Vesna Munic Kos

About me

Main focus of my 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 highly accumulating pharmaceuticals, especially of macrolide class. Now I am studying endocrine disrupting chemicals and the mechanisms of their impact on metabolic disorders as well as their toxicokinetic properties.

Research description

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. 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/

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.

 

Developing cell based methods

Additionally, I am helping develop cell-based methods for various types of screenings of environmental toxicants and pharmaceuticals. We mostly use cell function assays, high content quantitative imaging techniques and gene expression analyses on human and murine primary cells and cell lines.

 

RECENT 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/

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/

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

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

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/

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

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/

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/

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

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

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

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

Education

I am open to disscus potential master student or internship projects. Please contact me via email.