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Hedgehog signalling, tissue stem cells, and cancer development - Rune Toftgård

Inappropriate reactivation of developmental signalling pathways such as the Hedgehog (Hh) pathway is a common event during cancer development.

Illustration showing the interaction of SUFU with GLI. A GLI3 peptide (blue) containing the recognition motif SYGH binds in a channel between the N-terminal (beige) and C-terminal (green) domains of SUFU.

Hedgehog Signaling

Mutational inactivation or activation of core components of the Hh-pathway underlies cell autonomous activation in basal cell carcinoma of the skin (BCC) and in medulloblastoma. In other tumour types such as colorectal, pancreatic and breast cancer additional activation mechanisms are present.

A major focus of our research is to understand the details of Hh signalling at the genetic, molecular and structural level with emphasis on the key intracellular SUFU and GLI components. Secondly, to understand how aberrant activation of this pathway can drive cancer development and to devise new methods aimed at pharmacological inhibition of the Hh signalling pathway at the level of the GLI transcriptional effectors building on our detailed biological and molecular studies of the pathway.

To understand cancer biology and how to best eradicate tumour cells we must know the biology of normal tissues including the nature of tissue stem and progenitor cells, their interconversions and their ability to serve as cancer cells of origin. With this aim we are interested in the presence and functional properties of tissue stem cells marked by expression of Lgr5 and Lgr6 in skin and mammary gland.

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Rune Toftgård

Group Members

Leander Blaas, Assistant Professor

Marco Gerling, Researcher, Physician

Arash Chitsazan, Postdoc

Maryam Saghafian, Senior Lab Manager (on maternity leave)

Xiaoze Li-Wang, Senior Lab Manager

Agneta Andersson, Biomedical Scientist

Rune Toftgård, Senior Professor