Klefström’s research focuses on therapeutic strategies aiming to exploit oncogene-induced vulnerabilities and he has long-term interest in the apoptotic function of MYC protein. Currently, his research group explores the potential of oncogenic MYC in triggering immunogenic death of the tumor cells. The group recently discovered a clinically applicable combination regimen, which shows a strong apoptotic activity selectively in MYC-high breast tumors as tested in cell lines, patient-derived explant cultures and transgenic mice. The regimen is based on mitochondrial complex I inhibition by the safe diabetes drug metformin (M) and neutralization of the anti-apoptotic BCL-2 protein by ABT-199/venetoclax (Ve). Combination of VeM with the immune checkpoint inhibitor anti-PD-1 offers a persistent treatment response in mice that lasts months even after cessation of the treatment. The project is now in translational stage. In addition, the group studies therapeutically intervenable oncogenic functions of many neglected targets such as transmembrane serine proteases.
Klefström obtained PhD at University of Helsinki in 1997 and did postdoctoral with Gerard Evan at ICRF London (1998-1999) and UCSF Comprehensive Cancer Center, San Francisco (2000-2002). In 2009, he briefly worked as a visiting Professor in QB3 institute, UCSF.
Klefström’s research group has established variety of three-dimensional culture systems for mammary primary and stem cell-based organotypic breast structures as well as patient tumor-derived explants for ex vivo target validation and for studies of breast cancer development and translation.
PERSONAL DATA Juha Tapio Klefström
CURRENT MAIN POSITION FICAN Research Professor in Finnish Cancer Institute.
PRESENT PROFESSIONAL AFFILIATIONS
PROFESSOR (part-time). FICAN-South (HUS, Helsinki University Hospital).
RESEARCH DIRECTOR (part-time). Research Programs Unit, Medical Faculty, University of Helsinki (since August 2013). The Research Director position includes the following duties:
- Member of the Research Programs Unit (RPU) of Medical Faculty (2019-2025). RPU is one of three units of the Medical Faculty with focus on top quality medical research. The unit’s research is organized in 9 internationally peer-reviewed programs, which include 90 research groups in total.
Member of the Translational Cancer Medicine Research Program (2019-2025). The program provides a platform for translational discovery that bridges the gap between the fundamental cancer re- search in the Academic Medical Center Helsinki and the early-stage clinical trials of the Helsinki University Hospital. In this platform, genomic, epidemiological and pathological analyses, analysis of patient-specific cancer organoids, mechanistic validation and drug efficacy studies will be inte- grated with data from the national databases, registries and biobanks.
Principal Investigator in the Medical Faculty & HiLIFE fellow. Current size of research group (01.2020): PI, 1 Adj. Professor, 4 postdocs, 4 Ph.D students, 2 M.D/Ph.D students, 1 undergraduate, 2 RAs .
Breast Cancer Pilot. The iCAN Digital Precision Cancer Medicine flagship (2019- 2026). The iCAN is a cancer research and innovation platform established by the University of Helsinki and the Helsinki University Hospital HUS with the support of Academy of Finland. The national flagships selected for 2019-2026 aim to leverage a strong research base to build long-lasting competence clusters in their areas and thus provide societal and economic impact.
RESEARCH DIRECTOR (INFRASTRUCTURE, DEVELOPMENT). Medical Faculty and Helsinki Institute of Life Science (HiLIFE). The position includes the following duties:
Co-Director of Biomedicum Functional Genomics Unit, University of Helsinki (Since 2006). Bio- medicum Functional Genomics Unit is a comprehensive functional genomics service provider with Biocentrum Helsinki and Biocenter Finland affiliation.
Director of HiLFE’s Genome Editing and Stem Cell platform (Since 2017). This comprehensive functional genomics and stem cell service platform integrates functional genomics resources and services with modern somatic and stem cell technologies. The platform offers genome scale shRNA, cDNA/ORF and CRISPR libraries, viral gene transfer methods, and induced pluripotent stem cell (iPSC) technologies.
PREVIOUS PROFESSIONAL AFFILIATIONS
1990-1994 UNDERGRADUATE. University of Helsinki, Finland. Dr Sakari Knuutila and Prof. Eero Saksela.
1994-1997 PHD STUDENT. University of Helsinki, Finland. Laboratory of Prof. Kari Alitalo.
1997-11/2002 POSTDOCTORAL. Laboratory of Prof. Gerard Evan. Imperial Cancer Research Fund,
UK and UCSF Comprehensive Cancer Center, USA.
2003-2005 JUNIOR FELLOW. Academy of Finland.
2005 (4 mo) UNIVERSITY LECTURER (acting). Institute of Biomedicine/Faculty of Medicine,
University of Helsinki
2006-2008 DIRECTOR. Biomedicum Genomics Oy. Chairman of the Board of Directors 07/2007-
2009; Board member 2009-2019.
2009 (2 mo) VISITING PROFESSOR, California Institute for Quantitative Biosciences (QB3), UCSF
08/2008-07/2013 ACADEMY RESEARCH FELLOW. The Academy of Finland.
08/2013-12/2019 VICE DIRECTOR. Translational Cancer Biology Research Program (TCB).
08/2015-12/2019 VICE DIRECTOR. Research Programs Unit (RPU), Medical Faculty. Uni. Helsinki
EDUCATION AND DEGREES
1994. M.Sc (Genetics). University of Helsinki 1995. Ph.D. (Genetics). University of Helsinki 1996. Docent (Molecular Genetics). University of Helsinki
NATIONAL AND INTERNATIONAL TRUSTEE ACTIVITIES
Organized Conferences and Symposia 2004 Programme committee member and organizer of BioFinland 2005 conference, Finland 2011 Cell Polarity in Health and Disease Workshop (Organized by Lu, Tapon, O’Neill, Klefstrom), Oxford, UK 2004 – Local minisymposia with international guest speakers: >10 Ad Hoc reviewer for regulatory issues 2007 Board of Gene Technology, Finland – Biosafety Risk Group 2 recommendations for work involving recombinant viruses (under the European law regarding genetically modified organisms) Scientific Networks – member 2006-2011 (active member 06-07). ENFIN- Enabling Systems Biology, European Network of Excellence. 2011-2014. Nordforsk network “Chromatin, Transcription and Cancer” organized from KI, Stockholm. 2009-2013. Biocenter Finland – Member of Viral Gene Transfer and Cell Therapy Network. 2013-2018. Research Programs Unit, Medical Faculty, UH – Board member
2007-2011. Co-founder, chairman and member in the Fin-QB3 joint steering committee. 2011-2015. Innovative Medicines Initiative – PREDECT. Founding member and WP leader of a consortium of 9 universities, 3 biotechnology companies and 9 pharmaceutical companies. 2010-2012. Biocenter Finland – Coordinator of LentiGEMM Emerging Technology Platform. 2013-2016. Biocenter Finland – Coordinator of Tissue Engineered Disease Models Emerging Technology Platform. 2013-2018. Vice-Director (shared) of Translational Cancer Biology Research Program, Medical Faculty, University of Helsinki. 2015-2016. Vice Director of Research Programs Unit, Medical Faculty, University of Helsinki. 2017- HiLIFE – Coordinator of GoEditStem stem cell and functional genomics platform.
RESEARCH INFRASTRUCTURE AND INNOVATION
11/2002-present. Biomedicum Virus Core facility (Biocentrum Helsinki) – Founder and Director. 2006- present. Biomedicum Genomics and (2010 onwards) Biomedicum Functional Genomics Unit (www.biomedicumgenomics.fi) – Research Director. Biomedicum Functional Genomics Unit (Biomedicum Genomics Unit) is a comprehensive functional genomics service provider with Biocentrum Helsinki and Biocenter Finland affiliation. The Unit, which is co-directed by Klefström, has about 10 employees and 0,5 M€ annual cashflow. 07/2007-2009. Biomedicum Genomics Ltd – Chairman of the Board of Directors. 2009- present. Board member.