Rare disease models

The research group of Dr. Haicui Wang aims to develop the next generation disease cell models for neuromuscular disorders (NMD), a wide range of rare diseases affecting muscles, nerves, neuromuscular junctions, and or the brain (Figure 1). 
More and more disease-causing genes have been discovered with development of the next generation sequencing, yet the underlying disease mechanisms remain unclear and there is lack of efficient treatment for most cases. Disease specific, functional related in vitro models are at urgent need. 
Along with the previous models from limited and valuable patient primary cells, the next generation cell models will take the good use of unlimited human induced pluripotent stem cell (iPSC) lines or other continuous cell lines, in combination with the state of the art CRISPR techniques to generate the disease genetic background.

We focus on two major types of disease models in our group:

1. 2D Neuronal disease models 
For the NMDs affecting the nerves or brain, the in vitro neuronal model allows the systematic evaluation of the mutated neuronal receptors or transporters, further providing a genotype-phenotype correlation or suggesting treatment strategies. 

2. 2D/3D muscle disease models
The muscle stem cells or myoblasts are the valuable source to model muscle diseases due to their remarkable ability to regenerate new myofibers. The primary muscle cells are significantly limited in applications by their inability to expand in culture for long term. The immortalized myoblasts or iPSCs are becoming alternative, in particular the patient-derived iPSCs due to its characteristics such as immortality, multi-lineage differentiation potential to 3D muscles, and patient genomic specificity. The CRIPSR tools can either be used to correct mutations in the disease models or generate mutation carrying cell lines to model muscle diseases.

If you are interested in our disease cell models, please contact us and we are glad to collaborate. Young students and scientists are also welcome to join our team.

Selected References

  1. H Wang*, A Krause, H Escobar, S Müthel, E Metzler, S Spuler*. LMNA Co-Regulated Gene Expression as a Suitable Readout after Precise Gene Correction. International Journal of Molecular Sciences 2022; 23 (24), 15525. (Co-corresponding authors).
  2. H Wang, A Kaçar Bayram, R Sprute, O Ozdemir, E Cooper, M Pergande, ... et al. Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking. Frontiers in Neuroscience 2019; 13, 974.
  3. H Wang*, A Schänzer*, B Kampschulte, HS Daimagüler, T Logeswaran, ... et al. A novel SPEG mutation causes non-compaction cardiomyopathy and neuropathy in a floppy infant with centronuclear myopathy. Acta Neuropathologica Communications 2018; 6 (1), 1-5. (Co-first authors)
  4. H Wang*, CG Salter*, O Refai*, H Hardy, KES Barwick, U Akpulat, ... et al. Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization. Brain 2017; 140 (11), 2838-2850. (Co-first authors)
  5. C Baarlink, H Wang, R Grosse. Nuclear actin network assembly by formins regulates the SRF coactivator MAL. Science 2013; 340 (6134), 864-867.