Kliniken & Institute … Institute Institute of Human… Research Department of Human… 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 research focuses on developmental genes that need a specific and dynamic regulation e.g. by enhancers. That regulation ensures establishing their precise expression patterns during development, which might have pathological consequences when being disrupted. In this context, 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.

Figure 1: Scheme of generation and possible applications of hiPSC. Human cells of any origin can be reprogramed into hiPSC by transient overexpression of a combination of certain transcription factors. Due to their renewing potential, hiPSC can be expanded and engineered. Finally, hiPSC can be differentiated into the desired cell type and applied for disease modelling, drug screening or transplantation.

JOIN THE LAB

YOU are a curiosity-driven researcher, passionated for science, have good written and verbal communication skills in English, can work both independently and as part of our team.

WE offer you a creative and inspiring environment of highly enthusiastic and motivated scientists. You will find here an international and multi-disciplinary group and a friendly working atmosphere that supports individual career development. Our team and our outstanding national and international collaborations apply cutting-edge approaches to investigate the craniofacial and brain development using hiPSC models.

MASTER AND BSC. STUDENTS, INTERN students

Talented students with a strong interest in stem cell, molecular biology, and bioinformatics are welcome in our laboratory. However, the opportunities strongly depend on our ongoing scientific questions and capacities.

OPEN PHD AND POSTDOC POSITIONS

Currently, there are no open positions available, but excellent candidates are always encouraged to contact Magdalena Laugsch.

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.

* shared authorship

Group Members:

Group Leader dr. rer. nat. Magdalena Laugsch
After her diploma studies in biology (University of Braunschweig and University of Cologne), she obtained her Ph.D. degree at the Institute of Pharmacology and Toxicology (University of Magdeburg). For her following career, scientific projects with Prof. Rolf Jessberger (Institute of Biochemistry, Dresden) and Dr. Alvaro Rda-Iglesias (CMMC, Cologne) were crucial. In Prof. Schaaf's lab (2019), she got the great opportunity to study neurodevelopmental disorders related to the neural crest (Institute of Human Genetics, Heidelberg). In 2020, Magdalena became a group leader. Since then, she is expanding her research in this area.

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

Mara Rudiger, intern
Mara is studying molecular and technical medicine in the bachelor's program at Villingen-Schwenningen University and joined our lab on the 1st of March 2021 for an internship. Her goal is to investigate the molecular causes of craniofacial abnormalities in human disease. She employs CRISPR/Cas9 technique in hiPSC to generate a conditional knockout of genes relevant to the differentiation of neural crest cells.

Sarah Cluff, BSc
Sarah is a master's student in the Molecular Cellular Biology program at the University of Heidelberg, working on her thesis project in the lab. She is interested in the regulation of gene expression controlled by the non-coding elements and their impact on human disease. Email: sarah.cluff@stud.uni-heidelberg.de

Ayat Ahmed, MSc
Ayat is doing her PhD in our lab; her research focuses on investigating the regulatory landscape of the transcription factor NR2F1 in the neural crest. Besides, she aims to determine the regulatory network controlled by NR2F1 in neural crest and neurodevelopmental disorder.

Luis Castillo, PhD
Luis supports hiPSC-differentiation towards neural crest cells and neurons, general lab management tasks, as well as epigenetic, transcriptomic, and functional analysis of our cell models. Email: luis.castillo-ramirez@med.uni-heidelberg.de

Susanne Theiß, Technician (AG Laugsch/AG Schaaf)
Susanne is working on genome organization (4C and Hi-C) and identifying genome-wide DNA binding sites for different transcription factors and histone modifications (ChIP-seq). She supports us in determining changes in regulatory landscapes and networks in various neurodevelopmental disorders. In addition, Susanne is an expert in the field of CRISPR/Cas9 mediated genome editing. E-Mail: Susanne.Theiss@uni-heidelberg.de

Aaron Sievers, MSc (AG Laugsch/AG Schaaf)
Aaron is a biophysicist working on in silico studies of DNA-sequence-dependent physiochemical properties of chromatin. He is responsible for bioinformatic analysis. Email: aaron.sievers@med.uni-heidelberg.de

Melanie Spanjaard, medical student (AG Laugsch/AG Schaaf)
Melanie is taking a year off of medical school in order to complete a research project for her medical dissertation. She is working on iPSCs and iNeurons in the context of Prader-Willi syndrome. Email: spanjaard@stud.uni-heidelberg.de

Ding Cao, MSc (collaboration with Dr. Christina Eichstaedt)
Cao is a student in the doctor of medicine program. He investigates the functional effect of genetic variants of pulmonary arterial hypertension patients. Email: Cao.Ding@med.uni-heidelberg.de

Marc Thomas BSc, intern
Marc is a Master's student in Biochemistry (University of Heidelberg) and creating a cellular model of human disease associated with anomalies in neural crest development (neurocristopathies). He started the lab work in Apil to learn how to knock out the genes by CRISPR/Cas9 by generating indels in hiPSCs.

Alumni:

Alexander Wirth
Alex performed an internship in our lab during his Biochemistry Master studies in 2020/2021 at the University of Heidelberg. He learned how to use the CRISPR/Cas9 technique in hiPSC.

Rocio Olmos Romero
Rocio studied translational medical research and conducted her master thesis in our lab. Using CRISPR/Cas9 mediated genome editing, she generated several clonal hiPSC lines with heterozygous NR2F1 deletion.