Prof. Dr. med. Jan Krönke

University Education

• 1999 -2006 Medical School, Ruprecht-Karls-University Heidelberg, Germany

Professional Experience

• 2006-2015 Resident/Research fellow in Internal Medicine and Hematology/Oncology at the Department of Internal Medicine III, University Hospital Ulm
• 2011-2014 Research Fellow at the Brigham and Women's Hospital/Harvard Medical School, Laboratory of Prof. Dr. Benjamin L. Ebert, MD/PhD (DFG Research fellowship)
• 2015 Emmy Noether Reseach Group Leader (DFG)
• 2020 Professorship/Attending for Hematology, Charité Berlin

Awards, grants and scientific achievments

• SFB 1074 member
• Emmy-Noether Research Group Leader
• Paul-Martini Award
• Artur Pappenheim award
• Franziska-Kolb award for Leukemia research

Scientific Scope

The ubiquitin-proteasome-system is an essential cellular pathway that regulates stability and function of proteins. In cancer cells ubiquitination is frequently deregulated by mutation or aberrant expression of ubiquitin ligases and deubiquitinating enzymes. Moreover, recently we and others found that drugs like thalidomide analogs hijack ubiquitin ligases to rapidly degrade cancer-related proteins including those that were previously considered undruggable such as transcription factors. The focus of our research is to determine the impact of deregulated protein ubiquitination and protein stability in hematologic malignancies. We apply comprehensive proteomic and genetic analyses in primary patient samples combined with CRISPR/Cas9 functional genetics to uncover disease driving and resistance mediating alterations in the ubiquitin-proteasome system. In addition, we study new compounds like proteolysis-targeting chimeras (PROTACs) that direct ubiquitin ligases to proteins as targeted treatments for cancer. The ultimate goal is to translate our findings into the clinic for personalized treatments.

https://haema-cbf.charite.de/forschung/wissenschaftliche_arbeitsgruppen/kroenke_group/

Group members

• Dora Ng (Charité)
• Dr. Evelyn Ramberger (Charité)
• Jan Braune (Clinician Scientist)
• Patrizia Lemnitzer (VTA)
• Sina Müller (B.Sc.)
• Jacqueline Jansen (B.Sc.) 
• Max Zuleeg (MD Student)
• Annika Müller (MD Student) 
• Kazimi Maiwand (MD Student)

Selected References

• Ng, Y.L.D., Ramberger, E., Bohl, S.R., Dolnik, A., Steinebach, C., Conrad, R., Müller, S., Popp, O., Kull, M., Haji, M., Gütschow, M., Döhner, H., Walther, W., Keller, U., Bullinger, L., Mertins, P., Krönke, J. (2022) "Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma." Nature. Communications 13, 1009.
• Steinebach, C., Ng, Y.L.D., Sosič, I., Lee, C., Chen, S., Lindner, S., Vu, L., Bricelj, A., Haschemi, R., Monschke, M., Steinwarz, E., Wagner, K.G., Bendas, G., Luo, J., Gütschow, M., Krönke, J.(2020) "Systematic exploration of different E3 ubiquitin ligases: an approach towards potent and selective CDK6 degraders." Chemical Science. 2020; 11(13): 3474-3486
• Meyer ,T., Jahn, N., Lindner, S., Röhner, L., Dolnik, A., Weber, D., Scheffold, A., Köpff, S., Paschka, P., Gaidzik, V.I., Heckl, D., Wiese, S., Ebert, B.L., Döhner, H., Bullinger, L., Döhner, K., Krönke, J. (2020) "Functional characterization of BRCC3 mutations in acute myeloid leukemia with t(8;21)(q22;q22.1)." Leukemia. 2020 Feb;34(2):404-415.
• Krönke, J.*, Fink, E.*, Hollenbach, P., MacBeth, K., Hurst, S., Udeshi, N., Chamberlain, P., Mani, D., Man, H., Gandhi, A., Svinkina, T., Schneider, R., McConkey, M., Järås, M., Griffiths, E., Wetzler, M., Bullinger, L., Cathers, B., Carr, S., Chopra, R., Ebert, B.(2015) "Lenalidomide induces ubiquitination and degradation of casein kinase 1A1 in del(5q) MDS." Nature. 2015;523(7559):183-8. *Equal contribution.
• Krönke, J., Udeshi, N.D., Narla, A., Grauman, P., Hurst, S.N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., Ciarlo, C., Hartman, E., Munshi, N., Schenone, M., Schreiber, S.L., Carr, S.A., Ebert, B.L. (2014) "Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells." Science.  2014;343(6168):301-5.