Urban Lendahl's Group
Our long-term goal is to understand how the Notch signaling pathway operates at the molecular level, and how it controls cell fate decisions in normal development and disease.
We work on several aspects of Notch signaling. An important focus is to gain mechanistic insights into various steps in the pathway, ranging from endocytic processing of both ligands and receptor to establishing the immediate downstream signaling output through transcriptome analysis in different cell types.
We study the role of Notch signaling in differentiation of various cell types, such as ES cells, myogenic and vascular progenitors. We also address the role of Notch in disease processes, notably in vascular disease and Alagille syndrome, as well as in cancer, with a particular focus on breast cancer.
Last, but not least, we try to unravel how Notch signaling cross-talks with other principal signaling mechanisms, and how such cross-talk allows for a larger number of physiological responses in a cell. We have previously demonstrated a cross-talk between Notch and BMP signaling, and, together with Lorenz Poellinger's group at CMB, provided evidence for integration between Notch and the cellular response to low oxygen (hypoxia).
Therapeutic modulation of Notch signalling--are we there yet?
Andersson E, Lendahl U
Nat Rev Drug Discov 2014 May;13(5):357-78
PKCζ regulates Notch receptor routing and activity in a Notch signaling-dependent manner.
Sjöqvist M, Antfolk D, Ferraris S, Rraklli V, Haga C, Antila C, et al Cell Res. 2014 Apr;24(4):433-50
Non-canonical Notch signaling activates IL-6/JAK/STAT signaling in breast tumor cells and is controlled by p53 and IKKα/IKKβ.
Jin S, Mutvei A, Chivukula I, Andersson E, Ramsköld D, Sandberg R, et al Oncogene 2013 Oct;32(41):4892-902
Notch signaling mediates hypoxia-induced tumor cell migration and invasion.
Sahlgren C, Gustafsson M, Jin S, Poellinger L, Lendahl U
Proc. Natl. Acad. Sci. U.S.A. 2008 Apr;105(17):6392-7
Hypoxia requires notch signaling to maintain the undifferentiated cell state.
Gustafsson M, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, et al
Dev. Cell 2005 Nov;9(5):617-28