Helene Knævelsrud's project group: Mapping and disrupting cancer circuits
How do multicellular organisms turn off autophagy?
Cells in a living organism need to be able to readily respond to changes in nutritional status. Upon starvation, certain tissues respond by autophagy, to provide energy and building blocks to sustain essential cellular functions. Importantly, these cells must also turn off autophagy when nutrient supplies are replenished, because unrestricted autophagy is harmful to cellular fitness. Surprisingly little is known about how autophagy is terminated, especially in the context of a multicellular organism. We work on uncovering and understanding novel mechanisms of autophagy termination, using Drosophila as a model.
Methodologies: RNAi-based high-content imaging screens in insect cell culture, Drosophila genetics, confocal imaging and autophagy assays.
Fruit flies as a model to find new therapies for leukemia.
Fruit flies are increasingly being used as models for different processes and signaling pathways in cancer, since basic cellular processes and protein networks are strongly conserved among metazoans and ~75% of disease-causing genes in humans have fly counterparts. In our group we take advantage of the of the powerful genetic tools of Drosophila in a fly model of MLL-r leukemia.
Chromosomal rearrangements of the MLL gene are associated with development of high-risk acute leukemia that occurs in both children and adults. MLL-rearranged (MLL-r) leukemia is treated with aggressive chemotherapy, but patients often relapse and survival rates are dismal. Clearly, there exists a need for novel forms of therapy. However, development of new treatment is hampered by our very limited understanding of the genetic framework that underpins MLL-r leukemia. We are working on unraveling this genetic framework, because exposing the genetic factors that are critical for survival of MLL-r leukemia cells may provide novel inroads for targeted therapy. To do this, we perform genetic modifier screens and study the hematopoietic system of Drosophila larvae.
Methodologies: genetic modifier screens, confocal imaging, flow cytometry, transcriptional profiling and drug screening.
Our research is supported by:
Helene Knævelsrud, Department of Molecular Cell Biology, Institute for Cancer Research
Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Phone +47 22 78 19 82