As societies age, cancer is quickly becoming one of the most important medical problems. Deciding hallmarks of tumors are deregulated signaling pathways, which significantly change the transcriptional profile of malignant cells. MYC family proteins play a prominent role as transcription factors in this oncogenic reprogramming.
The three main areas of my scientific work, transcription, MYC and cancer are tightly connected. My group works on both, the discovery of so far unknown molecular mechanisms, as well as the development of novel pharmaceutical strategies for cancer treatment.
Our vision is to understand the transcriptional changes during carcinogenesis and, in particular, the oncogenic function of Myc to the extent that new pharmaceutical strategies for the fight against cancer can be developed on this basis. To this end, my research group uses genome- and proteome-wide methods to better understand the biology of tumors as well as genetic screens to find potential therapeutic targets of tumor cells. Together with our partners, we have recently developed substances that inhibit the function of Myc. In the next few years, we want to improve these molecules, of the PROTAC substance class, to such an extent that they can be clinically tested and applied.
Narain A, Bhandare P, Adhikari B, Backes S, Eilers M, Dölken L, Schlosser A, Erhard F*, Baluapuri A*, Wolf E*: Targeted protein degradation reveals a direct role of SPT6 in POL2 elongation and termination, Molecular Cell, 2021, 81, *corresponding authors
Dölle A, Adhikari B, Krämer A, Weckesser J, Berner N, Berger L-M, Diebold M, Szewczyk MM, Barsyte-Lovejoy D, Arrowsmith CH, Gebel J, Löhr F, Dötsch V, Eilers M, Heinzlmeir S, Kuster B, Sotriffer C, Wolf E*, Knapp S*: Design, Synthesis, and Evaluation of WD-Repeat-Containing Protein 5 (WDR5) Degraders, Journal of Medicinal Chemistry, 2021, 64, 10682-10710, *corresponding authors
Adhikari B, Bozilovic J, Diebold M, Schwarz JD, Hofstetter J, Schröder M, Wanior M, Narain A, Vogt M, Dudvarski Stankovic N, Baluapuri A, Schönemann L, Eing L, Bhandare P, Kuster B, Schlosser A, Heinzlmeir S, Sotriffer C, Knapp S* Wolf E*: PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase, Nature Chemical Biology, 2020, 5, 1390-1402, *corresponding authors
Baluapuri A, Hofstetter J, Dudvarski N, Endres T, Bhandare P, Vos SM, Adhikari B Schwarz JD, Narain A, Vogt M, Wang SJ, Düster R, Jung LA, Vanselow JT, Wiegering A, Geyer M, Maric HM, Gallant P, Walz S, Schlosser A, Cramer P, Eilers M, Wolf E: MYC recruits SPT5 to RNA polymerase II to promote processive transcription elongation, Molecular Cell, 2019, 74, 674-687
Lorenzin F, Benary U, Baluapuri A, Walz S, Jung LA, von Eyß B, Kisker C, Wolf J, Eilers M, Wolf E: Different promoter affinities account for specificity in MYC-dependent gene regulation, eLife, 2016, 5
Walz S, Lorenzin F, Morton J, Wiese KE, von Eyss B, Herold S, Rycak L, Dumay-Odelot H, Karim S, Bartkuhn M, Roels F, Wuestefeld T, Fischer M, Teichmann M, Zender L, Wei CL, Sansom O, Wolf E*, Eilers M*: Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles, Nature, 2014, 511, 483-487, * senior/corresponding authors