Dr Yu-Chiang Lai PhD

Dr Yu-Chiang Lai

School of Sport, Exercise and Rehabilitation Sciences
Birmingham Fellow in Molecular and Biochemical Physiology
Director of Mitochondrial Profiling Centre

Contact details

Address
School of Sport, Exercise and Rehabilitation Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Yu-Chiang is a Birmingham Fellow in the School of Sport, Exercise and Rehabilitation Sciences and affiliated in the Mitochondrial Profiling Centre (MPC), MRC-ARUK Centre for Musculoskeletal Ageing Research and the Institute of Metbolism and Systems Research (IMSR).   

Yu-Chiang’s group focuses on deciphering the signalling networks that regulate muscle metabolic functions. We seek to understand the molecular mechanisms that lead to muscle wasting and how exercise is able to improve muscle health when faced with various muscle wasting conditions.

Qualifications

  • PhD in Exercise Physiology & Metabolism, Norwegian School of Sport Science, Oslo, Norway (2010)
  • MSc in Sport Science, University of Taipei, Taiwan (2005)

Biography

Yu-Chiang graduated with an MSc in Sport Science from the University of Taipei, Taiwan and completed his PhD in Exercise Physiology at the Norwegian School of Sport Sciences and National Institute of Occupational Health, Oslo, Norway under the supervision of Professor Jorgen Jensen. During his PhD, Yu-Chiang investigate the role of glycogen content and contraction in skeletal muscle glucose metabolism. 

Yu-Chiang was awarded the Christian de Duve Institute Fellowship in 2010 and joined Professor Mark Rider’s laboratory at the de Duve Institute (note: Professor Christian de Duve received the Nobel Prize in Medicine or Physiology in 1974), Université Catholique de Louvain, Brussels, Belgium. From 2011, his work was funded by FNRS (The National Fund for Scientific Research for French community in Belgium) to study the energy sensing AMPK signaling pathways in the regulation of cellular metabolism and function. He worked closely with AstraZeneca, a global pharmaceutical company, to develop muscle AMPK activators and also identified PDE4B a new AMPK substrate in hepatocytes that counteracts glucagon-stimulated cyclic-AMP and glucose productions.

In 2014, Yu-Chiang Joined Professor Miratul Muqit’s laboratory as a senior postdoctoral researcher at the MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, to investigate PINK1 and Parkin signalling pathway in Parkinson’s disease and mitophagy. Using SILAC-phosphoproteomic approach he identified that several small GTPase Rab proteins are down-stream substrates of PINK1.

In 2018, Yu-Chiang was awarded a Birmingham Fellowship to establish his own laboratory aiming to understand the signaling mechanisms of muscle atrophy and exercise.

Postgraduate supervision

If you are interested in joining Yu-Chiang’s research group, please contact him directly through email with a brief motivation letter and CV.

Email: y.lai.1@bham.ac.uk

Research

The signalling mechanisms of skeletal muscle wasting and the beneficial effect of exercise.

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

  1. Elucidate how MuRF1 (TRIM63) and MAFbx (FBXO32) contribute to muscle atrophy
  2. Identify novel ubiquitin E3 ligases, deubiquitylases (DUBs), and binding proteins in muscle atrophy
  3. 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.

Our published research reagents are available to scientific community. To request meterials please contact Yu-Chiang directly by email: y.lai.1@bham.ac.uk.

Publications

Publications since 2012:

Vieweg S, Mulholland K, Brauning B, Kachariya N, Lai YC, Toth R, Sattler M, Groll M, Itzen A, Muqit M. (2019) PINK1-dependent phosphorylation of Serine111 within the SF3 motif of Rab GRPases impairs effector interactions and LRRK2 mediated phosphorylation at Threonine72. BioRxiv (Cold Spring Harbor Laboratory) doi: https://doi.org/10.1101/764019.

Elhassan Y, Kluckova K, Fletcher R, Schmidt M, Garten A, Doig C, Cartwright D, Oakey L, Burley C, Jenkinson N, Wilson M, Lucas S, Akerman I, Seabright A, Lai YC, Tennant D, Nightinggale P, Wallis G, Manolopoulos K, Brenner C, Philp A, Lavery G. (2019) Nicotinamide riboside augment the aged human skeletal muscle NAD+ metabolome and induces transcriptiomic and anti-inflammatiory signatures. Cell Report 28 :1717-1728.

Fenton C, Webster J, Martin C, Fareed S, Wehmeyer C, Mackie H, Jones R, Seabright A, Lewis J, Lai YC, Goodyear C, Jones S, Cooper M, Lavery G, Langen R, Raza K, Hardy R. (2019) Theraputic glucocorticoids prevent bone loss but drive muscle wasting when administered in chronic polyarthritis. Arthritis Research & Therapy 21 :182.

Osgerby L*, Lai YC*, Thornton P, Amalfitano J, Le Duff C, Kadri H, Miccoli A, Tucker J, Muqit M , Mehellou Y. (2017) Kinetin riboside and its ProTides activate Parkinson’s disease associated kinase PINK1 independent of mitochondrial depolarisation. Journal of Medicinal Chemistry 60(8):3518-3524

Bultot L, Jensen TE, Lai YC, Madsen ALB, Collodet C, Kviklyte S, Deak M, Yavari A, Foretz M, Ghaffari S, Bellahcene M, Ashrafian H, Rider MH, Richter EA, Sakamoto K. (2016) Bensimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle. Am J Physiol Endocrinol Metab 311(4):E706-E719

Johanns M*, Lai YC*, Hsu MF, Vertommen D, Van Sande J, Dumont J, Woods A, Carling D, Hue L, Viollet B, Foretz M, Rider MH. (2016) AMPK antagonizes hepatic cyclic AMP signalling by glucagon via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B. Nature Communications 7:10856, DOI: 10.1038/ncomms10856.

Pao KC, Stanley M, Han C, Lai YC, Murphy P, Balk K, Wood N, Corti O, Corvol J, Muqit M, Virdee S. (2016) Engineered Protein-based Probes Profile Transthiolation Activity of E3 Ligases Enabling Systematic Dissection of the E3 Ligase, Parkin. Nature Chemical Biology 12(5):324-331.

Lai YC*, KondapalliC*, LehneckR, ProcterJB, DillBD, Woodroof HI, GourlayR, PeggieM, MacartneyTJ, CortiO, CorvolJ, CampbellDG, ItzenA, TrostM, Muqit MMK. (2015) Phosphoproteomic screening identifies Rab GTPases as novel downstream targets of PINK1. EMBO Journal 12;34(22):2840-61.

Plaideau C*, Lai YC*, Zanou N, Kviklyte S, Lofgren L, Andersen H, Vertommen D, Gailly P, Hue L, Bohlooly M, Hallen S, Rider MH. (2014) Pharmacological inhibition of AMP-deaminase in skeletal muscle during contraction: effects on purine nucleotide concentrations and AMPK activation in comparison with genetic Ampd1 deletion. Cell Chemical Biology 20;21(11):1497-1510.

Lai YC, Kviklyte S, Vertommen D, Lantier L, Foretz M, Viollet B, Hallen S, Rider MH. (2014) A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: Comparison with effects of contraction and other AMPK activators. Biochemical Journal 460(3):363-375.

Liu Y, Lai YC, Hill EV, Tyteca D, Carpentier S, Ingvaldsen A, Vertommen D, Lantier L, Foretz M, Dequiedt F, Courtoy PJ, Erneux C, Viollet B, Shepherd PR, Tavare JM, Jensen J, Rider MH. (2013) Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle. Biochemical Journal 455(2):195-206.

Liu Y, Vertommen D, Rider MH, Lai YC*. (2013) Mammalian target of rapamycin-independent S6K1 and 4E-BP1phosphorylation during contraction in rat skeletal muscle. Cellular Signalling 25(9):1877-1886.

Lai YC, Liu Y, Jacobs R, Rider MH. (2012) A novel PKB/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle. Biochemical Journal 447(1):137-147.

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