Professor Benjamin Kile

Details

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Division: Chemical Biology

Research Overview

Understanding the regulation of blood cell production and function is critical to the development of new therapies in transplantation medicine, myeloproliferative disease, leukaemia, cancer, heart attack and stroke. Our laboratory is interested primarily in the development and function of the megakaryocytic lineage and its progeny: platelets. These tiny anucleate cells are essential for blood clotting—the human body produces more than a 100 billion of them every day.

In addition to the standard range of reverse genetic technologies (gene knockouts, transgenics) we are pursuing forward genetic screens in the mouse to identify genes that are directly involved in blood cell formation and function. We are also collaborating with groups interested in using genetics to address other biological processes and disease states, including inflammation, lymphangiogenesis and atherosclerosis.

Selected Publications

  1. Fu Y, Mukhamedova N, Ip S, D'Souza W, Henley KJ, Ditommaso T, Kesani R, Ditiatkovski M, Jones L, Lane RM, Jennings G, Smyth IM, Kile BT, Sviridov D. ABCA12 Regulates ABCA1-Dependent Cholesterol Efflux from Macrophages and the Development of Atherosclerosis. Cell Metab. 2013 Aug 6;18(2):225-38. PMID: 23931754
  2. Tang JZ, Carmichael CL, Shi W, Metcalf D, Ng AP, Hyland CD, Jenkins NA, Copeland NG, Howell VM, Zhao ZJ, Smyth GK, Kile BT, Alexander WS. Transposon mutagenesis reveals cooperation of ETS family transcription factors with signaling pathways in erythro-megakaryocytic leukemia. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6091-6. PMID: 23533276
  3. Masters SL, Gerlic M, Metcalf D, Preston S, Pellegrini M, O'Donnell JA, McArthur K, Baldwin TM, Chevrier S, Nowell CJ, Cengia LH, Henley KJ, Collinge JE, Kastner DL, Feigenbaum L, Hilton DJ, Alexander WS, Kile BT, Croker BA. NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells. Immunity. 2012 Dec 14;37(6):1009-23. PMID: 23219391
  4. Carmichael CL, Metcalf D, Henley KJ, Kruse EA, Di Rago L, Mifsud S, Alexander WS, Kile BT. Hematopoietic overexpression of the transcription factor Erg induces lymphoid and erythro-megakaryocytic leukemia. Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15437-42. PMID: 22936051
  5. Debrincat MA, Josefsson EC, James C, Henley KJ, Ellis S, Lebois M, Betterman KL, Lane RM, Rogers KL, White MJ, Roberts AW, Harvey NL, Metcalf D, Kile BT. Mcl-1 and Bcl-xL coordinately regulate megakaryocyte survival. Blood. 2012 Jun 14;119(24):5850-8. PMID: 22374700
  6. White MJ, Schoenwaelder SM, Josefsson EC, Jarman KE, Henley KJ, James C, Debrincat MA, Jackson SP, Huang DC, Kile BT. Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function. Blood. 2012 May 3;119(18):4283-90. PMID: 22294729
  7. Josefsson EC, James C, Henley KJ, Debrincat MA, Rogers KL, Dowling MR, White MJ, Kruse EA, Lane RM, Ellis S, Nurden P, Mason KD, O'Reilly LA, Roberts AW, Metcalf D, Huang DC, Kile BT. Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. J Exp Med. 2011 208(10):2017-31. PMID:21911424.
  8. Kruse EA, Loughran SJ, Baldwin TM, Josefsson EC, Ellis S, Watson DK, Nurden P, Metcalf D, Hilton DJ, Alexander WS, Kile BT. Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage. Proc Natl Acad Sci USA 2009 106(33):13814-9. PMID:19666492.
  9. Loughran SJ, Kruse EA, Hacking DF, de Graaf CA, Hyland CD, Willson TA, Henley KJ, Ellis S, Voss AK, Metcalf D, Hilton DJ, Alexander WS, Kile BT. The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol. 2008 9(7):810-9. PMID:18500345.
  10. Mason KD, Carpinelli MR, Fletcher JI, Collinge JE, Hilton AA, Ellis S, Kelly PN, Ekert PG, Metcalf D, Roberts AW, Huang DC, Kile BT. Programmed anuclear cell death delimits platelet life span. Cell 2007 128(6):1173-86. PMID:17382885.

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Current Laboratory Members

Faculty Member: Benjamin Kile, BSc(Hons) Melb LLB Mon PhD Melb

Postdoctoral Fellow: Catherine Carmichael, BBiomedSc(Hons) PhD Melb

Postdoctoral Fellow: Stephane Chappaz, MSc Paris, PhD Basel

Postdoctoral Fellow: Marlyse Debrincat, BSc(Hons) Melb PhD Melb

Postdoctoral Fellow: Irina Pleines Dipl. Biol. Wuerzburg PhD Wuerzburg

Postdoctoral Fellow: Michael White, BBus BSc Swinburne

Postgraduate Student: Kate McArthur, BSc(Hons) Melb

Research Assistant: Rachael Lane, BSc Monash