Dr Katie Mylonas

Dr Katie Mylonas

Kidney Research UK (KRUK) Senior Research Fellow (with the Thompson Family Charitable Trust) and Principal Investigator

• Centre for Inflammation Research

Contact details

• Website: Academic Profile
• Work: 0131 651 8215
• Email: kmylonas@exseed.ed.ac.uk

Group Members

• Ross Campbell - PhD Student – Wellcome Trust PhD Programme in Tissue Repair
• Haotian Zhou - MSc Student- BioMedical Sciences, from March 2024

Former Members: Co-supervised:

• Dr Marie-Helena Docherty - PhD Student – MRC Clinical Training Fellow
• Dr David Baird - PhD Student – NHS and MRC Clinical Research Fellow

Background

The world’s population is ageing rapidly. The Office for National Statistics predicts that in 50 years there will be an additional 8.6 million people aged 65+ in the UK. While it is good news that people are living longer, they are not getting healthier. The body’s ability to repair diminishes with age, for example older people are more susceptible to kidney and heart disease.

Kidney Disease: 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). CKD affects about 850 million people worldwide and more than 10% of the population in the UK. Elderly patients (>65 years) are particularly susceptible to AKI/CKD as ageing causes changes that impair the regenerative capacity of the kidney following injury. Patients with CKD exhibit an elevated risk of heart disease and other co-morbidities. 

Senescent cells accumulate in the kidney with age and injury. They are metabolically active, promoting inflammation and fibrosis via their secretome, the senescence associated secretory phenotype (SASP). Studies highlight correlations between increased renal senescence with CKD and diabetes progression and adverse outcomes after transplantation. Selective SC depletion increases murine lifespan, including healthier kidneys whilst SASP blockade is beneficial. We recently demonstrated (Mylonas et al, Science Translational Medicine 2021) that administration of the senolytic ABT-263 to aged and irradiated mice augmented kidney repair, limited scarring and preserved kidney tissue and function after AKI. Ageing and disease also reduce immune clearance of SCs, decreasing macrophage phagocytosis and NK Cell destruction. Patients with CKD, diabetes and heart disease exhibit features of premature ageing- my work is addressing the effect of age and disease upon the interaction of macrophage and NK cells with renal and cardiac SCs.

Research Overview

I am testing the hypothesis that senescence is a major driver of multi-organ fibrosis with ageing and disease, and a novel therapeutic target. During my scientific career I have studied leukocyte biology and inflammation in both the kidney and heart. I bring my accumulated expertise to this work. My specific goal is to develop therapeutics and diagnostics to target harmful senescent cells.

These investigations will improve our understanding of kidney disease, heart disease and diabetes, as well as ageing in general, and we hope that they will lead to new clinical treatments to save lives and make important contributions to future human health and quality of life. As part of this work, we are developing a novel method to detect and quantify senescent cells in vivo in the kidney and heart, in collaboration with chemists and PET experts. With help from healthy volunteers and patients who donate their blood, we are investigating how senescent cells interact with the immune system to avoid clearance, leading to renal and cardiac pathologies. I am using my previous experience working in the heart to investigate the link between senescence in kidney disease and cardiac disease. Working with my Edinburgh based and external collaborations (all world-renowned experts in their fields) allows me to effectively carry out my research here in Edinburgh. These include collaborators at the School of Veterinary Medicine, who I will work with to investigate senescence in companion animals, which I believe to be an interesting model of ageing.

The following PDF provides a brief visual summary of this group’s current research.

Biographical Profile

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 awarded an MSc in Life Sciences with Distinction. I subsequently 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 postdoctoral researcher for many years, in various labs both in the Centre for Inflammation Research (CIR) and Centre for Cardiovascular Science (CVS) at Edinburgh University on projects investigating the role of macrophages in injury and wound healing, both in the kidney and heart. In 2017, I joined the Ferenbach 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 first fellowship with the Chief Scientist Office CSO/KRUK- “Driving kidney repair through modulation of senescent cells and macrophages”.

In 2023, I was awarded a KRUK Senior Fellowship – “Targeting senescent cells in kidney disease, heart disease and diabetes”

Honours and Awards

• Kidney Research UK Senior Fellowship - Awarded March 2023
• Tenovus Scotland Grant - Awarded Sep 2022
• NHS Lothian Small Renal Grant - Awarded March 2022
• Chief Scientist Office (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
• As Co-Investigator - MRC Clinical Research Training Fellowship - Awarded Aug 2021

Other Responsibilities

I teach Reproductive Biology 3 Lecture "Immunology in Pregnancy".

I am an Edinburgh BioQuarter Staff Equality, Diversity and Inclusion (EDI) Group Member.

I believe in the power of mentorship and mentor a postdoctoral researcher, formerly of the CIR.

I believe that it is important to contribute to the careers of others through peer review, and as such, am an expert panel member of the grants committee at the Dunhill Medical Trust.

Member of multiple thesis committees within the University.

Collaborators

Internal

Centre for Inflammation Research

• Prof David Ferenbach
• Prof Jeremy Hughes
• Dr Steve Jenkins
• Dr Clare Pridans
• Dr Sofia Ferreira
• Prof Sarah Walmsley

Centre for Cardiovascular Science

• Dr Laura Denby
• Dr Brian Conway
• Prof Marc Dweck

Other Schools and Colleges

• Chemistry: Prof Marc Vendrell and Dr Lorena Mendive Tapia
• Pre-clinical PET: Dr Adriana Tavares
• Edinburgh School of Veterinary Medicine: Prof Richard Mellanby, Prof Dylan Clements, Dr Natalie Ring.

External

• Dr Maria Kaisar – Transplantation Scientist, University of Oxford 
• Dr Helen Weavers – Senior Research Fellow, University of Bristol
• Prof Sian Henson – Professor of Immunology, Queen Mary University of London
• Prof Mary Sheppard – Cardiac Pathologist, St George’s University of London
• Prof James Burton - Honorary Consultant Nephrologist and Professor of Renal Medicine and Associate Dean for Clinical Research, University of Leicester.
• Dr Conor Finlay - Senior Research Fellow, Trinity College, Dublin

Patient and Public Engagement

I am part of the Edinburgh Kidney Research Group: https://edinburghkidney.co.uk/

Public and Patient Involvement (PPI): Patients often provide the ‘initiating spark’ for our research projects. Conversations at Edinburgh Kidney's PPI meeting which happens multiple times a year, and other informal meetings, ensure the patient voice contributes to our research decision making, keeping patient-centred outcomes at the heart of our clinical and discovery biology research projects

Sources of Funding

KRUK Senior Fellowship