Starczynowski Lab

Starczynowski Research Lab

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.

Lab Publications

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2016

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Fang J, Liu X, Bolanos L, Barker B, Rigolino C, Cortelezzi A, Oliva EN, Cuzzola M, Grimes HL, Fontanillo C, Komurov K, MacBeth K, Starczynowski DT. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes. Nat Med. 2016 Jul;22(7):727-34.

2015

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Rhyasen GW, Starczynowski DT. IRAK signalling in cancer. Br J Cancer. 2015 Jan 20;112(2):232-7.

Gañán-Gómez I, Wei Y, Starczynowski DT, Colla S, Yang H, Cabrero-Calvo M, Bohannan ZS, Verma A, Steidl U, Garcia-Manero G. Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia. 2015 Mar 12.

Adams AK, Bolanos LC, Dexheimer PJ, Karns RA, Aronow BJ, Komurov K, Jegga AG, Casper KA, Patil YJ, Wilson KM, Starczynowski DT, Wells SI. IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival. Oncotarget. 2015 Dec 22;6(41):43395-407.

Varney ME, Niederkorn M, Konno H, Matsumura T, Gohda J, Yoshida N, Akiyama T, Christie S, Fang J, Miller D, Jerez A, Karsan A, Maciejewski JP, Meetei RA, Inoue J, Starczynowski DT. Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling. J Exp Med. 2015 Oct 19;212(11):1967-85. \

Gentner B, Pochert N, Rouhi A, Boccalatte F, Plati T, Berg T, Sun SM, Mah SM, Mirkovic-Hösle M, Ruschmann J, Muranyi A, Leierseder S, Argiropoulos B, Starczynowski DT, Karsan A, Heuser M, Hogge D, Camargo FD, Engelhardt S, Döhner H, Buske C, Jongen-Lavrencic M, Naldini L, Humphries RK, Kuchenbauer F. MicroRNA-223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia. Exp Hematol. 2015 Oct;43(10):858-868.e7.

Varney ME, Melgar K, Niederkorn M, Smith MA, Barreyro L, Starczynowski DT. Deconstructing innate immune signaling in myelodysplastic syndromes. Exp Hematol. 2015 Aug;43(8):587-98.

Fang J, Starczynowski DT. Genomic instability establishes dependencies on acquired gene regulatory networks: A novel role of p62 in myeloid malignancies with del(5q). Mol Cell Oncol. 2015 Feb 23;2(4):e1014219.

2014

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Zhao JL, Starczynowski DT. Role of microRNA-146a in normal and malignant hematopoietic stem cell function. Front Genet. 2014 Jul 9;5:219.

Beverly LJ, Starczynowski DT. IRAK1: oncotarget in MDS and AML. Oncotarget. 2014 Apr 15;5(7):1699-700.

Rhyasen GW, Wunderlich M, Tohyama K, Garcia-Manero G, Mulloy JC, Starczynowski DT. An MDS xenograft model utilizing a patient-derived cell line. Leukemia. 2014 May;28(5):1142-5.

Starczynowski DT. Errant innate immune signaling in del(5q) MDS. Blood. 2014 Jul 31;124(5):669-71.

Wilson IM, Vucic EA, Enfield KS, Thu KL, Zhang YA, Chari R, Lockwood WW, Radulovich N, Starczynowski DT, Banáth JP, Zhang M, Pusic A, Fuller M, Lonergan KM, Rowbotham D, Yee J, English JC, Buys TP, Selamat SA, Laird-Offringa IA, Liu P, Anderson M, You M, Tsao MS, Brown CJ, Bennewith KL, MacAulay CE, Karsan A, Gazdar AF, Lam S, Lam WL. EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk. Oncogene. 2014 Sep 4;33(36):4464-73.

Fang J, Barker B, Bolanos L, Liu X, Jerez A, Makishima H, Christie S, Chen X, Rao DS, Grimes HL, Komurov K, Weirauch MT, Cancelas JA, Maciejewski JP, Starczynowski DT. Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-κB gene network. Cell Rep. 2014 Sep 11;8(5):1328-38.

Chang KH, Sengupta A, Nayak RC, Duran A, Lee SJ, Pratt RG, Wellendorf AM, Hill SE, Watkins M, Gonzalez-Nieto D, Aronow BJ, Starczynowski DT, Civitelli R, Diaz-Meco MT, Moscat J, Cancelas JA. p62 is required for stem cell/progenitor retention through inhibition of IKK/NF-κB/Ccl4 signaling at the bone marrow macrophage-osteoblast niche. Cell Rep. 2014 Dec 24;9(6):2084-97.

2013

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Rhyasen GW, Bolanos L, Starczynowski DT. Differential IRAK signaling in hematologic malignancies. Exp Hematol. 2013 Dec;41(12):1005-7.

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.

2012

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Rhyasen GW, Starczynowski DT. Deregulation of microRNAs in myelodysplastic syndrome. Leukemia. 2012 Jan;26(1):13-22.

Vercauteren SM, Starczynowski DT, Sung S, McNeil K, Salski C, Jensen CL, Bruyere H, Lam WL, Karsan A. T cells of patients with myelodysplastic syndrome are frequently derived from the malignant clone. Br J Haematol. 2012 Feb;156(3):409-12.

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 ;18(22):3170-9.

2011

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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.

2010

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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.

Other Significant Publications

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Starczynowski DT, S Vercauteren, S Sung, A Brooks-Wilson, J Spinelli, C Eaves, A Eaves, D Horsman, W Lam, and A Karsan. High-resolution array comparative genomic hybridization of CD34⁺ cells from patients with low-risk myelodysplastic syndromes predicts overall and leukemia-free survival . Blood. Oct 15;112(8):3412-24. 2008.

Contact Us

Daniel Starczynowski, PhD
Principle Investigator
Email: daniel.starczynowski@cchmc.org
Phone: 513-803-5317

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Starczynowski Lab