Emma Andersson's Group
Ultra-rapid manipulation of gene expression in utero, and Alagille syndrome development
Our group at the department of Cell and Molecular Biology studies the genetic underpinnings of specific diseases; for example how genetic mutations translate into tubular structures forming incorrectly, compromise vascular integrity, or predispose to neural dysfunction. Within this, our lab has two main focuses:
- Notch signaling deregulation in Alagille syndrome, and Notch control of biliary and vascular development therein.
- Development of ultrasound-guided in utero nanoinjection as a powerful tool to manipulate gene expression in specific organs during development.
Alagille syndrome is a pediatric disorder caused by mutations in the ligand JAGGED1 or the receptor NOTCH2. Patients with this syndrome display paucity of bile ducts, heart defects, vertebral and ocular malformations and stereotypic facial features. We investigate the role of Notch signaling in bile duct development, liver regeneration and liver malignancy in a mouse model for Alagille syndrome and in human patient material using RNA sequencing of liver and biliary organoids, as described by Hans Clevers lab (with whom we collaborate). We also investigate the role of Notch signaling in the vasculature, since a large portion of Alagille patients in fact die from vascular accidents. In this part of the project, we examine the cell-autonomous and non-cell-autonomous roles of Jagged1 in the development of endothelial and vascular smooth muscle cells in the vascular system.
In order to rapidly manipulate gene expression in the developing embryo, to answer basic biological questions in various organ systems, we have collaborated with Elaine Fuchs’s group and further developed ultrasound-guided nanoinjection to target other organ systems than the skin. We use this technology to screen gene libraries for roles in cancer or normal development of various organ systems, with a focus on the nervous system.
Ultrasound-guided nanoinjection targets many developing organs, including the tongue papillae. Lentivirus infected cells express nuclear Histone2B-red fluorescent protein, Pax6 (in green) labels papillae and Tuj1 (in cytosolic red) labels innervation of these. Nuclei are counterstained with DAPI.
|Emma Andersson||Assistant professor, Senior researcher|
|Albert Blanchart Aguado||Laboratory coordinator|
|Jingyan He||PhD student, Student|
|Naomi Hensens||Graduate Student|
|Katrin Mangold||PhD student|
|Aiman Elmansuri||Post Doc|
|Ileana Guzzetti||Post Doc shared with Katja Petzold|
|Simona Hankeova||PhD student shared with Vitezslav Bryja (KI-MU collaboration)|
|Anita Hoogendoorn||Bachelor’s student|
|Bettina Semsch||Animal technician Specialist|
|Marika Sjöqvist||Post Doc|
Therapeutic modulation of Notch signalling--are we there yet?
Nat Rev Drug Discov 2014 May;13(5):357-78
Notch signaling maintains neural rosette polarity.
PLoS ONE 2013 ;8(5):e62959
Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells.
Proc. Natl. Acad. Sci. U.S.A. 2013 Feb;110(7):E602-10
The role of endocytosis in activating and regulating signal transduction.
Cell. Mol. Life Sci. 2012 Jun;69(11):1755-71
Control of Notch-ligand endocytosis by ligand-receptor interaction.
J. Cell. Sci. 2010 Sep;123(Pt 17):2931-42