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Division of Molecular Medicine

The mission of the Division of Molecular Medicine is to expand and enhance our knowledge of the nature of diseases and to develop and improve new strategies for the diagnosis, treatment and prevention of disease.

Administration 

Ankica Vratarić

tel.+385-1-4561-114, fax.+385-1-4561-010

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The mission of DMM is closely correlated with the major areas of human medicine, covering a broad spectrum reflected in the name of its laboratories. The majority of research topics have been oriented to the molecular aspects of cancer, neuroscience (neuropsychiatry, neurodegeneration, neuropharmacology), stress-related diseases and their models. Particular attention and research has been devoted to  mechanisms of disease etiology through disturbed methylation of macromolecules (DNA/proteins), molecular mechanisms of disease etiopathogenesis and experimental therapy. The DMM, with its Human Tumor Bank and numerous  clinical samples collected through collaborations with clinicians (e.g. in neuropsychyatry and neurodegeneration), represents an important biomedical core, dedicated to establishing and refining new strategies and methods for understanding the molecular mechanisms of disease, for improving diagnostic procedures and therapies and, of primary importance, for disease prevention.

Our facility breeds inbreed strains of mice (BALB/cBkl, CBA/H, C3Hf/Bu, C57BL/Go, C57BL/6-Ly5, NOD, Hsd:ICR (CD-1)) for the research projects conducted mainly in Rudjer Boskovic Institute. In our animal unit two colonies of rats are developed from the Wistar stock, i.e. “Hyperserotoninemic rat” and “Wistar-Zagreb 5HT rat”. Both models are used in neuroscience research as rodent models for selected neuropsychiatric disorders as well as in related neuropsychopharmacological research.

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Grupa za Translacijsku Medicinu koristi bolest nedostatka SAHH kao modelni sistem za proučavanje dinamičnih procesa u ljudskom epigenomu, t.j. istraživanje metilacija DNA i proteina.

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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
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The focus of the Laboratory for Neurodegenerative Disease Research (LAND) is to elucidate the molecular mechanism(s) of Alzheimer's disease and other neurodegenerative disorders. In our research we use wide range of cell lines, primary neuronal cultures, organotypic slice culture and different mouse models.

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Major activities

  • Studies on physiology and pathology of oxidative stress and in particular lipid peroxidation
  • Molecular aspects of growth regulating activities of lipid peroxidation product 4-Hydroxynonenal (HNE)
  • Experimental diagnostics and therapies of malignant diseases associated with oxidative stress
  • Experimental therapies of cancer
  • Cell and tissue culture models
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Research conducted in the LPMed involves the study of molecular and genetic mechanisms underlying colorectal cancer development and progression as well as pharmacogenetic studies associated with the effectivness and toxicity of cancer therapies.

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The research activities of the laboratory are based on research and understanding of protein dynamics as the key determinant for the formation and development of tumors, metastasis, determining the therapeutic target and the basis for their response to therapy.

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Research activity in LET has been dealing with tumor cells and their response to therapy.

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Laboratory of Molecular Neuropsychiatry investigates the role of endocrine and neurotransmitter systems and their corresponding genes in the etiology and treatment of neuropsychiatric and stress related disorders.

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The lab focuses on molecular analysis of infectious diseases, primarily human papillomaviruses (HPV) and cervical cancer

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Amela Hozić
dr. sc.

Senior professional associate

Ana Čipak Gašparović
PhD

research associate
+385 1 456 1017
1520 1705

Ana Šarić
PhD

senior assistant
+385 1 456 1172
1572

Anđela Horvat
B.Sc.

PhD student (assistant)
+385 1 456 0997
1752 1754

Ankica Vratarić

+385 1 468 0094
1514 1610

Diana Trnski
B.sc.

Junior researcher
1849

Dubravka Švob Štrac
Ph.D.

Senior Research Associate
+385 1 457 1365
1749

Emilija Zapletal
PhD

senior assistant
+385 1 457 1383
1557 1731

Goran Goleš

+385 1 456 0950
1815 1813

Gordana Jurinić

+385 1 456 1011
1611

Gordana Nedić Erjavec
PhD

Senior assistant
+385 1 457 1265
1818

Iva Pešun Međimorec

+385 1 456 1172
1572

Iva Škrinjar
PhD

Postdoc
+385 1 456 1064
1507

Ivan Sabol
PhD

Research associate
+385 1 456 1110
1510

Jasminka Golubić Talić

+385 1 456 1110
1510

Jelena Knežević
dr.sc.

Research associated
+385 1 456 0964
1736

Josipa Vlainić
Ph.D.

assistant
+385 1 457 1268
1838

Katja Ester
PhD

Research associate
1772 1285

Koraljka Gall Trošelj
MD, Ph.D.

Senior Research Associate
+385 1 456 0972
1552

Kristina Dominko

+385 1 457 1284
1841

Lidija Milković
PhD

Postdoc
1520 1764

Magdalena Grce
PhD

Senior Scientist
+385 1 456 1110
1510 1509

Maja Herak Bosnar
PhD

senior research associate
+385 1 456 0996
1752

Maja Jazvinšćak Jembrek
PhD

Research Associate
+385 1 456 0997
1753

Maja Pokas

+385 1 456 0950
1815 1813

Maja Sabol
PhD

research associate
+385 1 456 0997
1753 1849

Maja Šutić

1811

Marijana Popović Hadžija
PhD

Research Associate
+385 1 456 1064
1507

Marijeta Kralj
PhD

Senior scientist
+385 1 457 1235
1789 1773

Marina Marš

+385 1 456 1064
1507

Mario Cindrić
dr. sc.

senior research associate

Marko Košiček
PhD

assistant
+385 1 457 1284
1841

Marko Marjanović
PhD

Research associate
1772 1285

Martina Pehar

+385 1 456 1113
1513 1754

Matea Nikolac Perković
PhD

research assistant
1818

Mirela Baus Lončar
PhD

Senior Research Associate
+385 1 457 1284
1841

Mirko Hadžija

+385 1 456 1064
1507 1524

Morana Jaganjac
PhD

Research Associate
+385 1 457 1212
1520 1764

Neda Slade
Ph.D.

senior scientist
+385 1 456 0926
1511

Nela Pivac
DVM, PhD

senior scientist
+385 1 457 1207
1321 1749
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Neven Žarković
MD,PhD

Senior Scientist, Professor
+385 1 456 0937
1607 1790

Oliver Vugrek
PhD

Research associate
+385 1 457 1381
1649
+385-(0)914680778

Paško Konjevoda
Ph.D.

Research associate
+385 1 468 0193
1334

Petar Ozretić
PhD

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

Ranko Stojković
PhD., D.M.V.

Senior scientist
LAS Director
+385 1 456 0992
1704
+385 91 514 1256

Renata Novak Kujundžić
D.V.M., Ph.D.

Research Associate
+385 1 456 0949
1343 1714

Sandra Sobočanec
PhD

Senior Research Associate
+385 1 456 1082
1612

Sanja Kapitanović
MD, PhD

Senior Scientist
+385 1 456 1108
1611 1508

Silva Katušić Hećimović
Doc, Ph.D.

Senior Research Associate
+385 1 457 1327
1593 1841

Siniša Ivanković
PhD

+385 1 456 0950
1816 1815

Snježana Juler

+385 1 457 1284
1841

Snježana Jurilj

1850

Sonja Levanat
Ph.D.

principal investigator
+385 1 457 1267
1551

Suzana Borović Šunjić
PhD

senior research associate
+385 1 457 1212
1520 1764

Tamara Čačev
PhD, MBA

Senior research associate
+385 1 457 1383
1557

Tanja Matijević Glavan
PhD

senior assistant
+385 1 457 1384
1558

Tea Kečkeš
Life science technician

+385 1 457 1212
1520 1737

Tea Vuković

+385 1 457 1212
1520 1737

Tihomir Balog
PhD

senior scientist
+385 1 457 1337
1560

Tina Catela Ivković
B.Sc.

Assistant, PhD student
+385 1 456 1108
1611

Vesna Musani
PhD

research associate
+385 1 457 1292
1849

Višnja Novalić

+385 1 456 0950
1815 1813

Višnja Stepanić
Ph.D.

+385 1 457 1248
1763

Vjekoslav Tomaić

+385 1 456 1110
1510

Zlatko Panđić

+385 1 456 0950
1848
MultiCaST Work Packages scheme

A multidisciplinary approach to discover selective drugs targeting cancer stem cells: The role of potassium transport - MultiCaST

Glavni istraživač / voditelj: Marijeta Kralj

The main goal of the proposed research is to understand cancer stem cell (CSC) biology and to develop novel CSC-directed compounds. We will strive to elucidate the molecular basis of potassium ion transport involvement in CSC-phenotype acquisition, modulation and targeting and identify key mechanisms of these processes as novel biomarkers for improved diagnostic options and innovative mechanism-based therapeutic approaches.

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Alzheimer's disease - the role of cholesterol on processing and localization of APP-family members

Alzheimer's disease - the role of cholesterol on processing and localization of APP-family members

Glavni istraživač / voditelj: Silva Katušić Hećimović

This project aims to analyze whether the molecular mechanisms of the cholesterol effect on APP and amyloid-β peptide (Aβ) may involve APP-family members, APLP1 and APLP2.  We will elucidate whether cholesterol affects processing of APLP1 and APLP2, like APP, and whether the cholesterol effect on APP is mediated by APLP1/2-regulated trafficking of APP.

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BIOXYARN – In vitro evaluation of the biocompatibility of nanofibrous yarns from an oxidative stress perspective

Glavni istraživač / voditelj: Neven Žarković

Fibres and textiles have been used as biomaterials for thousands of years, mainly as sutures and in dressings for wound care. Recently, it has become of increasing interest to use fibres as implantable materials to support the repair of damaged tissues and organs.

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BrainProtect - Presenilin 2 - a protector against Alzheimer's disease

BrainProtect - Presenilin 2 - a protector against Alzheimer's disease

Glavni istraživač / voditelj: Silva Katušić Hećimović

Marie Curie Actions - Intra-European Fellowship for Career Development (IEF)

FP7-PEOPLE-2013-IEF

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Elucidating BACE1 as a potential target for treating Niemann-Pick type C disease

Elucidating BACE1 as a potential target for treating Niemann-Pick type C disease

Glavni istraživač / voditelj: Silva Katušić Hećimović

BACE1 The β-secretase, known as β-site amyloid precursor protein cleavage enzyme 1 (BACE1), plays a central role in Alzheimer’s disease (AD) pathogenesis as it initiates processing of APP and the production of the toxic amyloid-β peptides (Aβ) that accumulate in the brains of AD patients. BACE1 has become a prime therapeutic target for lowering Aβ, and clinical development of BACE1 inhibitors is being intensely pursued as avenue for treatment of AD. Interestingly, a rare inherited - yet untreatable - lysosomal storage disorder Niemann-Pick type C (NPC) and AD have several key features in common. We have recently shown that APP cleavage by BACE1 is significantly enhanced in NPC1-model cells vs. wt cells..In light with the recently discovered similarities between AD and NPC, the goal of this project is to elucidate the role of BACE1 in the pathogenesis of NPC and whether BACE1 may represent a novel target for treating/ameliorating NPC disease.

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Elucidating BACE1-substrate processing and distribution in a transgenic mouse model of Alzheimer’s disease

Elucidating BACE1-substrate processing and distribution in a transgenic mouse model of Alzheimer’s disease

Glavni istraživač / voditelj: Silva Katušić Hećimović

Recent failures of clinical trials against Alzheimer’s disease (AD) with γ-secretase inhibitors have shifted the focus to BACE1 as a key AD drug target. However, the complex phenotypes of BACE1-null mice and the numerous recently identified BACE1 substrates suggest that the inhibition of BACE1 may cause unacceptable side-effects. This emphasizes the need to investigate more thoroughly the mechanisms of action of this enzyme and the functions of its substrates. The goal of this project is to characterize the processing and distribution of the two top BACE1 substrates, seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L) in a transgenic (tg) mouse model of Alzheimer’s disease. In line with the recently identified accumulation of BACE1 in human and tg-mouse AD brains we propose that accumulation of BACE1 within presynaptic terminals and enhanced cleavage of its substrates at or near the synapse, in addition to APP, may add to synaptic (dys)function, learning and memory deficits, neurodegeneration and the pathogenesis of Alzheimer’s disease. 

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Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development - InnoMol

Glavni istraživač / voditelj: Oliver Vugrek

The largest infrastructure project with the highest budget in natural sciences ever to be conducted in Croatia will foster a research pipeline at the RBI and facilitate innovation and technology for the investigation of relevant diseases such as cancer.

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Epigenetic changes in head and neck squamous cell carcinoma

Glavni istraživač / voditelj: Magdalena Grce

This project is a comprehensive interdisciplinary research on the basis of HNC development and potential new approaches for their diagnosis and treatment.

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Genetic factors as markers of suicide

Glavni istraživač / voditelj: Nela Pivac
Lysosomal dysfunction as a common mechanism of neurodegenerative diseases

Lysosomal dysfunction as a common mechanism of neurodegenerative diseases

Glavni istraživač / voditelj: Silva Katušić Hećimović

Using a lysosomal disorder NPC as a model, the goal of this project is to investigate a role of lysosomal impairment on accumulation of amyloid-beta peptide (Abeta) and alpha-synuclein (a-syn), the two characteristic features in the pathogenesis of AD and PD.

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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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Molecular basis and treatment of psychiatric and stress related disorders

Glavni istraživač / voditelj: Nela Pivac

Stress related (acute stress reaction, posttraumatic stress disorder) and eating disorders, addictions (alcoholism), aggressive/suicidal behavior, and attention deficit hyperactivity disorder are frequent multifactorial and polygenic psychiatric disorders that induce a great suffering in patients and their families, and carry financial burden to the whole society. Molecular basis of these disorders involves the changes in neurotransmitter (primarily serotonin - 5-HT, noradrenalin, dopamine) and neuroendocrine systems, and functional gene polymorphisms controlling  the activity of the corresponding proteins.

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Molecular genetics and pharmacogenetics of gastrointestinal tumors

Glavni istraživač / voditelj: Sanja Kapitanović

The main goal of this study is to investigate hereditary and sporadic genetic changes in benign and malignant gastrointestinal tumors in order to elucidate the mechanisms of their development and progression. Another goal of this study is to start with prospective pharmacogenetic study in order to examine the correlation between known polymorpisms and gastrointestinal cancer therapy.

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Molecular mechanism(s) of cholesterol-effect on APP and BACE1 metabolism  - the two key proteins of Alzheimer's disease

Molecular mechanism(s) of cholesterol-effect on APP and BACE1 metabolism - the two key proteins of Alzheimer's disease

Glavni istraživač / voditelj: Silva Katušić Hećimović

The goal of this project was to further elucidate the mechanism/s of cholesterol-effect on the metabolism of APP and BACE1 – the two key proteins in the pathogenesis of Alzheimer's disease. Using biochemical, molecular biological and cell biological approaches we have tested the hypotheses that alterations in cholesterol metabolism (due to NPC1 dysfunction) contribute to accumulation of Abeta and the pathogenesis of AD by modulating endocytic trafficking of BACE1 and/or by modulating lysosomal/autophagic function. 

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Molecular mechanism(s) of neurodegeneration in  Niemann-Pick type C disease

Molecular mechanism(s) of neurodegeneration in Niemann-Pick type C disease

Glavni istraživač / voditelj: Silva Katušić Hećimović

The goal of this project is to elucidate the molecular mechanism(s) of neurodegeneration in Niemann-Pick type C disease (NPC). We will investigate the role of protease BACE1, the key Alzheimer's disease (AD) enzyme, in the pathogenesis of NPC disease. We hope that our findings will elucidate BACE1 as a novel target for treating/ameliorating NPC disease.

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Nemo6 - Structure, Function and Evolution of Nme6/Nm23-H6 Protein

Nemo6 - Structure, Function and Evolution of Nme6/Nm23-H6 Protein

Glavni istraživač / voditelj: Maja Herak Bosnar

Nucleoside-diphosphate kinases (Nme/Nm23/NDPK) constitute a family of evolutionary conserved enzymes involved in many crucial biological processes. The family consists of ten members divided in two groups. Group I, which encompasses Nme1-Nme4, has been extensively studied, especially Nme1 in the context of metastasis formation. The Group II members are evolutionary older, especially the Nme5, Nme6 and Nme7 and little is known about their structure and function. Numerous proteins from evolutionary distinct organisms exhibit extraordinary similarity in primary structure with their orthologues in mammals including humans, as do their predicted secondary and tertiary structures. Therefore, it is presumed that they have similar or identical biochemical and biological functions. Building upon our previous work on the human and sponge Nme family proteins, the proposed project will focus on resolving the structure, as well as biochemical and biological functions of the human Nme6 and its changes during evolution. We will employ a range of biochemical methods and combine them with modern molecular biology methods supported by advanced confocal microscopy techniques.

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Pharmacogenomics and proteomics of serotonergic and catcholaminergic system

Glavni istraživač / voditelj: Dorotea Mueck Šeler

Serotonergic and catecholaminergic (dopaminergic, noradrenergic) neurotransmitter systems regulate physiological functions and are also connected to the etiology of complex and polygenic neuropsychiatric disorders (Alzheimer’s disease /AD/, frontotemporal dementia, schizophrenia and depression). Etiology and psychobiological mechanisms of neuropsychiatric disorders is not well understood, but could be the result of interaction of genetic factors, specific proteins and environment.

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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.

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Stress, GABA-A receptors and mechanisms of action of neuropsychoactive drugs

Stress, GABA-A receptors and mechanisms of action of neuropsychoactive drugs

Glavni istraživač / voditelj: Dubravka Švob Štrac

The purpose of the present research is to improve our understanding of the mechanisms of action of neuropshycoactive drugs, especially during their chronic administration and modification by stress. Particular emphasis is placed on the research of benzodiazepines and antidepressants, used to treat anxiety, insomnia and depression, which are acting via GABAergic and serotonergic systems in the brain. Therefore, we investigate the changes in the expression and function of GABA-A receptor in vitro after prolonged exposure to benzodiazepines, known to induce the development of tolerance and dependence. Moreover, by using experimental animals, we have been also investigating the interactions between the effects of stress and benzodiazepines and antidepressants, primarily on the susceptibility to convulsions, as well as the role of the serotonergic system in controlling brain excitability.

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SuMERA - Sirtuin 3 as a mediator of mitochondrial function in estrogen-dependent resistance to oxidative stress and high-fat diet

SuMERA - Sirtuin 3 as a mediator of mitochondrial function in estrogen-dependent resistance to oxidative stress and high-fat diet

Glavni istraživač / voditelj: Tihomir Balog

Investigation of the role of SIRT3 on mitochondrial function in E2-dependent resistance to oxidative stress both in vitro and in vivo.

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Tff3 protein at intersection of metabolism and neurodegeneration

Tff3 protein at intersection of metabolism and neurodegeneration

Glavni istraživač / voditelj: Mirela Baus Lončar

In this project  proposal we will investigate impact of Tff3 protein in liver/brain axis using Tff3 -/-mouse strain and modeling Type 1 and Type 2 diabesity conditions. We will correlate  the effect  of Tff3 deficiency on liver as major metabolic organ,  and hippocampus/cortex as affected brain regions is AD, monitoring neurodegenerative hallmarks and endoplasmatic reticulum stress markers. Using novel technology (XFe96 Extracellular Flux Analyzer) we will estimate impact of Tff3 on mitochondrial respiration and glycolysis in living primary hepatocytes. This systemic approach will help us understand common pathways in diabesity and neurodegeneration and possibly reveal novel therapeutic targets.

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The mechanism of cholesterol action in the pathogenesis of Alzheimer’s disease

The mechanism of cholesterol action in the pathogenesis of Alzheimer’s disease

Glavni istraživač / voditelj: Silva Katušić Hećimović

Recent studies reveal that cholesterol may play a role in the pathogenesis of Alzheimer’s disease (AD). The goal of this project is to elucidate the mechanism(s) of cholesterol-effect on APP metabolism, formation of amyloid-β peptide (Aβ)  and the genesis of Alzheimer’s disease. We speculate that cholesterol regulation of membrane and protein trafficking along the endocytic pathway leads to amyloidogenic processing of APP and Aβ formation.

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The molecular links between cholesterol homeostasis, membrane trafficking and Alzheimer's disease

The molecular links between cholesterol homeostasis, membrane trafficking and Alzheimer's disease

Glavni istraživač / voditelj: Silva Katušić Hećimović

Aberrant proteolytic cleavage of the amyloid precursor protein (APP) leading to increased formation/accumulation of β-amyloid peptide (Aβ) is considered a central event in the pahogenesis of Alzheimer's disease (AD). Although much has been known about the Aβ generation and its clearance, we still do not understand in great detail how Aβ metabolism is altered in the most common late-onset form of AD (LOAD) and what are the molecular trigger(s) that initiate these events. In this project we will test the hypothesis that cholesterol metabolism and membrane trafficking are tightly linked and that their dysregulation leads to Alzheimer's disease. 

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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)

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Screening for mutations in the ret proto-oncogene

This genetic analysis is indicated in all newly diagnosed medullary thyroid patients in order to exclude or confirm the existance of an inherited mutation. These analyses are based on the contract between  Clinical Hospital Center "Sister of Charity" and Rudjer Boskovic Institute.

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Item
Location
Contact
Florimeter i Luminometer Biology II
Maldi TOF/TOF Planinska 1
Luminex Lx100 IS 2.3  
Applied Biosystems 7300 Real-time PCR System V K, II floor, 301
ALLIANCE XD-79LS-26MX, 230V EU V K, II floor, 307A
Jasminka Pavelić - You do not have permission to view this object.
High-Pressure Homogenizator (MSES) Biology I

Oliver Vugrek

Oliver.Vugrek@irb.hr
+385 1 457 1381
+385-(0)914680778
High resolution microarray scanner
Microarray spotter robot
Bioanalyzer
-80 C freezer
ABI PRISM 310 Genetic Analyzer V K, basement, 002B
HR-1 High Resolution DNA melting instrument
Qubit fluorometer
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