Emma Andersson's Group

Ultra-rapid manipulation of gene expression in utero, and Alagille syndrome development

A group of people outside sitting and standing infront of the camera for a group portrait
David Kosek, Afshan Iqbal, Lenka Belicova, Paulina Zydowicz-Machtel, Jia Sun, Emma R Andersson, Luka Poppe, Jingyan He, Agustin Corbat, Bettina Semsch, Elisabeth Verboven, Sandra De Haan, Noemi Van Hul, Katrin Mangold

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:

  1. Notch signaling deregulation in Alagille syndrome, and Notch control of biliary and vascular development therein.
  2. 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.

Fundings

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).

Group Members

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

Selected Publications

Cover of EMBO, microscope image. Blue and pink.
EMBO Molecular Medicine. Volume 14, Issue 12, December 2022.

RNA:RNA interaction in ternary complexes resolved by chemical probing.
Banijamali E, Baronti L, Becker W, Sajkowska-Kozielewicz JJ, Huang T, Palka C, Kosek D, Sweetapple L, Müller J, Stone MD, Andersson ER, Petzold K
RNA 2023 Mar;29(3):317-329

Sex differences and risk factors for bleeding in Alagille syndrome.
Hankeova S, Van Hul N, Laznovsky J, Verboven E, Mangold K, Hensens N, Adori C, Verhoef E, Zikmund T, Dawit F, Kavkova M, Salplachta J, Sjöqvist M, Johansson BR, Hassan MG, Fredriksson L, Baumgärtel K, Bryja V, Lendahl U, Jheon A, Alten F, Fahnehjelm KT, Fischler B, Kaiser J, Andersson ER
EMBO Mol Med 2022 Dec;14(12):e15809

Modern therapeutic approaches to liver-related disorders.
Gardin A, Remih K, Gonzales E, Andersson ER, Strnad P
J Hepatol 2022 Jun;76(6):1392-1409

Murine Neural Plate Targeting by In Utero Nano-Injection (NEPTUNE) at Embryonic Day 7.5.
Mangold K, He J, Stokman S, Andersson ER
J Vis Exp 2022 Feb;(180):

Outside influence: The extrahepatic duct as a source for bile duct regeneration.
Andersson ER
Hepatology 2022 Mar;75(3):505-507

Cover of Cell Reports Methods, illustrations of the planets in space.
Cell Reports Methods. Volume 1, Number 4, August 2021.

Advances in genetic, epigenetic and environmental aspects of rare liver diseases.
Andersson ER, Lohse AW
Eur J Med Genet 2022 Feb;65(2):104411

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 Dec;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 Sep;(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):

Gender Bias Impacts Top-Merited Candidates.
Andersson ER, Hagberg CE, Hägg S
Front Res Metr Anal 2021 ;6():594424

Cover for Developmental Biology, illustration of different fetal development.
Developmental Biology. Volume 447, Issue 1, March 2019.

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 May;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 Feb;10():

In the zone for liver proliferation.
Andersson ER
Science 2021 Feb;371(6532):887-888

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 Mar;154(4):1080-1095

The developmental biology of genetic Notch disorders.
Mašek J, Andersson ER
Development 2017 May;144(10):1743-1763

Therapeutic modulation of Notch signalling--are we there yet?
Andersson ER, Lendahl U
Nat Rev Drug Discov 2014 May;13(5):357-78

Linda Lindell
08-03-2023