Division of Stem Cells and Cancer
Prof. Dr. Andreas Trumpp
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:
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.
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.