A systems microscopy approach to understand cell migration

Cell migration is critical in development, physiology and disease, including cancer metastasis. Cell migration is also a complex emergent phenomenon that arises across several spatial and temporal scales, and with a high degree of inter-cellular, intra-cellular, and temporal heterogeneity. To achieve a complete understanding of cell migration therefore constitutes a major challenge, requiring a strictly quantitative approach, with the concurrent recording of critical events at various scales during cell migration, followed by mathematical integration of the data. To this end, ... Read more

Role of p21-activated kinase 4 in cancer development and progression

PAK4 is overexpressed in various cancer forms, including ovary, pancreas and breast cancer. We are addressing the general role of PAK4 in breast cancer progression in MMTV-PAK4 transgenic mice, mimicking in the mammary gland the PAK4 overexpression observed in tumors, as well as in conditional PAK4 knock-out mice.
Interestingly, in addition to the role we previously identified for PAK4 in breast cancer cell motility, we have preliminary evidence for a role of PAK4 in breast cancer G1-phase cell cycle progression. We elucidate involved molecular mechanisms for this important new role of PAK4. Importantly, we are also developing novel synthetic PAK4 inhibitors, in collaboration with Actar AB (a small biotech company at the Karolinska Institute) with promising preliminary results, with the aim of identifying new candidate cancer therapies.

Role of the elasticity of the extracellular matrix for cancer progression

We examine the observation that increased extracellular matrix (ECM) stiffness is linked to poor prognosis in breast cancer by addressing the role of ECM stiffness in breast cancer cell invasion, as well as the influence of the ECM elasticity onto cancer associated fibroblasts and tumor initiating cells, both isolated from tumors.