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.
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 R. Andersson, Principle Investigator
Lenka Belicova, Postdoc
Agustin Corbat Postdoc
Sandra De Haan, PhD student
Jingyan He, PhD student
Afshan Iqbal, PhD student
David Kosek, PhD student
Noémi Van Hul, Senior Scientist
Elisabeth Verboven, Postdoc
Paulina Zydowicz-Machtel, Postdoc
Bettina Semsch, Team leader and technician at INFINIGENE
Outside influence: The extrahepatic duct as a source for bile duct regeneration.
Hepatology 2022 Mar;75(3):505-507
Murine neural plate targeting by in utero nano-injection (NEPTUNE)
Mangold K, He J, Stokman S, Andersson ER
E7.5. JoVE (In press)
In the zone for liver proliferation.
Science 2021 02;371(6532):887-888
Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver.
Hildebrandt F, Andersson A, Saarenpää S, Larsson L, Van Hul N, Kanatani S, Masek J, Ellis E, Barragan A, Mollbrink A, Andersson ER, Lundeberg J, Ankarklev J
Nat Commun 2021 12;12(1):7046
DUCT: Double Resin Casting followed by Micro-Computed Tomography for 3D Liver Analysis.
Hankeova S, Salplachta J, Van Hul N, Kavkova M, Iqbal A, Zikmund T, Kaiser J, Andersson ER
J Vis Exp 2021 09;(175):
Highly efficient manipulation of nervous system gene expression with NEPTUNE.
Mangold K, Mašek J, He J, Lendahl U, Fuchs E, Andersson ER
Cell Rep Methods 2021 Aug;1(4):
Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin.
Kameneva P, Artemov AV, Kastriti ME, Faure L, Olsen TK, Otte J, Erickson A, Semsch B, Andersson ER, Ratz M, Frisén J, Tischler AS, de Krijger RR, Bouderlique T, Akkuratova N, Vorontsova M, Gusev O, Fried K, Sundström E, Mei S, Kogner P, Baryawno N, Kharchenko PV, Adameyko I
Nat Genet 2021 05;53(5):694-706
DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome.
Hankeova S, Salplachta J, Zikmund T, Kavkova M, Van Hul N, Brinek A, Smekalova V, Laznovsky J, Dawit F, Jaros J, Bryja V, Lendahl U, Ellis E, Nemeth A, Fischler B, Hannezo E, Kaiser J, Andersson ER
Elife 2021 02;10():
Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations.
Andersson ER, Chivukula IV, Hankeova S, Sjöqvist M, Tsoi YL, Ramsköld D, Masek J, Elmansuri A, Hoogendoorn A, Vazquez E, Storvall H, Netušilová J, Huch M, Fischler B, Ellis E, Contreras A, Nemeth A, Chien KC, Clevers H, Sandberg R, Bryja V, Lendahl U
Gastroenterology 2018 03;154(4):1080-1095
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