Research Interests

Skeletal muscle loss is an underappreciated clinical disorder, not only reducing the quality of life but also contributing to morbidity and mortality. Loss of skeletal muscle is a cause of death in patients with cancers and several immune diseases, remarkably preservation of muscle mass increases survival. Currently, exercise is the only known countermeasure to slow this debilitating process, no approved therapeutic is available.

The loss of muscle mass and strength primarily results from excessive protein degradation, often accompanied by reduced protein synthesis, resulting in a negative net balance. It is known that the ubiquitin-regulated proteasomal and lysosomal systems are two major pathways responsible for muscle degradation. We thus aim to precisely dissect these signalling mechanisms.

Current projects are:

• Elucidate how MuRF1 (TRIM63) and MAFbx (FBXO32) contribute to muscle atrophy
• Identify novel ubiquitin E3 ligases, deubiquitylases (DUBs), and binding proteins in muscle atrophy
• The interplay of protein phosphorylation and ubiquitylation in muscle metabolism after exercise

We tackle these questions using a range of state-of-the-art techniques, including molecular & cellular engineering (such as CRISPR/Cas9 genetic editing), biochemistry, chemical biology, mass spectrometry and mouse genetics. Importantly, we are also exploring the physiological role of the ubiquitin system in skeletal muscle and therefore translating basic science to clinical research by employing human samples that are well established at the School of SportExR (University of Birmingham) and the MRC-ARUK Centre of Musculoskeletal and Ageing Research, joint with the University of Nottingham.

By 2050, the number of people over 60 years old will reach 2 billion worldwide (22% of the population). However, a longer life for many will mean more years of chronic diseases. Thus, only extending life is not enough and we need to find drugs that delay diseases of old age. A further aim of my research is therefore to identify which components of exercise-mediated signalling pathways are the most attractive drug target for the treatment of muscle loss and other age-related diseases.