Research team Brcic

Research focus: MOLECULAR PATHOGENESIS OF LUNG AND PLEURAL DISEASES

PI: Luka Brcic

Focus: Pathogenetic mechanisms of progression, migration, and metastasis of lung and pleural tumors. Mechanisms by which the tumor microenvironment and the immune system are involved in the development and progression of lung and pleural diseases. Comparison/correlation of the development of desmoplastic stromal reaction in tumors with the development of fibrotic processes in fibrosing lung diseases.

Network: Within the Med Uni Graz we cooperate with the Clinical Department for Oncology and Pulmonology, University Clinic for Internal Medicine, Clinical Department for Thoracic Surgery and Hyperbaric Surgery, University Clinic for Surgery, and Chair for Pharmacology. There is a very close connection to the LBI for Pulmonary Vascular Research, Graz. Our national and international cooperation partners are: AKH Vienna, University Clinic for Surgery, Clinical Department for Thoracic Surgery, University Medicine Göttingen, Institute for Pathology, The University Clinic of Pulmonary and Allergic Diseases Golnik, Department of Pathology, Golnik, Slovenia, Institute for Pathology am University Hospital Essen, University of Duisburg Essen, Essen, Germany, MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Center Léon Bérard, Lyon, France. Other partners in specific research projects are the Institute of Pathology, Klinik München-Bogenhausen, Germany, University of Groningen, Department of Pathology and Medical Biology, the Pathology Department of Yale School of Medicine, and Department of Pathology, Nagasaki University.

Projects

MTAP and p16 expression as markers of CDKN2A deletion

The project investigated the applicability of immunohistochemistry for MTAP and/or p16 in detecting CDKN2A deletion. This may be easier to apply since CDKN2A FISH, which costs more, takes more time to analyze, and is not performed by every pathology laboratory.
Duration: 2019-2021
Funded by: MESOBANK, Department of BioPathology Center Léon Bérard, Lyon, France
Project partners: MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Center Léon Bérard, Lyon, France

Pathogenesis of fibrosing pneumonia

Fibrosing pneumonia is classified into Usual Interstitial Pneumonia (UIP), Non-Specific Interstitial Pneumonia (NSIP), Organizing Pneumonia (OP), and unclassifiable Fibrosis. UIP is a deadly disease causing the death of patients within 3-4 years. Therapy can slow the process, but is not curative. The UIP pattern is either associated with chronic autoimmune disease, hypersensitivity, or comes as an idiopathic disorder. Several possible pathogenetic mechanisms have been identified, among them senescence and deregulation of the immune system. This is the focus of this project.
Duration: 2019-2021
Funded by: Medical University of Graz, D&R Institute of Pathology
Project partners: Institute of Pathology, Clinics München-Bogenhausen, München, Germany

MesoViBe- Mesothelioma Virtual Bank Austria

The idea of the project is to prospectively collect all newly diagnosed mesothelioma in Austria. The slides and blocks are sent to us, and we re-analyze them, perform additional immunohistochemistry, and FISH analysis for CDKN2A, and confirm the diagnosis. All slides are digitized and with minimal clinical data set stored on an online platform. The aim is to have all mesothelioma diagnosed in Austria in a virtual space by 2025.
Duration: 2020-2025
Funded by: AUVA, City of Graz, Takeda, BMS
Project partners: all pathological institutes in Austria that diagnose mesothelioma

Prognostic and predictive relevance of small cell lung carcinoma subtypes

Small cell lung carcinoma (SCLC) can be subtyped based on genes signaling for the neuroendocrine phenotype. Four different genes have been identified in cell cultures, ASCL1, and NeuroD, both neuroendocrine master regulators, POU2F3, a gene expressed in peripheral lung cells which inhibits a neuroendocrine phenotype, and YAP1. Immunohistochemical expression of those and some additional markers will be evaluated in the archival tissues. Same analyses will be performed on the cases of large cell neuroendocrine carcinoma
Duration: 2021-2022
Funded by: Medical University of Graz, D&R Institute of Pathology

The role of senescence, and the impact of neuronal receptors in Chronic Obstructive Lung Disease

This project analyses the role of senescence in maintaining chronic inflammation in Chronic Obstructive Lung Disease (COPD). Furthermore, the potential changes in neural structures their causes, and consequences are investigated.
Duration: 2021-2023
Funded by: Medical University of Graz, D&R Institute of Pathology
Project partners: Wim Timens, University of Groningen, University Medical Center, Dept. Pathology and Medical Biology

ANEMONE – The ANswer within the microEnvironment: Malignant pleural mesothelioma resistance to Old and New drugs

The main hypothesis of this project is that the tumor microenvironment (TME) plays a crucial role in the development and progression of pleural mesothelioma by influencing mesothelial cell survival and evasion of immune surveillance.
The main goal of the project is an accurate characterization of TME in clinical samples, assessment of genetic alterations and gene/protein expression modulation on TME, and identification of predictive biomarkers of ICI response by correlating pathological/molecular findings with clinical/radiological (radiomics) data under Using machine learning algorithms, in vitro and in vivo models.
Duration: 2022-2025
Funded by: ERANET TRANSCAN-3 Cofund
Project partners: Universitá Degli Studi Di Padova, Italy; University of Coimbra, Portugal; Riga Stradins University, Latvia; Azienda Ospedaliero Universitaria Pisana, Italy.