Uwe Rix, PhD

My scientific interest centers on chemical biology, targeted drugs, drug-protein interaction networks, synergy and molecular mechanisms of action in the context of cancer research, particularly lung cancer research. I am pursuing a multi-layered chemical biology/systems pharmacology strategy based on the systematic screening for drug synergy and subsequent identification of the molecular basis underlying the observed synergy by for instance combining chemical proteomics, phosphoproteomics and transcriptomics approaches. This integrated strategy can identify on one hand novel synergistic drug combinations, which due to the focus on clinical drug candidates will have high potential for translation into clinical settings. In addition, the mechanistic understanding will help to further dissect complex oncogenic signaling networks, as well as providing potential mechanism-based biomarkers that can guide patient stratification for future clinical trials of the respective drug combinations.

My core expertise lies in chemical proteomics, which is a postgenomic adaptation of classical drug-affinity chromatography that is powered by downstream mass spectrometry and bioinformatics analysis. This technology is optimally suited to support systematic investigations of cellular drug activities and mechanisms of action by characterizing in an unbiased fashion the cell-specific native drug-target interaction profiles, which are important starting points for identifying the engaged signaling pathways and networks. By applying this strategy, we have been able to identify a large number of new drug-protein interactions, predict drug side effects, characterize circuitries of oncogenic signaling and identify novel synergistic drug combinations.

• Winter GE, Rix U, Carlson SM, Gleixner KV, Grebien F, Gridling M, Müller AC, Breitwieser FP, Bilban M, Colinge J, Valent P, Bennett KL, White FM, Superti-Furga G. Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML. Nat Chem Biol. 2012 Nov;8(11):905-912. Pubmedid: 23023260.
• Brandt O, Mildner M, Egger AE, Groessl M, Rix U, Posch M, Keppler BK, Strupp C, Mueller B, Stingl G. Nanoscalic silver possesses broad-spectrum antimicrobial activities and exhibits fewer toxicological side effects than silver sulfadiazine. Nanomedicine. 2012 May;8(4):478-488. Pubmedid: 21839058.
• Colinge J, Rix U, Bennett KL, Superti-Furga G. Systems biology analysis of protein-drug interactions. Proteomics Clin Appl. 2012 Jan;6(1-2):102-116. Pubmedid: 22213655.
• Rix U, Gridling M, Superti-Furga G. Compound immobilization and drug-affinity chromatography. Methods Mol Biol. 2012;803:25-38. Pubmedid: 22065216.
• Winter GE, Rix U, Lissat A, Stukalov A, Müllner MK, Bennett KL, Colinge J, Nijman SM, Kubicek S, Kovar H, Kontny U, Superti-Furga G. An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B. Mol Cancer Ther. 2011 Oct;10(10):1846-1856. Pubmedid: 21768330.
• Gleixner KV, Mayerhofer M, Cerny-Reiterer S, Hörmann G, Rix U, Bennett KL, Hadzijusufovic E, Meyer RA, Pickl WF, Gotlib J, Horny HP, Reiter A, Mitterbauer-Hohendanner G, Superti-Furga G, Valent P. KIT-D816V-independent oncogenic signaling in neoplastic cells in systemic mastocytosis: role of Lyn and Btk activation and disruption by dasatinib and bosutinib. Blood. 2011 Aug;118(7):1885-1898. Pubmedid: 21680801.
• Burkard TR, Rix U, Breitwieser FP, Superti-Furga G, Colinge J. A computational approach to analyze the mechanism of action of the kinase inhibitor bafetinib. PLoS Comput Biol. 2010 Nov;6(11):e1001001. Pubmedid: 21124949. Pmcid: PMC2987840.
• Ubaida Mohien C, Hartler J, Breitwieser F, Rix U, Remsing Rix L, Winter GE, Thallinger GG, Bennett KL, Superti-Furga G, Trajanoski Z, Colinge J. MASPECTRAS 2: An integration and analysis platform for proteomic data. Proteomics. 2010 Jul;10(14):2719-2722. Pubmedid: 20455215.
• Li J, Rix U, Fang B, Bai Y, Edwards A, Colinge J, Bennett KL, Gao J, Song L, Eschrich S, Superti-Furga G, Koomen J, Haura EB. A chemical and phosphoproteomic characterization of dasatinib action in lung cancer. Nat Chem Biol. 2010 Apr;6(4):291-299. Pubmedid: 20190765. Pmcid: PMC2842457.
• Kim LC, Rix U, Haura EB. Dasatinib in solid tumors. Expert Opin Investig Drugs. 2010 Mar;19(3):415-425. Pubmedid: 20113198.
• Rix U, Remsing Rix LL, Terker AS, Fernbach NV, Hantschel O, Planyavsky M, Breitwieser FP, Herrmann H, Colinge J, Bennett KL, Augustin M, Till JH, Heinrich MC, Valent P, Superti-Furga G. A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells. Leukemia. 2010 Jan;24(1):44-50. Pubmedid: 19890374.
• Sillaber C, Herrmann H, Bennett K, Rix U, Baumgartner C, Böhm A, Herndlhofer S, Tschachler E, Superti-Furga G, Jäger U, Valent P. Immunosuppression and atypical infections in CML patients treated with dasatinib at 140 mg daily. Eur J Clin Invest. 2009 Dec;39(12):1098-1109. Pubmedid: 19744184.
• Fernbach NV, Planyavsky M, Müller A, Breitwieser FP, Colinge J, Rix U, Bennett KL. Acid elution and one-dimensional shotgun analysis on an Orbitrap mass spectrometer: an application to drug affinity chromatography. J Proteome Res. 2009 Oct;8(10):4753-4765. Pubmedid: 19653696.
• Rix U, Superti-Furga G. Target profiling of small molecules by chemical proteomics. Nat Chem Biol. 2009 Sep;5(9):616-624. Pubmedid: 19690537.
• Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Müller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G. Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009 Mar;23(3):477-485. Pubmedid: 19039322.
• Hantschel O, Rix U, Superti-Furga G. Target spectrum of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib. Leuk Lymphoma. 2008 Apr;49(4):615-619. Pubmedid: 18398720.
• Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P. The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar;111(6):3097-3107. Pubmedid: 18180381.
• Rix U, Hantschel O, Dürnberger G, Remsing Rix LL, Planyavsky M, Fernbach NV, Kaupe I, Bennett KL, Valent P, Colinge J, Köcher T, Superti-Furga G. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood. 2007 Dec;110(12):4055-4063. Pubmedid: 17720881.
• Schuster C, Fernbach N, Rix U, Superti-Furga G, Holy M, Freissmuth M, Sitte HH, Sexl V. Selective serotonin reuptake inhibitors--a new modality for the treatment of lymphoma/leukaemia?. Biochem Pharmacol. 2007 Nov;74(9):1424-1435. Pubmedid: 17709099.
• Hantschel O, Rix U, Schmidt U, Bürckstümmer T, Kneidinger M, Schütze G, Colinge J, Bennett KL, Ellmeier W, Valent P, Superti-Furga G. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci U S A. 2007 Aug;104(33):13283-13288. Pubmedid: 17684099. Pmcid: PMC1940229.
• Zheng JT, Rix U, Zhao L, Mattingly C, Adams V, Chen Q, Rohr J, Yang KQ. Cytotoxic activities of new jadomycin derivatives. J Antibiot (Tokyo). 2005 Jun;58(6):405-408. Pubmedid: 16156517. Pmcid: PMC2881663.
• Chen YH, Wang CC, Greenwell L, Rix U, Hoffmeister D, Vining LC, Rohr J, Yang KQ. Functional analyses of oxygenases in jadomycin biosynthesis and identification of JadH as a bifunctional oxygenase/dehydrase. J Biol Chem. 2005 Jun;280(23):22508-22514. Pubmedid: 15817470. Pmcid: PMC2883817.
• Rix U, Wang C, Chen Y, Lipata FM, Remsing Rix LL, Greenwell LM, Vining LC, Yang K, Rohr J. The oxidative ring cleavage in jadomycin biosynthesis: a multistep oxygenation cascade in a biosynthetic black box. Chembiochem. 2005 May;6(5):838-845. Pubmedid: 15776503.
• Zhu L, Ostash B, Rix U, Nur-E-Alam M, Mayers A, Luzhetskyy A, Mendez C, Salas JA, Bechthold A, Fedorenko V, Rohr J. Identification of the function of gene lndM2 encoding a bifunctional oxygenase-reductase involved in the biosynthesis of the antitumor antibiotic landomycin E by Streptomyces globisporus 1912 supports the originally assigned structure for landomycinone. J Org Chem. 2005 Jan;70(2):631-638. Pubmedid: 15651811. Pmcid: PMC2884283.
• Rix U, Zheng J, Remsing Rix LL, Greenwell L, Yang K, Rohr J. The dynamic structure of jadomycin B and the amino acid incorporation step of its biosynthesis. J Am Chem Soc. 2004 Apr;126(14):4496-4497. Pubmedid: 15070349.
• Ostash B, Rix U, Rix LL, Liu T, Lombo F, Luzhetskyy A, Gromyko O, Wang C, Braña AF, Méndez C, Salas JA, Fedorenko V, Rohr J. Generation of new landomycins by combinatorial biosynthetic manipulation of the LndGT4 gene of the landomycin E cluster in S. globisporus. Chem Biol. 2004 Apr;11(4):547-555. Pubmedid: 15123249.
• Remsing LL, González AM, Nur-e-Alam M, Fernández-Lozano MJ, Braña AF, Rix U, Oliveira MA, Méndez C, Salas JA, Rohr J. Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus through combinatorial biosynthesis. J Am Chem Soc. 2003 May;125(19):5745-5753. Pubmedid: 12733914.
• Rix U, Remsing LL, Hoffmeister D, Bechthold A, Rohr J. Urdamycin L: a novel metabolic shunt product that provides evidence for the role of the urdM gene in the urdamycin A biosynthetic pathway of Streptomyces fradiae TU 2717. Chembiochem. 2003 Jan;4(1):109-111. Pubmedid: 12512084.
• Rix U, Fischer C, Remsing LL, Rohr J. Modification of post-PKS tailoring steps through combinatorial biosynthesis. Nat Prod Rep. 2002 Oct;19(5):542-580. Pubmedid: 12430723.
• Trefzer A, Blanco G, Remsing L, Künzel E, Rix U, Lipata F, Braña AF, Méndez C, Rohr J, Bechthold A, Salas JA. Rationally designed glycosylated premithramycins: hybrid aromatic polyketides using genes from three different biosynthetic pathways. J Am Chem Soc. 2002 May;124(21):6056-6062. Pubmedid: 12022840.
• Remsing LL, Garcia-Bernardo J, Gonzalez A, Künzel E, Rix U, Braña AF, Bearden DW, Méndez C, Salas JA, Rohr J. Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel ins. J Am Chem Soc. 2002 Feb;124(8):1606-1614. Pubmedid: 11853433.
• Macky TA, Oelkers C, Rix U, Heredia ML, Künzel E, Wimberly M, Rohrer B, Crosson CE, Rohr J. Synthesis, pharmacokinetics, efficacy, and rat retinal toxicity of a novel mitomycin C-triamcinolone acetonide conjugate. J Med Chem. 2002 Feb;45(5):1122-1127. Pubmedid: 11855992.
• Trefzer A, Hoffmeister D, Künzel E, Stockert S, Weitnauer G, Westrich L, Rix U, Fuchser J, Bindseil KU, Rohr J, Bechthold A. Function of glycosyltransferase genes involved in urdamycin A biosynthesis. Chem Biol. 2000 Feb;7(2):133-142. Pubmedid: 10662691.