Biomedicina
Laboratory for Functional Genomics and Proteomics

Laboratory for Functional Genomics and Proteomics

Activities

Resources

Results

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About us

The Laboratory for Functional Genomics and Proteomics (LFGP) is the youngest organizational unit of the Scientific Research Center for Biomedicine, established on 30.11.2007. after the Decision of the Assembly for Education and Science of the Faculty of Medicine University of Niš.

The Laboratory is situated on the basement floor of the Annex to the Faculty building, and consists of two departments: Department for Proteomic Research and Department for Genomic Research.

Coordinator of the Laboratory for Functional Genomics and Proteomics (LFGP):

Full Professor Tatjana Jevtović-Stoimenov (tjevtovic@yahoo.com).

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Activities

The basic purpose of the LFGP are studies in the field of biomedicine, biochemistry, molecular biology, support in scientifioc project realization, teaching in graduate, integrated, and academic doctoral studies, as well as international cooperation with similar institutions.

Research and projects

A large scope of research in the Lab is performed within the project of integral and interdisciplinary research “Preventive, therapeutic, and ethical approach to preclinical and clinical research of genes and modulators of redox cell signaling in immune, inflammatory and proliferative cellular response” funded by the Ministry of Education, Science, and Technological Development (No. 41018 Headed by prof. dr Dusica Pavlovic).

The LFGP deals with the functional study of genomic DNA, RNA, tissue proteins and body fluids as markers of various pathologies. The focus is on the study of molecular mechanisms of signal molecules underlying autoimmune, chronic inflammatory, malignant and neurodegenerative diseases, as well as the population analysis, i.e. the study of prevalence of gene polymorphisms as factors predisposing to various chronic inflammatory diseases.

Pharmacogenetically, the analyses of genetic polymorphisms are performed on the genes for alpha and beta adrenergic receptors, as well as on the genes for enzymes from the cytochrome p450 family 2D6, 3A5, 3A4, 2C19, 2C9, MDR1. At the same time, their impact is evaluated on the metabolism of drugs in patients with chronic heart failure, acute coronary syndrome, and chronic renal failure in close cooperation with the colleagues from the Clinical Center in Nish

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Resources

Methods and analyses

In the Laboratory for Functional Genomics and Proteomics relative quantification of gene expression is performed for:

  • nitrogen oxide synthase
  • caspase-3
  • superoxide dismutase
  • adenosin desaminase
  • desoxyribonucleotidase
  • calcium-binding proteins and other bone production markers

Basic techniques and analyses used in the Lab:

  • isolation of DNA, RNA and proteins
  • spectrophotometric quantification
  • target gene amplification and identification of frequency of polymorphic alleles,
  • measurement of gene expression of target genes (relative quantification of gene expression) employing the following methods:
  • PCR
  • reverse transcription PCR
  • restrictive digestion RFLP
  • horizontal electrophoresis on agarose
  • vertical electrophoresis on polyacrilamide gel (PAGE, SDS-PAGE)
  • purification of DNA from gel and preparation for sequencing
  • absolute and relative quantification on real time PCR

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Equipment

The Laboratory has got all the necessary equipment for modern research in the fields of genomics and proteomics:

  • Standard laboratory equipment;
  • Specific laboratory equipment for genomic and proteomic research:
  • Mass spectrometer MALDI-TOF/TOF;
  • PCR instruments
  • Instruments for real time PCR and sequencing

Staff/Researchers/Associates

  • In the activities of the Laboratory for Functional Genomics and Proteomics involved are the teachers and associates of the academic courses Biochemistry, Pharmacy, narrow scientific field Biology with Human Genetics and others.
  • Associate researchers:
    • Dr Stevan Vujić
    • Dr Branislav Apostolović

Scientific cooperation

The Laboratory for Functional Genomics and Proteomics has effectuated good cooperation with the Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Institute for Medical Research, University of Belgrade, Institute for Biomedical Research Sinisa Stankovic, University of Belgrade, Institute for Nuclear Sciences Vinca, University of Belgrade, and with researchers from other faculties of the universities in Nis, Kragujevac, Pristina (seated in Kosovska Mitrovica) and Belgrade.

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Results

In the LFGP some significant results have been achieved, that primarily relate to the study of frequency of polymorphisms in the genes for pro- or antiinflammatory cytokines (TNF alpha, LT alpha, TNFR-1, TNFR-2, TGF beta, IL-6, CARD15), genes involved in vitamin D metabolism (VDR, VDBP, CYP27B1, CYP2R1), genes coding for antioxidative protection enzymes (SOD, catalase, glutathion peroxidase, glutathion S transferase) in the healthy and in patients with chronic inflammatory diseases.

A bank has been formed for DNA specimens, with 300 DNAs of healthy examinees of all ages, DNAs of patients with systemic lupus erythematosus (100), rheumatoid arthritis (145), bronchial asthma (79), inflammatory bowel diseases (ulcerous colitis and Crohn’s disease) (90), sarcoidosis (90), insipid diabetes (80), and multiple sclerosis (84).

Defended doctoral dissertations:

  • Dr Jelena Bašic: Oxidative stress, matrix metalloproteinase-9, and polymorphism of the gene for TNF and its receptor in iuvenile idiopathic arthritis. 2010.
  • Dr Marija Vukelic: Evaluation of the role of bone marrow and blood components in ectopic osteogenesis on the model of subcutaneous implantation in singenig Balb/c mice. 2011
  • Dr Sonja Stojanovic: Significance of gene polymorphism for TNF alpha and the activity of metalloproteinases in rheumatoid arthritis. 2012.
  • Dr Valentina Nikolic: Impact of gene variability of adrenergic receptors and cytochrome P450 oxidase on the pharmacokinetics and therapeutic efficacy of beta blockers in patients with heart failure. 2013.
  • Dr Jelena Radovic: Prevalence of mutations and R202Q polymorphism of the gene for familial Mediterranean fever and their impact on oxidative stress and clinical inflammatory manifestations. 2014.
  • Dr Nikola Stefanovic: Impact of gene polymorphism of cytochrom P450 3A5 and antioxidative protection enzymes in patients with transplanted kidney treated with tacrolimus. 2015.
  • Dr Milena Despotovic: Polymorphisms of the genes involved in inflammatory, antioxidative, and immunoregulative processes in patients with bronchial asthma, 2016.
  • Dr Dragana Stokanovic: Impact of gene variability of P-glycoproteins and cytochrome P450 on the pharmacokinetics of clopidogrel in patients with acute coronary syndrome. 2016.

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Publications

M21 category journals

Stefanovic NZ, Cvetkovic TP, Jevtovic-Stoimenov TM, Zvezdanovic-Celebic L, Stojanovic DR, Ignjatovic AM, Zivkovic ND, Velickovic-Radovanovic RM. Potential role of tacrolimus in erythrocytes’ antioxidative capacity in long-term period after renal transplantation. EUR J PHARM SCI 2015; 70: 132-139 M21, IF 3,463

Kocic GM, Sokolovic DT, Jevtovic TM, Cvetkovic TP, Veljkovic AR, Kocic H, Stojanovic SR, Jovanovic A, Jovanovic J, Zivkovic P. Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34(+) stem cell potential in rat experimental hyperuricemia. J DAIRY SCIENCE 2014; 97(11): 6823-6827. M21, IF 3,071

Kocic GM, Pavlovic RM, Nikolic GM, Veljkovic AR, Panseri S, Chiesa LM, Andjelkovic TD, Jevtovic-Stoimenov TM, Sokolovic DT, Cvetkovic TP, Stojanovic SR, Kocic H, Nikolic RS. Effect of commercial or depurinized milk on rat liver growth-regulatory kinases, nuclear factor-kappa B, and endonuclease in experimental hyperuricemia: Comparison with allopurinol therapy. J DAIRY SCIENCE 2014; 97(7): 4029-4042

Kocic G, Bjelakovic Lj, Bjelakovic B, Jevtovic-Stoimenov T, Sokolovic D, Cvetkovic T, Kocic H, Stojanovic S, Langerholc T, and Jonovic M. Impact of Folic Acid Supplementation on Single- and Double-Stranded RNA Degradation in Human Colostrum and Mature Milk. J Medicinal Food. 2014: 17(7): 804-809. doi:10.1089/jmf.2013.0093 M22, IF 1,780

Nikolic VN, Jankovic SM, Velickovic-Radovanovic RM, Apostolovic SR, Stanojevic DM, Zivanovic SC, Stefanovic NZ, Pesic SZ, Jevtovic-Stoimenov TM, Djuric JM, Markovic V, Milovanovic JR. Population pharmacokinetics of carvedilol in patients with congestive heart failure. J PHARMACEUTICAL SCI 2013; 102(8): 2851-2858.

Djordjevic VB, Pavlovic RM, Cosic V, Deljanin-Ilic MZ, Ristic T, Krstic NH, Jevtovic-Stoimenov TM. High clinical accuracy of asymmetric dimethylarginine and symmetric dimethylarginine in patients with ischemic heart disease. AMINO ACIDS 2012; 43(6): 2293-2300

Kocić GM, Pavlovic RM, Nikolic G, Stojanovic D, Jevtovic TM, Sokolovic DT, Cencic A, Stojanovic SR, Jelic MK, Zivanovic S . The effect of depurinized milk draught diet on rat serum uric acid, lipid status and haematological parameters. J ANIMAL PHYSIOL ANIMAL NUTR 2012; 96(4): 648-655

Kocic GM, Nikolic JI, Jevtovic-Stoimenov TM, Sokolovic DT, Kocic H, Cvetkovic TP, Pavlovic DD, Cencic A, Stojanov D. L-Arginine Intake Effect on Adenine Nucleotide Metabolism in Rat Parenchymal and Reproductive Tissues. SCIENTIFIC WORLD JOURNAL 2012 2012:208239. doi: 10.1100/2012/208239.

Kocic GM, Pavlovic RM, Najman SJ, Nikolic G, Sokolovic DT, Jevtovic-Stoimenov TM, Musovic D, Veljkovic AR, Kocic RD, Djindjic N. Circulating Ribonucleic Acids and Metabolic Stress Parameters May Reflect Progression of Autoimmune or Inflammatory Conditions in Juvenile Type 1 Diabetes, THE SCIENTIFIC WORLD JOURNAL 2011;11: 1496-1508

Toncheva D, Mihailova-Hristova M, Vazharova R, Staneva R, Karachanak S, Dimitrov P, Simeonov V, Ivanov S, Balabanski L, Serbezov D, Malinov M, Stefanovic V, Čukuranović R, Polenakovic M, Jankovic-Velickovic L, Djordjevic V, Jevtovic-Stoimenov T, Plaseska-Karanfilska D, Galabov A, Djonov V, Dimova I. NGS nominated CELA1, HSPG2, and KCNK5 as candidate genes for predisposition to Balkan endemic nephropathy. Biomed Res Int 2014;2014:920723. doi: 10.1155/2014/920723.

Nikolic VN, Jevtovic-Stoimenov TM, Velickovic-Radovanovic RM, Ilic SN, Deljanin-Ilic MZ, Marinkovic D, Apostolovic SR, Stanojevic DM, Zivanovic SC, Stefanovic NZ, Pesic SZ, Ruzic-Zecevic DT, Milovanovic JR, Jankovic SM. Population pharmacokinetics of bisoprolol in patients with chronic heart failure. EUR J CLIN PHARMACOL 2013; 69(4): 859-865 (Article)

Nikolic VN, Jevtovic-Stoimenov TM, Stokanovic D, Milovanovic M, Velickovic-Radovanovic RM, Pesic SZ, Stoiljkovic M, Pesic G, Ilic SN, Deljanin-Ilic MZ, Marinkovic D, Stefanovic NZ, Jankovic SM. An inverse correlation between TNF alpha serum levels and heart rate variability in patients with heart failure. J CARDIOL 2013; 62(1-2): 37-43

Šmelcerovic Ž, Rangelov M, Cherneva E, Kocic GM, Stojanovic SR, Jevtovic-Stoimenov TM, Petronijevic ZB, Yancheva D. Inhibition mechanism and molecular modeling studies of the interactions of 6-(propan-2-yl)-3-methyl-morpholine-2,5-dione with xanthine oxidase, BULGARIAN CHEMICAL COMMUNICATIONS 2015;47(3): 783-787

Stefanovic NZ, Cvetkovic TP, Velickovic-Radovanovic RM, Jevtovic-Stoimenov TM, Vlahovic PR, Stojanovic IR, Pavlovic DD. Pharmacogenetics May Influence Tacrolimus Daily Dose, But Not Urinary Tubular Damage Markers in the Long-Term Period After Renal Transplantation. J MEDICAL BIOCHEMISTRY 2015;34(4): 422-430 (Article)

Djordjevic BS, Sokolovic DT, Kocic GM, Veljkovic AR, Despotovic M, Basic JT, Jevtovic-Stoimenov TM, Sokolovic DM. The effect of melatonin on the liver of rats exposed to microwave radiation, BRATISLAVA MEDICAL JOURNAL-BRATISLAVSKE LEKARSKE LISTY 2015;116(2): 96-100

Stefanovic NZ, Cvetkovic TP, Jevtovic-Stoimenov TM, Ignjatovic AM, Paunovic GJ, Velickovic-Radovanovic RM. Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function, EXPERIMENTAL AND THERAPEUTIC MEDICINE 2015;10(3): 1149-1156

Kocic GM, Cukuranovic J, Jevtovic-Stoimenov TM, Cukuranovic RI, Djordjevic VB, Bogdanovic DC, Stefanovic VB. Global and specific histone acetylation pattern in patients with Balkan endemic nephropathy, a worldwide disease, RENAL FAILURE 2014;36(7): 1078-1082

Milojkovic B, Kocic GM, Radenkovic SB, Pavlovic RM, Cvetkovic TP, Deljanin-Ilic MZ, Ilic SN, Bobana MD, Djindjic BJ, Stojanovic DR, Sokolovic DT, Jevtovic-Stoimenov TM. Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease. RENAL FAILURE 2014;36(4): 613-618 (Article)

Djordjevic VV, Jevtovic-Stoimenov TM, Lazarevic D, Stojanovic IR, Trajanovic LJ, Zikic OV, Djordjevic VB. Association Analysis for Neuronal Nitric Oxide Synthase Gene Polymorphism with Plasma Nitrite/Nitrate Concentration in Schizophrenia, J MEDICAL BIOCHEMISTRY 2014; 33(4): 364-370

Radovic J, Vojinovic J, Bojanic VV, Jevtovic-Stoimenov TM, Kocic GM, Milojkovic M, Veljkovic AR, Markovic I, Stojanovic SR, Pavlovic DD. Lipid Peroxidation and Oxidative Protein Products in Children with Episodic Fever of Unknown Origin. J MEDICAL BIOCHEMISTRY 2014;33(2):197-202 (Article)

Kocic GM, Bjelakovic LjLj, Bjelakovic BB, Jevtovic-Stoimenov TM, Sokolovic DT, Cvetkovic TP, Kocic H, Stojanovic SR, Langerholc T, Jonovic M. Impact of Folic Acid Supplementation on Single- and Double-Stranded RNA Degradation in Human Colostrum and Mature Milk. J MEDICINAL FOOD 2014;17(7): 804-809

Sokolovic DT, Nikolic JI, Kocic GM, Jevtovic-Stoimenov TM, Veljkovic AR, Stojanovic MP, Stanojkovic ZA, Sokolovic DM, Jelic MK. The effect of ursodeoxycholic acid on oxidative stress level and DNase activity in rat liver after bile duct ligation, DRUG AND CHEMICAL TOXICOLOGY 2013; 36(2): 141-148

Sokolovic DT, Djordjevic BS, Kocic GM, Veljkovic AR, Marinkovic MR, Basic JT, Jevtovic-Stoimenov TM, Stanojkovic ZA, Sokolovic DM, Pavlovic V, Djindjic BJ, Krstic DD. Melatonin protects rat thymus against oxidative stress caused by exposure to microwaves and modulates proliferation/apoptosis of thymocytes. GENERAL PHYSIOLOGY AND BIOPHYSICS 2013;32(1): 79-90

Budic I, Pavlovic DD, Kitic DV, Kocic GM, Cvetkovic TP, Simic D, Jevtovic-Stoimenov TM. Tourniquet-induced ischemia-reperfusion injuries during extremity surgery at children’s age: impact of anesthetic chemical structure. REDOX REPORT 2013;18(1): 20-26

Jevtovic-Stoimenov TM, Despotovic M, Pesic ZU, Cosic A. Lack of Association of Tumor Necrosis Factor-alpha G-308A and Transforming Growth Factor-beta 1 C-509T Polymorphisms in Patients with Deep Neck Space Infections, BALKAN J MED GENETICS 2013;16(2): 59-66

Radjenovic-Petkovic T, Pejcic TA, Videnovic-Ivanov JL, Jevtovic-Stoimenov TM, Jankovic ID, Nastasijevic-Borovac D, Radojkovic DB. Tumor Necrosis Factor Alpha Gene Polymorphism in Serbian Patients with Sarcoidosis, SRPSKI ARHIV ZA CELOKUPNO LEKARSTVO 2013;141(3-4): 169-172 (Article)

Bjelakovic GN, Stojanovic IT, Jevtovic-Stoimenov TM, Bjelakovic LjLj, Kamenov BA, Pavlovic DD, Kocic GM, Sokolovic DT, Basic JT, Bjelakovic GB. Is folic acid supplementation to food benefit or risk for human health? PTERIDINES 2013; 24 (3): 165-181

Milovanovic M, Pesic G, Nikolic VN, Jevtovic-Stoimenov TM, Vasic K, Jovic Z, Deljanin-Ilic MZ, Pesic SZ. Vitamin D Deficiency is Associated with Increased IL-17 and Tnf alpha Levels in Patients with Chronic Heart Failure, ARQUIVOS BRASILEIROS DE CARDIOLOGIA, 2012; 98(3): 259-264

Veljkovic AR, Nikolic RS, Kocic GM, Pavlovic DD, Cvetkovic TP, Sokolović DT, Jevtovic TM, Basic JT, Laketic DM, Marinkovic MR, Stojanovic SR, Djordjevic BS, Krsmanovic MM. Protective Effects of Glutathione and Lipoic Acid against Cadmium-Induced Oxidative Stress in Rat’s Kidney. RENAL FAILURE 2012; 34(10):1281-1287

Bjelakovic LjLj, Kocic GM, Stojanovic IT, Jevtovic-Stoimenov TM, Najman SJ, Sokolovic DT, Stojanovic SR, Bjelakovic GN. Folic Acid Effect on Arginase Activity in Human Colostrum and Mature Milk. PTERIDINES 2012; 23(1): 33-39

Radjenovic-Petkovic T, Pejcic TA, Jevtovic-Stoimenov TM, Nastasijevic-Borovac D. Polymorphism of Genes TNF alpha and LT alpha in First-Degree Relatives Suffering from Sarcoidosis-Case report. HEALTHMED 2011; 5(6): 2233-2236

Stojanovic SK, Jevtovic-Stoimenov TM, Stankovic AM, Pavlovic DD, Nedovic JM, Stamenkovic BN, Dimic AN, Marinkovic MR. Association of TNF-alpha Polymorphism (-308 A/G) with High Activity of Rheumatoid Arthritis and Therapy Response to Etanercept. SRPSKI ARHIV ZA CELOKUPNO LEKARSTVO 2011; 139(11-12): 784-789

Tesić Rajković S, Radovanović Dinić B, Jevtović Stoimenov T. The role and importance of biochemical markers in diagnosis of alcoholic acute pancreatitis. Med Pregl 2012; 65(3-4):152-157