Pathology and Molecular Genetics

In our research programme, we will focus on searching for new diagnostic, prognostic and predictive factors in various cancers and inflammatory conditions, and introduction of new techniques, e.g., bioinformatics, detection of non-coding RNAs, new panels in next generation sequencing (NGS), etc. A special attention will be paid to liquid biopsies as an alternative to tissue biopsies in a variety of diseases, improving early detection, prognosis, monitoring treatment responses and possible resistance to therapy. Primary brain tumours are heterogeneous neoplasms on both clinical and molecular levels. A novel NGS-glioma assay and research of (non)coding landscape of brain tumours will be implemented. We expect to identify new molecular biomarkers for a more precise characterisation, with contribution to development of subtype-specific treatment of glial tumours. Introduction of liquid biopsies of cerebrospinal fluid will enable incorporation of informative diagnosis and less invasive method of disease monitoring. Epithelial-mesenchymal transition and cancer stem cell properties will be studied on precancerosis and carcinomas in different organs. We will investigate whether any of the analysed markers can be used as a diagnostic marker to distinguish between precancerosis and carcinoma and as prognostic marker(s) to predict an unfavourable course of the disease. We will use liquid biopsy to search for potential prognostic and monitoring markers in plasma samples of patients with carcinoma. In inflammatory bowel diseases (IBD), we will analyse pathologic features of fibrosis in Crohn’s disease and ulcerative colitis, compared to normal bowel. We will analyse the distribution of fibrous tissue, myofibroblasts and pericytes within the bowel wall in IBD and normal bowel wall, with special attention to pericytes and their markers. We will identify fibrosis-related genes, proteins and microRNAs, that can be used as diagnostic and prognostic markers in IBD, in either endoscopic or liquid biopsies. In vasculitis, we plan to identify key dysregulated miRNAs in patients with giant cell (temporal) arteritis and granulomatosis with polyangiitis (Wegener’s granulomatosis), retrospectively on tissue samples and prospectively on fresh tissue and liquid biopsies. Overall, we aim to identify miRNAs which would enable, in combination with classical serological markers, early diagnosis of vasculitides, and possibly to predict their recurrence. In melanocytic lesions, a comprehensive morphological and molecular analysis of a large number of atypical Spitz tumours with a long follow-up will identify morphological and molecular parameters, enabling to accurately identify atypical Spitz tumours with aggressive clinical behaviour. We will improve characterisation of conjunctival nevi, by integrating morphological and molecular analysis and determine disease dynamics and the risk of hematogenous metastases in patients with uveal melanoma by using liquid biopsy.

Combining pathology, bioinformatics and new technologies in molecular genetics is an approach, which has the potential to discover novel pathogenetic mechanisms and diagnostic, prognostic and predictive markers. We will try to extend this approach to liquid biopsy, in order to enable early detection and monitoring treatment responses and reccurrences.   Gliomas are extremely heterogeneous neoplasms, both on clinical and molecular levels. Recently, World Health Organization began to incorporate molecular findings into the histopathological diagnosis of specific tumour types, i.e., integrated diagnosis. We aim to discover specific biomarkers that can be used as targets in precision based-PCR in circulating tumour DNA for a more precise characterization of gliomas, and also to identify new molecular biomarkers with potential to contribute to development of subtype-specific treatment.   Epithelial-mesenchymal transition (EMT) contributes to various physiological and pathological processes, such as wound healing, tissue regeneration, organ fibrosis and cancerogenesis. Transcriptional factors of EMT can also induce stem-cell like properties that are responsible for generation of cancer stem cells (CSCs), thus linking the EMT and CSC concepts. Despite extensive research, the significance of EMT and CSCs in various cancers remains controversial. We will analyse EMT and CSCs in precancerosis and carcinomas in different organs in order to understand their pathogenetic role and to search for new diagnostic and prognostic markers in precancerous lesions and carcinomas of various organs.   Fibrosis in inflammatory bowel diseases, particularly in Crohn’s disease is a poorly understood condition. Fibrosis is the final common pathway in organ failure in diseases of various organs, including the liver, kidney, lung and heart. It is believed to result from tissue damage due to chronic injury and/or inflammation and impaired mechanisms of wound healing, leading to progressive scarring and organ damage. Myofibroblasts are considered to be the key effector cell in fibrosis, being responsible for the synthesis of the extracellular matrix proteins. Despite a generally accepted central role of myofibroblasts in various physiologic and pathologic conditions, the origin of these important cells has not been entirely established and remains controversial. We will analyse the distribution of fibrous tissue, myofibroblasts and pericytes within the bowel wall layers in Crohn’s disease, ulcerative colitis and normal bowel wall and search for diagnostic markers of fibrosis.   Vasculitides are a group of heterogeneous inflammatory diseases, mainly characterised by the inflammation of blood vessels. Inflammation may result in damage, destruction and necrosis of blood vessel walls, leading to vessel wall remodelling, stenosis, ischemic and hemorrhagic events. Classical serological markers, clinical symptoms and histopathological changes may aid in determining specific vasculitis type. However, there is still a lack of novel specific noninvasive biomarkers that would enable, individually or combined, an efficient and reliable early diagnosis and prognosis of specific vasculitis, monitoring of vasculitis progression, remission and predicting recurrence, following treatment. We aim to identify candidate miRNA biomarkers for temporal arteritis and granulomatosis with polyangiitis, and to evaluate their performance in clinical practice. Overall, we aim to search for miRNAs, which would enable, in combination with classical serological markers, early diagnosis of giant cell (temporal) arteritis and granulomatosis with polyangiitis, and possibly to predict their recurrence.   Melanocytic lesions are among the most common tumours in humans, involving predominantly the skin and eye. Despite extensive research, diagnosis (distinction between a benign nevus and a malignant melanoma) still predominantly relies on morphological analysis with a relatively limited role of

The research of our group is highly relevant for Slovenian development. It contributes to health care and has the potential for new collaboration in the research field. The research could help in more accurate diagnosis in several neoplastic and inflammatory diseases. Our aim is also to introduce blood-based tests, which are more cost-effective and non-invasive.   Educational activity of the group members will improve the knowledge of younger generation. This knowledge and research experience will be hand over, which will improve, and continue to develop this research forward to new research hypothesis.   The results of our research could be a starting point for industrial research and can lead to novel diagnostic tests.