Vesna Munic Kos

Vesna Munic Kos

Affiliated to Research
Visiting address: Solnavägen 9, Biomedicum C5, 17165 Solna
Postal address: C3 Fysiologi och farmakologi, C3 FyFa Medicinsk hjärt- och skelettmuskelforskning, 171 77 Stockholm
Part of:

About me

  • Cell and molecular biologist and project leader experienced in pharmacology
    and toxicology.
    Main focus of my current research are chemicals (pharmaceuticals and
    environmental toxins) which accumulate in organisms, and the effects they
    have on cells. During 13 years of my career in the research of pharmaceutical
    industry large part of my research was dealing with anti-inflammatories and
    highly accumulating pharmaceuticals, especially of macrolide class. Now I am
    studying endocrine disrupting chemicals and the mechanisms of their impact on
    inflammation and metabolic disorders as well as their toxicokinetic
    properties.

Research

  • *PROJECTS*
    *EU Horizon 2020 project GOLIATH – Beating Goliath: Generation Of Novel,
    Integrated and Internationally Harmonised Approaches for Testing Metabolism
    Disrupting Compounds (2019-2023) – principal investigator for Karolinska
    Institutet*
    The aim of this project is to develop and evaluate in vitro and in silico
    methods for identification and testing of endocrine disrupting chemicals
    contributing to metabolic disorders. Karolinska Institutet is one of 14
    participating institutions from all over Europe and one from USA. Here, we
    work on the development and evaluation of in vitro methods for identification
    of metabolism disrupting chemiclas affecting adipogenesis and the development
    of insulin resistance in adipocytes.
    *The evaluation of /in vitro/ skeletal muscle models for the assessment of
    metabolism disrupting chemicals contributing to insulin resistance –
    Swedish Research Council Formas (2020-2023) - co-applicant*
    The aim of this project is to analyze the impact of metabolism disrupting
    chemicals on various in vitro skeletal muscle models mainly related to
    insulin sensitivity and glucose utilisation, and their possible contribution
    to the development of insulin resistance and type 2 diabetes.
    *Intracellular exposure: a new parameter for prediction of toxicological
    outcome after exposure to endocrine disrupting chemicals? – Swedish
    Research Council Formas (2018-2023) - co-applicant*
    This project is a collaboration with Prof. Per Artursson from Uppsala
    University (Department of Pharmacy), and Prof. Ian Cotgreave from RISE. The
    aim of the project is to determine the intracellular unbound fraction of
    selected endocrine disrupting chemicals (EDCs), and assess the impact of this
    understudied kinetic parameter on the assessment of adverse effects of
    endocrine disrupting chemicals (EDCs) in various cell based test systems.
    This research should ultimately help better prediction of toxic effects of
    chemicals from computational and cell based models.
    *Predicting the effects of highly accumulating compounds (2014-2019) –
    principal investigator*
    By being present in high concentrations, accumulating chemicals may pose a
    chronic threat for an organism. As our knowledge about biological systems
    expands, it is necessary to constantly revalidate our conclusions about the
    safety of such chemicals because of their prolonged presence.
    In my research, I am using in vitro techniques to analyze the consequences of
    compound’s accumulation in cells and their binding to biological membranes.
    I am looking at how these compounds affect various processes in cells,
    physiological functions of membranes and extracellular membrane vesicles,
    especially in the context of immune system and inflammation. In
    collaboration, we do structure-property relationship studies to improve
    detection and prediction of accumulating chemicals.
    *EU-ToxRisk – An Integrated European ‘Flagship’ Programme Driving
    Mechanism-based Toxicity Testing and Risk Assessment for the 21st century
    (2016-2022) - collaborator*
    http://www.eu-toxrisk.eu/ [1]
    For this project we have introduced a quantitative high content imaging assay
    that we now use for screening of various chemicals on their potential effects
    on neuron differentiation and degradation. Parameters describing neurite
    length, number, branching points and straightness, together with cell body
    area and cell number are quantified using our high content analysis system.
    *PUBLICATIONS:*
    *Obesity III: Obesogen assays: Limitations, strengths, and new directions.*
    Kassotis CD, Vom Saal FS, Babin PJ, Lagadic-Gossmann D, Le Mentec H, Blumberg
    B, Mohajer N, Legrand A, Munic Kos V, Martin-Chouly C, Podechard N, Langouët
    S, Touma C, Barouki R, Ji Kim M, Audouze K, Choudhury M, Shree N, Bansal A,
    Howard S, Heindel JJ. /Biochem Pharmacol./ 2022, 115014.
    https://pubmed.ncbi.nlm.nih.gov/35393121/ [2]
    *Obesity II: Establishing Causal Links Between Chemical Exposures and
    Obesity.* Heindel JJ, Howard S, Agay-Shay K, Arrebola JP, Audouze K, Babin
    PJ, Barouki R, Bansal A, Blanc E, Cave MC, Chatterjee S, Chevalier N,
    Choudhury M, Collier D, Connolly L, Coumoul X, Garruti G, Gilbertson M,
    Hoepner LA, Holloway AC, Howell G 3rd, Kassotis C, Kay MK, Ji Kim M,
    Lagadic-Gossmann D, Langouet S, Legrand A, Li Z, Le Mentec H, Lind L, Monica
    Lind P, Lustig RH, Martin-Chouly C, Munic Kos V, Podechard N, Roepke TA,
    Sargis RM, Starling A, Tomlinson CR, Touma C, Vondracek J, Vom Saal F,
    Blumberg B. /Biochem Pharmacol./ 2022, 115015.
    https://pubmed.ncbi.nlm.nih.gov/35395240/ [3]
    *High throughput screening of bisphenols and their mixtures under conditions
    of low-intensity adipogenesis of human mesenchymal stem cells
    (hMSCs). *Norgren K, Tuck A, Vieira Silva A, Burkhardt P, Öberg M, Munic
    Kos V. /Food Chem Toxicol/. 2022, 161:112842.
    https://doi.org/10.1016/j.fct.2022.112842 [4]
    *Neurotoxicity and underlying cellular changes of 21 mitochondrial
    respiratory chain inhibitors.* Delp J, Cediel‑Ulloa A, Suciu I, Kranaster
    P, van Vugt‑Lussenburg BMA, Munic Kos V, van der Stel W, Carta G, Hougaard
    Bennekou S, Jennings P, van de Water B, Forsby A, Leist M. /Arch Toxicol, /
    2021
  • 95, 591–615, https://doi.org/10.1007/s00204-020-02970-5 [5]
    *Novel class of fast acting antimalarial agents: substituted 15-membered
    azalides.* Peric M, Pesic D, Alihodzic S, Fajdetic A, Herreros E, Gamo FJ,
    Angulo-Barturen I, Jimenez-Diaz MB, Ferrer-Bazaga S, Martinez Martinez MS,
    Gargallo-Viola D, Mathis A, Kessler A, Banjanac M, Padovan J, Bencetic, V,
    Munic Kos V, Bukvic M, Erakovic Haber V, Spaventi R. /Br J Pharmacol, /2021

  • 178:363–377 https://pubmed.ncbi.nlm.nih.gov/33085774/ [6]
    *Existing highly accumulating lysosomotropic drugs with potential for
    repurposing to target COVID-19*. Norinder U, Tuck A, Norgren K, Munic Kos
    V. /Biomed Pharmacother/ 2020,
    130:110582 https://www.sciencedirect.com/science/article/pii/S0753332220307757?via%3Dihub
    [7]
    *The GOLIATH Project: Towards an Internationally Harmonised Approach for
    Testing Metabolism Disrupting Compounds.* Legler J, Zalko D, Jourdan F,
    Jacobs M, Fromenty B, Balaguer P, Bourguet W, Munic Kos V, Nadal A,
    Beausoleil C, Cristobal S, Remy S, Ermler S, Margiotta-Casaluci L, Griffin J,
    Blumberg B, Chesne C, Hoffmann S, Andersson P, Kamstra
    J. /Int J Mol Sci /2020

  • 21:3480. https://pubmed.ncbi.nlm.nih.gov/32423144/ [8]
    *QSAR Models for Predicting Five Levels of Cellular Accumulation of
    Lysosomotropic Macrocycles.* Norinder U, Munic Kos V. /Int J Mol Sci/.
    2019
  • 20(23):5938. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928787 [9]/
    *Quantification of intracellular accumulation and retention of lysosomotropic
    macrocyclic compounds by high-throughput imaging of lysosomal changes.
    *Easwaranathan A, Inci B, Ulrich S, Brunken L, Nikiforova V, Norinder U,
    Swanson S, Munic Kos V. /J Pharm Sci/. 2019
  • 108:652-660.
    https://www.ncbi.nlm.nih.gov/m/pubmed/30419273/#fft [10]
    *Lysosomotropic cationic amphiphilic drugs inhibit adipocyte differentiation
    in 3T3-L1K cells via accumulation in cells and phospholipid membranes, and
    inhibition of autophagy. *Kagebeck P, Nikiforova V, Brunken L, Easwaranathan
    A, Ruegg J, Cotgreave I, Munic Kos V. /Eur J Pharmacol./ 2018
  • 829:44-53.
    https://www.ncbi.nlm.nih.gov/pubmed/29627311 [11]
    *Cellular accumulation and lipid binding of perfluorinated alkylated
    substances (PFASs) - A comparison with lysosomotropic drugs. *Sanchez Garcia
    D, Sjödin M, Hellstrandh M, Norinder U, Nikiforova V, Lindberg J, Wincent E,
    Bergman Å, Cotgreave I, Munic Kos V. /Chem Biol Interact. /2018
  • 281:1-10.
    https://www.ncbi.nlm.nih.gov/pubmed/29248446 [12]
    *Around the macrolide - Impact of 3D structure of macrocycles on
    lipophilicity and cellular accumulation. *Koštrun S, Munic Kos V, Matanović
    Škugor M, Palej Jakopović I, Malnar I, Dragojević S, Ralić J, Alihodžić
    S. /Eur J Med Chem/. 2017
  • 133:351-364.
    https://www.ncbi.nlm.nih.gov/pubmed/28410508 [13]
    *A comparison of in vitro ADME properties and pharmacokinetics of
    azithromycin and selected 15-membered ring macrolides in rodents*. Milić A,
    Mihaljević VB, Ralić J, Bokulić A, Nožinić D, Tavčar B, Mildner B,
    Munić V, Malnar I, Padovan J. /Eur J Drug Metab Pharmacokinet. /2014

  • 39(4):263-76. http://www.ncbi.nlm.nih.gov/pubmed/24114177 [14]
    *Structure-property relationship for cellular accumulation of macrolones in
    human polymorphonuclear leukocytes (PMNs). Munić Kos V*, Koštrun S,
    Fajdetić A, Bosnar M, Kelnerić Ž, Stepanić V, Eraković Haber V. /Eur J
    Pharm Sci/. 2013
  • 49(2):206-19. http://www.ncbi.nlm.nih.gov/pubmed/23474356
    [15]
    *Macrolactonolides: a novel class of anti-inflammatory
    compounds.* Tomašković L, Komac M, Makaruha Stegić O, Munić V, Ralić J,
    Stanić B, Banjanac M, Marković S, Hrvačić B, Čipčić Paljetak H,
    Padovan J, Glojnarić I, Eraković Haber V, Mesić M, Merćep M. /Bioorg Med
    Chem/. 2013
  • 21(1):321-32. http://www.ncbi.nlm.nih.gov/pubmed/23199485 [16]
    *Fluorescently labeled macrolides as a tool for monitoring cellular and
    tissue distribution of azithromycin.* Matijašić M, *Munić Kos V*, Nujić
    K, Cužić S, Padovan J, Kragol G, Alihodžić S, Mildner B, Verbanac D,
    Eraković Haber V. /Pharmacol Res/. 2012

  • 66(4):332-42. http://www.ncbi.nlm.nih.gov/pubmed/22749903 [17]
    *Azithromycin drives in vitro GM-CSF/IL-4-induced differentiation of human
    blood monocytes toward dendritic-like cells with regulatory
    properties. *Polancec DS, *Munic Kos V*, Banjanac M, Vrancic M, Cuzic S,
    Belamaric D, Parnham MJ, Polancec D, Erakovic Haber V./J Leukoc Biol/. 2012

  • 91(2):229-43. http://www.ncbi.nlm.nih.gov/pubmed/22131344 [18]
    *Anti-inflammatory mechanism of action of azithromycin in LPS-stimulated
    J774A.1 cells.* Banjanac M, Munić Kos V, Nujić K, Vrančić M, Belamarić
    D, Crnković S, Hlevnjak M, Eraković Haber V. /Pharmacol Res/. 2012

  • 66(4):357-62. http://www.ncbi.nlm.nih.gov/pubmed/22766077 [19]
    *Impairment of lysosomal functions by azithromycin and chloroquine
    contributes to anti-inflammatory phenotype.* Nujić K, Banjanac M, Munić V,
    Polančec D, Eraković Haber V. /Cell Immunol/. 2012

  • 279(1):78-86. http://www.ncbi.nlm.nih.gov/pubmed/23099154 [20]
    *Azithromycin distinctively modulates classical activation of human monocytes
    in vitro.* Vrančić M, Banjanac M, Nujić K, Bosnar M, Murati T, Munić V,
    Stupin Polančec D, Belamarić D, Parnham MJ, Eraković Haber V. /Br J
    Pharmacol/. 2012
  • 165(5):1348-60. http://www.ncbi.nlm.nih.gov/pubmed/21726210
    [21]
    *Intensity of macrolide anti-inflammatory activity in J774A.1 cells
    positively correlates with cellular accumulation and phospholipidosis. Munić
    V*, Banjanac M, Koštrun S, Nujić K, Bosnar M, Marjanović N, Ralić J,
    Matijašić M, Hlevnjak M, Eraković Haber V. /Pharmacol Res/. 2011

  • 64(3):298-307. http://www.ncbi.nlm.nih.gov/pubmed/21473915 [22]
    *Modeling cellular pharmacokinetics of 14- and 15-membered macrolides with
    physicochemical properties.* Stepanić V, Koštrun S, Malnar I, Hlevnjak M,
    Butković K, Ćaleta I, Dukši M, Kragol G, Makaruha-Stegić O, Mikac L,
    Ralić J, Tatić I, Tavčar B, Valko K, Zulfikari S, *Munić V*. /J Med
    Chem/. 2011
  • 54(3):719-33. http://www.ncbi.nlm.nih.gov/pubmed/21207938 [23]
    *Characterization of rhodamine-123, calcein and
    5(6)-carboxy-2', 7'-dichlorofluorescein (CDCF) export via MRP2 (ABCC2) in
    MES-SA and A549 cells. Munić V*, Hlevnjak M, Eraković Haber V. /Eur J
    Pharm Sci/. 2011
  • 43(5):359-69. http://www.ncbi.nlm.nih.gov/pubmed/21605668
    [24]
    *Differences in assessment of macrolide interaction with human MDR1 (ABCB1,
    P-gp) using rhodamine-123 efflux, ATPase activity and cellular accumulation
    assays. Munić V*, Kelnerić Z, Mikac L, Eraković Haber V. /Eur J Pharm
    Sci./ 2010
  • 41(1):86-95. http://www.ncbi.nlm.nih.gov/pubmed/20621639 [25]
    *Cloning and molecular characterization of apical efflux transporters (ABCB1,
    ABCB11 and ABCC2) in rainbow trout (Oncorhynchus mykiss) hepatocytes.* Zaja
    R, Munić V, Klobucar RS, Ambriović-Ristov A, Smital T. /Aquat Toxicol/.
    2008
  • 90(4):322-32. http://www.ncbi.nlm.nih.gov/pubmed/19008001 [26]
    *Cloning and mRNA expression analysis of an ABCG2 (BCRP) efflux transporter
    in rainbow trout (Oncorhynchus mykiss) liver and primary hepatocytes.* Zaja
    R, Munić V, Smital T. /Mar Environ Res/. 2008

  • 66(1):77-9. http://www.ncbi.nlm.nih.gov/pubmed/18381223 [27]
    *Modulation of neutrophil and inflammation markers in chronic obstructive
    pulmonary disease by short-term azithromycin treatment.* Parnham MJ, Culić
    O, Eraković V, Munić V, Popović-Grle S, Barisić K, Bosnar M, Brajsa K,
    Cepelak I, Cuzić S, Glojnarić I, Manojlović Z, Novak-Mircetić R,
    Oresković K, Pavicić-Beljak V, Radosević S, Sucić M. /Eur J Pharmacol/.
    2005
  • 517(1-2):132-43. http://www.ncbi.nlm.nih.gov/pubmed/15964564 [28]
    *Cellular uptake and efflux of azithromycin, erythromycin, clarithromycin,
    telithromycin, and cethromycin.* Bosnar M, Kelnerić Z, Munić V, Eraković
    V, Parnham MJ. /Antimicrob Agents Chemother/. 2005

  • 49(6):2372-7. http://www.ncbi.nlm.nih.gov/pubmed/15917536 [29]
    *Azithromycin modulates neutrophil function and circulating inflammatory
    mediators in healthy human subjects.* Culić O, Eraković V, Cepelak I,
    Barisić K, Brajsa K, Ferencić Z, Galović R, Glojnarić I, Manojlović Z,
    Munić V, Novak-Mircetić R, Pavicić-Beljak V, Sucić M, Veljaca M,
    Zanić-Grubisić T, Parnham MJ. /Eur J Pharmacol/. 2002

  • 450(3):277-289. http://www.ncbi.nlm.nih.gov/pubmed/12208321 [30]
    *The link between met-enkephalin-induced down-regulation of APN activity and
    the release of superoxide anion.* Marotti T, Balog T, Munić V, Sobocanec S,
    Abramić M. /Neuropeptides/. 2000

  • 34(2):121-8. http://www.ncbi.nlm.nih.gov/pubmed/10985929 [31]
    [1] http://www.eu-toxrisk.eu/
    [2] https://pubmed.ncbi.nlm.nih.gov/35393121/
    [3] https://pubmed.ncbi.nlm.nih.gov/35395240/
    [4] https://doi.org/10.1016/j.fct.2022.112842
    [5] https://doi.org/10.1007/s00204-020-02970-5
    [6] https://pubmed.ncbi.nlm.nih.gov/33085774/
    [7] https://www.sciencedirect.com/science/article/pii/S0753332220307757?via%3Dihub
    [8] https://pubmed.ncbi.nlm.nih.gov/32423144/
    [9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928787/?report=classic
    [10] https://www.ncbi.nlm.nih.gov/m/pubmed/30419273/#fft
    [11] https://www.ncbi.nlm.nih.gov/pubmed/29627311
    [12] https://www.ncbi.nlm.nih.gov/pubmed/29248446
    [13] https://www.ncbi.nlm.nih.gov/pubmed/28410508
    [14] http://www.ncbi.nlm.nih.gov/pubmed/24114177
    [15] http://www.ncbi.nlm.nih.gov/pubmed/23474356
    [16] http://www.ncbi.nlm.nih.gov/pubmed/23199485
    [17] http://www.ncbi.nlm.nih.gov/pubmed/22749903
    [18] http://www.ncbi.nlm.nih.gov/pubmed/22131344
    [19] http://www.ncbi.nlm.nih.gov/pubmed/22766077
    [20] http://www.ncbi.nlm.nih.gov/pubmed/23099154
    [21] http://www.ncbi.nlm.nih.gov/pubmed/21726210
    [22] http://www.ncbi.nlm.nih.gov/pubmed/21473915
    [23] http://www.ncbi.nlm.nih.gov/pubmed/21207938
    [24] http://www.ncbi.nlm.nih.gov/pubmed/21605668
    [25] http://www.ncbi.nlm.nih.gov/pubmed/20621639
    [26] http://www.ncbi.nlm.nih.gov/pubmed/19008001
    [27] http://www.ncbi.nlm.nih.gov/pubmed/18381223
    [28] http://www.ncbi.nlm.nih.gov/pubmed/15964564
    [29] http://www.ncbi.nlm.nih.gov/pubmed/15917536
    [30] http://www.ncbi.nlm.nih.gov/pubmed/12208321
    [31] http://www.ncbi.nlm.nih.gov/pubmed/10985929

Teaching

  • Drug Discovery &
  • Development – An Industrial Perspective, Drug and Chemical
    Target Identification, Pharmacological and Toxicological Experimental Methods

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