal.pone.0126214

Stehn JR; Chen D; Currier MA; Eaves D; Desouza M; Moosavian M; Cripe TP; Gunning PW, 2014, 'Synergistic anti-neuroblastoma efficacy using combinatorial cytoskeletal inhibitors', CANCER RESEARCH, vol. 74, http://dx.doi.org/10.1158/1538-7445.PEDCAN-B50

Vindin H; Bischof L; Gunning P; Stehn J, 2014, 'Validation of an algorithm to quantify changes in actin cytoskeletal organization', Journal of Biomolecular Screening, vol. 19, pp. 354 - 368, http://dx.doi.org/10.1177/1087057113503494

Desouza M; Nguyen M; Gunning PW; Stehn JR, 2013, 'Targeting the actin cytoskeleton of neuroblastoma: Elucidating the mechanism by which a novel class of anti-cancer compounds induces tumor cell death.', MOLECULAR CANCER THERAPEUTICS, vol. 12, http://dx.doi.org/10.1158/1535-7163.TARG-13-C208

Wang B; Schevzov G; Coombes J; Hook J; Kee A; Lucas C; Stehn J; Sequeira V; Seger R; Hardeman E, 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=891bb5ab6ba270e68a29b250adbe88d1

Stehn JR; Haass NK; Bonello T; Desouza M; Kottyan G; Treutlein H; Zeng J; Nascimento PRBB; Sequeira VB; Butler TL, 2013, 'A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells', Cancer Research, vol. 73, pp. 5169 - 5182, http://dx.doi.org/10.1158/0008-5472.CAN-12-4501

Desouza M; Gunning PW; Stehn JR, 2012, 'The actin cytoskeleton as a sensor and mediator of apoptosis.', Bioarchitecture, vol. 2, pp. 75 - 87, http://dx.doi.org/10.4161/bioa.20975

Schevzov G; Coombes J; Hook J; Wang B; Kee A; Lucas C; Szokolai R; Sequeira V; Stehn J; Musgrove E, 2012, 'Regulation of cell proliferation mediated by the actin filament stabilizing protein, Tropomyosin 5NM1.', MOLECULAR BIOLOGY OF THE CELL, vol. 23, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000209348601219&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Creed SJ; Desouza M; Bamburg JR; Gunning P; Stehn J, 2011, 'Tropomyosin isoform 3 promotes the formation of filopodia by regulating the recruitment of actin-binding proteins to actin filaments', Experimental Cell Research, vol. 317, pp. 249 - 261, http://dx.doi.org/10.1016/j.yexcr.2010.10.019

Bach CTT; Creed S; Zhong J; Mahmassani M; Schevzov G; Stehn J; Cowell LN; Naumanen P; Lappalainen P; Gunning PW, 2009, 'Tropomyosin isoform expression regulates the transition of adhesions to determine cell speed and direction', Molecular and Cellular Biology, vol. 29, pp. 1506 - 1514, http://dx.doi.org/10.1128/MCB.00857-08

Bonello TT; Stehn JR; Gunning PW, 2009, 'New approaches to targeting the actin cytoskeleton for chemotherapy', Future Medicinal Chemistry, vol. 1, pp. 1311 - 1331, http://dx.doi.org/10.4155/fmc.09.99

O'Neill GM; Stehn J; Gunning PW, 2008, 'Tropomyosins as interpreters of the signalling environment to regulate the local cytoskeleton', Seminars in Cancer Biology, vol. 18, pp. 35 - 44, http://dx.doi.org/10.1016/j.semcancer.2007.08.004

Creed SJ; Bryce N; Naumanen P; Weinberger R; Lappalainen P; Stehn J; Gunning P, 2008, 'Tropomyosin isoforms define distinct microfilament populations with different drug susceptibility', European Journal of Cell Biology, vol. 87, pp. 709 - 720, http://dx.doi.org/10.1016/j.ejcb.2008.03.004

Stehn JR; Schevzov G; O'Neill GM; Gunning PW, 2006, 'Specialisation of the tropomyosin composition of actin filaments provides new potential targets for chemotherapy', Current Cancer Drug Targets, vol. 6, pp. 245 - 256, http://dx.doi.org/10.2174/156800906776842948

Ludowyke RI; Elgundi Z; Kranenburg T; Stehn JR; Schmitz-Peiffer C; Hughes WE; Biden TJ, 2006, 'Phosphorylation of nonmuscle myosin heavy chain IIA on Ser¹⁹¹⁷ is mediated by protein kinase CβII and coincides with the onset of stimulated degranulation of RBL-2H3 mast cells', Journal of Immunology, vol. 177, pp. 1492 - 1499

Nguyen A; Rothman DM; Stehn J; Imperiali B; Yaffe MB, 2004, 'Caged phosphopeptides reveal a temporal role for 14-3-3 in G1 arrest and S-phase checkpoint function', Nature Biotechnology, vol. 22, pp. 993 - 1000, http://dx.doi.org/10.1038/nbt997

Vázquez ME; Nitz M; Stehn J; Yaffe MB; Imperiali B, 2003, 'Fluorescent caged phosphoserine peptides as probes to investigate phosphorylation-dependent protein associations', Journal of the American Chemical Society, vol. 125, pp. 10150 - 10151, http://dx.doi.org/10.1021/ja0351847

Brunet A; Kanai F; Stehn J; Xu J; Sarbassova D; Frangioni JV; Dalal SN; Decaprio JA; Greenberg ME; Yaffe MB, 2002, '14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport', Journal of Cell Biology, vol. 156, pp. 817 - 828, http://dx.doi.org/10.1083/jcb.200112059

Johnson BA; Stehn JR; Yaffe MB; Keith Blackwell T, 2002, 'Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and -independent mechanisms', Journal of Biological Chemistry, vol. 277, pp. 18029 - 18036, http://dx.doi.org/10.1074/jbc.M110465200

Wilson JR; Ludowyke RI; Biden TJ, 2001, 'A redistribution of actin and myosin IIA accompanies Ca²⁺-dependent insulin secretion', FEBS Letters, vol. 492, pp. 101 - 106, http://dx.doi.org/10.1016/S0014-5793(01)02241-4

Mitchell CJ; Kelly MM; Blewitt M; Wilson JR; Biden TJ, 2001, 'Phospholipase C-γ Mediates the Hydrolysis of Phosphatidylinositol, but Not of Phosphatidylinositol 4,5-Bisphoshate, in Carbamylcholine-stimulated Islets of Langerhans', Journal of Biological Chemistry, vol. 276, pp. 19072 - 19077, http://dx.doi.org/10.1074/jbc.M101406200

Iismaa TP; Kerr EA; Wilson JR; Carpenter L; Sims N; Biden TJ, 2000, 'Quantitative and functional characterization of muscarinic receptor subtypes in insulin-secreting cell lines and rat pancreatic islets', Diabetes, vol. 49, pp. 392 - 398, http://dx.doi.org/10.2337/diabetes.49.3.392

Wilson JR; Ludowyke RI; Biden TJ, 1999, 'Potential role of PKC-Mediated myosin II phosphorylation in insulin secretion.', MOLECULAR BIOLOGY OF THE CELL, vol. 10, pp. 32A - 32A, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000083673500183&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Wilson JR; Biden TJ; Ludowyke RI, 1999, 'Increases in phosphorylation of the myosin II heavy chain, but not regulatory light chains, correlate with insulin secretion in rat pancreatic islets and RINm5F cells', Diabetes, vol. 48, pp. 2383 - 2389, http://dx.doi.org/10.2337/diabetes.48.12.2383

Wilson JR; Ludowyke RI; Biden TJ, 1998, 'Nutrient stimulation results in a rapid Ca²⁺-dependent threonine phosphorylation of myosin heavy chain in rat pancreatic islets and RINm5F cells', Journal of Biological Chemistry, vol. 273, pp. 22729 - 22737, http://dx.doi.org/10.1074/jbc.273.35.22729

Edwards MR; Knodler LA; Wilson JR; Schofield PJ, 1993, 'The transport and metabolism of alanine by Giardia intestinalis', Molecular and Biochemical Parasitology, vol. 61, pp. 49 - 57, http://dx.doi.org/10.1016/0166-6851(93)90157-S

Schofield PJ; Edwards MR; Matthews J; Wilson JR, 1992, 'The pathway of arginine catabolism in Giardia intestinalis', Molecular and Biochemical Parasitology, vol. 51, pp. 29 - 36, http://dx.doi.org/10.1016/0166-6851(92)90197-R

Conference Papers

Stehn JR; Haass NK; Bonello T; Desouza M; Kottyan G; Treutlein H; Zeng J; Nascimento PR; Butler T; Allanson M, 2012, 'Developing chemotherapeutics which selectively disable the actin cytoskeleton of tumor cells', in EXPERIMENTAL DERMATOLOGY, WILEY-BLACKWELL, Marburg, GERMANY, pp. e43 - e43, presented at 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung (ADF), Marburg, GERMANY, 01 - 03 March 2012, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000300931700252&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Bonello TT; Stehn J; Hitchcock-DeGregori S; Dixon I; Gunning P, 2011, 'Optimising models to examine the specificity of anti-tropomyosin compounds for Tm5NM1', in MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, Denver, CO, presented at Annual Meeting of the American-Society-for-Cell-Biology (ASCB), Denver, CO, 03 - 07 December 2011, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000305505500216&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Stehn J; Schevzov G; Bonello T; McCluskey A; Haass N; Palmer S; Hardeman E; Allanson M; Reeve V; Gunning P, 2010, 'Tropomyosin Tm5NM1: A novel target for cancer therapy', in EJC SUPPLEMENTS, PERGAMON-ELSEVIER SCIENCE LTD, Berlin, GERMANY, pp. 107 - 107, presented at 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Berlin, GERMANY, 16 - 19 November 2010, http://dx.doi.org/10.1016/S1359-6349(10)72041-3

Floyd SR; Stehn JR; Wilker E; Yaffe MB, 2006, 'Chk1 phosphorylates poly-A binding protein, triggering translocation to the nucleus', in INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, ELSEVIER SCIENCE INC, Philadelphia, PA, pp. S574 - S575, presented at 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO), Philadelphia, PA, 05 - 09 November 2006, http://dx.doi.org/10.1016/j.ijrobp.2006.07.1071

Mohammad D; Carrigan C; Nguyen A; Rothman DM; Manke IA; Stehn J; Lim D; Jouhin B; Tidor B; Imperiali B, 2005, 'Phosphoserine/threonine-binding domains as dynamic modulators of kinase-dependent protein-protein interactions', in FASEB JOURNAL, FEDERATION AMER SOC EXP BIOL, San Diego, CA, pp. A1689 - A1689, presented at Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences, San Diego, CA, 31 March - 06 April 2005, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000227610904661&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Conference Presentations

Jalilian I; Schevzov G; Fath T; Heu C; Bischof L; Vindin H; Stehn JR; Tate MK; Hardeman EC; Gunning PW, 2014, 'Determining the impact of the actin cytoskeleton on the mechanical properties of cells', in MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, Philadelphia, PA, Vol. 25, presented at ASCB/IFCB Meeting, Philadelphia, PA, 06 - 10 December 2014, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352094106265&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Stehn J; Chen D; Currier M; Eaves D; Desouza M; Cripe T; Gunning PW, 2014, 'Synergistic anti-cancer cell impact of anti-tropomyosin compounds with anti-microtubule drugs.', in MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, Philadelphia, PA, Vol. 25, presented at ASCB/IFCB Meeting, Philadelphia, PA, 06 - 10 December 2014, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352094104104&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Jalilian I; Schevzov G; Fath T; Heu C; Bischof L; Vindin H; Stehn JR; Tate MK; Hardeman EC; Gunning PW, 2014, 'Determining the impact of the actin cytoskeleton on the mechanical properties of cells.', in MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, Philadelphia, PA, Vol. 25, presented at ASCB/IFCB Meeting, Philadelphia, PA, 06 - 10 December 2014, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352094100060&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Conference Abstracts

Wang Y; Swain A; Stear JH; Bryce NS; Dugina VB; Alieva IB; Cripe TP; Stehn JR; Hardeman EC; Gunning PW, 2017, 'Synergy between anti-tropomyosin and anti-microtubule drugs reveals an interaction between actin and microtubule networks.', in MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, Philadelphia, PA, Vol. 28, presented at Annual Joint Meeting of the American-Society-for-Cell-Biology and the European-Molecular-Biology-Organization (ASCB/EMBO), Philadelphia, PA, 02 - 06 December 2017, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000426664301293&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Rynkiewicz M; Stehn J; Gunning P; Lehman W, 2017, 'Structure of the Anti-Cancer Compound TR100 Target-Sites on Tpm3.1 Tropomyosin', in BIOPHYSICAL JOURNAL, CELL PRESS, San Francisco, CA, Vol. 112, pp. 560A - 560A, presented at 58th Annual Meeting of the Biophysical-Society, San Francisco, CA, 15 - 19 February 2014, http://dx.doi.org/10.1016/j.bpj.2016.11.3019

Stehn JR; Haass NK; Desouza M; Kottyan G; Treutlein H; Zeng J; Nascimento PR; Han MH; Hill TA; McCluskey A, 2012, 'Developing chemotherapeutics which selectively disable the actin cytoskeleton of tumor cells', in CANCER RESEARCH, AMER ASSOC CANCER RESEARCH, Vol. 72, http://dx.doi.org/10.1158/1538-7445.AM2012-1827

Segueira VB; Stehn JR; Haass N; Bonello T; Guven K; Desouza M; Schevzov G; Kottyan G; McCluskey A; Bischof L, 2012, 'Improving the specificity of drugs which target the actin cytoskeleton for cancer therapy', in CANCER RESEARCH, AMER ASSOC CANCER RESEARCH, Vol. 72, http://dx.doi.org/10.1158/1538-7445.AM2012-5230

Patents

Gunning P; Stehn J; McCluskey A; Butler T; Dixon I, 2007, Compounds for treating Cancer, Australia, Patent No. Australian Provisional Patent Application No 2007906570, Patent Agent:

Gunning P; Stehn J; Schevzov G, 2005, Identification of compounds for the treatment of proliferative disorders, Australia, Patent No. Australian Provisional Patent Application No 2004906888, Patent Agent: