Background and vision
The overarching goal of our research is to increase the mechanistic knowledge of promising clinical interventions. We aim at facilitating patient tailored treatment in autoimmunity, neuro-degeneration and regenerative medicine through biomarker discovery. Our approach uses multi-omic solutions at single cell resolution. We use Mass Cytometry, both in suspension and imaging, to profile the cellular landscape in blood, brain and other tissues in comprehensive ways. In collaboration with mathematicians, we create computing tools to better leverage the complex data generated in clinical trials and research. We bring together expertise from relevant disciplines to fuel the discovery of diagnostic, predictive and prognostic biomarkers in the proper context and relevance to human medicine.
Biomarkers of mitochondrial dysfunction and neurodegeneration
Our aim is to identify biomarkers in MS. Biomarkers are highly sought after in MS, due to the unpredictable and heterogeneous disease course. We have previously found that levels of cell-free mitochondria-DNA are increased in the cerebrospinal fluid of MS patients, and that this might reflect early, active inflammatory activity (https://www.ncbi.nlm.nih.gov/pubmed/28017684).
Neurofilament light chain (NF-L) is another proposed biomarker. This is a neuron-specific cytoskeletal protein, and high levels of NF-L in cerebrospinal fluid and serum appears to reflect ongoing neuronal damage. We have recently found that serum NF-L could be a promising biomarker for disease activity and treatment response in RR-MS (https://www.ncbi.nlm.nih.gov/pubmed/29209636), and our objective is to further evaluate serum NF-L as a potential biomarker in MS.
Time frame: until 2021.
Please contact: Kristin Nielsen Varhaug
Assess the safety and efficacy of mesenchymal stem cell based therapy in bone regeneration procedure
Mesenchymal stem cells (MSC) are a promising source of cells in regenerative medicine. These cells harbor unique differentiation potential and immunomodulatory properties.The PhD project of Neha Rana, at the Department of Clinical Dentistry, aims at understanding the bio distribution of transplanted mesenchymal stem cells in pre-clinical models of bone regeneration and at studying the associated host response in clinical trials.
The post-doc of Christopher Elnan Kvistad builds upon the expertise gained in bone regeneration and aims at studying brain repair capabilities of MSC products in Multiple Sclerosis in a randomized, controlled clinical phase I-II study. We will use single cell high-dimensional immune profiling by mass cytometry and the liquid biopsy concept to deepen our knowledge of MSC regenerative processes and support clinical trials at Haukeland University Hospital.
Brain tissue imaging at single cell resolution
It is becoming obvious that brain diseases cannot be properly studied in depth without considering the tightly woven network of relationships between the various cell types such as infiltrating immune cells, the resident microglia and their surrounding tissue structures like the blood brain barrier and the brain lymphatic system.
This PhD project of Ida Herdlevær aims at studying the microenvironment of tissue damage in neurological diseases as well as the wide spread activation state of glia cells throughout different brain regions. We are using state of the art Imaging Mass Cytometry to analyze tissue at subcellular resolution in high dimension. Our panel uses 44 markers simultaneously on tissue slides and allows mining of data in high dimensional space without compromising special resolution.
Autologous Hematopoietic stem cell transplantation
Mobilization of autologous hematopoietic stem cells for transplantation is a promising therapeutic intervention in immune mediated diseases. In this project, we are using samples collected in the RAM-MS clinical trial.
The project aims to provide treating physicians with a tool to monitor stem cell transplantation and immune ablation during the course of treatment and during the slow recovery phase of immune reconstitution and to deepen our knowledge of stem cell transplantation in autoimmune disease. By mass cytometry, a state of the art technique that identifies common and rare cell subsets in blood and spinal fluid, we will be able to show which, when and how cell types are affected during these procedures, and when and which cell types will be reconstituting the patient’s immune system. This will offer a unique opportunity to address how to predict successful interventions and early warning signs for serious side effects.
Flow cytometry core facility at UiB/HUS. From the left: Britt Bergum and Sonia Gavasso.