Svava Steiner

About me

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 PhD student, working extra as a junior physician at the nephrology clinic and at the emergency ward at Karolinska University Hospital. In May 2018 I started my Medical Internship with research focus (Forskar-AT), meaning that I alternate between the clinic and the lab. 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.

Research description

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. Nervous sensing of a kidney infection

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. The role of inter-organ communication during a kidney infection

Accumulating evidence suggests that there is a complex crosstalk between the nervous and the immune system. In this project we continue investigating the role of nerves in mediating inter-organ communication, and dig deeper into the role of this inter-organ communication during a kidney infection.

Project 3. The role of coagulation during a transition from a localized kidney infection to urosepsis

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 sepsis. 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. In this project we want to identify possible mechanisms involved in the development of sepsis from a localized infection, focusing on coagulation and its role during a kidney infection. We are conducting an epidemiological study that investigates the risk of developing sepsis among patients on anticoagulant therapy.

Education

May 2018 - present               Medical Intern ("Forskar-AT"), Södersjukhuset

December 2014 - present     PhD Student in Agneta Richter-Dahlfors' group

2009 - 2015                            Karolinska Institutet, Medical School

Academic honours, awards and prizes

2017       Admitted to the "Forskar-AT" Programme (Medical Internship + Research)

2015       Awarded "Best thesis of graduating class"

2014       Admitted to the Clinical Scientist Training Programme (CSTP)