We are studying the centrosome, a tiny organelle that is a key determinant of microtubule (MT) organization, cilia formation and cell division. These processes are tightly co-ordinated/-regulated with the cell division cycle and cell differentiation, and are when disrupted or perturbed an underlying cause of cancer and developmental disorders. We are particularly interested in disease associated proteins involved in cilia formation and cell division, and in the mechanism(s) that regulate centrosome composition in response to radiation. By studying disease-associated centrosomal/ciliary proteins in cell line models and patient biopsies, we aim at a mechanistic understanding of their function at a molecular level, and at the identification of candidate biomarkers or targets for mono- and radiation-combination therapy. The quest for these is warranted, since significant side-effect burden as well as therapy-resistance are limiting factors of currently used MT-targeting chemotherapeutics. Specific co-targeting of cell division by new inhibitors and DNA integrity by radiation may prove as a valuable strategy due to the reduced DNA repair capacity during this pivotal stage of the cell cycle. Our cross-functional approaches include different molecular and imaging techniques and are conducted in collaboration with regional and international experts in cell, cancer and developmental disorder biology.

We greatly acknowledge the financial support by Kreftforeningen.

Disclaimer: S Patzke is holding a part-time position at Nordic Nanovector ASA.

Frikstad,K.M., Molinari,E., Thoresen,M., Ramsbottom,S.A., Hughes,F., Letteboer,S.F.J., Gilani,S., Schink,K.O., Stokke,T., Geimer,S., Pedersen,L.B., Giles,R.H., Akhmanova,A., Roepman,R., Sayer,J.A. and Patzke,S (2019). A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling. Cell Reports (in press)

Shearer,R.F., Frikstad,K.M., McKenna,J., McCloy,R.A., Deng,N., Burgess,A., Stokke,T., Patzke,S., and Saunders,D.N. (2018). The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia. Mol. Biol. Cell. 29, 1542-1554.

Sternemalm,J., Geimer,S., Frikstad,K.A., Schink,K.O., Stokke,T., and Patzke,S. (2015). CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation. PLoS. One. 10, e0134789.

Sternemalm,J., Russnes,H.G., Zhao,X., Risberg,B., Nordgard,S.H., Caldas,C., Borresen-Dale,A.L., Stokke,T., and Patzke,S. (2014). Nuclear CSPP1 expression defined subtypes of basal-like breast cancer. Br. J. Cancer 111, 326-338.

Patzke,S., Redick,S., Warsame,A., Murga-Zamalloa,C.A., Khanna,H., Doxsey,S.J., and Stokke,T. (2010). CSPP is a ciliary protein interacting with Nephrocystin 8 and required for cilia formation. Mol. Biol. Cell 21, 2555-2567.

Patzke,S., Stokke,T., and Aasheim,H.C. (2006). CSPP and CSPP-L associate with centrosomes and microtubules and differently affect microtubule organization. J. Cell Physiol 209, 199-210.

Patzke,S., Hauge,H., Sioud,M., Finne,E.F., Sivertsen,E.A., Delabie,J., Stokke,T., and Aasheim,H.C. (2005). Identification of a novel centrosome/microtubule-associated coiled-coil protein involved in cell-cycle progression and spindle organization. Oncogene 24, 1159-1173.

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