Otkrivanje biomarkera za bolest Hashimotov tireoiditis koristeći multi-omics pristup
Naziv HRZZ Istraživačkog projekta / The title of HRZZ research project:
Otkrivanje biomarkera za bolest Hashimotov tireoiditis koristeći multi-omics pristup/
Biomarker discovery using multi-omics profiles in Hashimoto's thyroiditis
Akronim projekta / Acronym of the project: HT-OMICS
Trajanje projekta / Project duration: 31.12.2023. - 30.12.2027.
Voditelj projekta / Principal Investigator: prof. dr. sc. Vesna Boraska Perica
Suradnici na projektu/ Project collaborators:
prof. dr. sc. Ante Punda,
doc. dr. sc. Ana Barić Žižić,
doc. dr. sc. Vesela Torlak Lovrić,
dr. sc. Dean Kaličanin,
mr. sc. Maja Cvek,
Marko Vuletić, dr.med,
Vanna Žnidar, univ. mag. math,
prof. dr. sc. Eleftheria Zeggini,
dr. sc. So-Youn Shin
Opis projekta:
Hashimotov tireoiditis (HT) je najučestalija autoimuna bolest današnjice. Molekularni mehanizmi u podlozi bolesti još uvijek nisu dovoljno poznati, stoga je ovaj projekt usmjeren na otkrivanje novih znanja vezanih uz molekularne i biološke putove vezane uz HT. Ovaj projekt predstavlja nastavak prethodne HRZZ Uspostavne potpore u kojoj je osnovana CRO-HT biobanka bioloških uzoraka i fenotipova za 500 ispitanika oboljelih od HT-a te je provedena cjelogenomska analiza povezanosti (GWAS). U međuvremenu smo prikupili još 200 kontrolnih ispitanika te u predloženom projektu kroz cilj 1 (C1 Proširenje CROHT biobanke) planiramo uključiti dodatnih 200 ispitanika s HT-om te genotipizirati njihov genom. Također, planiramo mjeriti i analizirati proteinske i metaboličke markere kroz ciljeve 2 (C2 Otkrivanje biomarkera koristeći proteomsko profiliranje) i 3 (C3 Otkrivanje biomarkera koristeći metabolomsko profiliranje). Kroz ove ciljeve ćemo nastojati: (a) identificirali različito izražene proteinske/metaboličke markere između HT ispitanika i kontrola i ispitati povezanost omics profila s težinom bolesti HT; (b) utvrditi povezanosti između značajnih markera i kliničkih obilježja HT-a; (c) integrirati sve dostupne omics podatke (cjelogenomske genotipove, proteom i metabolom) da bi dobili bolji uvid u manifestaciju same bolesti; (d) Ispitati postojanje uzročnih povezanosti između značajnih markera (metabolita i proteina) i HT-a koristeći metodu Mendelove randomizacije. Kroz posljednji cilj 4 (C4 Istraživanje uloge crijevne propusnosti s HT-om) planiramo mjerenje i analiziranje proteina zonulina koji je trenutno jedini mjerljivi marker crijevne propusnosti. Predloženi sveobuhvatni istraživački pristup pridonijet će razumijevanju temeljnih bioloških putova povezanih s mehanizmima nastanka HT-a i identifikaciji biomarkera koji mogu služiti pri stvaranju prediktivnih modela za razvoj te do razvoja novih terapijskih, prevencijskih i dijagnostičkih metoda.
Project summary:
Hashimoto's thyroiditis (HT) is the most common autoimmune disease today. The molecular mechanisms underlying the disease are still not sufficiently known, therefore this project is aimed at discovering new knowledge related to the molecular and biological pathways related to HT. This project is a continuation of the previous HRZZ Installation Grant, in which we formed the CRO-HT biobank of biological samples and phenotypes for 500 subjects with HT and performed a GWAS of this disease. In the meantime, we have collected another 200 control subjects. In the proposed project, through objective 1 (O1 Expansion of the CROHT biobank), we plan to include an additional 200 subjects with HT and to genotype their genome. Also, we plan to measure and analyze protein and metabolic markers through objectives 2 (O2 Proteomic profiling of HT for biomarker discovery) and 3 (O3 Metabolomic profiling of HT for biomarker discovery). Through these objectives, we will try to: a) Identify differentially expressed proteome/metabolome biomarkers between HT cases and control subjects and examine omics profiles with HT disease severity, (b) Assess associations between significant biomarkers and clinical features of HT, (c) Integrate all available omics data (whole genome genotypes, proteome and metabolome) to gain deeper insights in disease manifestation, (d) Examine causal relationships between significant biomarkers (metabolites and proteins) and HT using Mendelian randomization. Through the last objective 4 (O4 Evaluation of the role of intestinal wall permeability with HT) we plan to measure and analyse the protein zonulin, which is currently the only measurable marker of intestinal permeability. With the proposed comprehensive research, we strive to produce broader knowledge on molecular pathophysiology, diseases biomarkers, predictive models, preventive medicine and potential therapeutic, personalised, approaches for patients with HT.
