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About

We use genetics and genomics tools to probe physiological gene function and to discover the molecular regulators controlling blood cell production and activity. Through collaborations with other laboratories, we apply a multidisciplinary approach to dissect the biology, biochemistry, molecular biology and genetics of regulators of blood cells.

Major areas of interest include:

  • Cytokine control of blood cell production and function, particularly the roles of the cytokine thrombopoietin (TPO)
  • Molecular regulation of platelet production and haematopoietic stem cells

Publications

Selected publications from Prof Warren Alexander

Hildebrand JM, Kauppi M, Majewski IJ, Liu Z, Cox AJ, Miyake S, Petrie EJ, Silk MA, Li Z, Tanzer MC, Brumatti G, Young SN, Hall C, Garnish SE, Corbin J, Stutz MD, Di Rago L, Gangatirkar P, Josefsson EC, Rigbye K, Anderton H, Rickard JA, Tripaydonis A, Sheridan J, Scerri TS, Jackson VE, Czabotar PE, Zhang JG, Varghese L, Allison CC, Pellegrini M, Tannahill GM, Hatchell EC, Willson TA, Stockwell D, de Graaf CA, Collinge J, Hilton A, Silke N, Spall SK, Chau D, Athanasopoulos V, Metcalf D, Laxer RM, Bassuk AG, Darbro BW, Fiatarone Singh MA, Vlahovich N, Hughes D, Kozlovskaia M, Ascher DB, Warnatz K, Venhoff N, Thiel J, Biben C, Blum S, Reveille J, Hildebrand MS, Vinuesa CG, McCombe P, Brown MA, Kile BT, McLean C, Bahlo M, Masters SL, Nakano H, Ferguson PJ, Murphy JM, ALEXANDER WS, Silke J. A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction. Nat Commun. 2020 Jun 19;11(1):3150. PMID: 32561755.

Potts KS, Farley A, Dawson CA, Rimes J, Biben C, de Graaf C, Potts MA, Stonehouse OJ, Carmagnac A, Gangatirkar P, Josefsson EC, Anttila C, Amann-Zalcenstein D, Naik S, ALEXANDER WS, Hilton DJ, Hawkins ED, Taoudi S. Membrane budding is a major mechanism of in vivo platelet biogenesis. J Exp Med. 2020 Sep 7;217(9):e20191206. PMID: 32706855.

Ng AP, Coughlan HD, Hediyeh-Zadeh S, Behrens K, Johanson TM, Low MSY, Bell CC, Gilan O, Chan YC, Kueh AJ, Boudier T, Feltham R, Gabrielyan A, DiRago L, Hyland CD, Ierino H, Mifsud S, Viney E, Willson T, Dawson MA, Allan RS, Herold MJ, Rogers K, Tarlinton DM, Smyth GK, Davis MJ, Nutt SL, ALEXANDER WS. An Erg-driven transcriptional program controls B cell lymphopoiesis. Nat Commun. 2020 Jun 15;11(1):3013. PMID: 32541654

Choi J, Baldwin TM, Wong M, Bolden JE, Fairfax KA, Lucas EC, Cole R, Biben C, Morgan C, Ramsay KA, Ng AP, Kauppi M, Corcoran LM, Shi W, Wilson N, Wilson MJ, ALEXANDER WS, Hilton DJ, de Graaf CA. Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans. Nucleic Acids Res. 2019 Jan 8;47(D1):D780-D785.PMID:30395284.

Sanders MA, Chew E, Flensburg C, Zeilemaker A, Miller SE, Al Hinai AS, Bajel A, Luiken B, Rijken M, Mclennan T, Hoogenboezem RM, Kavelaars FG, Fröhling S, Blewitt ME, Bindels EM, ALEXANDER WS, Löwenberg B, Roberts AW, Valk PJM, Majewski IJ. MBD4 guards against methylation damage and germline deficiency predisposes to clonal hematopoiesis and early-onset AML. Blood. 2018 Oct 4;132(14):1526-1534. PMID: 30049810

Pleines I, Woods J, Chappaz S, Kew V, Foad N, Ballester-Beltrán J, Aurbach K, Lincetto C, Lane RM, Schevzov G, ALEXANDER WS, Hilton DJ, Astle WJ, Downes K, Nurden P, Westbury SK, Mumford AD, Obaji SG, Collins PW, Delerue F, Ittner LM, Bryce NS, Holliday M, Lucas CA, Hardeman EC, Ouwehand WH, Gunning PW, Turro E, Tijssen MR, Kile BT. Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia. J Clin Invest. 2017 Mar 1;127(3):814-829. PMID: 28134622

Alvarez-Diaz S, Dillon CP, Lalaoui N, Tanzer MC, Rodriguez DA, Lin A, Lebois M, Hakem R, Josefsson EC, O’Reilly LA, Silke J, ALEXANDER WS*, Green DR, Strasser A. The Pseudokinase MLKL and the Kinase RIPK3 Have Distinct Roles in Autoimmune Disease Caused by Loss of Death-Receptor-Induced Apoptosis. Immunity 2016 Sep 20;45(3):513-26. PMID: 27523270

Behrens K, Triviai I, Schwieger M, Tekin N, Alawi M, Spohn M, Indenbirken D, Ziegler M, Müller U, ALEXANDER WS, Stocking C. Runx1 downregulates stem cell/megakaryocytic transcription programs that support niche interactions. Blood. 2016 Jun 30;127(26):3369-81. PMID: 27076172.

Ng AP, Kauppi M, Metcalf D, Hyland CD, Josefsson EC, Lebois M, Zhang JG, Baldwin TM, Di Rago L, Hilton DJ, Alexander WS. Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation. Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5884-9. PMID: 24711413.

Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI, Young SN, Varghese LN, Tannahill GM, Hatchell EC, Majewski IJ, Okamoto T, Dobson RC, Hilton DJ, Babon JJ, Nicola NA, Strasser A, Silke J, Alexander WS. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity. 2013 Sep 19;39(3):443-53. PMID: 24012422.

Lee SC, Phipson B, Hyland CD, Leong HS, Allan RS, Lun A, Hilton DJ, Nutt SL, Blewitt ME, Smyth GK, Alexander WS, Majewski IJ. Polycomb repressive complex 2 (PRC2) suppresses Emu-myc lymphoma. Blood. 2013 Oct 10;122(15):2654-63. PMID: 23982173.

Ng AP, Kauppi M, Metcalf D, Di Rago L, Hyland CD, Alexander WS. Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2364-9. PMID: 22308484.

Lab research projects

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