members of laboratory

Laboratory for Hereditary Cancer

Major research directions of the Laboratory for Hereditary Cancer are:

  • Basic scientific research of signal transcduction with special emphasis on implementation of new research technologies;
  • Applied scientific research of cancer and hereditary diseases focused on procedures which can be used in diagnostics of hereditary diseases and cancer therapy;
  • Development of bioinformatics and in silico modeling based on the results of main research directions
Sonja Levanat

Head

Ph.D. Sonja Levanat

+385 1 457 1267
Fax: +385 1 456 1010
left right

Major research directions of the Laboratory for Hereditary Cancer are:

  • Basic scientific research of signal transcduction with special emphasis on implementation of new research technologies;
  • Applied scientific research of cancer and hereditary diseases focused on procedures which can be used in diagnostics of hereditary diseases and cancer therapy;
  • Development of bioinformatics and in silico modeling based on the results of main research directions

The major focus of our research activities is the Hh-Gli signaling pathway, also known Hh-Ptc, Hh/Ptc/Smo,  Hedgehog-Gli or Hedgehog-Patched. It is an evolutionary highly conserved pathway of signal transduction from the cell membrane to the nucleus. The pathway plays a major role in normal development, and its malfunctioning is associated with developmental malforamtions and cancer.

The aims of our research are mechanisms of aberrant Hh-Gli signaling pathway activation in selected tumors (including interactions with other genes and signaling pathways) as well as potential inhibition of tumor growh via inhibtion of the pathway. Epigenetic regulation of the Hh-Gli signaling pathway is also being investigated, and have so far resulted in a hypothesis that PTCH1 gene promoter methylation is one of the possible regulatory mechanisms.

Based on latest estimates, this signaling pathway is involved in almost 1/3 of all lethal tumors, and is becoming a relevant target for potential cancer therapy. Our experiments on pathway inhibition have contributed to this hypothesis. This points to the extreme importance of further research on mechanisms leading to aberrant activation of the pathway, as well as the searc for new potential inhibitors.

Applied research is focused on hereditary breast cancer, especially BRCA1 and BRCA2 genes. The analysis of these two genes can be used in early diagnostics and therapy of breast cancer, and the new methods used for their analysis could also be used for other tumors and hereditary diseases. The method for BRCA1 and BRCA2 mutation detection has been commercialized, and additional genes relevant for breast cancer development may soon be included in the analysis (CHEK2...).

Within the laboratory we have a service for DNA sequencing and fragmental analysis which is available for the public.

Ruđer Innovations and Medikol Polyclinic have founded a spin-off company Ruđer Medikol diagnostics which performs genetic testing for hereditary breast and ovarian cancer.

Diana Trnski
PhD

Senior research assistant
1849 1512

Maja Sabol
PhD

research associate
+385 1 456 1110
1849 1510

Petar Ozretić
Asst. Prof., PhD

Research Associate
+385 1 457 1292
1849
+385 98 659 083

Sonja Levanat
Ph.D.

principal investigator
+385 1 457 1267
1551

Vesna Musani
PhD

research associate
+385 1 457 1292
1849
GLIcode - Differential regulation of the GLI code in BRAF/NRAS driven tumors

GLIcode - Differential regulation of the GLI code in BRAF/NRAS driven tumors

Glavni istraživač / voditelj: Maja Sabol

The Hedgehog signaling pathway has been implicated in development of various tumors, but the exact roles and molecular mechanisms are still not understood. The focus of this research are the tumors harboring BRAF or NRAS mutations, and their differential response to Hedgehog pathway inhibition. Both BRAF and NRAS non-canonically activate the three GLI proteins, but the activity and interplay of this interaction is still unclear. With this project we propose to determine the exact transcriptional targets of GLI1, GLI2 and GLI3 proteins in melanoma with different genetic backgrounds, either harboring a BRAF mutation, a NRAS mutation, or no mutation in these two genes.

more »
MIRnaGLI - Novel Molecular Mechanisms for New Therapeutic Approaches: Interactions of microRNAs and Hedgehog-GLI Signaling Pathway in Serous Ovarian...

MIRnaGLI - Novel Molecular Mechanisms for New Therapeutic Approaches: Interactions of microRNAs and Hedgehog-GLI Signaling Pathway in Serous Ovarian...

Glavni istraživač / voditelj: Sonja Levanat

Serous ovarian cancer is urgent clinical problem whose molecular background is still unknown. Our previous studies showed aberrant activity of the Hedgehog-GLI (Hh-Gli) signaling pathway in ovarian tumors, but we have shown that aberrant activity is neither the result of mutations nor of promoter hypermethylation of the main pathway regulators. The next to study are microRNAs (miRNAs), one of the main regulators in post-transcriptional regulation of gene expression. Our hypothesis is that changes in the expression of miRNA molecules related to the Hh-Gli signaling pathway contribute to the development of high-grade serous ovarian cancer.

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ProNetMel - New Protein Networks for Novel Therapeutic Avenues in Human Melanoma

ProNetMel - New Protein Networks for Novel Therapeutic Avenues in Human Melanoma

Glavni istraživač / voditelj: Neda Slade

The main focus of this project is to reveal interactions of p53 with protein partners in melanoma that are capable of modifying its function. We are particularly interested in possible interactions of p53 with family members, namely p53 and p73 isoforms, with nm23, especially nm23-H1 and nm23-H2, and Gli family of proteins.

more »

DNA Sequencing and Fragmental Analysis

DNA Sequencing and Fragmental Analysis 

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Genetic Testing for Hereditary Breast and Ovarian Cancer (BRCA1 and BRCA2 Genes)

Genetic Testing for Hereditary Breast and Ovarian Cancer (Analysis of BRCA1 and BRCA2 Genes)

more »

Doctoral Thesis

Diana Trnski
Uloga protein-kinaze GSK3β u aktivaciji signalnog puta Hedgehog-Gli u stanicama karcinoma debelog crijeva čovjeka
Zagreb: University Postgraduate Interdisciplinary Doctoral Study of Molecular biosciences: Josip Juraj Strossmayer University of Osijek, University of Dubrovnik, Ruđer Bošković Institute, 24/03/2015 Mentor: Sonja Levanat

Petar Ozretić
Functional Analysis of the 5' Untranslated Region of the PTCH1 gene, transcript variant 1b
Zagreb: University Postgraduate Interdisciplinary Doctoral Study of Molecular biosciences: Josip Juraj Strossmayer University of Osijek, University of Dubrovnik, Ruđer Bošković Institute, 28/05/2013 Mentors: Sonja Levanat; Alberto Inga

Ivana Maurac
Signalni put Hh-Gli i njegova interakcija s genima BRCA1 i BRCA2 u zloćudnim epitelnim novotvorinama jajnika/doktorska disertacija
Zagreb: University of Zagreb School of Medicine, 15/12/2011 Mentor prof. dr. sc. Slavko Orešković, suradnik na projektu

Ante Gojević
Ekspresija izoformi onkogena Gli u sporadičnim karcinomima debelog crijeva
Zagreb: Faculty of Science, 12/12/2011 Mentor: Sonja Levanat

Zvonimir Užarević
Aktivnost signalnog puta Hh-Gli u estrogen ovisnim (MCF-7) i estrogen neovisnim (Sk-Br-staničnim linijama tumora dojke
Osijek: University Postgraduate Interdisciplinary Doctoral Study of Molecular biosciences: Josip Juraj Strossmayer University of Osijek, University of Dubrovnik, Ruđer Bošković Institute, 25/10/2011 Mentors: Sonja Levanat; Lidija Beketić-Orešković

Držislav Kalafatić
Aktivacija Hh-Gli signalnog puta u zloćudnim epitelnim tumorima jajnika
Zagreb: University of Zagreb School of Medicine, 09/03/2011 Mentor prof. dr. sc. Slavko Orešković, suradnik na projektu

Maja Sabol
Mehanizmi aktivacije signalnog puta Hh-Gli u primarnim kulturama dermoida jajnika
Zagreb: Faculty of Science, 17/06/2010 Mentor: Sonja Levanat

Dinko Leović
Ekspresija i značaj Hedgehog signalnog puta u karcinomima usne šupljine i orofarinksa
Zagreb: University of Zagreb School of Dental Medicine, 01/06/2010 Mentors: Darko Macan; Sonja Levanat

Vesna Musani
Mehanizmi regulacije signalnog puta Hedgehog/Patched/Gli u tumorima i nasljednim oboljenjima
Zagreb: Faculty of Science, 13/05/2008 Mentor: Sonja Levanat

Tonči Stipić
Istraživanje mutacija u novootkrivenom putu prijenosa signala u sporadičnih i nasljednih bazeocelularnih karcinoma kože
Zagreb: University of Zagreb School of Medicine, 28/02/2007 Mentors: Mirna Šitum; Sonja Levanat

Diploma Thesis and Final Projects

Nikolina Rinčić
CRISPR/Cas9-mediated generation of GLI1 knock out cell line [Croatian]
Zagreb: Faculty of Science, 11/07/2017 Supervisor: Maja Sabol

Tajana Majić
Uloga polimorfizama gena BIRC5 (survivin) u različitim tipovima tumora jajnika
Zagreb: Faculty of Science, 27/02/2015 Mentor: Vesna Musani

Marina Martinić
Ekspresija proteina Hedgehog-Gli signalnog puta u stanicama karcinoma debelog crijeva
Zagreb: Faculty of Science, 21/09/2011 Mentor: Sonja Levanat

Diana Car
Ekspresija gena signalnog puta Hh-Gli u tumorima kože
Zagreb: Faculty of Science, 06/10/2008 Mentor: Sonja Levanat

Sofia Ana Blažević
Blokiranje signalnog puta Hh-Gli u primarnim kulturama dermoida ovarija
Zagreb: Faculty of Science, 24/01/2007 Mentor: Sonja Levanat

Maja Marković
Funkcionalna i strukturna svojstva gena SMO u tumorima kože
Zagreb: Faculty of Science, 16/11/2007 Mentor: Sonja Levanat

Tamara Tijanić
Razrada i primjena imunokemijske metode u detekciji glavnih proteina signalnog puta Hh-Gli
Zagreb: Faculty of Science, 03/10/2007 Mentor: Sonja Levanat

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