Mission

The ONCOkinase lab studies the molecular interdependencies of mutated kinases and their regulator proteins to accelerate early-stage drug discovery efforts. Their cell-based analyses of the mode of action of kinases provide insights into disease mechanisms, with the hope of unveiling strategies for better therapeutic intervention.

Research

Our ONCOkinase lab is interested in several areas of basic research related to carcinogenesis and biotechnology:

  • Our working group is engaged in early-stage drug discovery efforts targeting oncokinases, transcription factors, and GPCR pathways. By analyzing bioactive small molecules that selectively modulate these key players in disease pathways, we aim to contribute to the development of more effective therapies for diseases such as cancer.
  • We investigate compartmentalized kinase signaling pathways, particularly those involving PKA, RAF, MEK, and RIPK downstream of receptor pathways. Understanding how these signaling molecules are spatially organized within cells helps us decipher their specific roles in cellular processes and disease development.
  • We explore the involvement of post-translational modifications, such as phosphorylation, ubiquitination and acetylation, in redirecting second messenger-controlled signal transmission. These modifications play critical roles in modulating the activity and localization of signaling proteins, and studying their effects helps us unravel the intricate mechanisms underlying cellular communication.
  • Lastly, we focus on generating unique cell-based reporter platforms that enable us to analyze the dynamics of protein and cancer-drug interactions. These platforms provide a powerful tool for studying the efficacy and mechanism of action of potential therapeutic agents, as well as for identifying new targets for drug development.

Research Team Members

Priv. Doz. Dr. Eduard Stefan

Principal Investigator

eduard.stefan@tkfi.at 

Andreas Feichtner, M.Sc.

Doctoral Student

Andreas.Feichtner@uibk.ac.at

Jakob Fleischmann, M.Sc.

Doctoral Student

Jakob.Fleischmann@uibk.ac.at

Valentina Kugler

Doctoral Student

Valentina.Kugler@uibk.ac.at

Selina Schwaighofer, M.Sc.

Doctoral Student

selina.schwaighofer@uibk.ac.at

OUR AIM IS TO FURTHER COMPREHEND THE MOLECULAR FACTORS BEHIND THE ONSET OF CANCER.

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Publications

Selected Publications

  • Fleischmann J., Schwaighofer S., De Falco L., Enzler F., Feichtner A., Kugler V., Tschaikner P., Huber RG & Stefan, E.. Tracking and blocking interdependencies of cellular BRAF-MEK oncokinase activities. PNAS Nexus, 2(6):pgad185. (2023)
  • Moesslacher C. S., Auernig E., Woodsmith J., Feichtner A., Jany-Luig E., Jehle S., Worseck J. M., Heine C. L., Stefan, E. & Stelzl U. Missense variant interaction scanning reveals a critical role of the FERM domain for tumor suppressor protein NF2 conformation and function. Life Sci Alliance, 6(8):e202302043. (2023).
  • Kugler V., Lieb A., Guerin N., Donald B. R., Stefan, E. & Kaserer T. DISRUPTOR: Computational identification of oncogenic mutants disrupting protein interactions. In press, 11.02.514903. (2022)
  • Fleischmann, J., Feichtner, A., DeFalco, L., Kugler, V., Schwaighofer, S., Huber, R. G., & Stefan, E. Allosteric kinase inhibitors reshape MEK1 kinase activity conformations in cells and in silico. Biomolecules, 11(4), 518. (2021).

All Publications

https://pubmed.ncbi.nlm.nih.gov/?term=Eduard+Stefan&sort=pubdate&size=200

Links

https://www.uibk.ac.at/molbiol/research/oncokinase-lab/