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Projects / Programmes source: ARIS

Role of lysosomes and lysosomal proteases in cellular signaling

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Research activity

Code Science Field Subfield
1.05.00  Natural sciences and mathematics  Biochemistry and molecular biology   

Code Science Field
B000  Biomedical sciences   

Code Science Field
1.07  Natural Sciences  Other natural sciences 
Keywords
Lysosomes, cathepsins, apoptosis, autophagy, cancer, therapy
Evaluation (rules)
source: COBISS
Evaluation of bibliographic research performance indicators according to ARIS methodology
Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases
source: WoS source: Scopus source: COBISS
Researchers (14)
no. Code Name and surname Research area Role Period No. of publications
1.  23573  PhD Dejan Caglič  Biochemistry and molecular biology  Researcher  2010  53 
2.  00449  PhD Iztok Dolenc  Biochemistry and molecular biology  Researcher  2012 - 2013  110 
3.  34090  PhD Gabriele Droga Mazovec  Biochemistry and molecular biology  Researcher  2012 - 2013  38 
4.  18801  PhD Marko Fonović  Biochemistry and molecular biology  Researcher  2010 - 2013  187 
5.  29470  PhD Katarina Pegan  Biochemistry and molecular biology  Researcher  2011 - 2013  44 
6.  24764  PhD Ana Petelin  Cardiovascular system  Researcher  2010 - 2011  231 
7.  25642  PhD Urška Požgan  Pharmacy  Researcher  2010  24 
8.  21560  PhD Urška Repnik  Microbiology and immunology  Researcher  2010 - 2011  149 
9.  28485  PhD Aleš Špes  Biochemistry and molecular biology  Junior researcher  2010 - 2012  24 
10.  15969  Ivica Štefe  Biochemistry and molecular biology  Technical associate  2010 - 2013  36 
11.  07561  PhD Boris Turk  Biochemistry and molecular biology  Head  2010 - 2013  1,037 
12.  01085  PhD Vito Turk  Biochemistry and molecular biology  Researcher  2012 - 2013  1,490 
13.  33762  PhD Robert Vidmar  Biochemistry and molecular biology  Technical associate  2012 - 2013  148 
14.  32171  PhD Matej Vizovišek  Biochemistry and molecular biology  Junior researcher  2010 - 2013  142 
Organisations (1)
no. Code Research organisation City Registration number No. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,682 
Abstract
Many physiological processes, including tissue development and homeostasis, require a balance between cell death and cell proliferation, whereas even slight imbalance of the system may stimulate proliferation of the cell, facilitating its' oncogenic transformation. There is increasing evidence that lysosomes and/or lysosomal proteases are importantly players in both cell death and cell proliferation, in addition to their critical role in autophagy, which is considered a major survival mechanism of cancer cells. However, molecular mechanisms underlying lysosome and lysosomal protease involvement in these processes are still not well understood. The main idea of this proposal is to identify the lysosomal protease signaling pathways in cell death and autophagy with a long-term goal to unravel the role of lysosomes and their components in hyperproliferative disorders such as cancer and their potential in anticancer treatment. This is based on a hypothesis that lysosomes and/or lysosomal proteases represent one of the major modulators of cellular signaling in these processes. This project should thus provide a fundamental insight into how lysosomes and lysosomal proteases promote cellular signaling in cell death. The gained knowledge will significantly contribute to our understanding of the complex biological phenomena and will be instrumental for biomedical research to understand and develop novel strategies to combat cancer and other hyperproliferative diseases based on the modulation of the activities of lysosomal proteases.
Significance for science
This project was certainly of high biomedical relevance. Lysosomes and lysosomal proteases have already been validated as relevant targets for cancer treatment, whereas several compounds targeting lysosomes and/or lysosomal proteases are already in preclinical or clinical testing. This is true not only for LeuLeuOMe, which entered Phase I clinical trials, but also for TNF-related death receptor ligands and various antioxidants. We believe that we have opened new avenues in the areas where the exact roles of lysosomes and cathepsins and their signaling pathways were unknown, largely unclear or controversial such as in the death receptor pathway and caspase independent cell death. The gained knowledge will thus not only significantly contribute to our understanding of the complex biological phenomena, but will in long run also be instrumental in biomedical research to understand and develop novel strategies to combat cancer and other hyperproliferative diseases based on modulation of the activities of lysosomal proteases. In addition, the project strengthened the research at the Department of Biochemistry and Molecular Biology at Jožef Stefan Institute in the field of cell biology and molecular medicine.
Significance for the country
Cancer is one of the most debilitating diseases of the developed world. Therapeutic removal of cancer cells by stimulating apoptosis and blocking autophagy, together with the use of protease inhibitors, are currently among the most perspective areas in cancer treatment. Thus, the results obtained will be highly relevant in evaluation of lysosomes and cysteine cathepsins as possible therapeutic targets in cancer. Continuation of the research in representative animal cancer models is therefore of high value for the evaluation of compounds at the preclinical level, which should be interesting for the pharmaceutical companies in Slovenia and abroad. Therefore we can say that although the research performed was largely basic research, it also has its applied component and can be classified as strategic basic research. This also helped us to establish contacts with our SME Acies d.o.o, which was also one of the longterm goals of the project. Similar connections have already been established in past, as seen from the numerous contracts. Moreover, the work also offered great opportunity for students to be trained in the most advanced methods and areas, such as proteomics (at IJS in our Depatment we have the only protoemics lab in Slovenia), and chemogenomics together with European and other international partners. Both fields have namely high international priority as they are of extreme importance in target identification and validation during drug development. In addition, members of the project have received widespread international recognition, which is very important for the worldwide promotion of Slovenia and as such also for preservation of national identity of Slovenia.
Most important scientific results Annual report 2010, 2011, 2012, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2010, 2011, 2012, final report, complete report on dLib.si
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