Faculty of Medical Sciences

Staff Profile

Dr Anna Moles Fernandez

Background

My translational research focuses on identifying new therapeutic targets for liver and kidney disease treatment. This is key in order to design better and more specific drugs. I am particularly interested in the cellular and molecular pathways driving disease progression, with an emphasis on protease biology. Proteases are currently in the spotlight for anti-cancer drug development. Despite being classically considered to be only protein-degrading enzymes, over the last decades this paradigm has changed with increasing numbers of physiological (antigen processing, apoptosis, etc.) and pathological (cancer, atherosclerosis, etc.) roles attributed to proteases.

 Our most recent research shows an important role for lysosome protease, CtsD, in acute and chronic kidney disease progression.

 Kidney disease represents the 12th cause of death in the world. It affects 8-16% of the population worldwide and in the UK it is estimated that there are 3.5 million people with kidney disease. Due to limited specific treatments, more than two million patients require dialysis or transplant worldwide every year. Therefore better and more specific treatments are urgently needed.

Our research has shown that CtsD inhibition slowed kidney disease progression, opening new avenues for the use of lysosomal protease inhibitors as possible treatments for kidney disease.


http://research.ncl.ac.uk/fibrosislab/staff/juniordevelopingprincipalinvestigators/molesanna/

https://www.linkedin.com/in/annamoles



 

 

 

 


Research

My translational research focuses on identifying new therapeutic targets to design new and better drugs for liver and kidney disease treatment. I am particularly interested in the cellular and molecular pathways driving disease progression, with an emphasis on protease biology.

During my PhD in JC Fernandez-Checa's lab, IDIBAPS, IIBB-CSIC, Barcelona, Spain we discovered a new therapeutic axis, acidic sphingomyelinase-cathepsin B/D in liver fibrosis (Hepatology, 2009;  Am J Pathol, 2010). In addition, we described CtsB as a potential target for the treatment of liver fibrosis in patients with Niemann-Pick disease (NPD), which is a rare lysosomal storage disorder caused by recessive mutations on the acidic sphingomylinase gene (J Biol Chem, 2012). After finishing my PhD I moved to Newcastle Upon Tyne, UK, to work with Prof Mann and Dr Oakley in the study of post-translational modifications of NFκ-B. During my postdoc I led three independent projects. Our first work demonstrated the use of competing NFκ-B peptides as beneficial therapy to reduce liver fibrosis without affecting the innate immune response (Hepatology, 2012). Our second paper unravelled a new TLR2/S100A9/CXCL-2 signalling network which is essential for neutrophil recruitment in liver disease (J Hepatol, 2014). Our last paper, in collaboration with Prof Perkins, ICaMB, described a novel regulatory mechanism for NFκ-B in vivo and dissected its implications in liver cancer (Oncogene, 2016).

 Over my career I have trained in top international and multidisciplinary teams. Learning from the best in the field has given me the knowledge, confidence and drive to develop my independent research. I am currently studying the role of proteases in kidney disease trying to identify relevant novel pathways for disease progression. Increasing our understanding around kidney disease biology is crucial in order to find new and better drugs. Better treatment options are urgently needed because:

1. Kidney disease is the 12th cause of death in the world.

2. According to the WHO kidney disease is the 17th cause for loss of quality “healthy” years of life.

3. It affects 8-16% of the population worldwide and in the UK it is estimated that there are 3.5 million people with kidney disease.

4. Due to limited specific treatments, more than two million patients require dialysis or transplant worldwide yearly

5. Acute and chronic kidney disease treatment represents combined 2.5% of the annual NHS budget at around £2 billion.

 My research is funded by Newcastle University, NIHR Newcastle Biomedical Research Centre, Wellcome Trust Institutional Strategic Support and Northern Counties Kidney Research Fund (NCKRF).

If you are interested about our past or current research please get in touch.


Teaching

Student Supervision

Ongoing, MRes supervision: Autophagy, implications for chronic kidney disease.

Ongoing, PhD supervision: Role of lysosomal cathepsins in chronic kidney disease

2016, PhD supervision: Lysosomal protease cathepsin D, new driver of apoptosis during acute kidney injury

2013, BSC student supervision: Identifying the signalling events controlling phosphorylation of the RelA.

2012, BSC student supervision: Determining the anti-fibrotic potential of a novel cell targeted peptide competitor of RelA serine 536 phosphorylation in liver injury.

Supervision on a daily basis of technical staff within the team.

 


Publications