RECAMO

The work of the Research Center for Applied Molecular Oncology (RECAMO) is focused on cancer biology. RECAMO is represented by a multidisciplinary team consisting of Czech and foreign researchers and medical specialists working within this cutting edge workplace.

„Research is meeting the unmet needs of our patients.“

doc. MUDr. Tomáš Kazda, Ph.D.


1Contacts

Director for Science & Research

doc. MUDr. Tomáš Kazda, Ph.D.

Scientific director of RECAMO

RNDr. Bořivoj Vojtěšek, DrSc.

2First-rate Cancer Research Center

Seven working groups have been operating at RECAMO since 2020. They have been conducting a long-term research within specific areas of cancer biology. RECAMO is located in the Morávek Pavilion. Laboratories on each of its floors respond to the specific requirements of research activity.


3Projects


4Research groups

Research group of Bořivoj Vojtěšek

Immune system checkpoints are effective targets for cancer therapy. In particular, antibody-based PD-L1 blockage restores immune response and increases anti-tumour immune activity in cancer patients. However, despite some successes, many patients show minimal response, or develop resistance to this therapy. HSP90 is a key molecular chaperone that stabilises several mutant proteins in tumour cells and thus helps to overcome the stress generated by genetic instability. Its “client” proteins include various receptors and/or signalling proteins, many of which are targets for anti-cancer therapy. In one of our research areas, we focus on identifying how HSP90 inhibitors (HSP90i) modify levels of “client” proteins that control the sensitivity/resistance of cancer cells to immune attack. Thus, we are studying the mechanisms of immune activation by HSP90i at multiple levels to provide a comprehensive view of the underlying principles, allowing combination immunotherapeutic approaches in the future.

We also focus on understanding the key ways by which wild type p53 protein, the main tumour suppressor in human cancer, can be inactivated. p53 is mutated in 50 % of cancers and, whilst the other half keeps wild type p53, its function is abrogated by other mechanisms. We are using screening methods such as CRISPR-CAS9 activation/knock-out libraries to describe possible mechanisms of p53 inactivation. Moreover, by using chromatin immunoprecipitation followed by next generation sequencing, we study p53 function as a transcription factor. Modulations in the ability of p53 to specifically bind p53 target genes can lead to inappropriate cellular outcomes and we try to understand how specific binding can be regulated. We also investigate the main p53 negative regulators, HDM2 and HDMX, by studying their protein-protein and protein-RNA interactions and we try to understand a complex regulatory loop in which HDM2 and HDMX switch from negative to positive regulators. By elucidating these questions of p53 inactivation, we lead to better targeted therapy based on p53 reactivation alone or in combined treatment.

The last subject of our laboratory is focussed on studying new potential therapeutic strategies for cancer treatment, using techniques of advanced molecular biology to elucidate mechanisms of action of experimental therapeutics. We work on preclinical testing of new low-molecular weight inhibitors and therapeutic antibodies for targeted therapy. We also study signalling pathways crucial for cancer cell response to therapy and their deregulation in various cancer types. Our understanding of these cellular processes is pivotal for choosing the right therapeutic option and its success.

Scientific director of RECAMO
Research group leader

RNDr. Bořivoj Vojtěšek, DrSc.

Research group of Roman Hrstka 

Our research team focuses on the identification and validation of novel tumour biomarkers, which can come in many forms, e.g. proteins, DNA or RNA, and should ideally be specific to a particular type of cancer and not be present in normal tissues or healthy individuals.

Based on their application, cancer biomarkers can be classified as i) diagnostic, indicating a presence of cancer in a patient; ii) predictive, predicting response to specific therapeutic interventions; iii) prognostic, informing physicians about the risk of clinical outcomes and, some but not all can be exploited as iv) therapeutic targets. We intend to identify, evaluate and put into clinical practice specific tumour biomarkers allowing for the improvement of recent diagnostic methods, monitoring of minimal residual disease, detection of metastasis presence or predict the risk of their development, and the application as therapeutic targets. Besides using the state-of-the-art technologies when analysing these biomarkers, we also develop our own methodological strategies and technologies for their detection, especially electrochemical DNA and RNA biosensors, representing a simple, rapid and inexpensive alternative to current methods.

Research group leader
Senior researcher

doc. Mgr. Roman Hrstka, Ph.D.

Research group of Philip Coates

The research group is focused on two related areas of cancer biology; the role of p63 in cancer formation, progression and resistance to treatment, and the biology of cancer stem cells. p63 is a member of a family of related proteins (p53, p63 and p73) and is present at high levels in squamous cell carcinomas and some other types of cancer.

High levels of p63 are associated with therapy failure, metastasis and death of patients. We are investigating the mechanisms that regulate p63, with the long-term intention that blocking specific pathways that cause increased p63 in cancer could be used therapeutically. In particular, we have found that some drugs that are widely used for treating non-cancer conditions also influence p63. Another aspect of this research tries to identify proteins that interact with p63 (including the other family members, p53 and p73) to regulate its activity. Our studies are also showing that p63 has roles in other cancer types, including about 50% of breast cancers and a small percentage of prostate cancers, where it acts as a regulator of cancer stem cells, our other main topic of research.

Cancer stem cells are proposed to be a unique sub-population of cancer cells that are responsible for overall growth of the tumour, especially for tumour spread to other sites in the body, and are relatively resistant to the common therapies used for most cancer patients (radiotherapy and chemotherapy). The existence of such tumour cell populations has been demonstrated many times, using a variety of different markers to identify these cells. However, it has become apparent that each marker identifies a different population of cells and that cancer stem cells are not a fixed population as originally thought, but may change their properties according to the situation they find themselves in. We are investigating whether we can identify specific properties that accurately define the cancer stem cell population in most or all cancers. The studies ask whether cancer stem cells have differences in their metabolism (specifically, in protein production and how they use glucose to produce energy). The ability to identify universal differences between cancer stem cells and the rest of the tumour cells would help both to study these specific cells in more detail, and to suggest drugs that selectively target these cells in cancer therapy.

Research group leader
Senior researcher

Philip John Coates, Ph.D.

Research group of Lenka Hernychová

The aim of clinical proteomics is to acquire detailed information about qualitative and quantitative alterations in proteins in the studied proteomes and about their connection with physiological and pathological changes. This knowledge can be used to identify markers suitable for early diagnosis or prediction of response to cancer therapy.

The activities of the research group involve its own research or in cooperation with clinicians and domestic or foreign scientific institutions. In addition, this group also provides service analyzes and contracted research. The research is focused on performing proteomic analyzes of samples related to cancer and aging, especially the detection of glycosylations and glycoproteins presented in sera and tissues of patients with solid tumors. Further goals include mapping of tyrosine kinase activity in tumors and also structural proteomic analysis based on protein-ligand interactions measured by the method based on the exchange of hydrogen for deuterium.

Research group leader
Senior researcher

prof. Ing. Lenka Hernychová, Ph.D.

Junior researcher

Ing. Tomáš Henek
RECAMO

Junior researcher

Jaromír Novák

Research group of Petr Müller

Increasing demands on the maintenance of protein homeostasis is one of the basic features of a tumour cell. Genome instability, high mutation frequency, and increased proteosynthesis lead to activation of stress signalling and increased production and activation of chaperones on which the tumour cells become dependent. Thus, tumours exhibit increased expression of stress-induced chaperones, represented mainly by Hsp70 and Hsp90.

In addition to changes in gene expression, pro-oncogenic chaperone activities are also enhanced by the formation of multimeric chaperone complexes. Therefore, one of our goals is to elucidate the prooncogenic behaviour of chaperones. Our project is focused on the analysis of posttranslational modifications of chaperones in tumours, their interactions and the effect on unstable oncoproteins. Another area of our research is stress signalling. Stress response is a key feature of cancer cells that ensures enhanced protein synthesis, compensates genomic instability and protects cancers from therapy induced stress. Heat shock factor-1 (HSF1) is a major stress-response transcription factor, and its activity is markedly enhanced in cancer. Proteotoxic stress activates HSF1 by conformational changes, leading to assembly of HSF1 trimers that bind DNA and control target gene expression. Although the function of HSF1 in transcription is known, the mechanisms leading to HSF1 activation and enhanced stress response in tumours are unclear. The research goal of our group is to describe the mechanisms that a tumour cell uses to maintain protein homeostasis. The aim of the research project focused on HSF1 is to reveal the mechanisms leading to HSF1 activation. Using structural proteomics, we describe the conformational changes that are responsible for its activation. The specific role of HSF1-regulated genes for tumour transformation is studied by gene expression analysis.

Research group leader
Senior researcher

MUDr. Petr Müller, Ph.D.

Research group of Bioinformatics

The Bioinformatics Research Group is focused on highly specialized analyses of a bioinformatics and statistical dates for individual departments of the MOU, other research groups and external collaborators. The department is also focused on molecular modelling and molecular dynamics of proteins and the development of statistical and analytical software's.

Research group leader
Senior researcher

Mgr. Bc. Filip Zavadil Kokáš, Ph.D.

Research group of Marek Svoboda

Cellular immunity plays a key role in the eradication of tumors; however, tumor cells can escape the immune system in the process called immunoediting. In contrast, immunotherapy is a strategy to reactivate and induce the immune system's ability to recognize and kill tumor cells. Immunotherapy is therefore a very dynamic and promising method of anticancer treatment for many types of tumors.

The actual interaction of immune and tumor cells occurs in the tumor microenvironment, which includes all cells as well as non-cellular components of tumor tissue and its immediate surroundings. Tumor microenvironment is characterized by acidic pH, hypoxia or low levels of nutrients, which are factors causing cellular stress, including the so-called "endoplasmic reticulum (ER) stress". Thus, it can be hypothesized that ER stress may play a major role both in the process of tumor immunoediting and in response to immunotherapy.

Therefore, our goal is to study the effect of ER stress on the immune status of the tumor, immunoediting and, last but not least, on the effectiveness of immunotherapy in renal and ovarian carcinomas.

Research group leader
Director of MMCI

prof. MUDr. Marek Svoboda, Ph.D.
RECAMO

Researcher

Mgr. Kateřina Vašíčková

Researcher – student

Mgr. Barbora Vavrušáková

5Studies


6Software

Bioinformatics software tools developed in RECAMO


7Publications


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