Research Interests
The Kindler lab is part of the Department of Hematology, Oncology, and Pneumology at the University Medical Center of the Johannes Gutenberg-University of Mainz, Germany.
In our laboratory, we are interested in understanding signal transduction pathways in cancer cells, with a focus on hematopoietic malignancies. A detailed understanding of aberrant signaling should provide insights into the process of malignant transformation, mechanisms of drug resistance and vulnerability of cancer cells. In addition, the identification of functional differences between cancer stem cells and their normal counterparts will allow us to develop novel therapeutic strategies. In this context we use a variety of distinct experimental approaches and tumor models, including cell culture, defined mouse models (e.g. Flt3-ITD knock-in, conditional KrasG12D knock-in, bone marrow transplantation) and primary tumor samples.
Our laboratory is located in a scientifically stimulating environment and broadly integrated in the research community of the Johannes Gutenberg-University.
If you are interested in an application for a thesis (medical or master) please do not hesitate to contact us. Students with a strong interest in hematology/oncology are always welcome to join the lab for rotations.
Current Projects
Project 1: Targeting leukemia-stroma cell interactions
Project 2: DNA damage repair in the context of mutated KRAS and other oncogenes
Project 3: Leukemic transformation, aberrant signaling and stress response
Project 4: Genomic instability and DNA damage repair in leukemia
Publications (Selection)
For a complete list of publications please click on the ResearcherID button. There also citation metrics can be found.
- Sasca D, Hähnel PS, Szybinski J, Khawaja K, Kriege O, Pante SV, Bullinger L, Strand S, Strand D, Theobald M, Kindler T. SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia. Blood. 2014;124(1):121-33.
- Hähnel PS, Enders B, Sasca D, Roos WP, Kaina B, Bullinger L, Theobald M, Kindler T. Targeting components of the alternative NHEJ pathway sensitizes KRAS mutant leukemic cells to chemotherapy. Blood. 2014;123(15):2355-66.
- Hartwell KA, Miller PG, Mukherjee S, Kahn AR, Stewart AL, Logan DJ, Negri JM, Duvet M, Järås M, Puram R, Dancik V, Al-Shahrour F, Kindler T, Tothova Z, Chattopadhyay S, Hasaka T, Narayan R, Dai M, Huang C, Shterental S, Chu LP, Haydu JE, Shieh JH, Steensma DP, Munoz B, Bittker JA, Shamji AF, Clemons PA, Tolliday NJ, Carpenter AE, Gilliland DG, Stern AM, Moore MA, Scadden DT, Schreiber SL, Ebert BL, Golub TR. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells. Nat. Chem. Biol. 2013;9(12):840-8.
- Cabezas-Wallscheid N, Eichwald V, de Graaf J, Löwer M, Lehr HA, Kreft A, Eshkind L, Hildebrandt A, Abassi Y, Heck R, Dehof AK, Ohngemach S, Sprengel R, Wörtge S, Schmitt S, Lotz J, Meyer C, Kindler T, Zhang DE, Kaina B, Castle JC, Trumpp A, Sahin U, Bockamp E. Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model. EMBO Mol. Med. 2013;5(12):1804-20.
- Tam WF, Hähnel P, Schüler A, Lee BH, Okabe R, Zhu N, Pante S, Raffel G, Mercher T, Wernig G, Bockamp E, Kreft A, Robinson GW, Hennighausen L, Gilliland DG, Kindler T. STAT5 is crucial for the maintenance of leukemic stem cells in MOZ-TIF2 induced acute myeloid leukemogenesis. Cancer Research. 2013;73(1):373-84.
- Breitenbuecher F, Markova B, Kasper S, Carius B, Stauder T, Schnittger S, Haferlach T, Boehmer F, Huber C, Kindler T*, Fischer T*. Rewired FLT3_ITD Signaling Pathways Confer Primary Resistance to FLT3-Kinase Inhibitors in Acute Myeloid Leukemia. Blood. 2009;23;113(17):4063-73. * Equal contribution
- Kindler T, Cornejo MG, Scholl C, Liu J, Leeman DS, Haydu JE, Fröhling S, Lee BH, Gilliland DG. K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to γ-secretase inhibitors. Blood. 2008;112(8):3373-82.
- Mercher T, Cornejo MG, Sears C, Kindler T, Moore SA, Maillard I, Pear WS, Aster JC, Gilliland DG. Notch Signaling Specifies Megakaryocyte Development from Hematopoietic Stem Cells. Cell Stem Cell. 2008;3(3):314-26.
- Kindler T, Breitenbuecher F, Kasper S, Estey E, Giles F, Feldman E, Ehninger G, Schiller G, Klimek V, Nimer SD, Gratwohl A, Choudhary CR, Mueller-Tidow C, Serve H, Gschaidmeier H, Cohen PS, Huber C, Fischer T. Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML). Blood. 2005;105(1):335-40.
- Kindler T, Breitenbuecher F, Kasper S, Stevens T, Carius B, Gschaidmeier H, Huber C, Fischer T. In BCR-ABL-positive cells, STAT-5 tyrosine-phosphorylation integrates signals induced by imatinib mesylate and Ara-C. Leukemia. 2003;17(6):999-1009.
Kindler Laboratory's Team
Principal Investigator
Univ.-Prof. Dr. Thomas Kindler
Tel.: 06131 17-5046
E-Mail: Thomas.Kindler@unimedizin-mainz.de
Laboratory Members
Alumni
- Sven Henninger, M. Sc.
- Dr. med. Undine Lange
- Dr. rer. nat. Saskia Pante
- Dr. med. Daniel Sasca
- Dr. rer. nat. Andrea Schüler
- Dr. rer. nat. Torsten Stauder, M. Sc.
- Jakub Szybinski Guerrero
