Změnit instituci
Pokročilé nano a mikrotechnologie Pokročilé materiály Strukturní biologie Gen. a prot. rostlin. systémů Molekulární medicína Výzkum mozku a lidské mysli Molekulární vet. medicína

Molekulární onkologie II - solidní nádory

Vedoucí výzkumné skupiny
Researcher ID
Telefon: +420 54949 6876
E-mail: ,
Kancelář:

Research areas

  • Biology of the non-coding RNAs (microRNA, T-UCR, LncRNA, pyknons, etc.) and their involvement in carcinogenesis
  • Significance of non-coding RNAs in solid cancer pathogenesis and identification of new therapeutic targets
  • Application of non-coding RNAs in solid cancer diagnostics and individualization of therapy in cancer patients

Main objectives

  1. Introduction of high-throughput analyses (whole genome sequencing and transcriptome profiling) of human genome mainly focused on non-coding RNAs. Utilization of these technologies in medicine and development of diagnostic tests based on high-throughput methods.
  2. Comprehensive analysis of non-coding RNAs (expression, SNPs, methylation profiles, according to Objective 1) in solid cancer (mainly colorectal cancer, renal cell carcinoma, esophageal cancer, breast cancer, lung cancer and glioblastoma multiforme). Integration of experimental data with clinico-pathological characteristics of patients aiming identification of potential susceptibility, diagnostic, prognostic, and predictive biomarkers, as well as new therapeutic targets in tumor tissue or patient’s body fluids. Design and coordination of large multi-centric validation studies.
  3. Detailed phenotypic characterization (e.g. validation of predicted targets of miRNAs and their integration into signalling pathways) and functional evaluation (proliferation, cell cycle, apoptosis, invasiveness, etc.) of non-coding RNAs suspected to be involved in carcinogenesis or cancer outcome (Objective 2) in vitro in a relevant cell line models. Studies examining oncogenic or tumor-suppressive function of particular non-coding RNA in vivo, with subsequent pharmacological analysis evaluating usage of this RNA as therapeutic target.
  4. Formulation and design of recommendations for potential implementation of novel biomarkers (according to Objectives 2 and 3) to clinical management of solid cancer patients leading to higher level of individualization and better therapeutic outcomes. Development and technological transfer of new targeted therapeutic strategies in solid cancer.

Content of research

According to the central dogma of molecular biology, it has been postulated that vast majority of genetic information encoding the biologic form and phenotype is rendered by proteins. Employing whole-genome analytical approaches and next-generation sequencing technologies (ENCODE Project), it has been observed that at least 90% of the human genome is actively transcribed. Although initially argued to be spurious transcriptional noise or accumulated evolutionary debris arising from the early assembly of genes and/or the insertion of mobile genetic elements, recent evidence suggests that such a “dark matter” of the genome, i.e. the non-coding RNAs (ncRNAs) may play the major biological roles in cellular development, physiology and pathologies.
NcRNAs could be grouped into two major classes – small ncRNAs and long ncRNAs. LncRNA are transcripts sized in a range of 200 nt up to 100 kb lacking open reading frames. LncRNA expression levels appear to be lower than protein-coding genes, and some lncRNAs are preferentially expressed in specific tissues. The small number of characterized human lncRNAs have been associated with a spectrum of biological processes, for example, epigenetics, alternative splicing, nuclear import, as structural components, as precursors to small RNAs and even as regulators of mRNA decay. Furthermore, accumulating reports of mis-regulated lncRNA (HOTAIR, MALAT1, HULC, T-UCRs, etc.) expressions across numerous cancer types suggest that aberrant lncRNA expression may be an important contributor to tumorigenesis. Small ncRNAs are represented by a broad range of known and newly discovered RNA species, with many being associated with 5’ or 3’ regions of coding genes. This class includes the well-documented miRNAs, and siRNAs, and most of them significantly extended the concept of molecular carcinogenesis, and recently are subject of the intensive translational research in this field.
Based on commonly accepted definition by Hanahan and Weinberg, the tumor is characterized by 6 features: self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis and tissue invasion and metastasis. It has been repeatedly confirmed that miRNAs may modify each of these six characteristics by multilevel targeting either oncogenes or tumor suppressors. For details see Vogelstein model of carcinogenesis in colorectal cancer.

In our research we are mainly focused on colorectal cancer (CRC), significance of ncRNAs in its pathogenesis, and potential utilization of ncRNAs as biomarkers or even therapeutic targets. One of our projects is aiming at new molecular markers enabling the response prediction to anti-EGFR therapy in patients with metastatic CRC (mCRC) with wild type KRAS. Such markers could possibly lead to better understanding of molecular mechanisms of resistance, but also to individualization of therapy and therefore achievement of better therapeutical results and higher quality of life in patients with metastatic colorectal cancer. Furthermore, we are focused on identification of new biomarkers in blood serum. The rationale of our project is to build diagnostic panel of microRNAs enabling early detection of CRC in asymptomatic patients for screening purposes or monitoring of CRC patients with hereditary syndroms, as well as sensitive detection of disease progression in follow-up of CRC patients. We study circulating miRNAs as potential biomarkers also in renal cell carcinoma and pancreatic cancer. Moreover, we are looking for miRNA based diagnostic panel which will enable improved stratification of patients with Barrett esophageus (BE) to subgroups according to their individual risk of progression to esophageal adenocarcinoma, particularly it will enable the „high-risk“ subgroups detection. More accurate risk prediction in BE patients enable more rationalized monitoring design and early detection of progression to higher dysplastic grade or EAC. Another field of interest of our research group is concentrated on study of miRNAs and genes associated with process of epithelial-to-mesenchymal transition. These miRNAs and genes could serve as potential markers of risk prediction and early detection of metastatic disease in renal cell carcinoma patients.  Regarding glioblastoma multiforme (GBM), the main goal of our project is to extend knowledge about molecular mechanisms involved in glioblastoma carcinogenesis and invasivness by analysis of miRNA expression profiles in tumors and use our findings for prediction of therapy response in patients with glioblastoma. Furthermore, we would like to contribute to the molecular characterization of glioblastoma stem cells (GSCs) which are involved in resistance to the therapy and relapse of GBM. In this project, miRNA expression profiles of GSCs and non-GSCs will be identified, and furthermore, the obtained data will be used for development of the predictive miRNA panel that will enable prediction of therapy response and prognosis, and development of new, miRNA-based therapies in GBM. 

seznam / vizitky

Jméno a pozice

E-mail

Telefon

doc. RNDr. Ondřej Slabý, Ph.D.
Vedoucí výzkumné skupiny
+420 54949 6876
doc. Mgr. Jan Paleček, Dr. rer. nat.
Vedoucí výzkumný pracovník
+420 54949 6128
doc. MUDr. Marek Svoboda, Ph.D.
Výzkumný pracovník
+420 54949 6899
Mgr. Elleni Ponechal Michu
Odborná pracovnice
+420 54949 7574
Mgr. Robert Iliev
PhD student
+420 54949 3559
Mgr. Jaroslav Juráček
PhD student
Mgr. Hana Mlčochová, Ph.D.
PhD student
+420 54949 3559
Mgr. Jiří Šána, Ph.D.
Odborný pracovník
+420 54949 5246
prof. MUDr. Zdeněk Kala, CSc.
+420 532 233 105
MUDr. Tomáš Grolich, Ph.D.
+420 532 232 961
doc. MUDr. Petr Szturz, Ph.D.
+420 532 232 932
Parwez Ahmad, M.Sc.
PhD student
+420 54949 3559
Mgr. Zuzana Ožanová
RNDr. Kamila Součková, Ph.D.
+420 54949 5371
Mgr. Tomáš Loja, Ph.D.
Výzkumný pracovník
+420 54949 7455
Mgr. Petra Vychytilová, Ph.D.
PhD student
+420 54949 3559
Mgr. Táňa Macháčková
Mgr. Marek Večeřa
Mgr. Hana Nosková, Ph.D.
PhD student
+420 54949 6295
MUDr. Beáta Hemmelová
MVDr. Martina Vodinská
+420 54949 5371
Mgr. Martina Lojová, Ph.D.
Výzkumný pracovník
+420 54949 3559
Mgr. Jana Merhautová
PhD student
+420 54949 7255
Mgr. Jitka Vaňáčková, Ph.D.
PhD student
+420 54949 5681
Mgr. Michal Obořil
PhD student
Jana Šujanová
MUDr. Tomáš Kazda
Mgr. Natalia Anna Gabło
Mgr. Soňa Klusová
Mgr. Pavel Vaňáček
Mgr. Kristína Greplová
prof. MUDr. Martin Smrčka, Ph.D., MBA
+420 547 192 742, +420 532 232 884, +420 532 232 190
MUDr. Hana Valeková
MUDr. Václav Vybíhal, Ph.D.
MUDr. Tomáš Rozkoš
MUDr. Igor Kiss, Ph.D.
Mgr. Lukáš Ponechal
+420 54949 5248
Ing. Dana Knoflíčková
Simon Vejtasa
MUDr. Miroslava Chovancová
Drahomíra Procházková
MUDr. Lukáš Frola
+420 532 232 366
Mgr. Anna Konieczna, Ph.D.

VYBRANÉ PUBLIKACE

2016

  • BUCKOVA, H; NOSKOVA, H; BORSKA, R; REBLOVA, K; PINKOVA, B; ZAPLETALOVA, E; KOPECKOVA, L; HORKY, O; NEMECKOVA, J; GAILLYOVA, R; NAGY, Z; VESELY, K; HERMANOVA, M; STEHLIKOVA, K; FAJKUSOVA, L, 2016:Autosomal recessive congenital ichthyoses in the Czech Republic. BRITISH JOURNAL OF DERMATOLOGY 174 (2), p. 405 - 407.
  • THORENOOR, N; FALTEJSKOVA-VYCHYTILOVA, P; HOMBACH, S; MLCOCHOVA, J; KRETZ, M; SVOBODA, M; SLABY, O, 2016:Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer. ONCOTARGET 7 (1), p. 622 - 637.
  • UHLIKOVA, H; OBORIL, M; KLEMPOVA, J; SEDO, O; ZDRAHAL, Z; KASPAROVSKY, T; SKLADAL, P; LOCHMAN, J, 2016:Elicitin-Induced Distal Systemic Resistance in Plants is Mediated Through the Protein-Protein Interactions Influenced by Selected Lysine Residues. FRONTIERS IN PLANT SCIENCE 7
  • ZABRADY, K; ADAMUS, M; VONDROVA, L; LIAO, C; SKOUPILOVA, H; NOVAKOVA, M; JURCISINOVA, L; ALT, A; OLIVER, AW; LEHMANN, AR; PALECEK, JJ, 2016:Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA. NUCLEIC ACIDS RESEARCH 44 (3), p. 1064 - 1079.

2015

  • BABULA, P; KLEJDUS, B; KOVACIK, J; HEDBAVNY, J; HLAVNA, M, 2015:Lanthanum rather than cadmium induces oxidative stress and metabolite changes in Hypericum perforatum. JOURNAL OF HAZARDOUS MATERIALS 286 , p. 334 - 342.
  • BESSE, L; SEDLARIKOVA, L; KRYUKOV, F; NEKVINDOVA, J; RADOVA, L; SLABY, O; KUGLIK, P; ALMASI, M; PENKA, M; KREJCI, M; ADAM, Z; POUR, L; SEVCIKOVA, S; HAJEK, R, 2015:Circulating Serum MicroRNA-130a as a Novel Putative Marker of Extramedullary Myeloma. PLOS ONE 10 (9)
  • KOZAKOVA, L; VONDROVA, L; STEJSKAL, K; CHARALABOUS, P; KOLESAR, P; LEHMANN, AR; ULDRIJAN, S; SANDERSON, CM; ZDRAHAL, Z; PALECEK, JJ, 2015:The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex. CELL CYCLE 14 (6), p. 920 - 930.
  • MLCOCHOVA, J; FALTEJSKOVA-VYCHYTILOVA, P; FERRACIN, M; ZAGATTI, B; RADOVA, L; SVOBODA, M; NEMECEK, R; JOHN, S; KISS, I; VYZULA, R; NEGRINI, M; SLABY, O, 2015:MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab. ONCOTARGET 6 (36), p. 38695 - 38704.
  • PALECEK, E; TKAC, J; BARTOSIK, M; BERTOK, T; OSTATNA, V; PALECEK, J, 2015:Electrochemistry of Nonconjugated Proteins and Glycoproteins. Toward Sensors for Biomedicine and Glycomics. CHEMICAL REVIEWS , p. 20452045 - 2108.

2014

  • SANA, J; RADOVA, L; LAKOMY, R; KREN, L; FADRUS, P; SMRCKA, M; BESSE, A; NEKVINDOVA, J; HERMANOVA, M; JANCALEK, R; SVOBODA, M; HAJDUCH, M; SLAMPA, P; VYZULA, R; SLABY, O, 2014:Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients. CARCINOGENESIS 35 (12), p. 2756 - 2762.

2012

  • GUERINEAU, M; KRIZ, Z; KOZAKOVA, L; BEDNAROVA, K; JANOS, P; PALECEK, J, 2012:Analysis of the Nse3/MAGE-Binding Domain of the Nse4/EID Family Proteins. PLOS ONE 7 (4)
  • RAJA, KRM; KUBICZKOVA, L; RIHOVA, L; PISKACEK, M; VSIANSKA, P; HEZOVA, R; POUR, L; HAJEK, R, 2012:Functionally Suppressive CD8 T Regulatory Cells Are Increased in Patients with Multiple Myeloma: A Cause for Immune Impairment. PLOS ONE 7 (11), p. e49446 - e49455.

2011

  • HUDSON, JJR; BEDNAROVA, K; KOZAKOVA, L; LIAO, CY; GUERINEAU, M; COLNAGHI, R; VIDOT, S; MAREK, J; BATHULA, SR; LEHMANN, AR; PALECEK, J, 2011:Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families. PLOS ONE 6 (2)

GRANTY

  • Identification and functional characterization of microRNAs with predictive significance in patients with glioblastoma (NT/11214), Ministry of Health - Ministry of Health's Departmental Research and Development Programme III (2010-2015), 2010 - 2013
  • Vytvoření diagnostické sady cirkulujících mikroRNA pro neinvazivní časnou diagnostiku a sledování pacientů s kolorektálním karcinomem (NT/13549), Ministry of Health - Ministry of Health's Departmental Research and Development Programme III (2010-2015), 2012 - 2015
  • Analýza mikroRNA v glioblastomových kmenových buňkách: predikce léčebné odpovědi a identifikace nových terapeutických cílů u pacientů s glioblastomem (NT/13514), Ministry of Health - Ministry of Health's Departmental Research and Development Programme III (2010-2015), 2012 - 2015
  • Analysis of EGFR signalling and microRNA expression profiles in prediction of response to anti-EGFR (NT/13860), Ministry of Health - Ministry of Health's Departmental Research and Development Programme III (2010-2015), 2012 - 2015
  • Complex characterization of molecular genetic changes in glioblastoma multiforme and its relapses, and evaluation of their possible significance in oncologic therapy and therapy effect (NT/13581), Ministry of Health - Ministry of Health's Departmental Research and Development Programme III (2010-2015), 2012 - 2015
  • Development of microRNA diagnostic panel for identification Barret esophagus patients at high-risk of progression to adenocarcinoma (NT13585), Ministry of Health - Ministry of Health's Departmental Research and Development Programme III (2010-2015), 2012 - 2014
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