Dr Katie Mylonas
My goal is to contribute to the fields of immunology and ageing. I wish to investigate the role of senescence cell/macrophage interactions in regeneration after kidney injury, and how senolytics can play a part in improving outcomes for patients.
With David Ferenbach, I co-superivise:
- Dr Marie-Helena Docherty - MRC Clinical Training Fellow
- Dr David Baird - NHS Research Fellow
Acute kidney injury (AKI, an abrupt decrease in renal function) occurs in 14% of hospital admissions, with a high acute mortality and risks of subsequent chronic kidney disease (CKD). Approximately 150 AKI events per 10,000/year occur in Scotland, with rates particularly high in older people. Elderly patients (>65 years) are particularly susceptible to AKI as ageing causes changes that impair the regenerative capacity of the kidney following injury. Thus, novel therapeutic approaches are required to increase kidney repair in elderly patents as well as prevent AKI to improve outcomes.
Senescent cells accumulate in the kidney with age and injury. They are metabolically active, promoting inflammation/fibrosis via release of senescence associated secretory phenotype (SASP) cytokines. Our data demonstrates that sublethal total body irradiation (TBI) induces premature renal senescence, with administration of the senolytic drug ABT-263 prior to renal ischaemia reperfusion injury (IRI) being protective; reducing tissue loss, fibrosis and inflammation, whilst promoting structural integrity and regeneration in senescent mice.
Macrophages in Kidney Repair: In acute and chronic kidney injury recruitment of inflammatory monocytes and accumulation of pro-inflammatory classically activated cytotoxic ‘M1’ macrophages is driven by chemokines, including SASP-associated CCL2. The renal regeneration that follows cessation of injury requires reparative wound-healing alternatively activated ‘M2’ macrophages induced by apoptotic cell ingestion and tissue-derived growth factors. M2 macrophages produce mitogenic, angiogenic and pro-survival signals and promote renal repair. Factors that drive a reparative M2 macrophage phenotype augment renal regeneration after surgical ischaemia reperfusion injury (IRI) in mice, a model for AKI.
With increasing human lifespan there are major increases in age-related diseases, including age-related chronic kidney disease (CKD). CKD is a major cause of mortality and morbidity in the UK, with a huge associated cost to the NHS. My programme of work will improve our understanding of kidney disease, and ageing in general. I have been active in macrophage biology since my PhD, working with leading internationally recognised groups in this area. I worked in the Ferenbach lab (CIR) interrogating senescence in renal injury. Based on this, I have secured a fellowship from CSO/Kidney Research UK to contribute to the field of senescence cell (SC)/leukocyte interactions and to ascertain their roles in organ regeneration after injury. Work indicates that inadequate removal of senescent cells by immune cells, including macrophages, and a subsequent enhancement of a prolonged macrophage inflammatory phenotype, contributes to ageing, and reduced regenerative capacity after tissue injury. My hypothesis is that ageing/injury affects the ability of macrophages to interact with senescent cells in the kidney. This in turn affects their ability to target/destroy them and drive repair. I now wish to investigate these interactions, building a research programme with clear translational importance. Along with my collaborators, I am establishing Edinburgh as the pre-eminent centre for senescence research in the UK. These studies have the potential to generate new clinical treatments to reduce morbidity and mortality in our ageing human population.
I graduated with a First Class Honours Degree in Biological Sciences from the Queen’s University of Belfast. Post-graduation, I worked for four years as a research associate at DeCode Genetics in Reykjavik, Iceland. I was then selected for the Wellcome Trust 4-Year PhD Programme at the University of Edinburgh where I was first awarded an MSc in Life Sciences. I then carried out my PhD in Professor Judith Allen’s Lab, Institute of Immunology and Infection Research on the “Plasticity of macrophages in helminth infection”.
After my PhD, I worked as a post-doctoral research for many years, in various labs both in the CIR and CVS at the QMRI on projects investigating the role of macrophages in injury and wound healing, both in the kidney and heart. More recently, I joined David Ferenbach’s lab in the CIR. This position involved investigating the role of senescent cells in mediating the initial severity and the eventual outcome of experimental acute kidney injury, and the effects of the targeted pharmacological depletion of these cells with senolytics. This work led to my current fellowship with the CSO/KRUK- “Driving kidney repair through modulation of senescent cells and macrophages”. My specific goal is to investigate the interactions of senescence cells with macrophages and to ascertain how these interactions affect the regeneration of the kidney after injury.
Honours and Awards
- CSO/Kidney Research UK Fellowship - Awarded Jan 2019
- British Society of Immunology Congress 2016, Poster Prize - Awarded Dec 2016
- BHF Research Excellence Award Fellowship Transition Award - Awarded Jan 2014
I teach Reproductive Biology 3 Lecture "Immunology in Pregnancy".
- Dr David Ferenbach
- Professor Jeremy Hughes
- Dr Steve Jenkins
- Dr Clare Pridans
Sources of Funding