Uwe Rix's Biography

Uwe Rix, Assistant Member/Professor, Moffitt Cancer Center

Born in Neumünster, Germany, Uwe studied chemistry in Kiel and Göttingen. He received his Master degree for his work on synthetic approaches to the cyclization of model polyketides under the supervision of Jürgen Rohr. He continued his work with Jürgen Rohr in the USA at the Medical University of South Carolina (Charleston, SC), and later at the University of Kentucky (Lexington, KY), receiving his Ph.D. degree in Pharmaceutical Sciences in 2003. His Ph.D. dissertation focussed on oxygenases, their mechanisms and their use for combinatorial biosynthesis of polyketide natural products, such as jadomycins and landomycins. Returning to Germany, he specialized in chemical proteomics during his post-doctoral studies with Giulio Superti-Furga. After a brief training period with him at Cellzome in Heidelberg, Germany, Uwe contributed to setting up Giulio’s academic lab in Vienna, Austria, at the Center for Molecular Medicine (CeMM) by establishing the chemical proteomics technology platform there. Employing this multidisciplinary approach, they were able to characterize the vastly different protein target profiles of the tyrosine kinase inhibitor (TKI) imatinib, the gold standard for targeted therapy, as well as several other kinase inhibitors for the treatment of CML, such as nilotinib, dasatinib and bosutinib, in cell lines and patient cells. In doing so, they identified and validated a large number of novel targets of these drugs, among these the first non-kinase target of imatinib and nilotinib, the oxidoreductase NQO2, and many tyrosine, receptor tyrosine and serine/threonine kinases. Furthermore, based on the potent inhibition of BTK they demonstrated the potential for immune system-related side effects of dasatinib. By combining several ‘omics’ approaches they were also able to identify and dissect the complex mechansim of action of the synergy between the two clinical multikinase inhibitors bosutinib and danusertib in BCR-ABLT315I gatekeeper-mutant CML and demonstrated beneficial combinatorial effects of off-targets for both drugs. In collaboration with Eric Haura from the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, they furthermore elucidated the complex molecular mechanisms underlying the pro-apoptotic effects of the multitargeted kinase inhibitor dasatinib in lung cancer cells by combining chemical and phosphoproteomic techniques with comprehensive downstream validation by functional genomics. This work has resulted in the identification of a synergistic drug combination using dasatinib together with the EGFR inhibitor erlotinib and the subsequent design of a combinatorial clinical trial in lung cancer. In October 2011, Uwe joined the Moffitt Cancer Center as an Assistant Member/Assistant Professor in Drug Discovery where he is currently setting up his own research lab. Uwe’s scientific interest centers on chemical biology, drugs and natural products in the context of cancer research. He is applying a chemical proteomics-based approach to identify and characterize new cancer-relevant drug-/small molecule-protein relationships and molecular mechanisms of action with a particular interest on drug synergy and lung cancer. He has co-authored 28 research articles, including 9 first author papers (Nat.Chem.Biol., Blood, Leukemia, PNAS, J.Am.Chem.Soc., Mol.CancerTher., ChemBioChem), and 6 review articles (e.g. Nat.Chem.Biol., Nat.Prod.Rep., Leuk.Lymphoma).