Cookie Settings

We use cookies to optimize our website. These include cookies that are necessary for the operation of the site, as well as those that are only used for anonymous statistic. You can decide for yourself which categories you want to allow. Further information can be found in our data privacy protection .

Essential

These cookies are necessary to run the core functionalities of this website and cannot be disabled.

Name Webedition CMS
Purpose This cookie is required by the CMS (Content Management System) Webedition for the system to function correctly. Typically, this cookie is deleted when the browser is closed.
Name econda
Purpose Session cookie emos_jcsid for the web analysis software econda. This runs in the “anonymized measurement” mode. There is no personal reference. As soon as the user leaves the site, tracking is ended and all data in the browser are automatically deleted.
Statistics

These cookies help us understand how visitors interact with our website by collecting and analyzing information anonymously. Depending on the tool, one or more cookies are set by the provider.

Name econda
Purpose Statistics
External media

Content from external video platforms is blocked by default. If cookies from external media are accepted, access to this content no longer requires manual consent.

Name Youtube
Purpose External media

Division of Stem Cells and Cancer

Prof. Dr. Andreas Trumpp

© dkfz.de

Stem cells are essential for maintaining and repairing regenerative tissues. However, genetic alterations of stem cells can lead to the generation of “cancer stem cells” (CSCs) that drive tumorigenesis and metastasis. Starting with mouse models, we extend our work to the analysis of primary patient samples (blood, bone marrow, tumor/metastasis samples) and link the results to clinical parameters with the goal to develop innovative strategies to detect and target cancer and metastatic stem cells and break therapy resistance (see also: www.hi-stem.de).
We are interested to unravel the molecular and cellular basis of hematopoietic stem cell (HSC) and embryonic stem cell (ESC) self-renewal. We have previously shown that the most potent HSCs are in a state of deep dormancy. In response to infections or chemotherapy mediated cell loss, dormant HSCs become activated and organize the repair of the system (Wilson, Cell 2008; Essers, Nature 2009). Using genome-wide transcriptomics, proteomics and methylome analysis, we have established the molecular landscape of HSCs and progenitors to understand the molecular basis of self-renewal and multipotency, as well as the interactions between stem cells and their niche (1). We then showed that the oncogene MYC controls dormancy of pluripotent cells in the embryo and HSCs in the adult organism. Thus, MYC is the key regulator controlling entry and exit from dormancy of normal stem cells and potentially in cancer and metastasis stem cells (2). In our MDS and AML program we study signaling networks and the role of the microenvironment for disease progression and therapy resistance (Medyouf, Cell Stem Cell 2014). In solid tumors, we have identified circulating “metastasis initiating cells” (MICs) directly from the peripheral blood of breast cancer patients, which are able to initiate new bone and lung metastasis. Their cell surface receptors CD44+MET+CD47+ offer now novel possibilities for the design of better diagnostic and therapeutic tools for breast cancer (3). In pancreatic cancer we have identified novel tumor subclasses and developed biomarkers to allow the stratification of patients. One subclass shows a widespread resistance to current therapies. This is mediated by CYP3A5, which initiates an enzymatic cascade to metabolize and inactivate the drugs. Blockade of CYP3A5 breaks resistance and sensitizes the tumors to several drugs in preclinical settings (4). We are now developing CYP3A5 inhibitors for combination therapies to target pancreatic cancers.

Future Outlook:
We functionally characterize both normal and malignant stem cells by using in vitro and in vivo approaches. We then use stateof- the-art methods to uncover the mechanisms that control and drive normal and uncontrolled self-renewal as well as therapy resistance. From model systems, we typically extend our work to the analysis of primary patient derived samples and link the results to clinical parameters with the goal to develop innovative strategies to detect and target cancer and metastatic stem cells and break therapy resistance.

In addition to his role as Head of the Division of Stem Cells and Cancer, Prof. Trumpp is also Managing Director of the Heidelberg Institute for Stem Cell Technology and Experimental Medicine, located within the main building of the DKFZ. Click here for more details.

Contact

Prof. Dr. Andreas Trumpp
Stem Cells and Cancer (A010)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 3901

Selected Publications

  • Cabezas-Wallscheid, N. et al. (2017). Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy. Cell DOI: 10.1016/j.cell.2017.04.018
  • Raffel, S. et al. (2017). BCAT1 restricts ?KG levels in AML stem cells leading to IDHmut-like DNA hypermethylation. Nature DOI: 10.1038/nature24294
  • Scognamiglio, R. et al. (2016). Myc Depletion Induces a Pluripotent Dormant State Mimicking Diapause. Cell DOI: 10.1016/j.cell.2015.12.033
  • Noll, E. M. et al. (2016). CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. Nature Medicine DOI: 10.1038/nm.4038
to top
powered by webEdition CMS