RECAMO

The work of the Research Center for Applied Molecular Oncology (RECAMO) focuses 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

Since 2020, seven working groups have been operating at RECAMO, conducting long-term research within specific areas of cancer biology. RECAMO is located in the Morávek Pavilion, with laboratories on each of its floors tailored to the specific requirements of research activity.


3Projects


4Research groups

Research group of Bořivoj Vojtěšek

Immune system checkpoints are effective targets for cancer therapy. Specifically, antibody-based PD-L1 blockade restores immune response and enhances anti-tumor immune activity in cancer patients. However, despite some successes, many patients exhibit minimal response or develop resistance to this therapy. HSP90 is a key molecular chaperone that stabilizes several mutant proteins in tumor cells, thus aiding in overcoming the stress generated by genetic instability. Its 'client' proteins include various receptors and/or signaling 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, enabling 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 identifying and validating novel tumor biomarkers, which can take various forms such as proteins, DNA, or RNA. Ideally, these biomarkers should be specific to a particular type of cancer and absent 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 interconnected 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 objective of clinical proteomics is to gather comprehensive insights into qualitative and quantitative changes in proteins within the studied proteomes and their association with physiological and pathological shifts. This understanding can aid in identifying markers suitable to early diagnosis or predicting responses 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.

Research group of Petr Müller

The escalating demands for the maintenance of protein homeostasis represent one of the fundamental characteristics of a tumor cell. Genome instability, heightened mutation frequency, and elevated proteosynthesis trigger stress signaling activation, prompting increased production and activation of chaperones upon which tumor cells rely. Consequently, tumors demonstrate heightened expression of stress-induced chaperones, primarily represented 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 specializes in advanced analyses of bioinformatics and statistical data for individual departments of MMCI, other research groups, and external collaborators. The department also focuses on molecular modeling and molecular dynamics of proteins, as well as the development of statistical and analytical software.

Research group leader
Senior researcher

Mgr. Bc. Filip Zavadil Kokáš, Ph.D.

Research group of Tomáš Kazda

Cellular immunity plays a pivotal role in tumor eradication; however, tumor cells can evade the immune system through a process known as immunoediting. In contrast, immunotherapy is a strategy aimed at reactivating and enhancing the immune system's capacity to identify and eliminate tumor cells. As such, immunotherapy represents a highly dynamic and promising approach to anticancer treatment for various types of tumors.

The actual interaction between immune and tumor cells takes place within the tumor microenvironment, encompassing all cellular and non-cellular elements of tumor tissue and its immediate surroundings. The tumor microenvironment is characterized by acidic pH, hypoxia, or low levels of nutrients, all of which induce cellular stress, including endoplasmic reticulum (ER) stress. Therefore, it can be hypothesized that ER stress may play a significant role in both the process of tumor immunoediting and the 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 of Martin Bartošík

The research group develops novel in vitro biomedical technologies for the analysis of cancer biomarkers at the nucleic acid level. In particular, it uses isothermal amplification techniques as alternatives to conventional PCR in combination with electrochemical or electrochemiluminescent detection methods, which are suitable candidates for personalized decentralized medicine at the point of care due to their speed and instrumentation.

Tumour biomarkers are signalling molecules that can detect the presence of cancer with some accuracy, e.g. from a blood sample. Such determinations can partially replace expensive imaging methods, which are often not widely available. They can also help to adjust the right treatment or monitor the response to the chosen therapy.

The research group is focused on:

(1) the detection of cancer infections, in particular human papillomavirus (HPV) infection, which can lead to cervical cancer in women, or human cytomegalovirus (hCMV) infection, by determining viral DNA or RNA sequences;

(2) analysis of point mutations in tumor suppressor genes or oncogenes that play a key role not only in the development and progression of cancer, but also in predicting response to treatment (e.g. BRAF mutations in melanoma, KRAS mutations in colon cancer);

(3) analysis of epigenetic modifications (e.g. DNA/RNA methylation) or detection of short and long non-coding RNAs that play an important role in the regulation of gene expression.


5Studies


6Software

Bioinformatics software tools developed in RECAMO


7Publications


8Project NICR

 

About project:

National Institute for Cancer Research (NICR) 

 

Registration number:     LX22NPO5102

Implementation period:  01.06.2022 - 31.12.2025

Governing body:             Ministry of Education, Youth, and Sports of the Czech Republic

 

Benefciary:                      Charles University

Partners:                          Masaryk Memorial Cancer Institute

                                            Masaryk University

                                            Palacký University Olomouc

                                            Institute of Biotechnology CAS

                                            Institute of Microbiology CAS

                                            Institute of Experimental Medicine CAS

                                            Institute of Photonics and Electronics CAS

                                            Institute of Molecular Genetics CAS

                                            Institute of Macromolecular Chemistry CAS

                                            Institute of Organic Chemistry and Biochemistry CAS

                                  

For more information see https://www.nuvr.cz/en

 

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