Dr Yung-Yao Lin, PhD, FHEA
Centre: Centre for Genomics and Child Health
Email: email@example.comTelephone: 020 7882 2339
My most important research contributions to date are elucidating pathological mechanisms of previously unexplained neuromuscular disorders and developing disease models that can facilitate therapeutic development.
My postdoctoral work at Wellcome Sanger Institute brought novel insights into the pathological mechanisms underlying a group of neuromuscular disorders, referred to as dystroglycanopathies. In collaboration with Profs Francesco Muntoni (UCL), Hans van Bokhoven (RUNMC) and Kevin Campbell (HHMI), we pioneered the use of exome sequencing and zebrafish-based disease models to demonstrate gene mutations causative for dystroglycanopathies in previously unresolved patient cohorts, and contributed to the complete elucidation of a novel pathway of laminin-binding glycan on α-dystroglycan.
Since establishing my own laboratory at the Blizard Institute, I acquired expertise in generation and differentiation of human induced pluripotent stem cells (iPSCs), as well as CRISPR-based genome manipulation technologies. My group developed the first patient-derived iPSC model for dystroglycanopathies, recapitulating glycosylation defects of α-dystroglycan with CRISPR-corrected isogenic controls. In collaboration with Prof Muntoni, our human iPSC-dystroglycanopathy model validated a compound identified from an unbiased high-throughput chemical screen for increased glycosylation of α-dystroglycan. Future studies using our patient iPSC-derived disease models with isogenic controls hold significant promise in early-stage drug discovery and assessing efficacy of potential therapeutics.
MSc Regenerative Medicine
Research in the Lin group is focused on muscular dystrophy and mechanisms regulating muscle regeneration. The Lin group has established essential expertise in generation and differentiation of human induced pluripotent stem cells (iPSCs) and CRISPR-mediated genome manipulation technology. We are interested in integrating human iPSC and Organ-on-a-Chip technologies to enable neuromuscular research in health and disease, as well as drug discovery.
Kim J, Lana B, Torelli S, Ryan D, Catapano F, Ala P, Luft C, Stevens E, Konstantinidis E, Louzada S, et al., Lin YY. (2019) A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan. EMBO Rep 20: e47967.
Paredes‐Redondo A, Lin YY. (2019) Human induced pluripotent stem cells: challenges and opportunities in developing new therapies for muscular dystrophies. In eLS, pp. 1–10, John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0028371
Praissman JL, Willer T, Osman Sheikh M, Toi A, Chitayat D, Lin YY, Lee H, Stalnaker SH, Wang S, Prabhakar PK, et al. (2016) The functional O-mannose glycan on α-dystroglycan contains a phospho-ribitol primed for matriglycan addition. Elife 5: 1–28.
Carss KJ, Stevens E, Foley AR, Cirak S, Riemersma M, Torelli S, Hoischen A, Willer T, van Scherpenzeel M, Moore SA, et al. Lin YY, Muntoni F. (2013) Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies as-sociated with hypoglycosylation of α-dystroglycan. Am J Hum Genet 93: 29–41.
Roscioli T, Kamsteeg EJ, Buysse K, Maystadt I, Van Reeuwijk J, Van Den Elzen C, Van Beusekom E, Riemersma M, Pfundt R, Vissers LELM, et al. Lin YY*, van Bokhoven H*. (2012) Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan. Nat Genet 44: 581–585. (*Senior corresponding authors)
Current PhD Students
- Anna Kowala (QMUL-LSI PhD studentship)
- Darren Wilson (BHF PhD studentship)
- Natalia Andrea Moreno Sierra (NC3Rs PhD studentship)
Former PhD Student
- Amaia Paredes-Redondo (QMUL-Blizard PhD studentship)