lab 03

Glavni pravac istraživanja naše laboratorije je korelacije genotipa sa fenotipom. Cilj nam je da otkrijemo kombinovanu modulatornu ulogu ispitivanih gena u respiratornim (HOBP, cistična fibroza), kardiovaskularnim (tromboza, kardiomiopatije) i malignim (adenikarcinom pankreasa, kolorektalni kancer, karcinom pluća) bolestima. Većina odabranih gena učestvuje u regulaciji hemostaze, inflamatornim procesima, remodelovanju tkiva, signalnim putevima, ćelijskoj proliferaciji, i zaštiti od oksidativnog stresa. Takođe, ispitujemo korelaciju mutacija i polimorfizama u genu za cističnu fibrozu (CFTR) sa fenotipom kod obolelih od CFTR-patija (CFTR related diseases) kao što su hronični pankreatitis, CBAVD i diseminovane bronhiektazije.

U cilju definisanja molekularnih mehanizama neuromišićnih oboljenja i kardiomiopatija izučavamo strukturnu i regulatornu uloge senzora stresa u mišićnoj ćeliji, proteina Ankrd1 i Ankrd2. Oni povezuju elastičnu I-traku sarkomere sa kontrolom transkripcije u jedru. Naša istraživanja su usmerena na otkrivanje signalnih puteva u kojima Ankrd1 i Ankrd2 učestvuju, na identifikaciju njihovih nizvodnih targeta, kao i molekularnih mehanizama regulacije njihove ekspresije. Takođe smo uključeni u identifikaciju mutacija u genu Ankrd1 kod pacijenata obolelih od hipertrofične kardiomiopatije, a izučavamo i status proteina Ankrd2 u neuromišićnim oboljenjima.

Zebrice (Danio rerio) koristimo za istraživanja kardiovaskularnog sistema i testiranje genotoksičnosti. Prednost zebrica kao animalnog model sistema se ogleda u visokoj genetičkoj i sistemskoj homologiji sa čovekom, velikim brojem potomaka, lakim genetičkim manipulacijama i transparentnošću organizma koja je pogodna za imaging.

U saradnji sa medicinskim ustanovama obavljamo molekularnu dijagnostiku cistične fibroze, deficijencije A1-antitripsina i trombofilije, kao i farmakogenetičko testiranje za procenu individualnog odgovora na antikoagulantnu terapiju.

 
Tekući projekti:
  • Zebra-ribica (Danio rerio) kao model system za izučavanje uloge mišićnih proteina sa ankirinskim ponovcima Ankrd1 i Ankrd2 u razviću i regeneraciji srca
    Naučno-istraživački projekat u okviru nаučno-tehnološke sаrаdnje Republike Srbije i Savezne Republike Nemačke
    Rukovodilac: Dr Snežana Kojić, IMGGI
Odabrane publikacije:
  1. Jasnic-Savovic J, Nestorovic A, Savic S, Karasek S, Vitulo N, Valle G, Faulkner G, Radojkovic D, Kojic S. Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes. 2015;143(6):583-597.
  2. Kojic S, Nestorovic A, Rakicevic L, Protic O, Jasnic-Savovic J, Faulkner G, Radojkovic D. Cardiac transcription factor Nkx2.5 interacts with p53 and modulates its activity. Arch Biochem Biophys 2015;569:45-53.
  3. Ljujic M, Divac Rankov A, Kojic S, Miranda E, Radojkovic D. Functional analysis of novel alpha-1 antitrypsin variants G320R and V321F. Mol Biol Rep 2014;41:6133-6141.
  4. Nikolic A, Milosevic K, Boskovic S, Nestorovic B. Neutrophil Elastase Gene Polymorphisms: Modulators of Response to Therapy in Childhood Bronchiectasis? Lung 2014;192(4):595-599.
  5. Pruner I, Djordjevic V, Gvozdenov M, Tomic B, Radojkovic D. Determination of transgene copy number in stably transfected mammalian cells by PCR-capillary electrophoresis assay. Biochem Genet 2014;52:159-165.
  6. Djordjevic V, Kovac M, Miljic P, Murata M, Takagi A, Pruner I, Francuski D, Kojima T, Radojkovic D. A novel prothrombin mutation in two families with prominent thrombophilia--the first cases of antithrombin resistance in a Caucasian population. J Thromb Haemost 2013;11:1936-1939.
  7. Rakicevic LB, Kusic-Tisma JS, Kovac MK, Backovic DT, Radojkovic DP. Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy. Scand J Clin Lab Invest 2013;73:523-527.
  8. Djordjevic V, Mitic G, Pruner I, Kovac M, Radojkovic D. Are thrombophilia more multifactorial than we thought: report of mosaicism for FII G20210A and novel FII T20061C gene variants. J Thromb Haemost 2012;10:301-303.
  9. Nikolic A, Ristanovic M, Perovic V, Trifunovic J, Perovic M, Radojkovic D. Genetic alterations in SMAD4 and K-ras in Serbian patients with endometrial carcinoma. Int J Gynecol Cancer 2012;22:442-446.
  10. Nikolic A, Kojic S, Knezevic S, Krivokapic Z, Ristanovic M, Radojkovic D. Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: detection of two novel polymorphic nucleotide repeats. Cancer Epidemiol 2011;35:265-271.
  11. Kojic S, Nestorovic A, Rakicevic L, Belgrano A, Stankovic M, Divac A, Faulkner G. A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein. Arch Biochem Biophys 2010;502:60-67.
  12. Kusic J, Tomic B, Divac A, Kojic S. Human initiation protein Orc4 prefers triple stranded DNA. Mol Biol Rep 2010;37:2317-2322.
  13. Ljujic M, Topic A, Nikolic A, Divac A, Grujic M, Mitic-Milikic M, Radojkovic D. Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients. Genet Mol Biol 2010;33:5-8.
  14. Pruner I, Djordjevic V, Miljic P, Kovac M, Antonijevic N, Rakicevic L, Radojkovic D. +1040 C/T polymorphism in coding region of thrombin-activatable fibrinolysis inhibitor gene and the risk of idiopathic recurrent fetal loss. Blood Coagul Fibrinolysis 2010;21:679-682.
  15. Djordjevic V, Stankovic M, Brankovic-Sreckovic V, Rakicevic L, Radojkovic D. Genetic risk factors for arterial ischemic stroke in children: a possible MTHFR and eNOS gene-gene interplay? J Child Neurol 2009;24:823-827.
  16. Stankovic MM, Nestorovic AR, Tomovic AM, Petrovic-Stanojevic ND, Andjelic-Jelic MS, Dopudja-Pantic VB, Nagorni-Obradovic Lj M, Mitic-Milikic MM, Radojkovic DP. TNF-alpha-308 promotor polymorphism in patients with chronic obstructive pulmonary disease and lung cancer. Neoplasma 2009;56:348-352.
  17. Stankovic M, Nikolic A, Divac A, Rakicevic L, Tomovic A, Mitic-Milikic M, Nagorni-Obradovic L, Grujic M, Petrovic-Stanojevic N, Andjelic-Jelic M, Dopudja-Pantic V, Radojkovic D. Matrix metalloproteinases gene variants in idiopathic disseminated bronchiectasis. J Investig Med 2009;57:500-503.
  18. Ljujic M, Topic A, Divac A, Nikolic A, Petrovic-Stanojevic N, Surlan M, Mitic-Milikic M, Radojkovic D. Isoelectric focusing phenotyping and denaturing gradient gel electrophoresis genotyping: a comparison of two methods in detection of alpha-1-antitrypsin variants. Transl Res 2008;151:255-259.
  19. Stankovic M, Nikolic A, Divac A, Tomovic A, Petrovic-Stanojevic N, Andjelic M, Dopudja-Pantic V, Surlan M, Vujicic I, Ponomarev D, Mitic-Milikic M, Kusic J, Radojkovic D. The CFTR M470V gene variant as a potential modifier of COPD severity: study of Serbian population. Genet Test 2008;12:357-362.
  20. Stefanovic D, Kusic J, Divac A, Tomic B. Formation of noncanonical DNA structures mediated by human ORC4, a protein component of the origin recognition complex. Biochemistry 2008;47:8760-8767.
Kontakt:
Vojvode Stepe 444a
Poštanski fah 23,
11010 Beograd, Srbija
Tel:+381 11 3976658,
Faks:+381 11 3975808
labmolbio@imgge.bg.ac.rs