http___www.irb.hr_Istrazivanja_Zavodi_Zavod-za-molekularnu-medicinu_1.xml
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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. Head PhD Tihomir Balog Administration 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.more » 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.more » 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 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.more » 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 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.more » 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.more » Research activity in LET has been dealing with tumor cells and their response to therapy.more » 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.more » The lab focuses on molecular analysis of infectious diseases, primarily human papillomaviruses (HPV) and cervical cancermore » Amela Hozić Ana Čipak Gašparović PhD Ana Šarić PhD Ana-Matea Mikecin Dražić PhD Anđela Horvat Ankica Vratarić Diana Trnski Dubravka Švob Štrac Emilija Zapletal PhD Goran Goleš Gordana Jurinić Gordana Nedić Erjavec PhD Irena Martin Kleiner Iva Pešun Međimorec Iva Škrinjar PhD Ivan Sabol PhD Jasminka Golubić Talić Jelena Knežević dr.sc. Josipa Vlainić Katja Ester PhD Koraljka Gall Trošelj MD, Ph.D. Kristina Dominko Ksenija Božinović mag. mol. biol. Lidija Milković PhD Lidija Uzelac Lucija Kovačević Lucija Tudor Magdalena Grce PhD Maja Herak Bosnar PhD Maja Jazvinšćak Jembrek PhD Maja Pokas Maja Sabol PhD Marcela Konjevod Marija Ćosić Marija Pinterić Marijana Popović Hadžija PhD Marijeta Kralj PhD Marina Marš Mario Cindrić Marko Košiček PhD Marko Marjanović PhD Martina Malnar PhD Martina Pehar Matea Nikolac Perković PhD Mirela Baus Lončar PhD Mirko Hadžija Morana Jaganjac PhD Nathaniel Edward Bennett Saidu Neda Slade Nela Pivac DVM, PhD Neven Žarković MD,PhD Nikolina Hanžić Nina Milutin Gašperov PhD Oliver Vugrek PhD Paško Konjevoda Petar Ozretić PhD Pierre-Alexis Mouthuy DPhil Ranko Stojković PhD., D.M.V. Renata Novak Kujundžić Robert Belužić Sandra Sobočanec PhD Sanja Kapitanović MD, PhD Silva Katušić Hećimović Doc, Ph.D. Siniša Ivanković PhD Snježana Juler Sonja Levanat Suzana Borović Šunjić PhD Tamara Čačev PhD, MBA Tanja Matijević Glavan PhD Tea Kečkeš Life science technician Tea Vuković Tihomir Balog PhD Tina Catela Ivković Vesna Musani PhD Višnja Novalić Višnja Stepanić Vjekoslav Tomaić Zlatko Panđić A multidisciplinary approach to discover selective drugs targeting cancer stem cells: The role of potassium transport - MultiCaST 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.more » Aberrant DNA methylation in HPV associated lesions Alzheimer's disease - the role of cholesterol on processing and localization of APP-family members This project aims to analyze whether the molecular mechanisms of the cholesterol effect on APP and amyloid-B peptide (AB) 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.more » BIOXYARN – In vitro evaluation of the biocompatibility of nanofibrous yarns from an oxidative stress perspective 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.more » BrainProtect - Presenilin 2 - a protector against Alzheimer's disease Marie Curie Actions - Intra-European Fellowship for Career Development (IEF) FP7-PEOPLE-2013-IEFmore » COST Action CM1001 - Chemistry of non-enzymatic protein modification - modulation of protein structure and function COST-Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminerg... Detection and tracking of biological markers for early therapeutic intervention in sporadic Alzheimer's disease Detection and tracking of biological markers for early therapeutic intervention in sporadic Alzheimer's disease Effect of novel Cu-doped 45S5 bioactive glass and lipid peroxidation products on bone regeneration Effects of oxidatively modified collagen on breast cancer stem cell growth and differentiation Elucidating BACE1 as a potential target for treating Niemann-Pick type C disease BACE1 The B-secretase, known as B-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-B peptides (AB) that accumulate in the brains of AD patients. BACE1 has become a prime therapeutic target for lowering AB, 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.more » Elucidating BACE1-substrate processing and distribution in a transgenic mouse model of Alzheimer’s disease Recent failures of clinical trials against Alzheimer’s disease (AD) with Y-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.more » Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development - InnoMol 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.more » Epigenetic and Immunomodulatory Changes in Malignant Head and Neck Tumours Epigenetic changes in head and neck squamous cell carcinoma This project is a comprehensive interdisciplinary research on the basis of HNC development and potential new approaches for their diagnosis and treatment.more » Genetic factors as markers of suicide Improvement of adhesive properties of biomedical materials by plasma treatment Lipids, Free Radicals and their Messengers in Integrative Oncology Lysosomal dysfunction as a common mechanism of neurodegenerative diseases 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.more » MIRnaGLI - Novel Molecular Mechanisms for New Therapeutic Approaches: Interactions of microRNAs and Hedgehog-GLI Signaling Pathway in Serous Ovarian... 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.more » Molecular basis and treatment of psychiatric and stress related disorders 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.more » Molecular genetics and pharmacogenetics of gastrointestinal tumors 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.more » Molecular mechanism(s) of cholesterol-effect on APP and BACE1 metabolism - the two key proteins of Alzheimer's disease 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.more » Molecular mechanism(s) of neurodegeneration in Niemann-Pick type C disease 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.more » Nemo6 - Structure, Function and Evolution of Nme6/Nm23-H6 Protein 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.more » Pharmacogenomics and proteomics of serotonergic and catcholaminergic system 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.more » Pharmacogenomics, proteomics and psychophisiology of neuropsychiatric disorders ProNetMel - New Protein Networks for Novel Therapeutic Avenues in Human Melanoma 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 » Stress, GABA-A receptors and mechanisms of action of neuropsychoactive drugs 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.more » SuMERA - Sirtuin 3 as a mediator of mitochondrial function in estrogen-dependent resistance to oxidative stress and high-fat diet Investigation of the role of SIRT3 on mitochondrial function in E2-dependent resistance to oxidative stress both in vitro and in vivo.more » Tff3 protein at intersection of metabolism and neurodegeneration 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.more » The mechanism of cholesterol action in the pathogenesis of Alzheimer’s disease 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-B peptide (AB) 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 AB formation.more » The molecular links between cholesterol homeostasis, membrane trafficking and Alzheimer's disease Aberrant proteolytic cleavage of the amyloid precursor protein (APP) leading to increased formation/accumulation of B-amyloid peptide (AB) is considered a central event in the pahogenesis of Alzheimer's disease (AD). Although much has been known about the AB generation and its clearance, we still do not understand in great detail how AB 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.more » The role of different cell death responses to DNA-damage treatment The role of Sirtuin1 in non-small cell lung cancer, NSCLC DNA Sequencing and Fragmental Analysis DNA Sequencing and Fragmental Analysismore » 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 » 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.more »
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Zavod za molekularnu medicinu Misija Zavoda za molekularnu medicinu je proširivanje znanja i razumijevanja prirode bolesti čovjeka te poboljšanje i razvijanje novih pristupa dijagnozi, liječenju i prevenciji bolesti. Predstojnik Dr.sc Tihomir Balog Tajništvo Misija Zavoda za molekularnu medicinu je proširiti i ojačati naše poznavanje prirode bolesti, razviti i unaprijediti postojeće te razviti nove strategije za dijagnozu, liječenje i prevenciju bolesti. Ovi ciljevi se ostvaruju kroz istraživanja vezana uz procjene utjecaja genetičkih čimbenika u prevenciji bolesti, smanjenje čimbenika rizika te kroz razvoj i vrednovanje novih lijekova, istraživanje biokemijskih i staničnih učinaka lijekova na stanice i organizme, unapređivanje znanstvene metodologije, i obrazovanja znanstvenika i studenata. Zavod trenutno razvija nekoliko strateških projekata koji uključuju razvoj molekulske ciljane terapije protiv raka i virusnih bolesti, razvoj novih dijagnostičkih alata i istraživanja s ciljem dešifriranja molekularnih osnova bolesti, kao i razvoj alata temeljenih na "-omics" pristupu. Zavod se profilira kao centar izvrsnosti za istraživanja temeljenih na molekularnim pristupima u proučavanju bolesti. Članovi zavoda značajno doprinose visokom obrazovanju u Republici Hrvatskoj kroz pružanje brojnih tečajeva i održavanje nastave na dodiplomskoj i poslijediplomskoj razini u Zagrebu, Splitu, Osijeku, Rijeci, Dubrovniku i Zadru. Laboratorij se bavi različitim aspektima terapije tumora.više » Laboratorij se bavi molekularnim analizama infektivnih bolesti, posebice papiloma virusom čovijeka i rakom vrata materniceviše » Laboratorij za naprednu genomiku ima za cilj omogućiti ubrzani napredak u području genomskih istraživanja naslanjajući se na integraciju rekombinantne DNA tehnologije, funkcionalne genomike te NGS tehnologije.više » Glavna istraživačka usmjerenja Laboratorija za nasljedni rak su: Temeljna znanstvena istraživanja vezana su za prijenos signala uz poseban naglasak na uvođenje novih istraživačkih tehnologija; Primijenjena znanstvena istraživanja vezana uz rak i nasljedne bolesti usmjerena su na razvoj postupaka koji mogu poslužiti u dijagnostici nasljednih bolesti, te u terapiji raka; Razvoj bioinformatike i in silico modela na temelju rezultata glavnih istraživačkih usmjerenja.više » Glavna područja istraživanja su izučavanje fiziologije i patologije oksidacijskog stresa, molekularne značajke regulacije rasta putem 4-hidroksinonenala (HNE), eksperimentalna dijagnostika i terapija zloćudnih bolesti temeljenih na oksidacijskom stresu, bioterapija raka i uzgoj kultura tkiva kosti.više » Znanstvena djelatnost LPMed-a je usmjerena na istraživanja molekularno-genetičke osnove nastanka i napredovanja sporadičnih tumora debelog crijeva te farmakogenetske studije vezane uz učinkovitost ili toksičnost tumorske terapije.više » Istraživačke aktivnosti laboratorija temelje se na istraživanju i razumijevanju dinamike proteina kao ključnoj odrednici za nastanak i razvoj tumora, metastaziranje, određivanje terapeutskih meta i osnova za njihov odgovor na terapiju.više » Pogon laboratorijskih životinja (PLŽ) djeluje u sklopu Zavoda za molekularnu medicinu Instituta «Ruđer Bošković». U Pogonu laboratorijskih životinja se uzgajaju jezgre pet srođenih mišjih sojeva BALB/c, CBA/H C3Hf/Bu, C57BL/6-Ly5 i NOD, kao i jedan nesrođeni soj HSD:ICR (CD-1), te štakori (Wistar Zagreb 5HT - podsoj selekcioniran prema razini perifernog serotonina). Životinje se uzgajaju na način koji omogućava genetsku stabilnost sojeva, a životinje se nalaze pod stalnim veterinarskim nadzorom zdravstvenog stanja.više » Ana Čipak Gašparović dr.sc. Ana Šarić dr. sc. Ana-Matea Mikecin Dražić dr.sc. Anđela Horvat dr. sc. Ankica Vratarić Diana Trnski dipl.inž. Dubravka Švob Štrac dr.sc. Emilija Zapletal dr. sc. Goran Goleš Gordana Jurinić Gordana Nedić Erjavec dr. sc. Irena Martin Kleiner dr.sc. Iva Pešun Međimorec Iva Škrinjar dr.sc. Ivan Sabol Dr. sc. Jasminka Golubić Talić Jelena Knežević dr.sc. Josipa Vlainić dr.sc. Katja Ester dr.sc. Koraljka Gall Trošelj dr. sc. Kristina Dominko mag.biol.mol. Ksenija Božinović mag. mol. biol. Lidija Milković dr.sc. Lidija Uzelac dipl. ing. Lucija Kovačević Lucija Tudor Luka Andrišić dipl.ing Magdalena Grce dr.sc. Maja Boranić Maja Herak Bosnar dr.sc. Maja Jazvinšćak Jembrek dr.sc. Maja Sabol dr.sc. Marcela Konjevod Marija Ćosić Marija Pinterić Marijana Popović Hadžija dr.sc. Marijeta Kralj dr. sc. Marina Marš Mario Cindrić dr. sc. Marko Košiček dr.sc. Marko Marjanović dr.sc. Martina Malnar dr. sc. Martina Pehar Matea Nikolac Perković dr. sc. Mirela Baus Lončar dr.sc. Mirko Hadžija dr.sc. Morana Jaganjac dr. sc. Nathaniel Edward Bennett Saidu Neda Slade dr. sc. Nela Pivac dr sc, znanstveni savjetnik u trajnom zvanju, izvanredni profesor Neven Žarković Nikolina Hanžić mag. biol. mol. Nina Milutin Gašperov dr. sc. Oliver Vugrek dr. sc. Paško Konjevoda dr.sc. Petar Ozretić dr. sc. Pierre-Alexis Mouthuy DPhil Ranko Stojković dr.sc., dr.med.vet. Renata Novak Kujundžić dr.sc. Robert Belužić dr.sc. Sandra Sobočanec dr.sc. Sanja Kapitanović dr.sc., dr.med. Silva Katušić Hećimović doc.dr.sc. Siniša Ivanković dr.sc. Snježana Juler Sonja Levanat dr. sc. Suzana Borović Šunjić dr.sc. Tamara Čačev dr.sc. Tanja Matijević Glavan dr. sc. Tea Kečkeš Tea Vuković Tihomir Balog Dr.sc Tina Catela Ivković dipl.ing. Vesna Musani dr.sc. Višnja Novalić Višnja Stepanić dr.sc. Vjekoslav Tomaić Doc.dr.sc. Zlatko Panđić A multidisciplinary approach to discover selective drugs targeting cancer stem cells: The role of potassium transport - MultiCaST 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.više » Alzheimerova bolest - uloga kolesterola na procesiranje i lokalizaciju obitelji proteina APP Cilj ovog projekta je ispitati je li kolesterol modulira proteolitičku razgradnju i drugih članove obitelji proteina APP, proteine APLP1 i APLP2. Osim toga, ispitat ćemo je li učinak kolesterola na metabolizam proteina APP posredovan djelovanjem proteina APLP1/2 na proteolitičku razgradnju i/ili na unutarstanični transport proteina APP.više » BIOXYARN – In vitro evaluation of the biocompatibility of nanofibrous yarns from an oxidative stress perspective 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.više » BrainProtect - Presenilin 2 - a protector against Alzheimer's disease Marie Curie Actions - Intra-European Fellowship for Career Development (IEF) FP7-PEOPLE-2013-IEFviše » COST Action CM1001 - Chemistry of non-enzymatic protein modification - modulation of protein structure and function COST- Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminer... Djelovanje plazme na poboljšanje adhezivnih svojstava biomedicinskih materijala Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development - InnoMol 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.više » Epigenetic changes in head and neck squamous cell carcinoma This project is a comprehensive interdisciplinary research on the basis of HNC development and potential new approaches for their diagnosis and treatment.više » Epigeničke i imunomodulatorne promjene u zloćudnim tumorima glave i vrata Farmakogenomika i proteomika serotoninskog i kateholaminskog sustava Serotoninski i kateholaminski (dopaminski i noradrenalinski) neurotransmitorski sustavi reguliraju fiziološke funkcije u organizmu, a povezuju se i s etiologijom složenih, poligenetskih neuropsihijatrijskih poremećaja kao što su Alzheimerova bolest (AD), frontotemporalna demencija, shizofrenija i depresija. Etiološka i psihobiološka podloga neuropsihijatrijskih poremećaja nije u potpunosti jasna, a mogla bi biti posljedica međusobnog djelovanja genetskih čimbenika, specifičnih proteina i utjecaja okoline.više » Farmakogenomika, proteomika i psihofiziologija neuropsihijatrijskih poremećaja Znanstveni programviše » Genetski markeri kao pokazatelji suicida Genomski i glikanski biomarkeri PTSP-a (GlikoGenPTSP) Napredak u razumijevanju glikanskih funkcija i struktura može ponuditi nove biomarkere PTSP-a. Rezultati GWAS studija kombiniranih s metodama visoke djelotvornosti, kao što su analize fluorescentno obilježenih glikana, pokazali su da su geni B3GAT1, SLC9A9, MGA5, FUT8, FUT3/FUT6 i HNF1A povezani s glikozilacijom u zdravih osoba iz Hrvatske. Određivanje plazmatskih i IgG N-glikana u PTSP-u, dodatno korigiranih za mogući genetski i epigenetski utjecaj, poboljšat će naše razumijevanje biološke osnove PTSP-a. Cilj predloženog projekta je istražiti povezanost između genetskih, epigenetskih i glikomskih mehanizama odgovornih za otpornost ili ranjivost na razvoj PTSP-a nakon izlaganja traumatskom iskustvu/iskustvima.više » Lipidi, slobodni radikali i njihovi glasnici u integrativnoj onkologiji Mehanizam djelovanja kolesterola u nastanku Alzheimerove bolesti Nedavna istraživanja ukazuju na ulogu kolesterola u nastanku Alzheimerove bolesti (AB). Cilj ovog projekta je utvrditi mehanizam djelovanja kolesterola na metabolizam proteina APP, stvaranje peptida AB i nastanak Alzheimerove bolesti. Pretpostavljamo da regulacijom transporta membrana i proteina u endosomalnom putu kolesterol regulira proteolitičku razgradnju proteina APP i stvaranje peptida AB.više » MIRnaGLI - Novi molekularni mehanizmi kao mete ciljanih terapija: Interakcije molekula mikroRNA i signalnog puta Hedgehog-GLI u seroznom karcinomu j... Serozni karcinom jajnika gorući je klinički problem čija molekularna podloga još nije dovoljno istražena. Naša dosadašnja istraživanja pokazala su promijenjenu aktivnost signalnog puta Hedgehog-GLI (Hh-Gli) u tumorima jajnika, a do sada smo pokazali da ta aberantna aktivnost nije rezultat ni mutacija niti epigenetskih promjena na razini hipermetilacije promotora najznačajnijih regulatora signalnog puta. Daljnji smjer naših istraživanja su molekule mikroRNA (miRNA) koje imaju ključnu ulogu u post-transkripcijskoj regulaciji genske ekspresije. Naša hipoteza je da promjene u ekspresiji molekula miRNA vezane uz signalni put Hh-Gli doprinose nastanku seroznog karcinoma jajnika visokog gradusa.više » Molekularna genetika i farmakogenetika gastrointestinalnih tumora Cilj ovog istraživanja je ispitati nasljedne i sporadične genetske promjene u gastrointestinalnim tumorima radi boljeg razumijevanja mehanizama njihovog nastanka i napredovanja kao i uspostaviti prospektivnu farmakogenetičku studiju kojom bi se ispitala korelacija između poznatih polimorfnih biljega i terapije gastrointestinalnih karcinoma.više » Molekularna podloga i liječenje psihijatrijskih i stresom izazvanih poremećaja Stresom izazvani poremećaji (akutni stresni poremećaj, posttraumatski stresni poremećaj), ovisnosti (alkoholizam), agresivno/suicidalno ponašanje, poremećaji hranjenja i deficit pažnje i hiperaktivni poremećaj su česti, multifaktorijalni i poligenski psihijatrijski poremećaji. Oni izazivaju značajnu patnju bolesnika i njihovih obitelji i opterećuju troškovima cijelo društvo. Molekularna podloga tih poremećaja uključuje promjene neurotransmitorskih (prvenstveno serotonina - 5-HT, noradrenalina, dopamina) i neuroendokrinih sustava i funkcionalne polimorfizme gena koji kontroliraju aktivnost pripadajućih proteina. više » Molekularna povezanost između homeostaze kolesterola, membranskog transporta i Alzheimerove bolesti Molekularni mehanizam djelovanja kolesterola na metabolizam proteina APP i BACE1 - dva ključna proteina Alzheimerove bolesti Cilj ovog projekta je razjasniti mehanizam kojim kolesterol utječe na metabolizam proteina APP i BACE1 - dva ključna proteina u patogenezi Alzheimerove bolesti. Kombinacijom biokemijskih, molekularno bioloških i stanično bioloških pristupa, istražili smo hipotezu da povećana razina kolesterola uzrokovana nefunkcionalnošću proteina NPC1 doprinosi nakupljanju peptida Ab.više » Nedostatak Adenozilhomocistein hidrolaze: Molekularni mehanizmi novog oboljenja Nemo6 - Struktura, funkcija i evolucija proteina Nme6/Nm23-H6 Nukleozid difosfatske kinaze (Nme/nm23/NDPK) čine obitelj evolucijski sačuvanih enzima ključnih za odvijanje brojnih važnih bioloških procesa. Obitelj proteina Nme sastoji se od deset članova podijeljenih u dvije grupe. Grupa I, koja obuhvaća proteine Nme1-Nme4 dosad je intenzivno istraživana, posebno Nme1 u kontekstu stvaranja metastaza. Članovi Grupe II pojavili su se ranije tijekom evolucije, pogotovo Nme5, Nme6 i Nme7 i vrlo su slabo istraženi. Brojni proteini iz evolucijski različitih organizama pokazuju visoku sačuvanost ne samo u primarnoj strukturi već i u predviđenoj sekundarnoj i tercijarnoj strukturi s ortolozima kod sisavaca, uključujući i čovjeka. Stoga se može pretpostaviti da najvjerojatnije imaju slične ili identične biokemijske i biološke funkcije. Predloženi projekt oslanja se na naša prijašnja istraživanja obitelji Nme kod čovjeka i spužvi s ciljem rješavanja strukture, biokemijske i biološke funkcije te evolucije ljudskog Nme6. U tu svrhu koristit ćemo niz biokemijskih metoda u kombinaciji s najnovijim metodama u molekularnoj biologiji te naprednu konfokalnu mikroskopiju.više » Prijenos signala u tumorima: Hh-Gli put, interakcije i potencijalne terapije Signalni put Hh-Gli evolucijski je visoko očuvan put prijenosa signala od stanične membrane do jezgre. Put ima ključnu ulogu u normalnom razvoju, a njegovo poremećeno funkcioniranje povezuje se s razvojnim deformacijama i rakom. Uloga Hh-Gli puta u manjem broju tumora tipičnih za Gorlinov sindrom proučava se već desetak godina, no tek u posljednjih nekoliko godina otkriva se njegovo sudjelovanje u tumorima pluća, dojke, prostate, probavnog trakta i drugima. Cilj predloženog projekta je potvrđivanje hipotetičkih modela poremećenog aktiviranja Hh-Gli puta u odabranim tumorima i razjašnjavanje specifičnih mehanizama aktivacije (uključujući interakcije s drugim genima), a napose istraživanje mogućnosti da se inhibiranjem signalnog puta spriječi rast tumora.više » Promijenjeno stanje DNA-metilacije u HPV-povezanim oštećenjima ProNetMel - Otkrivanje novih proteinskih interakcija kao podloga za nove pristupe liječenju melanoma čovjeka Glavni cilj ovog istraživačkog projekta je u melanomima otkriti interakcije proteina p53 s partnerskim proteinima koji su sposobni mijenjati njegovu funkciju. Posebno smo zainteresirani za moguće interakcije proteina p53 s članovima njegove obitelji kao što su p53- i p73-izoforme; s proteinima nm23, osobito nm23-H1 i nm23-H2; kao i s obitelji proteina Gli.više » Razvoj novih pristupa molekularne i serološke dijagnostike infekcije s humanih papiloma virusima (HPV) Stres, GABA-A receptori i mehanizmi djelovanja neuropsihofarmaka Svrha istraživanja jest unaprijediti spoznaje o mehanizmima djelovanja neuropsihofarmaka, posebice tijekom njihove kronične primjene, te primjene u uvjetima stresa. Poseban naglasak stavljen je na istraživanje benzodiazepina i antidepresiva, koji se koriste u liječenju anksioznosti, nesanice i depresije, a koji u mozgu djeluju putem GABAergičnog i serotoninskog sustava. Stoga u okviru projekta pratimo promjene u ekspresiji i funkciji GABA-A receptorain vitronakon dugotrajnog izlaganja benzodiazepinima koje može izazivati pojavu tolerancije i ovisnosti. Na eksperimentalnim životinjama također se istražuju interakcije između učinaka stresa i djelovanja benzodiazepina i antidepresiva, prvenstveno na osjetljivost prema konvulzivima, te uloga serotoninskog sustava u kontroli moždane podražljivosti.više » SuMERA - Sirtuin3 kao posrednik mitohondrijske funkcije u estrogen-ovisnoj otpornosti na oksidativni stres i prehranu s visokim udjelom masti Proučavanje uloge SIRT3 i funkcije mitohondrija u E2-ovisnoj otpornosti na oksidacijski stres in vitro i in vivo.više » Uloga disfunkcije lizosoma u nastanku neurodegenerativnih bolesti Koristeći stanični model lizosomalne bolesti NPC cilj ovog projekta je ispitati ulogu lizosoma i njihove disfunkcije na nakupljanje peptida amiloid-beta (Abeta) i alfa-sinukleina (a-syn), dva ključna proteina u patogenezi Alzheimerove, odnosno Parkinsonove bolesti.više » Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA Uloga sirtuina 1 (SIRT1) u zloćudnim tumorima ne-malih stanica pluća Uspostava istraživačke infrastrukture za translacijsku medicinu i primijenjenu genomiku Uspostava istraživačke infrastrukture za translacijsku medicinu i primjenjenu genomiku s ciljem korištenja visoko-propusnih metoda temeljena na DNA čip tehnologiji za buduće aktivnosti tehnološkog transferaviše » Utjecaj kolagena modificiranog produktom lipidne peroksidacije na rast i diferencijaciju matičnih stanica karcinoma dojke Utjecaj novog Cu-biostakla i produkata lipidne peroksidacije na regeneraciju kosti Genetičko testiranje na nasljednu sklonost za rak dojke i jajnika (analiza gena BRCA1 i BRCA2) Genetičko testiranje na nasljednu sklonost za rak dojke i jajnika (analiza gena BRCA1 i BRCA2)više » Molekularna dijagnostika bakterijskih i viralnih infekcija Dokazivanje prisustva bakterijskih i virusnih infekcija u uzorcima (biopsije, obrisci, eksudati)više » Molekularna dijagnostika genetskih bolesti U našem laboratoriju bavimo se dijagnosticranjem slijedećih genetskih bolesti - Fragilni X kromosom, Huntingronova bolest, Miotonična distrofija, Friedrichova ataksija, Spinalno cerebralna ataksija i Duchenne-ova mišična distrofija.više » Molekularno-genetičke analize Laboratorij za personaliziranu medicinu pruža usluge molekularno-genetičkih analiza nasljednih bolesti povezanih s povećanim rizikom oboljevanja od raka te analize farmakogenetičkih biljega.više » Određivanje mutacija u protoonkogenu ret Ova se genetička analiza provodi u oboljelih od medularnog karcinoma štitne žlijezde kako bi se isključilo/potvrdilo postojanje nasljedne mutacije. Ova se suradnja provodi s KBC "Sestre milosrdnice".više » Određivanje slijeda nukleotida (sekvenciranje DNA) i fragmentalna analiza Određivanje slijeda nukleotida (sekvenciranje DNA) i fragmentalna analizaviše » Proizvodnja laboratorijskih životinja U Pogonu laboratorijskih životinja se uzgajaju jezgre pet srođenih mišjih sojeva BALB/c, CBA/H C3Hf/Bu, C57BL/6-Ly5 i NOD, kao i jedan nesrođeni soj HSD:ICR (CD-1), te štakori (Wistar Zagreb 5HT - podsoj selekcioniran prema razini perifernog serotonina). Životinje se uzgajaju na način koji omogućava genetsku stabilnost sojeva, a životinje se nalaze pod stalnim veterinarskim nadzorom zdravstvenog stanja. Pogon laboratorijskih životinja proizvodi miševe i štakore za potrebe znanstvenika Instituta «Ruđer Bošković» kao i za vanjske naručioce.više »