Associate Professor Jean-Pierre Levesque

PhD, BSc

Principal Research Fellow

Projects

Role of macrophages in regulating haematopoiesis and leukaemia

Role of hypoxia-sentsing pathway in regulating haematopoietic stem cells

Understanding the mechanisms of heterotopic ossification following spinal cord injuries

1) Role of macrophages in regulating haematopoiesis and leukaemia, Role of hypoxia inducible factors inregulating haematopoiesis and leukaemia, 3) Mechanisms of heterotopic ossification following spinal cord injuries

About me

A/Prof Jean-Pierre Levesque is a NHMRC Senior Research Fellow. He is co-head the Blood and Bone Diseases Program and head of the Stem Cell Biology Group at Mater Research Institute- University of Queensland. His major research interest is to understand how the bone marrow microenvironment regulates the fate of haematopoietic and leukaemia stem cells. His is also interested in the cross-regulations between the haematopoietic, immune, bone and nervous systems. His major contributions include the discovery of many of the mechanisms responsible for the mobilisation of haematopoietic stem cells into the blood. He was the first to identify the role of hypoxia, macrophages and endothelial selectins as critical regulators of haematopoietic stem cells in their bone marrow niches. His interest in the abnormal differentiation of adult somatic stem cells has led him to investigate the mechanisms of heterotopic ossification following spinal cord injuries. His group has created the first mouse model of this frequent complication of spinal cord injuries.

 

 

Publications

63. Winkler IG, Barbier V, Wadley R, Zannettino A, Williams S, Levesque JP. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: Serially reconstituting hematopoietic stem cells reside in distinct non-perfused niches. 2010 Blood 116(3), 375-385. [see Editorial commentary: “Stem cells hold their breath” by Adams GA pp307-308”.]

64. Shen Y, Winkler IG, Barbier V, Sims NA, Hendy J, Levesque JP. Tissue inhibitor of metalloproteinase-3 (TIMP-3) regulates hematopoiesis and bone formation in vivo. 2010 PLoS One 5, e13086.

65. Winkler IG, Sims MA, Pettit AR, Barbier V, Nowlan B, Helwani F, Poulton IJ, van Rooijen N, Alexander KA, Raggatt LJ, Levesque JP. Bone marrow macrophages are essential to hematopoietic stem cell (HSC) niches and their depletion mobilizes HSC. 2010 Blood 116(23), 4815-4828.

66. Levesque JP, Helwani FM, Winkler IG. The “osteoblastic” niche and its role in hematopoietic stem cell homing and mobilization. 2010 Leukemia 24(12), 1979–1992.

67. Lévesque JP, Winkler IG. Hierarchy of immature hematopoietic cells related to blood flow and niche. 2011 Curr Opin Hematol 18(4), 220-225.

68. Herbert KE, Lévesque JP, Mills AK, Gottlieb DJ, Cooney J, Szer J, Rasko J, To LB. How we mobilise haemopoietic stem cells? 2011 Intern Med J 41(8):588-594.

69. To LB, Levesque JP, Herbert KE, Winkler IG, Bendall LJ, Hiwase D, Antonenas V, Rice A, Gottlieb DJ, Mills AK, Rasko JE, Larsen SR, Beligaswatte A, Nilsson SK, Cooney J, Cambareri T, Lewis I. Mobilisation strategies for normal and malignant cells. 2011 Pathology 43(6), 547-565.

70. To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. 2011 Blood 118(17), 4530-4540.

71. Barbier V, Nowlan B, Levesque JP, Winkler IG. Flow cytometry analysis of cell cycling and proliferation in mouse hematopoietic stem and progenitor cells. 2012 Methods Mol Biol, 844, 31-44.

72. Barbier V, Winkler IG, Wadley R, Levesque JP. Flow Cytometry measurement of bone marrow perfusion in the mouse and sorting of progenitors and stems cells according to position relative to blood flow in vivo. 2012 Methods Mol Biol 844, 45-63.

73. Winkler IG, Pettit AR, Raggatt LJ, Jacobsen R, Barbier V, Nowlan B, Cisterne A, Bendall LJ, Sims NA, Lévesque JP. Hematopoietic stem cell (HSC) mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation. 2012 Leukemia 26(7), 1594-1601.

74. Levesque JP. N(o)-cadherin role for hematopoietic stem cells. 2012 Blood 120(2), 237-238.

75. Barbier V, Winkler IG, Levesque JP. Mobilization of hematopoietic stem cells by depleting bone marrow macrophages. 2012 Methods Mol Biol 904, 117-138.

76. Winkler IG, Barbier V, Nowlan B, Jacobsen RN, Forristal CE, Patton JT, Magnani JL, Levesque JP. Vascular E-selectin regulates hematopoietic stem cell dormancy, self-renewal and chemoresistance. 2012 Nature Medicine  18(11), 1651-1657. [See News an Views: “Waking up HSCs: a new role for E-selectin” by Moore MAS, pp1613-1614].

77. Forristal CE, Winkler IG, Nowlan B, Barbier V, Walkinshaw G, Levesque JP. Pharmacological stabilization of the oxygen-labile transcription factor HIF-1α increases hematopoietic stem cell quiescence and accelerates blood recovery following irradiation. 2013 Blood 121(5), 759-769.

78. Winkler IG, Bendall LJ, Helwani F, Forristal CE, Nowlan B, Barbier V, Shen Y, Cisterne A, Sedger LM, Levesque JP. B-lymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2. 2013 Haematologica 98(3), 325-333.

79. Levesque JP, Winkler IG, Rasko JEJ. Nichotherapy for stem cells: There goes the neighbourhood. 2013 BioEssays 35(3), 183-190.

80. Oancea I , Png CW, Das I, Lourie R, Winkler IG, Eri R, Subramaniam VN, McWhinney B, Jinnah H, Levesque JP, McGuckin M, Duley J, Florin T. A novel mouse model of veno-occlusive disease provides strategies to prevent thioguanine-induced hepatic toxicity. 2013 Gut 62(4), 594-605.

81. Levesque JP, Winkler IG. La E-selectine, un régulateur clé de la division des cellules souches hématopoïétiques et de leur résistance à la chimiothérapie. 2013 Med Sci 29(3), 249-251.

82. Levesque JP. A niche is a dish : pericytes support HSCs. 2013 Blood 121(15): 2816-2818.

83. Levesque JP, Winkler IG. It takes nerves to recover from chemotherapy. 2013 Nature Medicine 19(6): 669-671.

84. Cook MM, Doran MR, Kollar K, Barbier V, Winkler IG, Levesque JP, Brooke GP, Atkinson K. Engraftment outcomes after HPC co-culture with mesenchymal stromal cells and osteoblasts. 2013 J Clin Med 2(3): 115-135.

85. Karpova D, Dauber K, Spohn G, Chudziak D, Wiercinska E, Schulz M, Pettit AR, Levesque JP, Romagnoli B, Patel K, Chevalier E, Dembowsky K, Bonig H. The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor. 2013 Leukemia 27(12): 2322-2331.

86. Forristal CE, Levesque JP. Targeting the hypoxia sensing pathway in clinical hematology. 2014 Stem Cells Translation Medicine 3(2): 135-140.

87. Pattabiraman DR, McGirr C, Shakhbazov K, Barbier V, Krishnan K, Mukhopadhyay P, Hawthorne P, Trezise AEO, Ding J, Grimmond SM, Papathanasiou P, Alexander WS, Perkins AC, Levesque JP, Winkler IG,Gonda TJ. Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes. 2014 Blood 123(17); 2682-2690.

88. Jacobsen RN, Forristal CE, Raggatt LJ, Nowlan B, Barbier V, Kaur S, van Rooijen N, Winkler IG, Pettit AR, Levesque JP. Mobilization with granulocyte colony-stimulating factor blocks medullar erythropoiesis by depleting F4/80+VCAM1+CD169+ER-HR3+Ly6G+ erythroid island macrophages in the mouse. 2014 Exp Hematol, in press.

 

Research fields

Haematology, Stem Cell Biology, Stem Cell Niche, Bone marrow transplantation, Leukaemia, Heterotopic Ossification