Johan Holmberg's Group
Our group is interested in two fundamental questions:
How is neuronal identity acquired during development and subsequently maintained in the adult?
How do errors in the mechanisms governing neuronal differentiation and maintenance affect tumor formation and degenerative processes in the nervous system?
The vertebrate nervous system consists of a multitude of different cell types each with a unique identity and function. We are interested in how this cellular diversity is generated during development and how the established neuronal identity is subsequently maintained. A particular focus of our research is on how alternative gene programs are permanently silenced. In addition to exploring fundamental mechanisms of neuronal differentiation and identity, our research also aims to understand how errors in these processes can influence tumor formation and cellular degeneration in the nervous system. We mainly utilize different mouse models both to investigate the mechanisms underlying regulation of neuronal identity and nervous system tumor formation.
Aberrant splicing in neuroblastoma generates RNA-fusion transcripts and provides vulnerability to spliceosome inhibitors.
Shi Y, Yuan J, Rraklli V, Maxymovitz E, Cipullo M, Liu M, Li S, Westerlund I, Bedoya-Reina OC, Bullova P, Rorbach J, Juhlin CC, Stenman A, Larsson C, Kogner P, O'Sullivan MJ, Schlisio S, Holmberg J
Nucleic Acids Res 2021 Feb;():
A comprehensive map coupling histone modifications with gene regulation in adult dopaminergic and serotonergic neurons.
Södersten E, Toskas K, Rraklli V, Tiklova K, Björklund ÅK, Ringnér M, et al
Nat Commun 2018 03;9(1):1226
Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression.
Westerlund I, Shi Y, Toskas K, Fell SM, Li S, Surova O, et al
Proc. Natl. Acad. Sci. U.S.A. 2017 07;114(30):E6137-E6146
Elevated levels of ZAC1 disrupt neurogenesis and promote rapid in vivo reprogramming.
Rraklli V, Södersten E, Nyman U, Hagey DW, Holmberg J
Stem Cell Res 2016 Jan;16(1):1-9
CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression.
Egan CM, Nyman U, Skotte J, Streubel G, Turner S, O'Connell DJ, et al
Dev. Cell 2013 Aug;26(3):223-36
Maintaining differentiated cellular identity.
Holmberg J, Perlmann T
Nat. Rev. Genet. 2012 May;13(6):429-39