Kliniken & Institute … Institute Humangenetik Forschung Abt. Humangenetik AG Laugsch

AG Laugsch

WHAT?

We explore the relationship between craniofacial and brain development and their intimate interactions in health and disease.

WHY?

In vertebrates, the head forms from a transient and multipotent population of neural crest cells that appears after the embryonic neural tube closes. From this point onward, head and brain formation are intertwined throughout development. The head protects the developing brain and facilitates its functional integration, and many neurodevelopmental disorders also include craniofacial malformations. Our investigations of the similarities and differences between human neural crest cells and neuronal cells will provide valuable insights into the causes of neurodevelopmental conditions.

HOW?

A great breakthrough in the field of human disease modeling was the possibility to obtain human stem cells by reprogramming adult somatic cells. Since then, these so-called human induced pluripotent stem cells (hiPSC) have been generated from patient donors and then differentiated into disease-relevant cell types that can be used to expand our knowledge about the molecular basis of disease. The power of disease modeling has further expanded with the development of CRISPR/Cas9 technology, which simplifies introducing or correcting mutations in cellular DNA.
Leveraging our expertise in hiPSC culture, genome editing (CRISPR/Cas9), and their directed differentiation (neural and neural crest), we have been recapitulating early human embryogenesis. To analyze that process, we have been combining epigenomic (ChIP-seq, 4C-seq, Hi-ChIP-seq) and transcriptomic data (RNA-seq) with advanced computational approaches. Our genomewide data should provide an excellent foundation for innovative studies on the intimate interactions and relationships between craniofacial and brain development.

SELECTED RECENT PUBLICATIONS

Kargapolova Y, Rehim R, Kayserili H, Brühl, ZirkelA, Li Y, Yigit, G, Hoischen A, Frank S, Russ N, Trautwein J, Laugsch M, Gade Gusmao E, Josipovic N, Altmüller J, Nürnberg P, Kaiser FJ, Wartin E, Brunner H, Rada-Iglesias A, Kurian L, Wollnik B, Bouazoune K, Papantonis A. Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology. doi: https://doi.org/10.1101/2020.01.27.921171

Zanella M, Vitriolo A, Andirko A, Tiago Martins P, Sturm S, O’Rourke T, Laugsch M, Malerba N, Skaros A, Trattaro S, Germain P, Mihailovic M, Merla G, Rada-Iglesias A, Boeckx C, Testa G (2019). Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication. Sci Adv. 2019 Dec 4;5(12):eaaw7908.

Crutcher E, Pal R, Naini F, Zhang P, Laugsch M, Kim J, Bajic A, Schaaf CP. (2019) mTOR and autophagy pathways are dysregulated in murine and human models of Schaaf-Yang syndrome. Sci Rep. 9(1):15935.

Laugsch M, Bartusel M, Rehimi R, Alirzayeva H, Karaolidou A, Crispatzu G, Zentis P, Nikolic M, Bleckwehl T, Kolovos P, van Ijcken WFJ, Šarić T, Koehler K, Frommolt P, Lachlan K, Baptista J, Rada-Iglesias A (2019). Modelling the pathological long-range regulatory effects of human structural variation with patient-specific hiPSCCell Stem Cell. 5, 736-752.

Laugsch M, Rostovskaya M, Velychko S, Richter C, Zimmer A, Klink B, Schröck E, Haase M, Neumann K, Thieme S., et al. (2016). Functional Restoration of gp91phox-Oxidase Activity by BAC Transgenesis and Gene Targeting in X-linked Chronic Granulomatous Disease iPSCs. Mol. Ther. 4, 812-22.
 

Dr. rer. nat. Magdalena Laugsch
Tel. +49 6221 56-39128
E-Mail: Magdalena.Laugsch@uni-heidelberg.de