• Max von Kleist

    max2_jpg_small

    Max von Kleist, PhD (*17.10.1979, Berlin, Germany)

    Principle Investigator

    2011-        Junior research group leader “Systems Pharmacology & Disease Control”, Dep. of Mathematics, Freie Universität Berlin, Germany

    2010-11      Post-doctoral research assistant, Dep. of Mathematics & Computer Science (AG Schütte), Freie Universität Berlin, Germany

    2006-09      Doctoral research in mathematics, DFG-research center MATHEON & Hamilton Institute/National University of Ireland, Maynooth, Ireland

    2004-05      Research internship pharmaceutical industry, AstraZeneca R&D, Mölndal Sweden

    2002-03      Research internship in virology, University of Zürich, Switzerland

    2000-05      Undergraduate studies in bioinformatics, Freie Universität Berlin, Germany

    Research interests

    My primary interest is in developing- and applying mathematical methods for systems pharmacology. While we usually work in inter-disciplinary teams, my interlectual contributions include numerics [modeling & simulation of biomedical processes; hybrid stochastic-deterministic simulation algorithms; inverse problems (parameter inference, model inference); numerical algorithms for solving optimal control problems; model reduction], network clustering and -analysis, statistics and computing/programming, e.g. high performance computing & parallelization.

    I am interested in applying my expertise to understand and control drug resistance emergence and -spread in infectious disease (viral & bacterial). This includes pharmacokinetic-pharmacodynamic (PK-PD) modelling; optimal therapy/diagnostics (disease control); modelling and analysis of biological- and epidemiological networks; population dynamics; analysis of omics data and the design of omics-based assays (see here). Besides infectious disease, we are also studying osteoarthritis of the knee.

    Publications

     

    1. Local c-di-GMP signaling in the control of synthesis of the E. coli biofilm exopolysaccharide cellulose. A.M. Richter, KP. Yousef, M. von Kleist, R. Hengge, submitted, 2017
    2. Statistical analysis of the first passage path ensemble of jump processes. M.  von Kleist, Ch. Schütte, W. Zhang, submitted (arXiv), 2017
    3. Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors. K. Meixenberger, K. P. Yousef, S. Somogyi, Sybille, S. Fiedler, B. Bartmeyer, O.  Hamouda, N. Bannert, M.  von Kleist, C. Kücherer, submitted 2017
    4. Optimal control of markov jump processes: Asymptotic analysis, algorithms and application to modelling of chemical reaction systems. W. Zhang, C. Hartmann and M. von Kleist, submitted (arXiv), 2016
    5. In silico cytotoxicity assessment on cultured rat intestinal cells deduced from cellular impedance measurements. P. Gupta, A. Gramatke, R. Einspanier, C. Schütte, M.von Kleist*, J. Sharbati*Toxicology in vitro (accepted), 2017 * equally contributed
    6. Coupling cellular phenotype and mechanics to understand extracellular matrix formation and homeostasis in osteoarthritis. V. Sunkara, M. von Kleist,
      IFAC-PapersOnLine 49(26), 38, 2016 (online,preprint)
    7. MIMEAnTo-Profiling functional RNA in Mutational Interference Mapping Experiments. M. Smith, R. P. Smyth, R. Marquet and M. von KleistBioinformatics, 32, 3369, 2016 (open access)
    8. Multi-scale Systems-Pharmacology pipeline to assess the prophylactic efficacy of NRTIs against HIV-1. S. Duwal, V. Sunkara and M. von Kleist, CPT: Pharmacometrics & Systems Pharmacology, 5, 377, 2016 (open access)
    9. Inferring HIV-1 transmission dynamics in Germany from recently transmitted viruses. K. P. Yousef, K. Meixenberger, M. R. Smith, S. Somogyi, S. Gromöller, D. Schmidt, B. Gunsenheimer-Bartmeyer. O. Hamouda, C. Kücherer and M. von Kleist, Journal of Acquired Immune Deficiency Syndromes, 73, 356, 2016 (online)
    10. Top-down and bottom-up modelling in system pharmacology to understand clinical efficacy : An example with NRTIs of HIV-1. S. Duwal, M. von Kleist, Eur J Parm Sci, 94, 72, 2016 (online)
    11. Mutational Interference Mapping Experiment (MIME) for studying the relationship between RNA structure and function. R.P. Smyth*, L. Despons, G. Huili, S. Bernacchi, M. Hijnen, J. Mak, F. Jossinet, L. Weixi, J-C. Paillart, M. von Kleist*, R. Marquet*, Nature Methods+, 12, 866 , 2015 (online) *shared corresponding authorship. +see also cover of the september issue
    12. Logical-continuous modelling of post-translationally regulated bistability of curli fiber expression in Echerichia coli. K. P. Yousef, A. Streck, C. Schütte, H. Siebert, R. Hengge and M. von Kleist, BMC Systems Biology, 9, 39, 2015 (open access)
    13. Optimal treatment strategies in the context of ‘treatment for prevention’ against HIV-1 in resource-poor settings. S. Duwal, S. Winkelmann, C. Schütte and M. von Kleist, PLoS Comput. Biol., 11, e1004200, 2015 (open access)
    14. Characterization of natural polymorphic sites of the HIV-1 integrase before the introduction of HIV-1 integrase inhibitors in Germany. K. Meixenberger, K. P. Yousef, S. Somogyi, S. Fiedler, B. Bartmeyer, M. von Kleist, C. Kücherer. Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19746.
    15. Assessment of ambiguous base calls in HIV-1 pol population sequences as a biomarker to indentify recent infections in HIV-1 incidence studies. K. Meixenberger, A. Hauser, K. Jansen, K. P. Yousef, S. Fiedler, M. von Kleist, S. Norley, S.Somogyi, O. Hamouda, N. Bannert, B. Bartmeyer, C. Kücherer. Journal of Clinical Microbiology52, 2977, 2014 (online)
    16. Awareness and Utilization of Standards and Pathways for the Reporting of Adverse Events Following Immunization among Pediatricians in Russia and Germany. S. Muehlhans, M. von Kleist, T. Gretchukha, T. Martin, U. Fegeler, W. Maurer, L. Namazova-Baranova, G. Gaedicke, A. Baranov, B. Rath. Pediatric Drugs16, 321, 2014 (online)
    17. Characterization of natural polymorphic sites of the HIV-1 integrase before the introduction of HIV-1 integrase inhibitors in Germany. K. Meixenberger, K. Pouran Yousef, S. Somogyi, S. Fiedler, B. Bartmeyer, M. von Kleist, C. Kücherer. Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19746.
    18. “Time-to-Amphotericin B” in Cryptococcal Meningitis in a European Low-Prevalence Setting: Analysis of Diagnostic Delays. J. Katchanov, M. von Kleist, K. Arasteh, H. Stocker QJM: An International Journal of Medicine, 107, 799, 2014 (online)
    19. Quantitative influenza follow-up testing (QIFT) – a novel biomarker for the monitoring of disease activity at the point-of-care. X. Chen, K. P. Yousef, S. Duwe, K. Karsch, S. Grover, S. Wählisch, P. Obermeier, F. Tief, S. Muehlhans, L. Seeber, M. von Kleist, B. Schweiger, B. Rath. Plos One 9, e92500, 2014 (open access)
    20. Markov Control Processes with Rare State Observation: Theory and Application to Treatment Scheduling in HIV-1 S. Winkelmann, C. Schütte and M. von Kleist. Communications in Mathematical Sciences 12, 859, 2014 (online)
    21. “Markov Control with Rare State Observation”: Sensitivity Analysis with Respect to Optimal Treatment Strategies against HIV-1. S. Winkelmann, C. Schütte and M. von Kleist. International Journal of Biomathematics and Biostatistics 2, 1, 2013 (pdf of preprint)
    22. Towards a personalized approach to managing of influenza infections in infants and children – food for thought and a note on oseltamivir B. Rath, F. Tief, K. Karsch, S. Muehlhans, P. Obermeier, E. Adamou, X. Chen, L. Seeber, C. Peiser, C. Hoppe, M. von Kleist, T. Conrad, B. Schweiger. Infectious Disorders – Drug Targets 13 , 25, 2013 (online)
    23. In Vitro HIV-1 Evolution in Response to Triple Reverse Transcriptase Inhibitors & In Silico Phenotypic Analysis
      B. Rath, K. P. Yousef, D. K. Katzenstein, R. W. Shafer, Ch. Schütte, M. von Kleist and T. C. Merigan. PLoS One 8 , e61102, 2013 (open access)
    24. Antiviral Resistance and Predictors of Virologic Failure in the first Cohort of HIV-infected Children Gaining Access to Structured Antiretroviral Therapy in Lima, Peru: A Cross-Sectional Analysis B. Rath, M. von Kleist, M. E. Castillo, L. Kolevic, P. Caballero, G. Soto-Castellares, A. M. Amedee, J. E. Robinson, D. K. Katzenstein, R. B. Van Dyke and R. Oberhelman BMC Infect Dis 13, 1, 2013 (open access)
    25. Pharmacokinetics and Pharmacodynamics of the Reverse Transcriptase Inhibitor Tenefovir and Prophylactic Efficacy against HIV-1 Infection. S. Duwal, C. Schütte and M. von Kleist. PLoS One 8, e40382, 2012 (open access)
    26. Virus Load Kinetics and Resistance Development during Oseltamivir Treatment in Infants and Children Infected with Influenza A (H1N1) 2009 and Influenza B Viruses B. Rath, M. von Kleist, F. Tief, K. Karsch, E. Türk, S. Mühlhans, F. Louis, H. Skopnik, B. Schweiger and S. Duwe. Pediatr Infect Dis J. 31, 9, 2012(online)
    27. HIV-1 polymerase inhibition by nucleoside analogs: Cellular- and kinetic parameters of efficacy, susceptibility and resistance selection M. von Kleist, P. Metzner, R. Marquet and C. Schütte. PLoS Comput. Biol.8, e1002359, 2012 (open access)
    28. Quantifying the impact of nevirapine-based prophylaxis strategies to prevent mother-to-child transmission of HIV-1: A combined pharmacokinetic, pharmaco- and viral dynamic analysis to predict clinical outcomes. M. Frank*, M. von Kleist*, A. Kunz, G. Harms, C. Schütte and C. Kloft. Antimicrob. Agents Chemother 55, 5529, 2011 (open access)* equally contributed
    29. Reduction technique for pharmacological models to support planning, execution and analysis of clinical studies (patent).
      M. von Kleist (67%) and Christof Schutte (33%) . German patent office. Pat.Nr.: 10 2010 060 311, 2010 (link)
    30. HIV quasi-species dynamics during pro-active treatment switching: impact on multi-drug resistance and resistance archiving in latent reservoirs. M. von Kleist, S. Menz, H. Stocker, K. Arasteh, C. Schütte and W. Huisinga. PLoS ONE 6, e18204, 2011 (open access)
    31. A Drug-Class specific impact of antivirals on the reproductive capacity of HIV. M. von Kleist, Stephan Menz and W. Huisinga. PLoS Comput. Biol. 6, e1000720, 2010 ( open access )
    32. Pharmacokinetic-Pharmacodynamic relationship of NRTIs and its connection to viral escape: An example based on Zidovudine M. von Kleist and W. Huisinga Eur J Pharm Sci 36, 532, 2009 (online)
    33. Combining Systems Biology with physiologically-based pharmacokinetics to support the understanding of drug effects. M. von Kleist, C. Kloft and W. Huisinga. Proceedings of Foundations of Systems Biology in Engeneering FOSBE, 231, 2007 (pdf of preprint)
    34. Physiologically based pharmacokinetic modelling: A sub-compartmentalized model of tissue distribution
      M. von Kleist and W. Huisinga. J. Pharmakokinet. Pharmacodyn. 34, 789, 2007 (online)
    35. Software Supported Modelling in Pharmacokinetics R. Telgmann, M. von Kleist, and W. Huisinga LNCS 4216, 216, 2006 (online)
    36. Update on Antiviral DNA Vaccine Research (2000-2003) D. Franke, J. Pavlovic, T. S. Utesch, M. von Kleist, J. Schultz, G. Dollenmaier and K. Moelling. in Novel Vaccination Strategies Stefan H. E. Kaufmann (ed.), Wiley 2004 (online)