Drs. Egle Kvedaraite (Karolinska Institutet, Solna, Sweden)
Dr. Egle Kvedaraite is a Postdoctoral Fellow with the Department of Pathology and Cancer Diagnostics at the Karolinska University Hospital – Unit of Molecular Neurobiology in Stockholm, Sweden. Dr. Kvedaraite was awarded the Early Career Investigator Award for $50,000 to conduct the study Spatial understanding of Erdheim-Chester Disease origin and lesional microenvironment.
Amount: 50,000 USD
Interim Report
The overall aim of our research is to gain deep insights into disease mechanisms of Erdheim-Chester Disease (ECD), that may can affect many different organs, such as skin, bones, heart, and brain. ECD is today classified as a certain type of blood cancer, and mutation called BRAFV600E, as well as other mutations, have been found in tumor cells. The disease may be life-threatening, and new treatment targeting the mutation in tumor cells has significantly improved mortality in ECD patients. However, once the treatment is stopped, the disease usually comes back, and new treatment approaches, aiming at complete elimination of the mutant cells are urgently needed. But how can we eliminate the mutant cell pool? What is the cell of tumor origin in ECD? How the cells surrounding the tumor in the affected organs are helping the tumor cells to survive? To answer these questions, we have been using state-of-art technologies connecting detailed understanding of one cell at a time together with spatial information of how these disease-causing cells are positioned in the affected tissues.
In more detail, during the first year of the project, we have completed patient recruitment and sample selection, as well as optimization of experimental and analytic pipelines, that have been specifically adjusted to analyze selected ECD samples. In addition, we have published two studies on a ECD-like disease, and data from those studies will be used to compare ECD data with (Kvedaraite et al, Science Immunology 2022; Shi, He, Cui, Kvedaraite … et al, Blood 2021). These newly established protocols optimized for ECD, as well as already generated data, are going to be used in the next phase of the project and allow us to perform our investigations not on all cells together, but one cell at the time – using so called single-cell techniques, that have been proven to be extremely helpful for understanding normal and mutated cells, and different flavors of those cells. That is important, because in different patients, there might be differences within the tumor cells, and to be able to eliminate all of them we need to first find out exactly what they are, and how they differ from each other. Importantly, our analyses of the neighbors of mutated cells in different organs, including the brain, will provide insights into tissue environmental cues survival of the disease-causing cells. In summary, significant progress has been made during the first year of the project regarding all objectives/aims, and deliverables necessary for achievement of each aim have been completed according to the time plan.