I am a PhD-student in Agneta Richter-Dahlfors' group, a part of the Swedish Medical Nanoscience Center at Karolinska Institute.
I received my medical degree from Karolinska Institutet in 2015, and have since then been a full time PhD student, working extra as a junior physician at the nephrology clinic and at the emergency ward at Karolinska University Hospital. I am highly interested in research bridging basic science and clinical applications, which is one of the reasons I joined Agneta Richter-Dahlfors' group. In my PhD projects I study pyelonephritis and the transition into urosepsis, with focus on inter-organ communication and coagulation.
December 2014 - present PhD Student in Agneta Richter-Dahlfors' group
2009 - 2015 Karolinska Institutet, Medical School
My research focuses on the intra- and inter-organ communication in pyelonephritic infection, and during the transition into urosepsis. We hypothesize that interplay between coagulation, innate immune and nervous systems play a role in determining the outcome of a kidney infection (pyelonephritis), and that disturbances in these systems may contribute to the systemic dissemination of bacteria from a local infection and the subsequent sepsis pathology.
To study the pathophysiology at the site of infection in the kidney, as well as the inter-organ communication between the kidney and the spleen, we are using both in vitro and in vivo models. Intravital imaging of exposed kidneys in living rodents plays a central role in the in vivo projects. By combining two-photon (2-P) microscopy with innovative surgical procedures, and micro-infusion of GFP expressing UPEC into the proximal tubule of the nephron, we are able to analyze the progression of infection in real-time. Finally, we are trying to translate results obtained in our in vivo and in vitro experiments in an epidemiological study.
Project 1. The cholinergic anti-inflammatory pathway
Early during a pyelonephritic infection the spleen starts producing and secreting IFN-γ. We hypothesize that a neural reflex, the cholinergic anti-inflammatory reflex, is responsible for this inter-organ communication between the kidney and the spleen. In this project we are studying both the afferent and efferent part of the cholinergic anti-inflammatory pathway and how they affect infection outcome. We hypothesize that sensory neurons in the kidneys signal the presence of bacteria, that vagus nerve signaling enables an inter-organ communication between the kidney and the spleen resulting in splenic IFN-γ secretion, and that splenic IFN-γ secretion has a role in the outcome of the infection.
Project 2. Vascular and innate immune responses during pyelonephritis
Innate immunity and coagulation are traditionally studied as separate entities, but there is accumulating evidence of a complex crosstalk between the two systems during infection. Early during a pyelonephritic infection blood clotting occurs in the local peri-tubular capillaries, resulting in ischaemia in the vicinity of the infection. While the ischaemia causes local tissue damage, clotting has been shown to provide a physical barrier that hinders bacteria from being spread systemically. Through this project we aim to visualize these pathophysiological changes during pyelonephritis, and investigate what role micro-environmental changes during the course of pyelonephritis plays with regards to immune cell recruitment.
Project 3. The development of sepsis
The immune response is normally well regulated and keeps bacterial infection localized. However, excessive activation of the system can occur, resulting in a dangerous cycle that can lead to substantial tissue destruction or, if bacteria access the bloodstream, sepsis. In this project we want to identify possible mechanisms involved in the development of sepsis from a localized infection. By using our rodent micro-puncture model and intravital imaging we want to visualize the transition from a localized pyelonephritic infection to urosepsis. In parallel, we are conducting an epidemiological study that investigates the risk of developing sepsis among patients on anticoagulation therapy.
Academic honours, awards and prizes
2015 Awarded "Best thesis of graduating class"
2014 Admitted to the Clinical Scientist Training Programme (CSTP)
Oral presentation at the 32nd Annual meeting of NSCMID - Infection and Antibiotics, 2015, Umeå, Sweden.
Intra- and inter-organ communication during early pyelonephritis.
SE. Steiner, FX. Choong, D. Bas, A. Schulz, O. Chuquimia-Flores, C. Svensson, A. Richter-Dahlfors.