Cell Fate Engineering and Disease Modeling

Junior Research Group Cell Fate Engineering and Disease Modeling

Dr. Moritz Mall

Microscopy image of engineered neurons derived from fibroblasts.
© dkfz.de

One of the most exciting concepts in biology is the plasticity of cell fate that allows cellular identity to be reset. Strikingly, this plasticity is essential for normal development, but several human diseases are also associated with unwanted changes in cell identity. For example dedifferentiation and adoption of stem cell-like properties are hallmarks of cancer and aberrant gene expression is linked to neuropsychiatric diseases. Investigating the mechanisms that safeguard cell identity will therefore provide new opportunities to understand and treat these devastating diseases.
Cell fate engineering enables researchers to change the identity of cells from one type to another. It allows for example to take blood or skin cells from a patient suffering autism and to reprogram them into functional human neurons in order to study the disease in the culture dish. This revolutionizing technology offers a novel platform to analyze cell identity and disease in cells that are normally not available, such as patient brain cells (Mall and Wernig, 2017; Yang, 2017).
Our work showed that active repression of unwanted genetic programs is important to safeguard the identity of neurons (Treutlein, Nature 2016; Mall, Nature 2017). Since the factors involved are also linked to mental disorders and brain malignancies we will investigate the exciting possibility how loss of neuronal identity can contribute to these devastating diseases.

Future Outlook
We mainly employ pluripotent stem cells and cell fate engineering to reconstruct and investigate human development and disease. Our mission is to understand the mechanisms that determine and maintain cell fate with the goal to treat diseases associated with loss of cell identity. Our immediate research focus is to understand the role of cell identity loss in brain malignancies and mental disorders that affect millions of patients worldwide and are a major medical and economic challenge to our modern society.

Contact

Dr. Moritz Mall
Cell Fate Engineering and Disease Modeling (A340)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42-3195

Selected Publications

  • M. Mall & M. Wernig (2017). The novel tool of cell reprogramming for applications in molecular medicine. Journal of Molecular Medicine, 95:695-703
  • M. Mall, M.S. Kareta, S. Chanda, H. Ahlenius, N. Perotti, B. Zhou, S.D. Grieder, X. Ge, S. Drake, C.E. Ang, B.M. Walker, T. Vierbuchen, D.R. Fuentes, P. Brennecke, K.R. Nitta, A. Jolma, J. Taipale, L.M. Steinmetz, T.C. Südhof, M. Wernig (2017). Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates. Nature, 544:245-249
  • N. Yang, S. Chanda, S. Marro, S., Y.H. Ng, J. Janas, D. Haag, C.E. Ang, Y. Tang, Q. Flores, M. Mall, O. Wapinski, M. Li, H. Ahlenius, J. Rubenstein, H.Y. Chang, A. Alvarez-Buylla, T.C. Südhof, M. Wernig (2017). Generation of pure GABAergic neurons by transcription factor programming. Nature Methods, 95:695-703
  • B. Treutlein, Q.Y. Lee, J.G. Camp, M. Mall, W. Koh, S.A.M. Shariati, S. Sim, N.F. Neff, J.M. Skotheim, M. Wernig, S.R. Quake (2016). Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq. Nature, 534:391-395
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