Department of Transplantation is a part of Clinical Immunology and Transplantation Chair of Jagiellonian University Medical College. Research conducted in the Department is focused on stem cells and tumor biology.

Tumor growth and metastasis is a multi-step process. There are numerous factors responsible for process including growth factors, surface receptors, transcription factors and miRNA.

Rhabdomyosarcoma (RMS) is a soft tissue tumor, which may originate from stem cells due to their differentiation defect. It can be divided into two major subtypes: embryonal (ERMS) and alveolar (ARMS), which displays worse prognosis probably due to translocations leading to formation of PAX3-FKHR fusion proteins.Despite a lot of effort, precise mechanism of RMS development is not known. In the project we investigate the role of SNAIL1 in development and progression of RMS. By defining the role of SNAIL1 in rhabdomyosarcoma biology we have a chance to get a deeper insight into the complexity of interactions between SNAIL1, different proteins and microRNA in regulation of RMS development, growth and progression and we could discover novel mechanisms underlying biology of tumors originating from defective differentiation of stem cells. Therefore the study may open the possibility to design the specific molecular tools, which can be applied in the future clinical trials aimed at preventing tumors growth.

Ongoing studies are looking for a correlation between the activity of individual miRNAs and the onset and/or progression of tumor. The role of miRNA in pathogenesis and progression of colorectal cancer (CRC) remains mostly unknown. The goal of this project is to assess the correlations between miRNAs expression profile and clinical course of CRC as well as to perform drug susceptibility evaluation at the cell level using iPS technology and correlate it with miRNA expression.

AMP-activated kinase (AMPK) is the main energetic switch of a single cell as well as full organism, however numerous processes controlled by this enzyme, such as cell growth, proliferation, apoptosis and polarity, have been discovered. Tumor growth and metastasis is related to increasing metabolic deregulation of cancer cell (Warburg effect), though the role of AMPK in tumorigenesis still remains unclear. The aim of the study is to investigate the impact of changes in AMPK expression and activity on metastasis of cancer cells. Additionally, the influence of hepatocyte  growth factor (HGF) on activation of AMPK and expression will be tested. The goal will be achieved byanalyzing expression of metastasis and EMT associated proteins.

Despite the extensive progress of conventional medicine in the diseases treatment, mostly due to the major advances in the field of pharmacology and disease early diagnosis and prevention, large numbers of patients suffering from civilization diseases who have reached ‘untreatable’ stage are still awaiting for development of an effective treatment while they are a substantial burden to themselves, their families and the society. This is particularly true for cardiovascular diseases where in spite of a significant improvement that has occurred in the last decade in prevention, pharmacotherapy, and rehabilitation, those remain a key cause of death and disability in the modern society that rival many cancers (Roger Circ Res 2013, Jeon YH BMC Health Serv Res 2010, Bui Al et al Nature Rev Cardiol 2011).

Although early diagnosis and prompt revascularization treatment reduce the degree of ischemic injury, current strategies are unable to reverse the ischemic damage that has already occurred. Social and personal costs of living with heart failure are, paradoxically, on the increase (Jeon YH BMC Health Serv Res 2010) because of development of palliative rather than causal therapies, with a significant proportion of patients, on the one hand, unable to work and, on the other, requiring repeated hospitalizations due to heart failure exacerbations (Bu AL et al Nat Rev Cardiol. 2011). In Poland, clinical heart failure currently affects 1 million citizens and, unless disease-reversing treatment is developed, this number will escalate to 1,25 million by 2035 (www.zdrowie.pl, www.pzh.gov.pl).

The project “Cardiovascular ischemic injury regeneration using Wharton Jelly as unlimited therapeutic stem cells source” (CIRCULATE) proposes a new approach for the treatment of selected cardiovascular diseases based on use of allogeneic transplantation of Wharton’s Jelly derived Mesenchymal Stem Cells (WJMSC).

Partners of the Consortium will accomplish goals of the CIRCULATE project by:
1. Establishment of WJMSC repository,
2. Characterization of the WJMSC using cellular and molecular methods,
3. Evaluation of the clinical WJMSCs potential in selected cardiovascular diseases using novel MRI methodology and
4. Assessment of seeding properties and regenerative potential of WJMSC using iv vivo models.

Implementation of CIRCULATE project will generate novel knowledge about the WJMSC biology and new MRI technology to monitor regeneration process. It will allow development of new treatment strategies for cardiovascular diseases using cell replacement therapy. The project will have strong impact on developing the field of regenerative medicine, which is still in its infancy. Moreover, the project will allow in future introduction of allogeneic stem cells, in the form of the “out of shelf” product, capable of regeneration of various organs and tissues.

Neurodegenerative diseases affect growing number of elderly people. Among neurodegenerative disorders Parkinson’s Disease (PD) is second most common. In PD specific loss of dopamine-producing (dopaminergic) neurons takes place.The exact etiology of Parkinson’s Disease is not fully elucidated, and study conducted to date suggests several hypothesis e.g. environmental factors, genetic lesions or involvement of immunological system causing chronic inflammation that results in degeneration of dopaminergic neurons.

For majority of patients there is no efficient treatment available today, and available chronic pharmacotherapy is far from perfect and its efficiency deteriorates in time. Data collected during this study will extend our knowledge about the mechanism responsible for development of PD and might help to developing personalized, cellular regenerative therapy.

Chronic or permanent damage to brain structures by various factors is called encephalopathy. The main two causes that often lead to encephalopathy in childhood are mechanical damage or bacterial infections. The consequences of brain damage at such a young age are motor disabilities as well as neurological disorders including epilepsy. Pathomechanisms of the central nervous system damage that lead to the encephalopathy and subsequent dysfunctions are largely unknown. Our lab is focused on finding new ways to treat encephalopathy and its complications using stem cells-based approach and immunomodulation strategy.