Molecular Cancer Research

Rönnstrand Group

Our Research

The focus of our laboratory is to understand the molecular mechanisms of cancer, specifically acute leukemia and malignant melanoma. In particular, in acute myeloid leukemia, oncogenic mutations in the receptor tyrosine kinase FLT3 is commonly occurring and correlates with poor prognosis of patients. For this reason, several selective inhibitors of FLT3 have been developed and tried in the clinic. However, the result is disappointing. Responses are usually not strong and last only for a limited time. We are interested in identifying the mechanisms of acquired resistance to targeted inhibitors. In order to improve our understanding of acute leukemia, we are also in the process of identifying novel signal transduction proteins involved in leukemogenesis and how they are regulated by e.g. phosphorylation, how they can be linked to various biological responses etc. Identification of novel signal transduction molecules and the signal transduction networks they are involved, that are of crucial importance for transformation, will help in development of novel targeted therapies. Apart from FLT3, we are also investigating the role of other receptor tyrosine kinases in cancer, e.g. AXL and KIT.

Aims

To understand the molecular mechanisms of transformation in acute leukemia with special focus on RTKs and their downstream signaling
To use this knowledge to manipulate the signal transduction pathways, either by identification of novel molecules with a combination of proximity-dependent biotinylation labeling of proteins combined with mass spectrometry and identification of their posttranslational modification, CRISPR/CAS9-mediated knockout or mutagenesis, by using transgenic mice and by employing PDX-based models of acute myeloid leukemia

Impact

List of Team Rönnstrand's publications

Enhanced understanding of the molecular mechanisms behind various forms of acute leukemia will improve our possibilities of targeting these signal transduction events for the benefit of patients. Increased knowledge of proteins involved in transformation, their posttranslational modification status etc will also provide us with potential tools for development of novel diagnostic tools and novel biomarkers for prediction of treatment efficacy.