Transcription regulation in leukemias
Prof. Dr. Martin Horstmann
»Cancer research is an enormous challenge. We must not let up in our efforts to elucidate the underlying molecular mechanisms of cancer because they are the key to new innovative therapeutic strategies.«
Transcription regulation in Leukemias
Blood formation is largely determined by the hierarchically organized activity of transcription factors. Critical disorders of the orchestrated interplay of these transcription factors can lead to the malignant transformation of white blood cells (e.g. mutations in Runx1, PAX5, Ikaros (IKZF1) into acute B-precursor cell leukemias). In addition, epigenetically aberrant activated transcription modulators such as the zinc finger factor (ZNF) 423 and the Early B-cell factor 1 (EBF1) may impair lymphopoiesis and potentially contribute to the development of leukemia by inhibiting differentiation factors.
Communication of cancer cells
In a variety of tumor diseases, mutations in the central molecular switches in signal transduction have been identified, which lead to a dependence of tumor cells on the activity of the signaling pathway involved. A comprehensive characterization of dependent signaling networks opens up new avenues for the identification of oncogenic and non-oncogenic signaling proteins, which give important signals for the growth and survival of the tumor cell.
General transcription and oncogenesis
The importance of the general transcription factor machinery in the development and progression of tumors is increasingly recognized. Sequence-specific transcription factors regulate general transcription factors in many ways and open up unexpected perspectives for the study of transcription-targeted therapeutic strategies.
Following his studies of medicine in Marburg and Münster, in 1988 Martin Horstmann earned his PhD in medicine at the University of Münster Medical School. As a physician, he began his research activities in the Institute of Pathology, University of Cologne and completed his advanced clinical training in pediatrics, specializing in pediatric hematology, oncology, and stem cell transplantation at the University Medical Center Hamburg-Eppendorf.
His research activities at the Dana Farber Cancer Institute and at Harvard Medical School in Boston, USA, from 1997 to 2000 formed the basis for his current research. Following his return to Germany, he worked as a physician and researcher at the University Medical Center Hamburg-Eppendorf. His research activities focus on the biology of acute childhood leukemia and on the fundamental mechanisms of cellular communication and transcriptional regulation in tumor diseases. The objective of this research is to achieve a new molecular understanding of the pathogenesis of the disease, which will flow into the diagnosis, risk-adapted treatment and prevention of cancer diseases. In 2006 he became head of the newly founded Research Institute Children’s Cancer Center Hamburg. In the following year he was appointed Professor of Molecular Hematology and Oncology of the Faculty of the University of Hamburg. As a scientist and practicing clinical physician, he works at the interface between the research institute and the hospital.
Korf K, Wodrich H, Haschke A, Ocampo C, Harder L, Gieseke F, Pollmann A, Dierck K, Prall S, Staege H, Ma H, Horstmann MA, Evans RM, Sternsdorf T. The PML domain of PML-RARα blocks senescence to promote leukemia. Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12133-8. doi: 10.1073/pnas.1412944111. Epub 2014 Aug 4
Harder L, Eschenburg G, Zech A, Kriebitzsch N, Otto B, Streichert T, Behlich AS, Dierck K, Klingler B, Hansen A, Stanulla M, Zimmermann M, Kremmer E, Stocking C, Horstmann MA. Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome of ETV6-RUNX1 negative B precursor acute lymphoblastic leukemia. J Exp Med. 2013 Oct 21;210(11):2289-304. doi: 10.1084/jem.20130497. Epub 2013 Sep 30.
Zenatti PP, Ribeiro D, Li W, Zuurbier L, Silva MC, Paganin M, Tritapoe J, Hixon JA, Silveira AB, Cardoso BA, Sarmento LM, Correira N, Toribio ML, Kobarg J, Horstmann M, Pieters R, Brandalise SR, Ferrando AA, Meijerink JP, Durum SK, Yunes JA, Barata JT. Oncogenic IL7R gain of function mutations in childhood T-cell acute lymphoblastic leukemia. Nature Genet. 43, 10: 932-941.
Homminga I, Langerak A, de Laat W, Klous P, de Rooi JJ, Stubbs A, Buijs-Gladdines J, Kooi C, van Vlierberghe P, Ferrando A, Cayuela JM, Blanchet O, Verhaaf B, Beverloo HB, Horstmann M, de Haas V, Pieters R, Soulier J, Sigaux F, Meijerink JPP. NKX2-1 and MEF2C oncogenes delineate novel subtypes in T-cell acute lymphoblastic leukemia. Cancer Cell 2011, 19, 484-497.
Widlund HR, Horstmann MA, Price ER, Cui J, Lessnick SL, Wu M, He X, Fisher DE: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. J Cell Biol 158(6):1079-87, 2002. (Widlund and Horstmann: shared first authorship).
McGill GG, Horstmann M, Widlund HR, Du J, Motyckova G, Nishimura EK, Lin YL, Ramaswamy S, Avery W, Ding HF, Jordan SA, Jackson IJ, Korsmeyer SJ, Golub TR, Fisher DE: Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 109(6):707-18, 2002. (McGill and Horstmann: shared first authorship)
Complete List of Publications: Pubmed
Prof. Dr. Martin Horstmann
Phone: 040 / 42605- 1211
Dr. Zoya Eskandarian
Dipl. Biologist, postdoctoral fellow
Phone: +49(0)40 / 42605-1217
Diego González López
Physician, PhD student
Phone: +49 (0) 40 / 42605 - 1224
Physician, PhD student
Phone: +49 (0) 40 / 42605-1224
Dr. Pablo Iglesias Vázquez
Dipl. Biotechnologist, postdoctural fellow
Phone: +49 (0)40 / 42605-1217
Phone: +49 (0) 40 / 741035336
Biological Technical Assistant
Phone: +49 (0) 40 / 42605-1213