Diabetes mellitus is a complex metabolic disorder that can be presented in two major forms, as type 1 diabetes (T1D) and the much more common type 2 diabetes (T2D). While their etiologies are different, both diabetes types are characterized by hyperglycemia resulting either from insufficient insulin levels in T1D, or an insensitivity of target cells to insulin in T2D. In T1D, the death of insulin-producing pancreatic β-cells in an autoimmune response is a comparatively rapid event, whereas in T2D loss of β-cell mass occurs over years as interactions of extrinsic stressors and intrinsic factors continually impair β-cell functioning. The decline in the total mass of functional β-cells required to provide insulin for maintaining glucose homeostasis underlies diabetes development. Insight into the molecular control mechanisms in β-cells and the pathology of diabetes has laid the foundation for the paradigm for diabetes treatment based on the application of strategies that support functional β-cells by suppressing cytotoxic cell signaling and preventing the activation of cell death pathways. Our research is focused on β-cells as the principal element in diabetes development, and on hepatocytes and cardiomyocytes as the targets of diabetic complications. Our experimental systems include the in vivo model of streptozotocin (STZ)-induced diabetes in the rat, and in vitro models employing different cell lines maintained in culture.
Modulation of immune response and cell death represents a key strategy in the therapy of cancer and inflammatory disorders such as multiple sclerosis, and diabetes. However, targeting inflammation for therapeutic reasons is very complex, due to numerous underlying damaging pathways. The main goal is therefore to gain insight into control molecular mechanisms of these disorders and, thus, contribute to the design of therapeutics for prevention and treatment of the diseases. It is proposed to investigate the role and mode of action of biologically active microenvironment molecules (cytokines, ROS, NOS, hormones) and genetic factors in regulation of proliferation, differentiation, function, and cell death of immune and target tissue cells, in both physiological and pathological conditions. To establish basic control mechanisms of inflammation, immune response to (auto)antigens and resistance to anti-tumor immune response, the role of relevant intercellular mediators and intracellular signaling pathways, our research will be performed by in vivo and in vitro approaches using animal models of human diseases in inbred and/or genetically modified murine strains, and primary or transformed cell populations of various origins. In addition, cytotoxic, cytoprotective and immunomodulatory potential of various pharmacological agents or natural plant and animal products will be investigated, as well as intra- and intercellular mechanisms underlying the observed biological effects.
Multiple sclerosis is inflammatory, autoimmune disease of the central nervous system (CNS). The immune response directed towards cells and structures of CNS tissue causes demyelinization and neurodegeneration, thus inducing various neurological deficits in patients. In majority of patients multiple sclerosis takes relapsing-remitting or chronic progressive course. Experimental autoimmune encephalomyelitis (EAE) induced in DA rats is a model of multiple sclerosis and shares numerous immunopathogenic features with the human disease. Still, there is a major difference in the clinical course, as EAE in DA rats is acute monophasic disease. DA rats completely recover from EAE and are highly resistant to further attempts of the disease induction. The main goal of this project is to identify cell populations and molecular mechanisms responsible for the recovery of DA rats from EAE and their resistance to EAE re-induction. Consequently, the obtained knowledge should be useful for improvement of multiple sclerosis therapy.
The aim of our research is to examine the effects of selected plant extracts, phytoestrogens (genistein, daidzein), steroid (estradiol, progesterone, testosterone, dexamethasone) and peptide hormones (somatostatin, calcitonin, ghrelin) on neuroendocrine and mineral homeostases in rats. Herbal and nature alternatives to hormone replacement therapy are intensively advertised for maintenance of hormone balance, prevention of cardiovascular problems, atherosclerosis and osteoporosis in both sexes. Assessments of effects of these substances on: (i) hypothalamo-pituitary -adrenal, -somatotropic, -thyroid and -gonadal axes; (ii) neuroendocrine C-cells, bones, parathyroid glands and kidneys; and (iii) cellular mechanics are important for evaluation of their health risks / benefits and potential use in treatment of cancer, cardiovascular and other diseases. The examinations are carried out in rats of different age (adult, middle and old age) and sex, with special emphasis on models of andropause and menopause. In vitro studies of cellular mechanics are performed using erythrocytes or prostate cancer cells. Glucocorticoids are used in human pregnancies at risk of preterm delivery because they reduce neonatal mortality and morbidity. However, this treatment enhances maturational processes and provokes permanent changes in physiological systems. Thus, short-term beneficial effects of prenatal glucocorticoids are, at the same time, the ones that increase the long-term risks of dysregulation of the metabolic function and endocrine axes, including stress response, growth and reproduction. Effects of prenatal glucocorticoid overexposure are examined in rats from their fetal period of life till adulthood.
The Laboratory of Professor Matić gathers a group of young scientists committed to the study of neuroendocrine and dietary aspects of the development of Metabolic Syndrome, which is one of the leading health problems worldwide. Our scientific endeavors are primarily focused on the molecular mechanisms of glucocorticoid hormones actions in the development of Metabolic Syndrome, since these hormones are important regulators of energy homeostasis, metabolic inflammation, as well as of insulin and leptin signalling pathways. In the next three years the role of stress and fructose diet in the development of Metabolic Syndrome will be elucidated through collaboration with Professor Luc Tappy's group from Switzerland as a part of the SCOPES Joint Research Project entitled: Interactions between stress and dietary fructose in the development of the metabolic syndrome: role of glucocorticoids.
"Ekološko-genetičke studije varijabilnosti populacija Drosophila" #1527, Project Leader: Dr. Marko Anđelković
"Indikatori narušenosti strukture i metaboličkih funkcija u terestričnim ekosistemima" #1565, Project Leader: Dr. Branko Karadžić
"Adaptacije u prirodnim i laboratorijskim populacijama" #1570, Project Leader: Dr. Branka Tucić
"Fiziološki, citološki i biohemijski aspekt in vitro regeneracije reliktnih, endemičnih i ugroženig biljnih vrsta" #1573, Project Leader: Dr. Ljiljana Radojević
"Plastičnost rasta i fiziološka plastičnost u odgovoru na sredinski stres kod fitofagnih šumskih insekata" #1615, Project Leader: Dr. Jelica Lazarević
"Integrativna istraživanja vodozemaca i gmizavaca centralnog Balkana" #1623, Project Leader: Dr. Miloš Kalezić
"Limnološka ispitivanja Dunava i Đerdapske akumulacija (1171-943 km)" #1628, Project Leader: Dr. Vesna Martinović-Vitanović
"Efekti magnetnih polja i neuroaktivnih supstanci kao modulatora aktivnosti centralnog nervnog sistema" #1636, Project Leader: Dr. Zlatko Prolić
"Plastičnost mozga: ekspresija neuronalnih gena u fiziološkim i patološkim stanjima" #1641, Project Leader: Dr. Selma Kanazir
"Neurohemijski i neurofiziološki mehanizmi oštećenja i oporavka centralnog nervnog sistema" #1647, Project Leader: Dr. Mirjana Stojiljković
"Modulacija funkcije glukokortikoidnog receptora u toku ćelijskog odgovora na stres" #1654, Project Leader: Dr. Gordana Matić
"Modulacija ekscitabilnosti membrane i ritmovi bioelektrične aktivnosti neurona beskičmenjaka i kičmenjaka. Analiza i modeliranje" #1660, Project Leader: Dr. Milka Ćulić
"Sistemski odgovor na promenjen redoks status" #1669, Project Leader: Dr. Mihajlo Spasić
"Genetički polimorfizam u prirodnim populacijama sisara – poreklo, održavanje i efekti B hromozoma" #1693, Project Leader: Dr. Mladen Vujošević
"Svetlosna i hormonalna kontrola rastenja i razvića biljaka" #1696, Project Leader: Dr. Dragoljub Grubišić
"Karakterizacija potencijalnog psihotrpnog dejstva nekih novosintetisanih i prirodnih neuroaktivnih supstanci" #1704, Project Leader: Dr. Mirko Tomić
"Morfofunkcionalna ispitivanja efekata hormona na neuroendokrini sistem tokom životnog ciklusa" #1710, Project Leader: Dr. Milka Sekulić
"Genetički modifikovane i in vitro gajene biljke – modifikacija morfogeneze, sekundarnog metabolizma i ekonomski značajnih osobina" #1716, Project Leader: Dr. Branka Vinterhalter
"Molekularni mehanizmi regulacije transkripcije gena za akutno-fazne proteine" #1722, Project Leader: Dr. Goran Poznanović
"Evolucija u heterogenim sredinama" #1725, Project Leader: Dr. Jelka Crnobrnja-Isailović
"Ćelijska i molekulska osnova modulacije imunskih poremećaja" #1664, Project Leader: Dr. Stanislava Stošić-Grujičić
"Biodiverzitet i očuvanje genofonda drveća u Srbiji" #1932, Project Leader: Dr. Srđan Bojović
„Razvoj visokoproduktivne akvakulture i njene primene u zaštiti i unapređenju ribljih resursa” #1354. Lead Partner: Institute for Multidisciplinary Research, University of Belgrade. Project Leader: Dr. Miroslav Nikčević.
„Diverzitet i fiziologija gljiva i antimikrobna aktivnost sekundarnih metabolita biljaka i gljiva” #1511. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Jelena Vukojević.
„Inventarizacija, monitoring i vrednovanje komponenti faune u integralnoj zaštiti biodiverziteta” #1525. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Ivica Radović.
„Vegetativno i generativno razmnožavanje in vitro ugroženih biljnih vrsta, u cilju ex situ zaštite i produkcije sekundarnih metabolita” #1530. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Radomir Konjević.
„Neuroendokrina kontrola enzimskih sistema i redoks regulacija u uslovima izmenjene homeostaze” #1550. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Vukosava Davidović.
„Hemijske i biohemijske konsekvence metal-ligand interakcija” #1569. Lead Partner: Scientific Institution Institute of Chemistry, Technology and Metallurgy, University of Belgrade. Project Leader: Dr. Svetozar Niketić.
„Steroidogeni i antioksidativni enzimi kao indikatori hemijskih stresora iz okoline” #1766. Lead Partner: Faculty of Sciences, University of Novom Sadu. Project Leader: Dr. Radmila Kovačević.
„Membrane i apoplast. uloga u spoljašnjem i oksidativnom stresu i biohemijskoj regulaciji redoks procesa simplasta” #1934. Lead Partner: Institute for Multidisciplinary Research, University of Belgrade. Project Leader: Dr. Željko Vučinić.
„Gensko testiranje u praksi” #2019. Lead Partner: Vinča Institute of Nuclear Sciences, University of Belgrade. Project Leader: Dr. Bogomir Dimitrijević.
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