Dr David Curtis - Royal Melbourne Hospital

Principal Investigator, BMRL

David J. Curtis MBBS, PhD, FRACP, FRCPA
Research Fellow and Bone Marrow Transplant Physician
Bone Marrow Research Laboratories

David Curtis completed his medical degree at the University of Melbourne in 1986 and Haematology speciality training in 1994. His PhD was performed at the Walter & Eliza Hall Institute of Medical Research under the mentorship of Professors Glenn Begley and Don Metcalf. David was awarded a CJ Martin Fellowship in 1999 to study the genetic regulation of haemopoietic stem cells at the NIH in Bethesda. He returned to the Bone Marrow Research Laboratories in 2001. In addition to leading his research group, David is a Clinical Haematologist and Bone Marrow Transplant Physician at The Royal Melbourne Hospital.

Research Interests

Transcriptional regulation of haemopoiesis and leukemia
Use of haemopoietic cytokines for tissue repair

His research group has focused on the regulation of haemopoietic stem cells, with emphasis on the role of SCL and other bHLH factors. His group has generated a conditional knockout of SCL to study its role in adult haemopoiesis. This has led to the discovery that unlike haemopoietic development, SCL is not critical for ongoing haemopoiesis. Despite redundancy, SCL is required for normal stem cell function and in particular production of red cells. The focus of research is now to identify the biological processes controlled by SCL, key target genes of SCL and the role of other bHLH factors such as Lyl-1 in haemopoiesis.

In addition to studies of normal haemopoiesis, the group is examining how SCL and related transcription factors induce T-cell leukemia. These studies aim to identify critical regions of SCL for targeted therapy of T-cell leukemias. Conditional transgenic mice are currently being generated to study the role of SCL and its interaction with LMO-2 in oncogenesis.

In vitro growth of haemopoietic stem cells remains a major clinical problem. A second focus of the group is the study of cytokines for ex vivo expansion. The role of hedgehog signalling in haemopoietic stem cells is being evaluated using a mouse strain with conditional targeted hedgehog receptor, Patched.

The possibility that haemopoietic stem cells can participate in tissue repair has generated much excitement over the last 4 years. In collaboration with Professor Alex Bobik, our research group has developed a mouse model of myocardial infarction to test the role of haemopoietic cells in repair of myocardial infarction. We have shown that haemopoietic cytokines can improve myocardial repair (manuscript in preparation). Currently, we are determining the mechanism of this effect and plan to initiate a clinical trial.

Publications

Siggins SL, Nguyen NN, McCormack MP, Vasudevan S, Villani R, Jane SM, Wainwright BJ and Curtis DJ. The hedgehog receptor patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms. Blood 114: 995-1004, 2009.

Zhao Q, Rank G, Tan YT, Li H, Moritz RL, Simpson RJ, Cerruti L, Curtis DJ, Patel DJ, Allis CD, Cunningham JM and Jane SM. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A coupling histone and DNA methylation in gene silencing. Nature Structural Cell Biology 16: 304-311, 2009.

Souroullas GP*, Salmon JM*, Sablitzky F, Curtis DJ* and Goodell MA*. Adult hematopoietic stem and progenitor cells require either Lyl1 or Scl for survival. Cell Stem Cell 4: 180-186, 2009. *equal senior author.

Way KJ, Dinh H, Keene MR, White KE, Clanchy FI, Lusby P, Roiniotis J, Cook AD, Cassady AI, Curtis DJ and Hamilton JA. The generation and properties of human macrophage populations from hemopoietic stem cells. J. Leukocyte Biology 85: 766-778, 2009.

Rank G, Sutton R, Marshall V, Lundie RJ, Caddy J, Romeo T, Fernandez K, McCormack MP, Cooke BM, Foote SJ, Crabb BS, Curtis DJ, Hilton DJ, Kile BT and Jane SM. Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant. Blood 113: 3352-3362, 2009.

Tonkin JN, Knight B, Curtis DJ, Abraham LJ, Yeoh GC. Bone marrow cells play only a very minor role in chronic liver regeneration induced by a choline-deficient, ethionine-supplemented diet. Stem Cell Res. 3:195-204, 2008.

Croom HA, Izon DJ, Chong MM, Curtis DJ, Roberts AW, Kay TW, Hilton DJ, Alexander WS, Starr R. Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine signalling 1 and 3. Mol Immunol. 45: 2888-2896, 2008.

Hoyt R, Ritchie DS, Roberts AW, Macgregor L, Curtis DJ, Szer J, Grigg AP. Cyclosporin, methotrexate and prednisolone for graft-versus-host disease prophylaxis in allogeneic peripheral blood progenitor cell transplants. Bone Marrow Transplantation 41:651-658, 2008.

Salmon JM, Slater NJ, Hall MA, McCormack MP, Nutt SL, Jane SM and Curtis DJ. Aberrant mast cell differentiation in mice lacking the stem cell leukemia gene. Blood 110:3573-3581, 2007.

Stevenson WS, Hoyt R, Bell A, Guipponi M, Juneja S, Grigg AP, Curtis DJ, Scott HS, Szer J, Alexander WS, Tuckfield A, Roberts AW. Genetic heterogeneity of granulocytes for the JAK2 V617F mutation in essential thrombocythaemia: implications for mutation detection in peripheral blood. Pathology 38:336-42, 2006.

McCormack M, Hall MA, Schoenwaelder SM, Zhao Q, Ellis S, Prentice JA, Clarke AJ, Slater NJ, Salmon JM, Jackson SP, Jane SM, and Curtis DJ. A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis. Blood 108:2248-2256, 2006.

Kanellakis P, Slater NJ, Du X-J, Bobik A and Curtis DJ. Granulocyte Colony-Stimulating Factor and Stem Cell Factor Improves Endogenous Repair after Myocardial Infarction. Cardiovascular Research 70; 117-25, 2006.

Hall MA and Curtis DJ. SCL/Tal1 and lymphoid versus myeloid lineage assignment Blood 105: 1365-1366, 2005.

Curtis DJ. Modifier screens in the mouse: Time to move forward with reverse genetics. Proc Natl Acad Sci U S A 101: 7209-10, 2004.

Hall MA, Slater NJ, Begley CG, Salmon JM, Van Stekelenburg LJ, McCormack MP, Jane SM and Curtis DJ. Functional but abnormal adult erythropoiesis in the absence of the stem cell leukemia gene. Molecular and Cellular Biology (in press).

Curtis DJ, Hall MA, Van Stekelenburg LJ, Robb L, Jane SM, Begley CG. SCL is required for normal function of short-term repopulating hematopoietic stem cells. Blood 103: 3342-3348, 2004.

Curtis DJ. Modifier screens in the mouse: Time to move forward with reverse genetics. Proc Natl Acad Sci U S A 101: 7209-10, 2004.

Nemeth MJ*, Curtis DJ*, Kirby MR, Garrett-Beal LJ, Seidel NE, Cline AP, Bodine DM. Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation. Blood 102:1298-306, 2003.

Hall MA, Curtis DJ, Metcalf D, Elefanty AG, Sourris K, Robb L, Gothert JR, Jane SM and Begley CG. The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis and for lineage choice in CFU-S12. Proc Natl Acad Sci U S A 100: 992-7, 2003.

Curtis DJ, Dougherty L and Bodine DM. NF-Y regulates LIF-induced transcription of the signaling adaptor SKAP55R in myeloid cells. Leukemia 15: 1932-40, 2001.

Curtis DJ, Jane SM, Hilton DJ, Dougherty L, Bodine DM and Begley CG. The adaptor protein SKAP55R is associated with myeloid differentiation and growth arrest. Experimental Hematology 28: 1250-1259, 2000.

Curtis DJ, Metcalf D, Alexander B and Begley CG. Leukemic cells from murine myeloid leukemia display an intrinsic ability for autonomous proliferation. Experimental Hematology 28: 36-45, 2000.

Szer J, Curtis DJ, Bardy PG and Grigg AP. The addition of allogeneic peripheral blood-derived progenitor cells to bone marrow for transplantation: results of a randomised clinical trial. Australian & New Zealand Journal of Medicine 29: 487-493, 1999.

Wooley I, Curtis D, Szer J, Fairley C, Vujovic O, Ugoni A and Spelman D. High dose cytosine arabinoside is a major risk factor for the development of hepatosplenic candidiasis in patients with leukemia. Leukemia and Lymphoma 27: 469-474, 1997.

Curtis DJ, Robb L, Strasser A and Begley.CG. The CD2-scl transgene alters the phenotype and frequency of T-lymphomas in N-ras transgenic or p53 deficient mice. Oncogene 15: 2975-2983, 1997.

Curtis DJ, Hilton DJ, Roberts B, Murray L, Nicola N Begley CG. Recombinant soluble interleukin-11 receptor a-chain can both mediate and inhibit an interleukin-11 response. Blood 90:4403-4412, 1997.

Fuller A, Moaven L, Spelman D, Spicer WJ, Wraight H, Curtis D, Leydon J, Doultree J, Locarnini S. Parvovirus B19 in HIV infection: a treatable cause of anaemia. Pathology 28:277-280, 1996.

Begley CG, Rasko JEJ, Curtis D, Tagagi K, Metcalf D, Hilton D, Roberts B, Nicola NA and Rossner MT. Murine flt3 ligand protects M1 leukemic cells from LIF-induced differentiation and suppression of self-renewal. Experimental Hematology 24:1247-1257, 1996.

Curtis DJ, Smale A, Thien F, Schwarer AP, Szer J. Chronic airflow obstruction in long-term survivors of allogeneic bone marrow transplantation. Bone Marrow Transplantation 16:169-173, 1995.

Curtis D, Sparrow R, Brennan L, Van der Weyden MB. Elevated serum homocysteine as a predictor for vitamin B12 or folate deficiency. European Journal of Haematology 52:227-232, 1994.

Van der Weyden MB, CurtisDJ, Szer J. Vitamin therapy for acute leukaemia. Australian & New Zealand Journal of Medicine 22:446-448, 1992.