{"id":22339,"date":"2024-07-26T09:48:40","date_gmt":"2024-07-26T07:48:40","guid":{"rendered":"https:\/\/ilh-giessen.de\/?page_id=22339"},"modified":"2024-07-26T09:48:40","modified_gmt":"2024-07-26T07:48:40","slug":"drug-repurposing-hub","status":"publish","type":"page","link":"https:\/\/ilh-giessen.de\/en\/platforms\/drug-repurposing-hub\/","title":{"rendered":"Drug Repurposing Hub"},"content":{"rendered":"

Prof. Dr. Ralph Schermuly<\/h3>\n
    \n
  1. Omic technologies for identification of novel targets in pulmonary hypertension and right heart hypertrophy.<\/b><\/strong> Genomics, proteomics, transcriptomics, and metabolomics, are revolutionizing cardiopulmonary science by enabling a comprehensive understanding of the molecular underpinnings of cardiovascular and respiratory diseases. These high-throughput approaches allow for the simultaneous analysis of large datasets, revealing intricate networks of genes, proteins, and metabolites involved in disease pathogenesis and progression. In cardiopulmonary research, omics technologies have facilitated the identification of novel biomarkers for early diagnosis, prognostication, and therapeutic targeting. For instance, proteomic studies have uncovered new markers associated with pulmonary hypertension (Rhodes et al., Lancet Respir Med. 2017;5(9):717; Harbaum et al., Am J Respir Crit Care Med. 2022;205(12):1449<\/i><\/em>). In addition, the Schermuly group offers a platform for kinase activity profiling based on the PamStation (Pamgene) system (Figure 1). Based on the tyrosine or serine\/threonine phosphorylation profile, specific kinases can be identified allowing the development of kinase inhibitors for lung and heart diseases. In particular, this technology led to the identification of cyclin dependent kinases (Weiss et al., Nat Commun. 2019;10(1):2204; Knight el al., Circ Res. 2023;133(12):966<\/i><\/em>) and tyrosine kinase inhibitors (Pullamestti et al., Int J Mol Sci. 2023;24(16):12653;<\/i><\/em> Weiss et al., Br J Pharmacol. 2021;178(1):31; Yerabolu et al., Am J Respir Cell Mol Biol. 2021;64(1):100; Veeroju et al., Int J Mol Sci. 2021;22(3):1502; Berghausen et al., J Clin Invest. 2021;131(19):e136939<\/i><\/em>) for treatment of pulmonary hypertension.<\/li>\n<\/ol>\n

     <\/p>\n

    \"\"<\/p>\n

    Figure 1:<\/b><\/strong> Basic principle of the PamStation.<\/b><\/strong> Protein lysates containing active kinases are applied on the PamChips which contain kinase-specific substrate peptides (1). After recognition of the respective peptides, kinases phosphorylate their substrates at tyrosine, serine or threonine residues. Fluorescently labelled 2nd<\/sup> antibodies allow the detection of all phospho-sites (2). Images are recorded by a CCD camera and differential intensities of peptide phosphorylation comparing two experimental conditions, i.e. healthy versus diseased stage, can be observed. Future bioinformatic analyses will reveal which kinases are de-regulated between the two depicted conditions (3). Created with BioRender.com<\/i><\/em><\/span><\/p>\n

     <\/p>\n

    Proteomic and metabolomic analyses have elucidated pathways involved in myocardial infarction and heart failure, paving the way for precision medicine strategies. As these technologies continue to advance, they hold promise for transforming the diagnosis, treatment, and prevention of cardiopulmonary diseases, ultimately improving patient outcomes.<\/p>\n

     <\/p>\n

      \n
    1. Drug screening.<\/b><\/strong> For Drug Screening and Compound Repurposing, we provide comprehensive High-Throughput Screening services, Hit validation, and profiling capabilities. These are supported by a robust bioinformatics and IT infrastructure designed to facilitate rapid data processing and decision-making. Our primary focus is the development of biologically relevant, screening-compatible assays in standard microtiter plate formats, applicable to biomedical research, chemical biology, and drug discovery. These assays cover major protein target classes with readouts available in optical, label-free, and high-content imaging technologies, all operable via our fully integrated robotic screening platform.<\/li>\n<\/ol>\n

       <\/p>\n

      Core Competencies:<\/p>\n

      - Utilization of state-of-the-art tools and technologies for developing innovative assays<\/p>\n

      - Assay readout technologies, including optical, label-free, and high-content imaging<\/p>\n

      - Access to a wide variety of small molecule compound libraries<\/p>\n

      - Triaging of compounds based on mechanism-of-action, selectivity, and ADMET profiling<\/p>\n

      - Delivery of high-quality compounds as starting points for drug discovery<\/p>\n

      - Expertise in advancing compounds to industry-standard Lead and Candidate milestones<\/p>\n

       <\/p>\n

      \"\"<\/p>\n

        \n
      1. Drug Repurposing.<\/b><\/strong> Drug repurposing, also known as drug repositioning or reprofiling, involves the identification of new therapeutic applications for existing drugs outside their originally intended use. This innovative approach aims to leverage the known safety profiles, pharmacokinetics, and mechanisms of action of established medications to address unmet medical needs. By reevaluating existing drugs for different diseases or conditions, drug repurposing expedites the drug development process, potentially reducing costs and timelines. Therefore, the group Schermuly offers a drug repurposing hub based on transcriptomics to uncover gene signatures addressed by existing drugs. The development and availability of large-scale genomic, transcriptomic, and other molecular profiling technologies and publicly available databases, provide an unprecedented opportunity to repurpose existing drugs to heart and lung diseases. This will be combined with the deployment of the network concept of drug targets and the power of phenotypic screening.<\/li>\n<\/ol>\n

        \"\"<\/p>\n

        This strategy not only breathes new life into medications that may have reached the end of their patent life but also offers promising avenues to explore novel treatments for various ailments, fostering the optimization of healthcare interventions and patient care.<\/p>\n

        \u00a0<\/i><\/em><\/p>\n

        The hub will offer:<\/b><\/u><\/strong><\/p>\n

        Database Access<\/b><\/strong>: Comprehensive databases of existing drugs with potential for repurposing, including pharmacological profiles and mechanisms of action.<\/p>\n

        Data Integration and Analysis<\/b><\/strong>: Tools and platforms for integrating diverse data sources (e.g., genomic, proteomic, clinical) to identify new repurposing opportunities.<\/p>\n

        Screening Services<\/b><\/strong>: High-throughput screening facilities to test existing drugs against new targets or disease models.<\/p>\n

        Biomarker Discovery<\/b><\/strong>: Resources and expertise in identifying and validating biomarkers that can predict response to repurposed drugs.<\/p>\n

        Intellectual Property Support<\/b><\/strong>: Assistance with patent searches, filings, and strategies to protect intellectual property related to repurposed drugs (cooperation TransMit).<\/p>\n

         <\/p>\n

        Contact:<\/h4>\n

        Prof. Dr. rer. nat. Ralph Schermuly<\/p>\n

        Chair for Pulmonary Pharmacotherapy
        \nUniversity of Giessen and Marburg Lung Center (UGMLC)
        \nMember of the German Center for Lung Research
        \nJustus-Liebig-University Giessen
        \nBiomedizinisches Forschungszentrum (BFS)
        \nSchubertstr. 81 \u2013 Anlieferung Aulweg 130
        \n35392 Giessen<\/p>\n

        Phone:\u00a0\u00a0 +49 641 99 39883
        \nhttp:\/\/www.UGMLC.de<\/a><\/p>\n

        Excellence Cluster Cardio Pulmonary System (ECCPS) \/ German Center for Lung Research (DZL)
        \nAulweg 130
        \n35392 Giessen<\/p>\n

        Phone:\u00a0\u00a0 +49 641 99 42428 (Assistant: Ms Daniela Weber)
        \nPhone:\u00a0\u00a0 +49 641 99 42422 (Assistant: Ms\u00a0Elizabeta Krstic)
        \nFax:\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 +49 641 99 42419<\/p>\n

         <\/p>\n

        10 most important Publications<\/h4>\n
          \n
        1. Seimetz M, Sommer N, Bednorz M, Pak O, Veith C, Hadzic S, Gredic M, Parajuli N, Kojonazarov B, Kraut S, Wilhelm J, Knoepp F, Henneke I, Pichl A, Kanbagli ZI, Scheibe S, Fysikopoulos A, Wu CY, Klepetko W, Jaksch P, Eichstaedt C, Gr\u00fcnig E, Hinderhofer K, Geiszt M, M\u00fcller N, Rezende F, Buchmann G, Wittig I, Hecker M, Hecker A, Padberg W, Dorfm\u00fcller P, Gattenl\u00f6hner S, Vogelmeier CF, G\u00fcnther A, Karnati S, Baumgart-Vogt E, Schermuly RT<\/u>, Ghofrani HA, Seeger W, Schr\u00f6der K, Grimminger F, Brandes RP, Weissmann N. NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD. Nat Metab<\/i><\/b><\/em><\/strong>. 2020 Jun;2(6):532-546.<\/li>\n
        2. Weiss A, Neubauer MC, Yerabolu D, Kojonazarov B, Schlueter BC, Neubert L, Jonigk D, Baal N, Ruppert C, Dorfmuller P, Pullamsetti SS, Weissmann N, Ghofrani HA, Grimminger F, Seeger W, Schermuly RT<\/u>. Targeting cyclin-dependent kinases for the treatment of pulmonary arterial hypertension. Nat Commun<\/i><\/b><\/em><\/strong>. 2019 May 17;10(1):2204.<\/li>\n
        3. Pullamsetti SS, Kojonazarov B, Storn S, Gall H, Salazar Y, Wolf J, Weigert A, El-Nikhely N, Ghofrani HA, Krombach GA, Fink L, Gattenl\u00f6hner S, Rapp UR, Schermuly RT<\/u>, Grimminger F, Seeger W, Savai R. Lung cancer-associated pulmonary hypertension: Role of microenvironmental inflammation based on tumor cell-immune cell cross-talk. Sci Transl Med<\/i><\/b><\/em><\/strong> 2017,9(416).<\/li>\n
        4. Rhodes CJ, Wharton J, Ghataorhe P, Watson G, Girerd B, Howard LS, Gibbs JSR, Condliffe R, Elliot CA, Kiely DG, Simonneau G, Montani D, Sitbon O, Gall H, Schermuly RT<\/u>, Ghofrani HA, Lawrie A, Humbert M, Wilkins Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study. Lancet Respir Med<\/i><\/b><\/em><\/strong> 2017, 5(9):717-726.<\/li>\n
        5. El Agha E, Moiseenko A, Kheirollahi V, De Langhe S, Crnkovic S, Kosanovic D, Kwapiszewska G, Kosanovic D, Schwind F, Schermuly RT<\/u>, Henneke I, MacKenzie B, Quantius J, Herold S, Ahlbrecht, K, Morty RE, Gunther A, Seeger W, Bellusci S.<\/b><\/strong> Two-way conversion between lipogenic and myogenic fibroblastic phenotypes marks the progression and resolution of lung fibrosis. Cell Stem Cell<\/i><\/b><\/em> <\/strong>2016, 20(4):571.<\/li>\n
        6. Savai R, Al-Tamari HM, Sedding D, Kojonazarov B, Muecke C, Teske R, Capecchi MR, Weissmann N, Grimminger F, Seeger W, Schermuly RT<\/u>, Pullamsetti SS. Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension. Nat Med <\/i><\/b><\/em><\/strong>2014, 20:1289-1300.<\/li>\n
        7. Pullamsetti SS, Doebele C, Fischer A, Savai R, Kojonazarov B, Dahal BK, Ghofrani HA, Weissmann N, Grimminger F, Bonauer A, Seeger W, Zeiher AM, Dimmeler S, Schermuly RT<\/u>. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am J Respir Crit Care Med<\/i><\/b><\/em><\/strong>. 2012 Feb 15;185(4):409-19.<\/li>\n
        8. Pullamsetti SS, Savai R, Schaefer MB, Wilhelm J, Ghofrani HA, Weissmann N, Schudt C, Fleming I, Mayer K, Leiper J, Seeger W, Grimminger F, Schermuly RT<\/u>. cAMP phosphodiesterase inhibitors increases nitric oxide production by modulating dimethylarginine dimethylaminohydrolases. Circulation<\/i><\/b><\/em><\/strong> 2011, 123:1194-1204.<\/li>\n
        9. Schermuly RT*<\/u>, Klein M*, Ellinghaus P, Milting H, Riedl, B, Pullmasetti SS, Weissmann N, Nikolova S, Dony E, Ghofrani HA, Grimminger F, Busch AE, Sch\u00e4fer S. Tyrosine and serine-\/threonine kinase inhibition by sorafenib prevents experimental pulmonary hypertension and myocardial remodelling. Circulation<\/i><\/b><\/em><\/strong> 2008, 118:2081-2090. *equal contribution.<\/li>\n
        10. Schermuly RT<\/u>, Dony E, Ghofrani HA. Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest<\/i><\/b><\/em><\/strong> 2005, 115:2811-2821.<\/li>\n<\/ol>\n

          Here you can find all ILH-publications<\/a><\/h4>\n

           <\/p>\n

          Funding<\/h4>\n

          \"\"<\/p>\n

           <\/p>\n

          Group Members<\/h4>\n

          Post Docs<\/b><\/strong><\/p>\n

          Dr. Argen Mamazhakypov
          \nDr. Nabham Rai
          \nDr. Mazen Shihan
          \nDr. Astrid Wei\u00df
          \nDr. Swathi Veeroju<\/p>\n

          Doctoral Students<\/b><\/strong><\/p>\n

          Tobiah Antoine
          \nLeonhard Blumrich
          \nJaron Lukas Bornh\u00e4user
          \nVivian Feichtenschlager
          \nMuriel Fischer
          \nVandna Sapehia
          \nTim Schatull
          \nAnna Schumacher<\/p>\n

          Technical Assistants<\/b><\/strong><\/p>\n

          Julia Baldauf
          \nAndreas Hecker
          \nCarina Lepper
          \nChristina Vroom<\/p>\n

           <\/p>\n

           <\/p>\n

           <\/p>\n

           <\/p>\n

           <\/p>\n

           <\/p>\n

           <\/p>\n","protected":false},"excerpt":{"rendered":"

          Prof. Dr. Ralph Schermuly Omic technologies for identification of novel targets in pulmonary hypertension and right heart hypertrophy. Genomics, proteomics, transcriptomics, and metabolomics, are revolutionizing cardiopulmonary science by enabling a comprehensive understanding of the molecular underpinnings of cardiovascular and respiratory diseases. These high-throughput approaches allow for the simultaneous analysis of large datasets, revealing intricate networks […]<\/p>\n","protected":false},"author":20,"featured_media":19506,"parent":19266,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","_seopress_analysis_target_kw":"","footnotes":""},"class_list":["post-22339","page","type-page","status-publish","has-post-thumbnail","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/pages\/22339","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/users\/20"}],"replies":[{"embeddable":true,"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/comments?post=22339"}],"version-history":[{"count":5,"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/pages\/22339\/revisions"}],"predecessor-version":[{"id":22352,"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/pages\/22339\/revisions\/22352"}],"up":[{"embeddable":true,"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/pages\/19266"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/media\/19506"}],"wp:attachment":[{"href":"https:\/\/ilh-giessen.de\/en\/wp-json\/wp\/v2\/media?parent=22339"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}