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.
We are grateful for support from:
- The Swedish Research Council (3R project grant, Vetenskapsrådet)
- The Heart and Lung Foundation (Hjärtlungfonden)
- The Center of Innvoative Medicine (CIMED)
- The Knut and Alice Wallenberg Foudnation (KAW)
- Funding in the KI Career Ladder
- The Europan Association for the Study of the Liver (EASL, for the Daniel Alagille Award to ER Andersson and the Sheila Sherlock postdoctoral fellowship to Jan Masek.)
We are also grateful to support from Wera Ekströms STiftelse (to Afshan Iqbal).
We are also grateful for previous support from VR Projektbidrag Unga forskare, Alex & Eva Wallström Stiftelse, KID funding, KI NIH PhD Student, VR 3R, Ollie och Elof Ericssons Stiftelse, Tornspirans Stiftelse, KI Stiftelser, Jeansssons Stiftelse, Fredrik och Ingrid Thurings stiftelse, Lars Hiertas Minne, Barncancerfonden, Åhlen stiftelsen, StratNeuro Start-upp support, Åke Wibergs Stiftelse, Tore Nilssons Stiftelse, support from Wera Ekström Stiftelse (to Simona Hankeova), and Wennergren Stiftelser (post doc fellowship to Jan Masek).
|Emma Andersson||Assistant professor, Senior researcher|
|Albert Blanchart Aguado||Laboratory coordinator|
|Sandra De Haan||PhD student, Graduate Student|
|Jingyan He||PhD student, Student|
|Katrin Mangold||PhD student|
|Emine Ezel Cilek||Postdoc|
|Simona Hankeova||Laboratory engineer|
|Afshan Iqbal||PhD student|
|David Kosek||PhD student|
|Bettina Semsch||Animal technician specialist|
|Noemi Van Hul||Senior scientist|
Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations.
Gastroenterology 2018 03;154(4):1080-1095
A New Model of Alagille Syndrome With Broad Phenotypic Representation.
Gastroenterology 2018 03;154(4):803-806
The developmental biology of genetic Notch disorders.
Development 2017 05;144(10):1743-1763
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
Andersson, ER; Future therapeutic approaches for Alagille Syndrome, Alagille Syndrome - Pathogenesis and Clinical Management (Springer), edited by Kathleen Loomes and Binita Kamath, 2018
Noemi Van Hul, Urban Lendahl, Emma R Andersson, Chapter 16: Mouse models for diseases in the cholangiocyte lineage, edited by Mathieu Vinken, Methods in Molecular Biology, Protocols in Experimental Cholestasis research, Accepted, publication date expected in 2019