Laboratory for early human development

Head of Laboratory: Professor Katarina Vukojević MD, PhD

Members of the group:
Professor Mirna Saraga-Babić MD, PhD
Professor Marijan Saraga MD, PhD
Professor Ivana Bočina, PhD
Associate professor Violeta Šoljić MD, PhD
Associate professor Snježana Mardešić MD, PhD
Assistant professor Danijela Kalibović Govorko DDS, PhD
Assistant professor Darko Kero DDS, PhD
Benjamin Benzon
Ejazul Haque
Anita Racetin, Mirela Lozić, Ivana Šolić, Ivona Kosović, Marija Jurić
Mrs Marica Maretić, senior laboratory technician
Mrs Asija Miletić, laboratory technician
Gene expression in early human development
Investigations on the spatial and temporal expression of gene products- proteins involved in regulation of early human development are crucial for understanding the roles of those genes in normal development and morphogenesis of different human tissues and organs. Knowledge about their normal expression pattern detected directly in human tissues is important in revealing possible mechanisms underlying certain anomalies and diseases appearing as a consequence of disturbed human development. Our main interest is to analyze expression of pro-apoptotic, anti-apoptotic and mitotic developmental factors, intermediate filament proteins, growth factors, BMP-s and specific receptors during development of the human spinal cord, spinal ganglia, kidneys, upper and lower jaw, tooth and pituitary gland, using morphological and immunohistochemical techniques. Special emphasize is put on the pathways of differentiation of specific cell lineages from the immature cell populations. Ultrastructural characteristics of apoptotic and mitotic cells and their distribution within the developingtissues, as well as appearance of primary cilia in kidney tubules will be also analyzed. Additionally, ultrastructural and immunohistochemical characteristics of the notochord, nervous and muscular systems will be analyzed in Amphioxus and in the notochord of Ascidiae embryos. Recognition of genes participating during early human development has also important applications in clinical practice. Therefore, some anomalies and diseases resulting from disturbed temporal and spatial expression of the investigated genetic factors will be followed clinically in early childhood.
Characterization of Congenital Anomalies of the Kidney and the Urinary tract (CAKUT) candidate genes during mouse and human development -Croatian Science Fondation 
Gene expression in early human development - Ministry of Science, Education and Sport, Republic of Croatia (MZOS) project No 216-2160528-0507
Biomarkers of normal and abnormal development and associated multifactorial disorders, Croatia-Slovenia Cooperation in Science and Technology
Selected publications
           1.Westland R, Verbitsky M, Vukojevic K, Perry BJ, Fasel DA, Zwijnenburg PJ, Bökenkamp A, Gille JJ, Saraga-Babic M, Ghiggeri GM, D'Agati VD, Schreuder MF, Gharavi AG, van Wijk JA, Sanna-Cherchi S. Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney. Kidney Int. 2015 Sep 9. doi: 10.1038/ki.2015.239. [Epub ahead of print]
          2.Sanna-Cherchi S, Sampogna RV, Papeta N, Burgess KE, Nees SN, Perry BJ, Choi M, Bodria M, Liu Y, Weng PL, Lozanovski VJ, Verbitsky M, Lugani F, Sterken R, Paragas N, Caridi G, Carrea A, Dagnino M, Materna-Kiryluk A, Santamaria G, Murtas C, Ristoska-Bojkovska N, Izzi C, Kacak N, Bianco B, Giberti S, Gigante M, Piaggio G, Gesualdo L, Kosuljandic Vukic D, Vukojevic K, Saraga-Babic M, Saraga M, Gucev Z, Allegri L, Latos-Bielenska A, Casu D, State M, Scolari F, Ravazzolo R, Kiryluk K, Al-Awqati Q, D'Agati VD, Drummond IA, Tasic V, Lifton RP, Ghiggeri GM, Gharavi AG. Mutations in DSTYK and dominant urinary tract malformations. N Engl J Med 2013;369(7):621-9.
          3.Sanna-Cherchi S, Kiryluk K, Burgess KE, Bodria M, Sampson MG, Hadley D, Nees SN, Verbitsky M, Perry BJ, Sterken R, Lozanovski VJ, Materna-Kiryluk A, Barlassina C, Kini A, Corbani V, Carrea A, Somenzi D, Murtas C, Ristoska-Bojkovska N, Izzi C, Bianco B, Zaniew M, Flogelova H, Weng PL, Kacak N, Giberti S, Gigante M, Arapovic A, Drnasin K, Caridi G, Curioni S, Allegri F, Ammenti A, Ferretti S, Goj V, Bernardo L, Jobanputra V, Chung WK, Lifton RP, Sanders S, State M, Clark LN,Saraga M, Padmanabhan S, Dominiczak AF, Foroud T, Gesualdo L, Gucev Z, Allegri L, Latos-Bielenska A, Cusi D, Scolari F, Tasic V, Hakonarson H, Ghiggeri GM, Gharavi AG. Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet. 2012 Dec 7;91(6):987-97. 
              4. Caric A, Poljicanin A, Tomic S, Vilovic K, Saraga-Babic M, Vukojevic K. Apoptotic pathways in ovarian surface epithelium of human embryos during embryogenesis and carcinogenesis: Close relationship of developmental plasticity and neoplasm. Acta Histochem. 2013 
              5. Agnić I, Vukojević K, Saraga-Babić M, Filipović N, Grković I. Isoflurane post-conditioning stimulates the proliferative phase of myocardial recovery in an ischemia-reperfusion model of heart injury in rats. Histol Histopathol. 2013 Jul 12. 
              6. Vukusic Pusic T, Janjic T, Dujmovic I, Poljicanin A, Soljic V, Saraga-Babic M, Vukojevic K. The involvement of proliferation and apoptosis in the early human gonad development. Journal of molecular histology. 2013;44(1):55-63.
              7. Soljic V, Perak RB, Vukojevic K, Saraga-Babic M, Bubalo P, Karan D, et al. ZAP-70 expression and proliferative activity in chronic lymphocytic leukemia. Leukemia & lymphoma. 2012.
              8. Saraga-Babic M, Vukojevic K, Bocina I, Drnasin K, Saraga M. Ciliogenesis in normal human kidney development and post-natal life. Pediatr Nephrol. 2011
              9. Ilic T, Gracan S, Arapovic A, Capkun V, Subat-Dezulovic M, Saraga M. Changes in bacterial resistance patterns in children with urinary tract infections on antimicrobial prophylaxis at University Hospital in Split. Med Sci Monit. 17:CR355-61.
             10. Petricevic J, Forempoher G, Ostojic L, Mardesic-Brakus S, Andjelinovic S, Vukojevic K, et al. Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas. Acta Histochem. 2010
             11. Kalibovic Govorko D, Becic T, Vukojevic K, Mardesic-Brakus S, Biocina-Lukenda D, Saraga-Babic M. Spatial and temporal distribution of Ki-67 proliferation marker, Bcl-2 and Bax proteins in the developing human tooth. Arch Oral Biol. 2010
              12. Cavar I, Kelava T, Vukojevic K, Saraga-Babic M, Culo F. The role of prostaglandin E2 in acute acetaminophen hepatotoxicity in mice. Histol Histopathol. 2010;25:819-30.
              13. Brakus SM, Govorko DK, Vukojevic K, Jakus IA, Carev D, Petricevic J, et al. Apoptotic and anti-apoptotic factors in early human mandible development. Eur J Oral Sci. 2010;118:537-46.
              14. Aljinovic J, Vukojevic K, Kosta V, Guic MM, Saraga-Babic M, Grkovic I. Histological differences in healing following experimental transmural infarction in rats. Histol Histopathol.  2010;25:1507-17.
              15. Novakovic J, Mardesic-Brakus S, Vukojevic K, Saraga-Babic M Developmental patterns of Ki-67, bcl-2 and caspase-3 proteins expression in the human upper jaw.   
              16. Kalibović Govorko, Danijela; Bečić, Tina; Vukojević, Katarina; Mardešić-Brakus, Snježana; Biočina-Lukenda, Dolores; Saraga-Babić, Mirna.
 Spatial and temporal distribution of Ki-67 proliferation marker, Bcl-2 and Bax proteins in the developing human tooth. // Archives of oral biology.2010 Aug 22.
               17. Mardešić Brakus, Snježana; Kalibović Govorko, Danijela; Vukojević, Katarina; Alujević Jakus, Ivana, Carev, Dominko; Petričević, Joško; Saraga-Babić, Mirna. Apoptotic and antiapoptotic factors in early human mandible development. // European journal of oral sciences. (2010). [Epub ahead of print.
               18. Vukojevic K, Petrovic D, Saraga-Babic M. Nestin expression in glial and neuronal progenitors of the developing human spinal ganglia.Gene Expr Patterns. 2010.
               19. Bočina I, Ljubešić N, Saraga-Babić M.Cilia-like structures anchor the amphioxus notochord to its sheath.Acta Histochem. 2010.
               20. Bazina M, Vukojevic K, Roje D, Saraga-Babic M. Influence of growth and transcriptional factors, and signaling molecules on early human pituitary development.J Mol Histol. 2009
               21. Vukojević, K.; Škobić, H., Saraga-Babić, M. Proliferation and differentiation of glial and neuronal progenitors in the development of human spinal ganglia.Differentiation 2009
               22. Saraga-Babić M., Bazina M., Vukojević K., Bočina I, Stefanović V.: Involvement of pro-apoptotic and anti-apoptotic factors in the early development of the human pituitary gland. Histology and Histopathology 2008.
               23. Vukojević K,  Carev D, Sapunar D, Petrović D, Saraga-Babić M: Developmental patterns of caspase-3, bax and bcl-2 proteins expression in the human spinal ganglia. J Mol Histol. 2008.
               24. Carev D, Saraga M., Saraga-Babić M.: Involvement of FGF and BMP family proteins and VEGF in early human kidney development. Histology and Histopathology, 23(7):853-849, 2008
               25. Carev D.,  Saraga M., Saraga-Babić M.: Expression of intermediate filaments, EGF and TGF-a in early human kidney development. Journal of Molecular Histology, 39(2): 227-235, 2008.
               26. Saraga M, Resić B, Krnić D, Jelavić T, Krnić D, Sinovcić I, Tomasović M.A stereotypic "elbowing" movement, a possible new primitive reflex in newborns. Pediatr Neurol,36(2):84-7, 2007.
               27. Bazina M., Stefanović V., Božanić D., Saraga-Babić M.: Ultrastructural and immunohistochemical characteristics of developing human pituitary gland// Acta Histochemica. 109( 5): 2007.
               28. Bocina I, Saraga-Babić M.The notochordal sheath in amphioxus--an ultrastructural and histochemical study.Coll Antropol.30(2):361-7 , 2007.
               29. Bocina I, Saraga-Babić M.Immunohistochemical study of cytoskeletal and extracellular matrix components in the notochord and notochordal sheath of amphioxus.Int J Biol Sci.  2006
               30. Carev D, Krnić D, Saraga M, Sapunar D, Saraga-Babić M.Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney development. Pediatr Nephrol 21(5):627-36, 2006.
               31. Glamoclija V, Vilović K, Saraga-Babić M, Baranović A, Sapunar D.Apoptosis and active caspase-3 expression in human granulosa cells. Fertil Steril. 83(2):426-31, 2005.
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