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The Starczynowski laboratory is interested in the molecular, cellular, and genetic basis of hematologic malignancies, with a specific focus on Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). MDS is a hematopoietic stem cell (HSC) disorder resulting in abnormal blood cell production and a propensity to progress to AML. Unfortunately, the complexity and heterogeneity of MDS and lack of mouse models has impeded our understanding and treatment of this disease. The long-term objective of the Starczynowski laboratory is to identify altered genes and signaling pathways, and understand the contribution of these alterations to the pathogenesis of MDS and AML. The overarching goal is to eventually provide novel therapies to patients with myeloid malignancies.
Rhyasen GW, Bolanos L, Fang J, Jerez A, Wunderlich M, Rigolino C, Mathews L, Ferrer M, Southall N, Guha R, Keller J, Thomas C, Beverly LJ, Cortelezzi A, Oliva EN, Cuzzola M, Maciejewski JP, Mulloy JC, Starczynowski DT.Targeting IRAK1 as a Therapeutic Approach for Myelodysplastic Syndrome. Cancer Cell. Jul 8;24(1):90-104. 2013.
Guo F, Zhang S, Grogg M, Cancelas JA, Varney ME, Starczynowski DT, Du W, Yang JQ, Liu W, Zhu W, Thomas G, Kozma S, Pang Q, Zheng Y. Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis. Haematologica. Epub. 2013 May 28.
Fang J, Rhyasen G, Bolanos L, Rasch C, Varney M, Wunderlich M, Goyama S, Jansen G, Cloos J, Rigolino C, Cortelezzi A, Mulloy JC, Oliva EN, Cuzzola M, Starczynowski DT. Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1. Blood. Jul 26;120(4):858-67. 2012.
Fang J, M Varney, and DT Starczynowski. Implication of miRNAs in the pathogenesis of MDS. Current Pharmaceutical Design. 2012.
Vercauteren S, DT Starczynowski, S Sung, K McNeil, C Salski, C-L Jensen, W Lam, A Karsan. T cells of patients with Myelodysplastic syndrome are frequently derived from the malignant clone. British Journal of Haematology. Epub. 2011.
Starczynowski DT, WL Lockwood, S Delehouzee, S Lam, M-S Tsao, AF Gazdar, W Lam, and A Karsan. TRAF6 is an amplified oncogene bridging the Ras and nuclear factor-kB cascade in lung cancer. Journal of Clinical Investigation. Oct;121(10):4095-105. 2011.
Rhyasen G and DT Starczynowski. Deregulation of microRNAs in Myelodysplastic Syndromes. Leukemia. Jan;26(1):13-22. 2011.
Kuchenbauer F, SM Mah, M Heuser, A McPherson, J Ruschmann, A Rouhi, T Berg, L Bullinger, B Argiropoulos, RD Morin, D. Lai, DT Starczynowski, A Karsan, CJ Eaves, A Watahiki, Y Wang, SA Aparicio, A Ganser, J Krauter, H Doehner, K Doehner, MA Marra, FD Carmargo L Palmquist, C Buske, and RK Humphries. Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells. Blood. Sep 22;118(12):3350-8. 2011.
Starczynowski DT, F Kuchenbauer, J Wegrzyn, K Humphries, and A Karsan. Increased expression of microRNA-146 disrupts differentiation and survival of hematopoietic progenitor cells. Experimental Hematology. Feb;39(2):167-178.e4. 2011.
Starczynowski DT, RD Morin, A McPherson, J Lam, R Chari, J Wegrzyn, A Delaney, AL Prabhu, Y Zhao, M Hirst, W Lam, MA Marra, and A Karsan. Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations. Blood. 2011.
Starczynowski DT, S Vercauteren, S Sung, A Brooks-Wilson, J Spinelli, C Eaves, A Eaves, D Horsman, W Lam, and A Karsan. Evidence of somatic alterations of genomic copy number variants in clonally derived cells from patients with low-risk myelodysplastic syndromes. Leukemia Research. Apr;35(4):444-7. 2011.
Vercauteren SM, S Sung, DT Starczynowski, WL Lam, H Bruyere, DE Horsman, P Tsang, H Leitch, and A Karsan. Cryptic alterations detected by array comparative genomic hybridization in bone marrow CD34+ cells are not present in peripheral blood granulocytes of patients with myelodysplastic syndrome. American Journal of Clinical Pathology, 134(1):119-126. 2010.
Starczynowski DT and A Karsan. Innate immune signaling in Myelodysplastic Syndromes. Hematology/Oncology Clinics of North America, 24(2):343-359. 2010.
Starczynowski DT and A Karsan. Deregulation of innate immune signaling in myelodysplastic syndromes is associated with deletion of chromosome arm 5q. Cell Cycle. Mar 1;9(5):855-6. 2010.
Starczynowski DT, F Kuchenbauer, B Argiropoulos, S Sung, R Morin, A Muranyi, D Hogue, R Wells, M Marra, WL Lam, K Humphries, and A Karsan. Identification of miR-145 and miR-146a as microRNAs involved in the pathogenesis of 5q- syndrome. Nature Medicine, 16(1): 49-58. 2010.
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