Ulrich Steidl, MD. Ph.D

Assistant Professor, Department of Cell Biology Chanin Bldg., Room # 515 (718) 430-3437 usteidl@aecom.yu.edu Biosketch Complete list of publications Laboratory Home Page

Research interests Transciptional Regulation of Leukemia Stem Cells The goal of our research is to identify critical mechanisms that drive development and function of normal hematopoietic stem cells (HSC) and leukemia stem cells (LSC), and to better understand the mechanisms of how transcriptional regulators (e.g. transcription factors and chromatin-remodeling factors) cause formation of LSC. To identify implicated pathways we are utilizing rigorously defined stem and progenitor cell subsets isolated by means of multi-parameter high-speed fluorescence-activated cell sorting, linear RNA amplification, and transcriptional analysis. Identified targets are subjected to functional testing by lentiviral gene transfer, in vitro assays as well as murine transplantation models to assess their function in HSC and LSC. Our studies aim at providing the basis for development of LSC-directed therapeutic approaches.

Recent publications Steidl U*, Steidl C*, Ebralidze A, Chapuy B, Han HJ, Will B, Rosenbauer F,Becker A, Wagner K, Koschmieder S, Kobayashi S, Costa DB, Schulz T, O'Brien KB,Verhaak RG, Delwel R, Haase D, Trümper L, Krauter J, Kohwi-Shigematsu T,Griesinger F, Tenen DG. *contributed equally A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia.J Clin Invest. 2007; 117:2611-20. Neukirchen J, Meier A, Rohrbeck A, Garcia-Pardillos G, Steidl U, Fenk R, Haas R, Kronenwett R, Rohr UP. The proteasome inhibitor bortezomib acts differently in combination with p53 gene transfer or cytotoxic chemotherapy on NSCLC cells. Cancer Gene Ther. 2007; 14:431-9. Aivado M, Spentzos D, Germing U, Alterovitz G, Meng XY, Grall F, Giagounidis AA, Klement G, Steidl U, Otu HH, Czibere A, Prall WC, Iking-Konert C, Shayne M, Ramoni MF, Gattermann N, Haas R, Mitsiades CS, Fung ET, Libermann TA. Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease. Proc Natl Acad Sci U S A. 2007; 104:1307-12. Kobayashi S, Shimamura T, Monti S, Steidl U, Hetherington CJ, Lowell AM, Golub T, Meyerson M, Tenen DG, Shapiro GI, Halmos B. Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Res. 2006; 66:11389-98. Rehfeld N, Geddert H, Atamna A, Gabbert HE, Steidl U, Fenk R, Kronenwett R, Haas R, Rohr UP. Coexpression of fragile histidine triad and c-kit is relevant for prediction of survival in patients with small cell lung cancer. Cancer Epidemiol Biomarkers Prev. 2006; 15:2232-8. Steidl U, Rosenbauer F, Verhaak RG, Gu X, Ebralidze A, Otu HH, Klippel S, Steidl C, Bruns I, Costa DB, Wagner K, Aivado M, Kobbe G, Valk PJ, Passegué E, Libermann TA, Delwel R, Tenen DG. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nat Genet. 2006; 38:1269-77. Fenk R, Hieronimus N, Steidl U, Bruns I, Graef T, Zohren F, Ruf L, Haas R, Kobbe G. Sustained G-CSF plasma levels following administration of pegfilgrastim fasten neutrophil reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation in patients with multiple myeloma. Exp Hematol. 2006; 34:1296-302. Kronenwett R, Gräf T, Neumann F, Pechtel S, Steidl U, Diaz-Blanco E, Haas R. Absence of the JAK2 mutation V617F in CD34+ hematopoietic stem and progenitor cells from patients with BCR-ABL-positive CML in chronic phase and blast crisis. Leuk Res. 2006; 30:1323-4. Bruns I, Steidl U, Kronenwett R, Fenk R, Graef T, Rohr UP, Neumann F, Fischer J, Scheid C, Hübel K, Haas R, Kobbe G. A single dose of 6 or 12 mg of pegfilgrastim for peripheral blood progenitor cell mobilization results in similar yields of CD34+ progenitors in patients with multiple myeloma. Transfusion. 2006; 46:180-5. Rehfeld N, Geddert H, Atamna A, Rohrbeck A, Garcia G, Kliszewski S, Neukirchen J, Bruns I, Steidl U, Fenk R, Gabbert HE, Kronenwett R, Haas R, Rohr UP. The influence of the pituitary tumor transforming gene-1 (PTTG-1) on survival of patients with small cell lung cancer and non-small cell lung cancer. J Carcinog. 2006; 5:4. Graef T, Steidl U, Nedbal W, Rohr U, Fenk R, Haas R, Kronenwett R. Use of RNA interference to inhibit integrin subunit alphaV-mediated angiogenesis. Angiogenesis. 2005; 8:361-72. Rosenbauer F, Owens BM, Yu L, Tumang JR, Steidl U, Kutok JL, Clayton LK, Wagner K, Scheller M, Iwasaki H, Liu C, Hackanson B, Akashi K, Leutz A, Rothstein TL, Plass C, Tenen DG. Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Nat Genet. 2006; 38:27-37. Koschmieder S, Rosenbauer F, Steidl U, Owens BM, Tenen DG. Role of transcription factors C/EBPalpha and PU.1 in normal hematopoiesis and leukemia. Int J Hematol. 2005; 81:368-77. Fenk R, Schneider P, Kropff M, Huenerlituerkoglu AN, Steidl U, Aul C, Hildebrandt B, Haas R, Heyll A, Kobbe G; the West German Myeloma Study Group. High-dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment-related mortality in patients with multiple myeloma: results of a randomised study. Br J Haematol. 2005; 30:588-94. Steidl U, Schroeder T, Steidl C, Kobbe G, Graef T, Bork S, Pechtel S, Kliszewski S, Kuendgen A, Rohr UP, Fenk R, Schroeder M, Haase D, Haas R, Kronenwett R. Distinct gene expression pattern of malignant hematopoietic stem and progenitor cells in polycythemia vera. Ann N Y Acad Sci. 2005; 1044:94-108. Rosenbauer F, Koschmieder S, Steidl U, Tenen DG. Effect of transcription-factor concentrations on leukemic stem cells. Blood. 2005; 106:1519-24. Rohr UP, Heyd F, Neukirchen J, Wulf MA, Queitsch I, Kroener-Lux G, Steidl U, Fenk R, Haas R, Kronenwett R. Quantitative real-time PCR for titration of infectious recombinant AAV-2 particles. J Virol Methods. 2005; 127:40-5. Neumann F, Graef T, Tapprich C, Vaupel M, Steidl U, Germing U, Fenk R, Hinke A, Haas R, Kobbe G. Cyclosporine A and mycophenolate mofetil vs cyclosporine A and methotrexate for graft-versus-host disease prophylaxis after stem cell transplantation from HLA-identical siblings. Bone Marrow Transplant. 2005; 35:1089-93. Kronenwett R, Butterweck U, Steidl U, Kliszewski S, Neumann F, Bork S, Blanco ED, Roes N, Gräf T, Brors B, Eils R, Maercker C, Kobbe G, Gattermann N, Haas R. Distinct molecular phenotype of malignant CD34(+) hematopoietic stem and progenitor cells in chronic myelogenous leukemia. Oncogene. 2005; 24:5313-24. Kobbe G, Fenk R, Neumann F, Bernhardt A, Steidl U, Kondakci M, Graef T, Aivado M, Vaupel M, Huenerlituerkoglu AN, Kronenwett R, Pape H, Hildebrand B, Germing U, Haas R. Transplantation of allogeneic CD34+-selected cells followed by early T-cell add-backs: favorable results in acute and chronic myeloid leukemia. Cytotherapy. 2004; 6:533-42. Rohr UP, Rehfeld N, Geddert H, Pflugfelder L, Bruns I, Neukirch J, Rohrbeck A, Grote HJ, Steidl U, Fenk R, Opalka B, Gabbert HE, Kronenwett R, Haas R. Prognostic relevance of fragile histidine triad protein expression in patients with small cell lung cancer. Clin Cancer Res. 2005; 11:180-5. Neumann F, Teutsch N, Kliszewski S, Bork S, Steidl U, Brors B, Schimkus N, Roes N, Germing U, Hildebrandt B, Royer-Pokora B, Eils R, Gattermann N, Haas R, Kronenwett R. Gene expression profiling of Philadelphia chromosome (Ph)-negative CD34+ hematopoietic stem and progenitor cells of patients with Ph-positive CML in major molecular remission during therapy with imatinib. Leukemia. 2005; 19:458-60. Steidl U, Fenk R, Bruns I, Neumann F, Kondakci M, Hoyer B, Gräf T, Rohr UP, Bork S, Kronenwett R, Haas R, Kobbe G. Successful transplantation of peripheral blood stem cells mobilized by chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma. Bone Marrow Transplant. 2005; 35:33-6. Fenk R, Hoyer B, Steidl U, Kondakci M, Graef T, Heuk R, Ruf L, Strupp C, Neumann F, Rohr UP, Hildebrandt B, Haas R, Kobbe G. Single-agent thalidomide for treatment of first relapse following high-dose chemotherapy in patients with multiple myeloma. Leukemia. 2005; 19:156-9. Rohr UP, Rehfeld N, Pflugfelder L, Geddert H, Müller W, Steidl U, Fenk R, Gräf T, Schott M, Thiele KP, Gabbert HE, Germing U, Kronenwett R, Haas R. Expression of the tyrosine kinase c-kit is an independent prognostic factor in patients with small cell lung cancer. Int J Cancer. 2004; 111:259-63. Fenk R, Ak M, Kobbe G, Steidl U, Arnold C, Korthals M, Hünerlitürkoglu A, Rohr UP, Kliszewski S, Bernhardt A, Haas R, Kronenwett R. Levels of minimal residual disease detected by quantitative molecular monitoring herald relapse in patients with multiple myeloma. Haematologica. 2004; 89:557-66. Steidl U, Bork S, Schaub S, Selbach O, Seres J, Aivado M, Schroeder T, Rohr UP, Fenk R, Kliszewski S, Maercker C, Neubert P, Bornstein SR, Haas HL, Kobbe G, Tenen DG, Haas R, Kronenwett R. Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. Blood. 2004; 104:81-8. Rohr UP, Wulf MA, Stahn S, Heyd F, Steidl U, Fenk R, Opalka B, Pitschke G, Prisack HB, Bojar H, Haas R, Kronenwett R. Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector. Cancer Gene Ther. 2003; 10:898-906. Steidl U, Kronenwett R, Martin S, Haas R. Molecular biology of hematopoietic stem cells. Vitam Horm. 2003; 66:1-28. Steidl U, Kronenwett R, Haas R. Differential gene expression underlying the functional distinctions of primary human CD34+ hematopoietic stem and progenitor cells from peripheral blood and bone marrow. Ann N Y Acad Sci. 2003; 996:89-100. Rohr UP, Wulf MA, Stahn S, Steidl U, Haas R, Kronenwett R. Fast and reliable titration of recombinant adeno-associated virus type-2 using quantitative real-time PCR. J Virol Methods. 2002; 106:81-8. Kronenwett R, Gräf T, Nedbal W, Weber M, Steidl U, Rohr UP, Möhler T, Haas R. Inhibition of angiogenesis in vitro by alphav integrin-directed antisense oligonucleotides. Cancer Gene Ther. 2002; 9:587-96. Steidl U, Kronenwett R, Rohr UP, Fenk R, Kliszewski S, Maercker C, Neubert P, Aivado M, Koch J, Modlich O, Bojar H, Gattermann N, Haas R. Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells. Blood. 2002; 99:2037-44. Steidl U, Haas R, Kronenwett R. Intercellular adhesion molecular 1 on monocytes mediates adhesion as well as trans-endothelial migration and can be downregulated using antisense oligonucleotides. Ann Hematol. 2000; 79:414-23. Patzel V, Steidl U, Kronenwett R, Haas R, Sczakiel G. A theoretical approach to select effective antisense oligodeoxyribonucleotides at high statistical probability. Nucleic Acids Res. 1999; 27:4328-34. Kronenwett R, Steidl U, Kirsch M, Sczakiel G, Haas R. Oligodeoxyribonucleotide uptake in primary human hematopoietic cells is enhanced by cationic lipids and depends on the hematopoietic cell subset. Blood. 1998; 91:852-62.

Ulrich Steidl: Research interests | Biosketch Faculty research at a glance Birshtein | Bouhassira | Edelmann | Fyodorov | Keogh | Kielian | Kitsis | Nathenson | Query Scharff | Schildkraut | Shafritz | Singer | Skoultchi | Stanley | Steidl |Warner | Ye   Home