Ondřej Slabý

Translational Cancer Genomics

Head: Ondřej Slabý
Brno node

oslaby@med.muni.cz
website of the Institute

HOME INSTITUTION

Faculty of Medicine MU/CEITEC MU

RESEARCH PROGRAMME(S)

RP 3 - Biomarkers of cancers and cancer diagnostics
RP 5 - Translational oncology: Verification clinical studies of the proof-of-concept type

Discovering genetic pathways to recovery!

COLLABORATION WITH INFRASTRUCTURES

Mission: Conduct translational genomics research that advances our knowledge and transforms the lives of cancer patients.
Vision: Understand how cancer genomes control carcinogenesis and response to cancer therapy, and use this knowledge to benefit patients.

Non-coding RNAs (ncRNAs) have significantly expanded the concept of molecular pathogenesis of cancer and have shown great potential to serve as diagnostic tools and therapeutic targets. In the last two decades, hundreds of individual ncRNAs of different classes have been shown to act as tumor suppressors or oncogenes in a wide range of cancers. However, we still lack a synthesis of this knowledge using systems biology approaches to define ncRNA deregulation as a novel hallmark of cancer.

This gap is the focus of our group’s research. Also successful applications of ncRNAs as novel diagnostic or therapeutic targets are still limited. Building on our previous work, we are working on research into innovative ncRNA-based diagnostics and collaborating with industry to develop certified diagnostics for clinical practice. We are also studying novel ncRNAs as potential therapeutic targets and aiming to characterize them in vitro and in vivo along with innovative delivery systems to tumor tissue for potential future testing in non-commercial Phase I/II clinical trials.

Cancer is a disease of the genome. Medical genomics has changed the way we understand this disease today. It is expanding our knowledge of cancer biology and allowing us to identify new therapeutic targets. At the same time, it now helps directly in clinical practice by enabling individually formulated anti-cancer treatment. Harnessing the power of genomics in cancer care has also significantly improved therapeutic outcomes for cancer patients. Our research focuses on the search for genomic alterations in solid tumors, particularly high-risk refractory pediatric cancers, and on evaluating their relevance for precise diagnosis and individualizing treatment. We use various next-generation sequencing platforms to perform DNA and RNA sequencing, single-cell sequencing and methylome analysis. We aim to expand our knowledge of the biology of these rare tumors and potentially identify new therapeutic targets, while leveraging the real-time insights gained from the individual tumor genome for therapeutic planning.

Research objectives

Non-coding RNAs in solid cancers, studying the function of non-coding RNAs (microRNAs, PIWI-interacting RNAs, long non-coding RNAs, etc.) in the molecular pathology of tumors and their potential use as innovative diagnostic tools and novel therapeutic targets in oncology.
Cancer genomics and precision oncology. Research of cancer genomics and precision oncology enabling a higher degree of individualization of cancer treatment and a better understanding of tumor biology, using technologies enabling comprehensive genomic profiling.

SELECTED PUBLICATIONS

Vychytilova-Faltejskova P, Merhautova J, Machackova T, Gutierrez-Garcia I, Garcia-Solano J, Radova L, Brchnelova D, Slaba K, Svoboda M, Halamkova J, Demlova R, Kiss I, Vyzula R, Conesa-Zamora P, Slaby O. MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9. Oncogenesis. 2017;6(11):399. DOI: 10.1038/s41389-017-0006-6

Chen B, Dragomir MP, Fabris L, Bayraktar R, Knutsen E, Liu X, Tang C, Li Y, Shimura T, Ivkovic TC, De Los Santos MC, Anfossi S, Shimizu M, Shah MY, Ling H, Shen P, Multani AS, Pardini B, Burks JK, Katayama H, Reineke LC, Huo L, Syed M, Song S, Ferracin M, Oki E, Fromm B, Ivan C, Bhuvaneshwar K, Gusev Y, Mimori K, Menter D, Sen S, Matsuyama T, Uetake H, Vasilescu C, Kopetz S, Parker-Thornburg J, Taguchi A, Hanash SM, Girnita L, Slaby O, Goel A, Varani G, Gagea M, Li C, Ajani JA, Calin GA. The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling. Gastroenterology. 2020;159(6):2146-2162.e33. DOI: 10.1053/j.gastro.2020.08.018
Liu I, Jiang L, Samuelsson ER, Marco Salas S, Beck A, Hack OA, Jeong D, Shaw ML, Englinger B, LaBelle J, Mire HM, Madlener S, Mayr L, Quezada MA, Trissal M, Panditharatna E, Ernst KJ, Vogelzang J, Gatesman TA, Halbert ME, Palova H, Pokorna P, Sterba J, Slaby O, Geyeregger R, Diaz A, Findlay IJ, Dun MD, Resnick A, Suvà ML, Jones DTW, Agnihotri S, Svedlund J, Koschmann C, Haberler C, Czech T, Slavc I, Cotter JA, Ligon KL, Alexandrescu S, Yung WKA, Arrillaga-Romany I, Gojo J, Monje M, Nilsson M, Filbin MG. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location. Nat Genet. 2022;54(12):1881-1894. DOI: 10.1038/s41588-022-01236-3
Palova H, Das A, Pokorna P, Bajciova V, Pavelka Z, Jezova M, Pal K, Dimayacyac JR, Negm L, Stengs L, Bianchi V, Vejmelkova K, Noskova K, Jarosova M, Mejstrikova S, Mudry P, Kyr M, Merta T, Tinka P, Drabova K, Aulicka S, Jugas R, Tabori U, Slaby O, Sterba J. Precision immuno-oncology approach for four malignant tumors in siblings with constitutional mismatch repair deficiency syndrome. NPJ Precis Oncol. 2024;8(1):110. DOI: 10.1038/s41698-024-00597-8
Pokorna P, Palova H, Adamcova S, Jugas R, Al Tukmachi D, Kyr M, Knoflickova D, Kozelkova K, Bystry V, Mejstrikova S, Merta T, Trachtova K, Podlipna E, Mudry P, Pavelka Z, Bajciova V, Tinka P, Jarosova M, Ivkovic TC, Madlener S, Pal K, Stepien N, Mayr L, Tichy B, Drabova K, Jezova M, Kozakova S, Vanackova J, Radova L, Steininger K, Haberler C, Gojo J, Sterba J, Slaby O. Real-world performance of integrative clinical genomics in pediatric precision oncology. Lab Invest. 2024:102161. DOI: 10.1016/j.labinv.2024.102161