Projects / Programmes
Applied and Basic Physiology and Pathophysiology in Medicine
January 1, 2015
- December 31, 2018
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| 3.06.00 |
Medical sciences |
Cardiovascular system |
|
| Code |
Science |
Field |
| B007 |
Biomedical sciences |
Medicine (human and vertebrates) |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Aging, apoptosis, cell senescence, MRI, MRI microscopy, laser scanning confocal microscopy, brain segmentation, HR EKG, neurodegeneration, dementia, neurovascular coupling, heart, reactive oxygen species, CVI
Researchers (43)
Organisations (1)
Abstract
The study of basic processes leading to aging will be the main subject of our research. The goals are to provide new knowledge, to develop new diagnostic procedures and to provide new therapeutic approaches based on our previous research.
Intensive investigations of aging by scientists worldwide are aiming at a better prevention, early diagnostics and improved therapy of degenerative disorders in elderly. Innovative therapeutic procedures, such as therapy with stem cells, are rapidly developing. Our team member is leading this field (EU project). Interdisciplinary study of neurodegeneration, neurovascular coupling and the role of autonomic nervous system in the aging heart by combining studies from a molecule to man aiming at a better patient care is our goal and also the essence of “translational medicine”.
Understanding basic mechanisms of aging, including the role of environmental factors, is essential for appropriate prevention of a disease. We will study the role of ROS, metabolic disorders and ecotoxins in neurodegeneration. Mechanisms of stress responses, especially the pre-apoptotic cell stress response (discovered by our team), will be studied in detail. Effects of different stressors, including ecotoxins, on basic mechanisms of degeneration, apoptosis, cell senescence and adaptation to stress will be studied
Prevention is incomplete because our understanding of basic mechanisms of aging is scarce. This means that the development of new diagnostic procedures and the search for new therapeutic opportunities is needed. In this part of the program our focus will be the study of neurodegeneration in dementias, Huntington disease and stroke. By use of most advanced techniques we will study brain plasticity, neurovascular coupling and the autonomous control in order to contribute to the understanding of these processes and to develop new diagnostic procedures for early disease detection. Our previous research has already resulted in innovative, robust and reliable brain segmentation for diagnostic procedures. The software, developed in collaboration with NIH (Bethesda, USA), is already included in the software package AFNI.
We will also continue with the study and development of synthetic analogues of PAX, an AChE inhibitor from P. Axinellae that may become useful for the therapy of dementias. At the end of the program period t we plan to file patents for production and use of the analogues.
Our study on the aging heart and neurovascular coupling has already resulted in an USA patent. The part of the research will be extended with the goal to file several international patents.
Our team member is the leading scientist in the field of stem-cell therapy of the failing heart (leading an EU project), and we will continue this important part of the research.
Increased funding by ARRS would enable additional research in the field of (1) HBO, ROS and diabetic neuro- and angiopathy and (2) aging of tooth pulp by a 9.4 T MR tomograph for MR microscopy.
TIME PLAN: see attachment.
Significance for science
The proposed program aims at understanding the mechanisms of aging in the field of neurodegenerative diseases, neurovascular coupling and interactions between the heart function and neurovascular system. We intend to publish the results in top journals in the field. The originality of the results will also warrant high impact of the published results.
The first part of the program will contribute new knowledge to the field of cell adaptation to stress:
- Preapoptotic cell stress response has been discovered on hepatocytes by our team; results were published in the top journal in the field. To establish whether this process is universal (present also in other cells) we will test it on rat astrocytes and neurons and on human endothelial cells. The results will be published in high ranking journals, and may also be useful in cell therapy as well as in organ transplant handling.
- The study of the mechanism of microcystin (MC) induced neurodegeneration will answer these questions: (1) are OATPs present in neuronal and astrocyte membranes (2) the mechanism of MC-induced apoptosis of neurons (3) can we block the entry of MCs into neurons and (4) can we prevent MC-induced apoptosis by use of antioxidants?
- The study initiated together with research groups from four EU countries will clarify the link between the metabolic syndrome and psychoses.
- Testing the use the synthetic PAX analogues as neuroprotective substances.
The scientific importance of the second part of the program is a better understanding of the Huntington disease, dementias and stroke:
- The decline of cognitive and motor functions in these diseases is well studied, but very little is known about their effect on the autonomous nervous system (ANS). Our preliminary results indicate that ANS is affected in neurodegenerative diseases and understanding of this process is the goal of our future study.
- Cognitive and motor function is gradually and partly restored after a mild stroke (CVI) due to brain plasticity. This will be studied in detail: (1) study of brain connectivity (using DTI and resting state fMRI), (2) measurement of cortex thickness in different brain regions (using segmentation and voxel-based volumetry) and (3) study of changes in functional reorganization of brain cortex (using model-based task-related BOLD fMRI). Besides numerous publications we also expect to develop and test different therapeutic approaches for an increased and faster rehabilitation. Another goal is to further develop our software for use in the clinical practice.
- CVI is often a consequence of the carotid artery disease that may be treated by stenting the artery. A relatively common complication in some patients is the reocclusion of the artery. This process is insufficiently understood, but it differs from the underlying atherosclerosis. Testing different genes for cytokines will bring new knowledge about the risk factors for reocclusion after stenting.
The third part of the program is important for the development of science in the field of stem cell therapy of the failing heart and HR EKG.
- Stem cell therapy is still in the development and our team with its broad experience is leading this field. A member of our team is leading EU project on this subject and many original results are expected to be published in the top journals in the field.
- The study of the improved function of endothelium after the stem cell therapy, measured by means of laser fluximetry, will provide the answer whether (1) this is a direct consequence of the therapy or (2) the patients with the improved endothelial function are better responders to g-CSF induced mobilization of stem cells.
- Development of HR EKG in collaboration with NASA, Houston, has already resulted in US patent used by CardioSoft. Further development of the software will enable filing more international patents. Using HR EKG will also enable the study and understanding the ele
Significance for the country
Direct collaboration with industry, with Health care system and with other stakeholders:
In collaboration with industry a PhD student from Iskra ISD Company developed a prototype of device for measurement of force of contraction that can be used in MR tomographs. It is planned that the device will further be improved so that we can file a patent in 2015.
Long term collaboration with the company UNIOR Kovaška industrija d.d., Zreče has already started and will continue at least until 2016. A research team Razvoj centra za vrhunski šport na Rogli has been established with the aim to implement our knowledge into company plans and activities leading to new commercial products of international interest. The goals are: (1) building a new center for top sportsmen at Olympic centre Rogla (2) introduction of new methods for effective rehabilitation of sport injuries (3) development of preventive strategies for hazardous groups of professions (4) fighting obesity at high altitude.
In the field of neuroscience and cardiovascular research we are developing software for research and clinical applications. In the recent past we have already filed a patent in the USA, and it has already been used by the company Cardiosoft, TX, USA.
We will continue with organization of annual meetings »Consultations on chronic heart disease« for medical doctors and students. Participation at the meetings brings significant credit points for medical license renewal, and it warrants development of medical practice in primary, secondary and tertiary health care.
Indirect impact on development of the society and industry:
We have already educated a researcher from the industry (Iskra ISD) as a PhD student, and in the future we plan to continue with these activities.
Program group members are responsible for the graduate and postgraduate education at Faculty of Medicine and several other Faculties of the University of Ljubljana, and will continue to offer excellent education in their fields of expertise.
We will continue to accept graduate and postgraduate students for their electives
In the next years the members of the program group continue to be responsible for several activities at ULMF:
- Head of the postgraduate studies,
- Heads of Institutes and Departments,
- Coordinators of several fields of PhD study »Biomedicine«
- Dean of the Faculty of Medicine, University of Ljubljana
Well established collaboration with international partners warrants continuous exchange and transfer of knowledge:
- Texas Heart Institute and University of Texas, Houston, USA
- NIH, Bethesda, USA: collaboration after the successful conclusion of formal bilateral project continues in the field of brain MR image analysis and segmentation.
- Long term collaboration with CNRS in Gif sur Yvette continues in the field of toxinology and the study of AChE inhibitors and neuronal nAChR.
- Long term collaboration with INRA/INSERM group in Sophia Antipolis, F, continues in the field of ecotoxinology.
- AMC, Amsterdam, collaboration with B. De Mol in the study of microcirculation in health and disease.
- NASA, Houston and cooperation with Cardiosoft, US company.
Promotional activities relevant for Slovenia
Irina Milisav:
she is a member of the management committee of the European Cooperation in Science and Technology COST BM1203 EU ROS and representative of Slovenia in COST action related to the study of reactive oxygen species (ROS), web page: http://www.cost.eu/domains_actions/bmbs/Actions/BM1203? management
Dušan Šuput:
Executive committee of AMSE elected D. Šuput for the »Secretary General of the
Association of Medical Schools in Europe".
He is a member of the task force from the »Class Medicine« at the European Academy of Science and Arts he is involved in coordination and development of new »European« curriculum of medicine.
Collaboration with World Federation of Medical Education (WFME), Copenhagen, DK (prof. D. Gordon) in the fi
Most important scientific results
Annual report
2015,
2016,
2017,
final report
Most important socioeconomically and culturally relevant results
Annual report
2015,
2016,
2017,
final report
