Improving the outcomes of children with cancer

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.

Innovative zelluläre Therapie der ALL

Ein weiteres wichtiges Forschungsprojekt ist der adoptive Transfer von iPSC-CAR-NK Zellen in der Behandlung der Hoch-Risiko Leukämien.


Entschlüsselung von Signalkaskaden und Entwicklung innovativer, Zellbasierter immunologischer Ansätze zur Therapie von Neuroblastomen, Leukämien und anderen Malignomen

Dr. Peter Nollau

Dr. Peter Nollau

»We are interested in how cancer cells process signals. Cancer cells behave differently from normal cells. We want to elucidate these differences in order to develop new, targeted therapies.«

Es ist allgemein akzeptiert, dass Krebserkrankungen auf der Akkumulation von Veränderungen im Erbgut beruhen. Diese Mutationen haben tiefgreifende Veränderungen im Signalverhalten der Krebszellen zur Folge, die von der Zelloberfläche bis auf die Ebene des Zellkernes reichen. Ziel unserer Forschungs-bemühungen ist es, zentrale Stellschrauben im Signalverhalten von Hochrisikoleukämien des Kindesalters und Neuroblastomen aufzudecken, um auf dieser Basis neue und ergänzende therapeutische Konzepte zu entwickeln und präklinisch zu testen.

Ein besonderer Schwerpunkt unserer aktuellen Forschung liegt in der Charakterisierung der Oberflächenverzuckerung (Glykosylierung) von Krebszellen, deren Veränderungen vielfältig sind und ebenfalls großen Einfluss auf das zelluläre Signalverhalten nehmen. Die auf der Zelloberfläche lokalisierten Zuckerstrukturen bieten einen idealen Angriffspunkt für neue, Zell-basierte Immuntherapien, weshalb wir derzeit genetisch manipulierte, gegen Zucker-gerichtete zytotoxische T-Zellen zur Abtötung von Krebszellen entwickeln und deren Effektivität in präklinischen Modellen testen.

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.

After studying medicine in Hamburg, Peter Nollau earned his medical doctorate at the University of Hamburg Medical School in 1992. As a physician, he took up his research activities at the Diagnostic Center of the University Medical Center Hamburg-Eppendorf. The main focus of his research was on the detection of tumor mutations, protein glycosylation and the role of cell adhesion molecules in malignant diseases.

In 1999, funded by a research grant of the German Research Foundation (DFG), Peter Nollau started his research activities at Children's Hospital, Harvard Medical School in Boston, USA, focusing on phosphotyrosine-binding domains in signal transduction in cancer, which he continued after returning to the Institute for Clinical Chemistry at the University Medical Center Hamburg-Eppendorf in 2001. His research activities is focusing on decoding of aberrant signaling processes in human cancer cells with the major aim to better understand signaling in malignant diseases for the development of novel, targeted cancer therapies.

In spring 2014 Nollau became a research group leader at the Research Institute Children’s Cancer Center Hamburg, where on the basis of his longstanding cooperation with the institute, he is studying aberrant signal transduction, phosphorylation and glycosylation in high-risk childhood leukemia and neuroblastoma.

German Research Foundation

European Union

German Cancer Aid

Josep Carreras Leukaemia Foundation

Erich and Gertrud Roggenbuck Foundation

Madeleine Schickedanz Children’s Cancer Foundation

Wilhelm Sander-Foundation

European Union

German Cancer Aid

German Federal Ministry of Education and Research

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 

Nollau P, Wolters-Eisfeld G, Mortezai N, Kurze AK, Klampe B, Debus A, Bockhorn M, Niendorf A, Wagener C. Protein domain histochemistry (PDH): binding of the carbohydrate recognition domain (CRD) of recombinant human glycoreceptor CLEC10A (CD301) to formalin-fixed, paraffin-embedded breast cancer tissues. J Histochem Cytochem. 2013; 61:199-205.

Machida K, Khenkhar M, Nollau P. Deciphering Phosphotyrosine-Dependent Signaling Networks in Cancer by SH2 Profiling. Genes Cancer. 2012;3:353-61.

Brandt DT, Baarlink C, Kitzing TM, Kremmer E, Ivaska J, Nollau P, Grosse R. SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin. Nat Cell Biol. 2009; 11:557-68. 

Machida K, Thompson CM, Dierck K, Jablonowski K, Kärkkäinen S, Liu B, Zhang H, Nash PD, Newman DK, Nollau P, Pawson T, Renkema GH, Saksela K, Schiller MR, Shin DG, Mayer BJ. High-throughput phosphotyrosine profiling using SH2 domains. Mol Cell. 2007; 26:899-915.

Dierck K, Machida K, Voigt A, Thimm J, Horstmann M, Fiedler W, Mayer BJ, Nollau P. Quantitative multiplexed profiling of cellular signaling networks using phosphotyrosine-specific DNA-tagged SH2 domains. Nat Methods. 2006; 3:737-44.

Nollau P, Mayer BJ. Profiling the global tyrosine phosphorylation state by Src homology 2 domain binding. Proc Natl Acad Sci U S A. 2001; 98:13531-6. 

 

Complete List of Publications: Pubmed

Prof. Dr. Martin Horstmann

Scientific Director
Phone: 040 / 42605- 1211
horstmann@remove-this.kinderkrebs-forschung.de

Dr. Zoya Eskandarian

Dipl. Biologist, postdoctoral fellow
Phone: +49(0)40 / 42605-1217
eskandarian@remove-this.kinderkrebs-forschung.de

Darleen Fröhlich

Biological Technical Assistant
Phone: +49 (0) 40 / 42605-1213
froehlich@kinderkrebs-forschung.de

Marlene Goos

Physician, PhD student
Telefon: +49 (0) 40 / 42605-1225
goos@remove-this.kinderkrebs-forschung.de

 

Diego González López

Physician, PhD student
Phone: +49 (0) 40 / 42605 - 1224
gonzales@kinderkrebs-forschung.de

 

Anna-Lena Heitmann

Physician, PhD student
Phone: +49 (0) 40 / 42605-1224
heitmann@remove-this.kinderkrebs-forschung.de

 

Dr. Pablo Iglesias Vázquez

Dipl. Biotechnologist, postdoctural fellow
Phone: +49 (0)40 / 42605-1217
iglesias@remove-this.kinderkrebs-forschung.de

Maria Orthey

Physician, PhD student
Phone: +49(0)40 / 42605-1224
orthey@remove-this.kinderkrebs-forschung.de

 

Michael Spohn

Bioinformatician
Phone: +49 (0) 40 / 741035336
spohn@remove-this.kinderkrebs-forschung.de


Julia Strauss

Julia Strauss

Biological Technical Assistant
Phone: +49 (0) 40 / 42605-1213
strauss@remove-this.kinderkrebs-forschung.de

Dr. Antonina Wrzeszcz

Veterinarian
Phone: +49 (0) 40 / 42605-1225
wrzeszcz@remove-this.kinderkrebs-forschung.de

 

Dr. Peter Nollau

Physician, Research Group Leader
Phone: +49 (0) 40 / 42605-1215
nollau@remove-this.kinderkrebs-forschung.de

Helwe Gerull

Medical Technical Assistant
Phone: +49 (0) 40 / 4260 -1235
gerull@remove-this.kinderkrebs-forschung.de

Dr. Anna-Katharina Kurze

Dipl. Biologist, postdoctoral fellow
Phone: +49 (0) 40 / 42605-1214
kurze@remove-this.kinderkrebs-forschung.de

Dr. Gerrit Wolters-Eisfeld

Dipl. Biologist, postdoctoral fellow
Telefon: +49(0)40 / 42605-1217
wolters-eisfeld@remove-this.kinderkrebs-forschung.de