Matjaž Barborič, Principle Investigator at University of Helsinki
Meet the PI
Dr. Barborič received his B.Sc. in Microbiology from the University of Ljubljana, Slovenia in 1998. He then moved to the United States to perform research under the supervision of Dr. B. Matija Peterlin (University of California, San Francisco) and obtained his Ph.D. in Biomedicine and Molecular Biology from School of Medicine, University of Ljubljana, Slovenia in 2003 with the mentorship of Dr. Ana Plemenitaš. He continued his training as a postdoctoral fellow with Dr. Peterlin at the Department of Medicine, Microbiology and Immunology at the University of California, San Francisco, during which time he was supported in part by a fellowship from The American Foundation for AIDS Research.
During his graduate studies, Dr. Barborič was one of the pioneering researchers challenging the predominantly held view that eukaryotic transcription is regulated primarily at the initiation stage. On the basis of the previous work on HIV-1 transactivator Tat, he demonstrated for the first time that transcriptional activators and repressors could regulate gene expression at the level of Pol II elongation through P-TEFb kinase. During his postdoctoral tenure, he expanded this influential work by shedding a light on the control of P-TEFb by the non-coding 7SK snRNA within 7SK snRNP. Moreover, he showed that HIV Tat subverts this regulation for unfettered viral propagation and that keeping P-TEFb repressed within 7SK snRNP is critical for proper vertebrate development and pre-mRNA maturation.
Following receipt of the Academy of Finland Research Fellow Award in 2010, Dr. Barborič began his independent research career at the University of Helsinki, Finland. Fascination with the control of Pol II elongation by P-TEFb and 7SK snRNP remains one of the major themes of his investigations. By using biochemistry, genetics and functional genomics approaches, his laboratory is elucidating how cellular RNA binding proteins fine-tune transition from Pol II pausing into elongation. Another research direction focuses on understanding how misregulation of gene expression underlies human diseases such as cancer. Here, current emphasis is on elucidating how the novel and essential transcription elongation kinase Cdk12/CycK controls target gene transcription, as well as how recurrent mutations in CDK12 provoke cancerogenesis. Finally, his laboratory is developing methods that shall provide new perspectives on the integration between Pol II transcription and co-transcriptional maturation of precursor mRNA. Dr. Barborič’s research program has been supported by grants from the Academy of Finland, Sigrid Juselius Foundation, University of Helsinki and Marsha Rivkin Center for Ovarian Cancer Research.
- Sigrid Juselius Senior Investigator (2019-2021)
- Principal Investigator, Faculty of Medicine, University of Helsinki, Finland (2010-Present)
- Academy of Finland Research Fellow, University of Helsinki, Finland (2010-2015)
- Postdoctoral Fellow, Haartman Institute, University of Helsinki, Finland (2009-2010)
- Postdoctoral Fellow, Department of Medicine, University of California, San Francisco, California, USA (2004-2008)
- Postgraduate Researcher, Department of Medicine, University of California, San Francisco, California, USA (1999-2003)
- Graduate Student, School of Medicine, Programme in Biomedicine and Molecular Biology, University of Ljubljana, Slovenia (1999-2003)
- Transcriptional regulation
- Promoter-proximal pausing of RNA Pol II
- DNA damage response
- Transcription-associated CTD kinases
- RNA-binding proteins
- Misregulation of Transcription in Cancer
- Genomic instability
- Sigrid Juselius Senior Investigator Award (2019-2021)
- Academy of Finland Research Grant Award (2017-2021)
- University of Helsinki 375th Anniversary Award (2015)
- Sigrid Juselius Foundation Award (2012-2016)
- Marsha Rivkin Center Pilot Study Award (2012, 2013)
- University of Helsinki 3-year Research Grant (2012-2015)
- Academy of Finland Research Fellow Award (2010-2015)
- The American Foundation for AIDS Research Fellowship Award (2004-2006)
- Young Investigator Award, Republic of Slovenia (1999-2003)
- Bugai A, Quaresma AJC, Friedel CC, Lenasi T, Düster R, Sibley CR, Fujinaga K, Kukanja P, Hennig T, Blasius M, Geyer M, Ule J, Dölken L, Barboric M (2019). P-TEFb activation by RBM7 shapes a pro-survival transcriptional response to genotoxic stress. Molecular Cell, doi:https://doi.org/10.1016/j.molcel.2019.01.033, in press.
- Quaresma AJC, Bugai A, Barboric M (2016) Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. Nucleic Acids Res 44:7527-7539.
- Barboric M, Fujinaga K (2016) The two sides of Tat. Elife doi:10.7554/eLife.12686.
- Ekumi KM, Paculova H, Lenasi T, Pospichalova V, Bösken CA, Rybarikova J, Bryja V, Geyer M, Blazek D, Barboric M (2015) Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex. Nucleic Acids Res 43:2575-2589.
- Lenasi T, Peterlin BM, Barboric M (2011) CBC links pre-mRNA capping to transcription elongation and alternative splicing through P‑TEFb. J Biol Chem 286:22758-22768.
- Barboric M, Lenasi T (2010) Kick-sTARting HIV-1 transcription elongation by 7SK snRNPdeporTATion. Nat Struct Mol Biol 17:928-930.
- Barboric M, Lenasi T, Chen H, Johansen EB, Guo S, Peterlin BM (2009) 7SK snRNP/P‑TEFb couples transcription elongation with alternative splicing and is essential for vertebrate development. Proc. Natl. Acad. Sci. U S A 106:7798-7803.
- Barboric M, Yik YHN, Czudnochowski N, Chen R, Yang Z, Contreras X, Geyer M, Peterlin BM, Zhou Q (2007) Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic Acids Res 35:2003-2012.
- Barboric M, Kohoutek J, Price J P, Blazek D, Price DH, Peterlin BM (2005) Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb. EMBO J 24:4291-4303.
- Barboric M, Peterlin BM (2005) A New Paradigm in Eukaryotic Biology: HIV Tat and the control of transcriptional elongation. PLoS. Biol 3:e76.
- Zhang F*, Barboric M*, Blackwell TK, Peterlin BM (2003) A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb. Genes Dev 17:748-758. (*equal contribution)
- Barboric M, Nissen R M, Kanazawa S, Jabrane-Ferrat N, Peterlin Bm (2001) NF-kB binds P‑TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell 8:327-337.