Laboratorij za staničnu biologiju i prijenos signala

Laboratorij za staničnu biologiju i prijenos signala

Laboratorij za staničnu biologiju i prijenos signala (LSBPS) bavi se istraživanjem bioloških procesa u stanicama tumora čovjeka nakon izlaganja protutumorskim lijekovima i novosintetiziranim spojevima u cilju poboljšanja terapije tumora. Osim toga istražujemo biologiju adenovirusnih vektora za prijenos gena s mogućom upotrebom u genskoj terapiji tumora i vakcinaciji. U istraživanjima koristimo metode stanične i molekularne biologije, biokemije i moderne svjetlosne mikroskopije.

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Smjerovi istraživanja:

1.         Signalni putevi potaknuti integrinima u odgovoru tumorskih stanica na protutumorske lijekove i metastaziranju.

2.         Mehanizmi otpornosti tumorskih stanica na protutumorske lijekove, posebice uključenost miRNA i integrina u te procese.

3.         Novosintetizirani spojevi kao potencijalni protutumorski lijekovi.

4.         Adenovirusni vektori za prijenos gena i vakcinaciju.

Grupe:

Grupa Ambriović-Ristov

Grupa Ambriović-Ristov istražuje signalne puteve potaknute integrinima u stanicama tumora čovjeka i mogućnost modulacije ekspresije integrina u cilju povećanja osjetljivosti stanica tumora na protutumorske lijekove. Osim toga, istražujemo kako ekspresija različitih integrina utječe na migraciju i invaziju stanica tumora. Predmet naših istraživanja su i fokalne adhezije, definirane kao mjesta vezanja stanice s izvanstaničnim matriksom, i to njihov sastav, stvaranje i evolucija tijekom vezanja na podlogu i migracije.

Grupa Brozović

Uspješnost kemoterapije u liječenju tumora ograničena je razvojem otpornosti tumora na lijekove i nuspojavama. Grupa Brozović se bavi proučavanjem molekularnih mehanizama uključenih u otpornost stanica tumora na lijekove. Trenutna istraživanja su usmjerena na proučavanje odnosa epitelno-mezenhimalne tranzicije, procesa uključenog u metastaziranje tumora, i razvoja otpornosti stanica tumora na lijekove. Nadalje, u svrhu poboljšanja postojeće kemoterapije, grupa se bavi proučavanjem bioloških karakteristika novosintetiziranih kompleksa organskih molekula s metalima.

Grupa Majhen

Adenovirusni vektori imaju potencijalno translacijsku i komercijalnu vrijednost, a trenutno se istražuju kao vektori za prijenos gena i vakcinaciju. U grupi Majhen bavimo se istraživanjem temeljne biologije adenovirusnih vektora i to adenovirusa tipa 5 i 26. Glavni ciljevi našeg istraživanja su pronalazak poveznica između vezanja adenovirusnog vektora na receptor na površini stanice i unutarstaničnog putovanja vektora te posljedično poticanja imunosnog odgovora. Dodatno nas zanima i način preusmjeravanja adenovirusnih vektora prema ciljnoj molekuli kao i njihovo unutarstanično putovanje.

Publikacije

2016-2017

  • Kokan Z, Perić B, Kovačević G, Brozovic A, Metzler-Nolte N, Kirin SI. Cis- vs. trans- square-planar palladium(II) and platinum(II) complexes with triphenylphosphine amino acid bioconjugates. European Journal of Inorganic Chemistry. 33:3928-3937, 2017.
  • Hayek SS, Koh KH, Grams ME, Wei C, Ko Y-A, Li J, Samelko B, Lee H, Dande RR, Lee HW, Hahm E, Peev V, Tracy M, Tardi NJ, Gupta V, Altintas MM, Garborcauskas G, Stojanović N, Winkler CA, Lipkowitz MS, Tin A, Inker LA, Levey AS, Zeier M, Freedman BI, Kopp JB, Skorecki K, Coresh J, Quyyumi AA, Sever S, Reiser J. A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease. Nature Medicine. 23:945-953, 2017.
  • Teofilović NK, Bihi M, Stojković MR, Tumir LM, Ester K, Kralj M, Majhen D, Oršolić N, Lepur A, Vrbanec D, Markotić A, Dembić Z, Weber AN, Piantanida I, Vugrek O, Diken M, Knežević J. 1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro. Bioorg Med Chem Lett. 2017 Feb 20. pii: S0960-894X(17)30181-6. doi: 10.1016/j.bmcl.2017.02.048.
  • Brozovic A. The relationship between platinum drug resistance and epithelial-mesenchymal transition. Archives of Toxicology, 91:605–619, 2017. Invited review
  • Vajs J., Proud C., Brozovic A., Gazvoda M., Lloyd A., Roper D.I., Osmak M., Košmrlj J., Dowson C.G. Diaryltriazenes as antibacterial agents against methicillin resistant Staphylococcus aureus (MRSA) and Mycobacterium smegmatis. European Journal of Medicinal Chemistry. 127:223-234, 2016.
  • Ruščić J., Ambriović-Ristov A., Majhen D., Kolundžija S., Barut M., Benihoud K., Krajačić M. Manipulating adenoviral vector ion-exchange chromatography: Hexon versus fiber. Journal of Separation Science. 39(22):4299-4304, 2016.
  • Christmann M., Diesler K., Majhen D., Steigerwald C., Berte N., Freund H., Stojanović N., Kaina B., Osmak M., Ambriović-Ristov A., Tomicic MT. Integrin αVβ3 silencing sensitizes malignant glioma cells to temozolomide by suppression of homologous recombination repair. Oncotarget, 2016. DOI:0.18632/oncotarget.10897
  • Stojanović N., Brozovic A., Majhen D., Bosnar M.H., Fritz G., Osmak M., Ambriović-Ristov A. Integrin αvβ3 expression in tongue squamous carcinoma cells Cal27 confers anticancer drug resistance through loss of pSrc(Y418). Biochimica et Biophysica Acta. 1863(8):1969-78, 2016.
  • Sobočanec, S., Filić, V., Matovina, M., Majhen, D., Šafranko, ŽM., Hadžija, MP., Krsnik, Ž., Kurilj, AG., Šarić, A., Abramić, M., Balog, T. Prominent role of exopeptidase DPP III in estrogen-mediated protection against hyperoxia in vivo. Redox Biology. 8: 149-159, 2016. 
  • Steiner I.*, Stojanović N.*, Bolje A., Brozovic A., Polančec D., Ambriović-Ristov A., Radić Stojković M., Piantanida I, Eljuga D., Košmrlj J., Osmak M. Discovery of ‘click’ 1,2,3-triazolium salts as potential anticancer drugs. Radiology and Oncology. 19;50(3):280-8, 2016. *equal contribution

2014-2015

  • Brozovic A., Duran G.E., Wang Y.C., Francisco B.E., Sikic B.I. The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells. Molecular Oncology. 9(8):1678-93., 2015.
  • Vajs J.*, Steiner I.*, Brozovic A.*, Pevec A., Ambriović-Ristov A., Matković M., Piantanida I., Urankar D., Osmak M., Košmrlj J. The 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity. J Inorg Biochem. 153:42-8. 2015. *equal contribution
  • Krüger K., Thomale J., Stojanovic N., Osmak M., Henninger C., Bormann S., Fritz G. Platinum-induced kidney damage: Unraveling the DNA damage response (DDR) of renal tubular epithelial and glomerular endothelial cells following platinum injury. Biochimica et Biophysica Acta. 1853: 685-698, 2015.
  • Murati T., Šimić B., Brozovic A., Kniewald J., Miletić Gospić A., Bilandžić N., Kmetič I. PCB 77 action in ovary cells--toxic effects, apoptosis induction and cell cycle analysis. Toxicology Mechanisms and Methods. 25(4): 302-11., 2015.
  • Majhen D., Calderon H., Chandra N., Fajardo C.A., Rajan A., Alemany R., Custers J. Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field.Human Gene Therapy. 25, 301-317, 2014.
  • Majhen D., Stojanović N., Vukić D., Pichon C., Leduc C., Osmak M., Ambriović-Ristov A. Increased Adenovirus Type 5 Mediated Transgene Expression Due to RhoB Down-regulation, PLoS One. 9(1): e86698, 2014.
  • Moisan F., Francisco E.B., Brozovic A., Duran G.E., Wang Y.C., Chaturvedi S., Seetharamb S., Snyder L.A., Doshi P., Sikic B.I. Enhancement of Paclitaxel and Carboplatin Therapies by CCL2 Blockade in Ovarian Cancers. Molecular Oncology. 8: 1231-1239, 2014.
  • Rak S., De Zan T., Štefulj J., Kosović M., Gamulin O., Osmak M. FTIR spectroscopy reveals lipid droplets in drug resistant laryngeal carcinoma cells through detection of increased ester vibrational bands intensity. Analyst. 139, 13: 3407-3415, 2014.
  • Sommer M., Kureljak P., Urankar D., Schweinfurth D., Stojanović N., Bubrin M., Gazvoda M., Osmak M., Sarkar B., Košmrlj J. Combining [Arene–Ru] with Azocarboxamide to Generate a Complex with Cytotoxic Properties. Chemistry: A European Journal, Communication. 20: 17296-17299, 2014.
  • Vellinga J., Smith J.P., Lipiec A., Majhen D., Lemckert A., van Ooij M., Ives P., Yallop C., Custers J., Havenga M. Challenges in manufacturing adenoviral vectors for global vaccine product deployment. Human Gene Therapy. 25: 318-327, 2014.

 

2012-2013

  • Brozovic A., Vuković L., Polančac D.S., Arany I., Köberle B., Fritz G., Fiket Z., Majhen D., Ambriović-Ristov A., Osmak M. Endoplasmic reticulum stress is involved in the response of human laryngeal carcinoma cells to carboplatin but is absent in carboplatin-resistant cells. PLoS One. 8(9): e76397, 2013.
  • Rak S., Čimbora-Zovko T., Gajski G., Dubravčić K., Domijan A., Delaš I., Garaj-Vrhovac V., Batinić D.,  Sorić J., Osmak M. Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation. Toxicology In Vitro. 27, 2; 523-532, 2013.
  • Watanabe S., De Zan T., Ishizaki T., Yasuda S., Kamijo H., Yamada D., Aoki T., Kiyonari H., Kaneko H., Shimizu R., Yamamoto M., Goshima G., Narumiya S. Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis. Cell Reports. 20135:926-932, 2013. 
  • Watanabe S., De Zan T., Ishizaki T., Narumiya S. Citron kinase mediates transition from constriction to abscission through its coiled-coil domain. Journal of Cell Science. 126:1773-84, 2013.
  • Gabrilovac J., Čupić B., Zapletal E., Brozović A. IFN-γ up-regulates kappa opioid receptors (KOR) on murine macrophage cell line J774. Journal of Neuroimmunology. 245, 1/2; 56-65, 2012.
  • Majhen D., Richardson J., Vukelić B., Dodig I., Cindrić M., Benihoud K., Ambriović-Ristov A. The disulfide bond of an RGD4C motif inserted within the HI loop of the adenovirus type 5 fiber protein is critical for retargeting to αv-integrins. Journal of Gene Medicine. 14(12): 788-797, 2012.
  • Osmak M. Statins and cancer: Current and future prospects. Cancer Letters. 324, 1; 1-12, 2012.

 

2010-2011

  • Čimbora-Zovko T., Brozović A., Piantanida I., Fritz G., Virag A., Alič B., Majce V., Kočevar M., Polanc S., Osmak M. Synthesis and biological evaluation of 4-nitro-substituted 1, 3-diaryltriazenes as a novel class of potent antitumor agents. European Journal of Medicinal Chemistry. 46: 2971-2983, 2011.
  • Gabrilovac J., Čupić B.,Živković E., Horvat L., Majhen D. Expression, regulation and functional activities of aminopeptidase N (EC 3.4.11.2 ; APN ; CD13) on murine macrophage J774 cell line. Immunobiology. 216, 1/2; 132-144, 2011.
  • Helbig L., Damrot J., Hülsenbeck J., Köberle B., Brozović A., Osmak M., Fiket Ž., Kaina B., Fritz G. Late activation of stress-activated protein kinases/C-JUN-N- terminal kinases triggered by cisplatin-induced DNA damage repair defective cells. The Journal of Biological Chemistry. 286, 15; 12991-13001, 2011.
  • Majhen D., Stojanović N., Špeljko T., Brozović A., De Zan T., Osmak M., Ambriović-Ristov A. Increased expression of the coxsackie and adenovirus receptor downregulates alpha v beta 3 and alpha v beta 5 integrin expression, reduces cell adehesion and migration. Life Sciences. 89: 241-249, 2011.
  • Brozovic A., Ambriović-Ristov A., Osmak M. The relationship between cisplatin-induced reactive oxygen species, glutathione and BCL-2, and resistance to cisplatin. Critical Reviews in Toxicology. 40(4): 347-359, 2010.
  • Majhen D*, Brozovic A*, Buger T, Gabrilovac J, Osmak M, Ambriović-Ristov A. Vincristine-resistant human laryngeal carcinoma cells demonstrate increased Rous sarcoma virus promoter activity. Life Sciences. 87(15-16):468-474, 2010.  *equal contribution
  • Burja B., Čimbora-Zovko T., Tomić S., Jelušić T., Kočevar M., Polanc S., Osmak M. Pyrazolone-fused combretastatins and their precursors: synthesis, cytotoxicity, antitubulin activity and molecular modeling studies. Bioorganic & Medicinal Chemistry. 18: 2375-2387, 2010.
  • Cimbora-Zovko T., Fritz G., Mikac N., Osmak M. Downregulation of RhoB GTPase confers resistance to cisplatin in human laryngeal carcinoma cells. Cancer Letters.  295:182-190, 2010.

 

2008-2009

  • Brozović A., Damrot J., Tsaryk R., Helbig L., Nikolova T., Hartig C., Osmak M., Roos W., Kaina B., Fritz G. Cisplatin sensitivity is related to late DNA damage processing and checkpoint control rather than to the early DNA damage response. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 670, 1-2; 32-41, 2009.
  • Majhen D., Nemet J., Richardson J., Gabrilovac J., Hajsig M., Osmak M., Eloit M., Ambriović-Ristov A. Differential role of αvβ3 and αvβ5 integrins in internalization and transduction efficacies of wild type and RGD4C fiber-modified adenoviruses. Virus Research. 139(1): 64-73, 2009.
  • Brozović A., Majhen D, Roje V., Mikac N., Jakopec S., Fritz G., Osmak M., Ambriović-Ristov A. αvβ3 integrin mediated drug resistance in human laryngeal carcinoma cells is caused by glutathione dependent elimination of drug induced reactive oxidative species. Molecular Pharmacology. 74: 298-306, 2008.

 

2006-2007

  • Brozović A., Osmak M. Activation of mitogen-activated protein kinases by cisplatin and their role in cisplatin-resistance. Cancer Letters. 251 (2007), 1; 1-16, 2007.
  • Čimbora-Zovko T., Ambriović-Ristov A.; Lončarek J., Osmak M.: Altered cell-cell adhesion in cisplatin-resistant human carcinoma cells: A link between b-catenin/plakoglobin ratio and cisplatin resistance. European Journal of Pharmacology. 558: 27-36, 2007.
  • Zisowsky J., Koegel S., Leyers S., Devarakonda K., Kassack M., Osmak M., Jaehde U. Relevance of drug uptake and efflux for platinum sensitivity of tumour cells. Biochemical Pharmacology. 73, 2; 298-307, 2007.
  • Jakopec S., Dubravčić K., Polanc S., Košmrlj J., Osmak M.: Diazene JK-274 induces apoptosis-like cell death in human cervical carcinoma cells. Toxicology In Vitro. 20:217-226, 2006.
  • Majhen D., Ambriović-Ristov, A. Adenoviral vectors-how to use them in cancer gene therapy, Virus Research. 119: 121-133, 2006.
  • Majhen D., Gabrilovac J., Eloit M., Richardson J., Ambriović-Ristov A. Disulfide bond formation in NGR fiber-modified adenovirus is essential for retargeting to aminopeptidase N. Biochemical and Biophysical Research Communications. 348: 278-287, 2006.

Ana Dekanić
mag.biol.mol.

asistent
+385 1 456 1145
1545 1876

Anamaria Brozović
dr. sc.

viši znanstveni suradnik
+385 1 456 1145
1545 1877

Andreja Ambriović Ristov
dr. sc.

znanstvena savjetnica
+385 1 457 1240
1543 1545

Dragomira Majhen
dr.sc.

znanstvena suradnica
+385 1 456 1145
1545 1876

Mladen Paradžik
dr.sc.

Viši asistent
+385 1 456 1145
1545 1876

Nikolina Stojanović
dr.sc.

viši asistent
+385 1 456 1145
1545 1876

Sanjica Rak
dr.sc.

viši asistent
+385 1 457 1293
1545 1305

Tihana De Zan
dipl. ing.

Znanstveni novak u suradničkom mjestu asistenta
+385 1 456 1145
1545 1305