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Klefström lab

Oncogenic signaling pathways as therapeutic targets in breast cancer

Our laboratory studies oncogene and tumor suppressor induced cancer-specific cellular programs, which cause therapeutic vulnerabilities in breast cancer.

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Pharmacological intervention of SARS-CoV-2 entry mechanisms by blockade of TMPRSS activity

The Klefström laboratory has been identifying and developing chemical and pharmacological inhibitors against hepsin/TMPRSS family members for a long time with the goal of preventing cancer invasion. Some of our drugs or drug-like molecules could be repurposed to prevent SARS-CoV-2 entry to cells, potentially offering a fast-track treatment option for the COVID-19 disease.

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Juha Klefström

Juha Klefström, PhD, is a Research Director in the Medical Faculty, University of Helsinki. He is a vice-Director of Research Programs Unit, which is formed by 40 top quality research groups affiliated with five research programs chosen via international peer review. Klefström is an expert in translational cancer research, breast cancer biology, immuno-oncology, oncogenes and tumor suppressors, cell death, genetically engineered mouse models of breast cancer, mammary gland reconstitution techniques, ex vivo explant cultures and recombinant viral gene transfer methods. He has published in leading journals like Nature Communications, EMBO J, PNAS, Cancer Discovery and Cancer Cell.

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.

CV

PERSONAL DATA Juha Tapio Klefström

CURRENT MAIN POSITION Research Director. Research Programs Unit of the Medical Faculty, Univ. Helsinki

PRESENT PROFESSIONAL AFFILIATIONS 

RESEARCH DIRECTOR. Research Programs Unit, Medical Faculty, University of Helsinki (since August 2013). Sigrid Juselius Foundation Appointment for 2019-2021. 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 .

  • Co-Director/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 Hel- sinki and the Helsinki University Hospital HUS with the support of Academy of Finland. The na- tional 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

SCIENTIFIC LEADERSHIP

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.

Research

Information about our current SARS-CoV-2 research below under research topics

MYC-dependent metabolic vulnerabilities

We study different possibilities to exploit synthetic lethal interactions in drug discovery and recently, we have focused on MYC-dependent metabolic vulnerabilities. This particularly interesting cancer vulnerability is tightly linked to a conserved cellular energy sensing pathway controlled by a protein kinase AMPK. Another line of enquiry is related to the role of limited proteolysis in regulation of epithelial integrity-dependent survival of breast epithelial cells. In these studies, we focus on the type II transmembrane serine protease hepsin.

3D culture

We study cells in three-dimensional (3D) context using different extracellular matrices as scaffolds for reconstruction of mammary gland specific structures. In these 3D culture studies, we use epithelial cell lines and ex vivo primary epithelial cells. In addition, we have established a 3D culture platform for patient-derived breast cancer explants (PDEX) using specific scaffolds that preserve breast tumor cell function and identity. For in vivo validation, we use different immunocompetent in vivo models of breast cancer, including GEMMs and syngraft models. In addition, we study drug responses in patient-derived xenograft (PDX) models of breast cancer.

Cancer therapeutic strategies

We are currently testing several lead therapeutic intervention strategies related to cancer cell metabolism and apoptosis in our collection of preclinical in vitro, ex vivo and in vivo models of breast cancer, hoping to translate soon our scientific discoveries to clinical investigation and ultimately, to benefit of a cancer patient.

For more information contact the lab head Juha Klefstrom. For open positions in the lab, click here.

Publications

Selected publications

Please follow our latest publications in TUHAT or PubMed

Haikala HM, Anttila JM, Marques E, Raatikainen T, Ilander M, Hakanen H, Ala-Hongisto H, Savelius M, Balboa D, Von Eyss B, Eskelinen V, Munne P, Nieminen AI, Otonkoski T, Schüler J, Laajala TD, Aittokallio T, Sihto H, Mattson J, Heikkilä P, Leidenius M, Joensuu H, Mustjoki S, Kovanen P, Eilers M, Leverson JD, Klefström J.
Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy. Nature communications 1:620, 2019.
Partanen JI, Nieminen AI, Mäkelä TP, Klefstrom J.
Suppression of oncogenic properties of c-Myc by LKB1-controlled epithelial organization. Proceedings of the National Academy of Sciences of the United States of America 37:14694-9, 2007.
Werner S, Brors B, Eick J, Marques E, Pogenberg V, Parret A, Kemming D, Wood AW, Edgren H, Neubauer H, Streichert T, Riethdorf S, Bedi U, Baccelli I, Jücker M, Eils R, Fehm T, Trumpp A, Johnsen SA, Klefström J, Wilmanns M, Müller V, Pantel K, Wikman H.
Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic Acid-induced 2. Cancer discovery 5:506-19, 2015.
Nieminen AI, Eskelinen VM, Haikala HM, Tervonen TA, Yan Y, Partanen JI, Klefström J.
Myc-induced AMPK-phospho p53 pathway activates Bak to sensitize mitochondrial apoptosis. Proceedings of the National Academy of Sciences of the United States of America 20:E1839-48, 2013.
Partanen JI, Tervonen TA, Myllynen M, Lind E, Imai M, Katajisto P, Dijkgraaf GJ, Kovanen PE, Mäkelä TP, Werb Z, Klefström J.
Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity. Proceedings of the National Academy of Sciences of the United States of America 7:E388-97, 2012.
Haikala HM, Klefström J, Eilers M, Wiese KE.
MYC-induced apoptosis in mammary epithelial cells is associated with repression of lineage-specific gene signatures. Cell cycle (Georgetown, Tex.) 3:316-23, 2016.
Myant K, Qiao X, Halonen T, Come C, Laine A, Janghorban M, Partanen JI, Cassidy J, Ogg EL, Cammareri P, Laiterä T, Okkeri J, Klefström J, Sears RC, Sansom OJ, Westermarck J.
Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation. Cell reports 6:1019-31, 2015.
Marques E, Englund JI, Tervonen TA, Virkunen E, Laakso M, Myllynen M, Mäkelä A, Ahvenainen M, Lepikhova T, Monni O, Hautaniemi S, Klefström J.
Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers. Oncogene 11:1386-98, 2016.
Wiese KE, Haikala HM, von Eyss B, Wolf E, Esnault C, Rosenwald A, Treisman R, Klefström J, Eilers M.
Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells. The EMBO journal 11:1554-71, 2015.
Tervonen TA, Belitškin D, Pant SM, Englund JI, Marques E, Ala-Hongisto H, Nevalaita L, Sihto H, Heikkilä P, Leidenius M, Hewitson K, Ramachandra M, Moilanen A, Joensuu H, Kovanen PE, Poso A, Klefström J.
Deregulated hepsin protease activity confers oncogenicity by concomitantly augmenting HGF/MET signalling and disrupting epithelial cohesion. Oncogene 14:1832-46, 2016.
Louhimo R, Laakso M, Belitskin D, Klefström J, Lehtonen R, Hautaniemi S.
Data integration to prioritize drugs using genomics and curated data. BioData mining :21, 2016.

Full list of publications

Please follow our latest publications in TUHAT or PubMed

2020

Qiao X, Liu Y, Llamazares Prada M, Mohan AK, Gupta A, Jaiswal A, Sharma M, Merisaari J, Haikala HM, Talvinen K, Yetukuri L, Pylvänäinen JW, Klefström J, Kronqvist P, Meinander A, Aittokallio T, Hietakangas V, Eilers M, Westermarck J.
UBR5 is co-amplified with MYC in breast tumors and encodes an ubiquitin ligase that limits MYC-dependent apoptosis. Cancer research :, 2020.

2019

Haikala HM, Anttila JM, Marques E, Raatikainen T, Ilander M, Hakanen H, Ala-Hongisto H, Savelius M, Balboa D, Von Eyss B, Eskelinen V, Munne P, Nieminen AI, Otonkoski T, Schüler J, Laajala TD, Aittokallio T, Sihto H, Mattson J, Heikkilä P, Leidenius M, Joensuu H, Mustjoki S, Kovanen P, Eilers M, Leverson JD, Klefström J.
Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy. Nature communications 1:620, 2019.
Damalanka VC, Han Z, Karmakar P, O'Donoghue AJ, La Greca F, Kim T, Pant SM, Helander J, Klefström J, Craik CS, Janetka JW.
Discovery of Selective Matriptase and Hepsin Serine Protease Inhibitors: Useful Chemical Tools for Cancer Cell Biology. Journal of medicinal chemistry 2:480-490, 2019.

2018

Marques E, Peltola T, Kaski S, Klefström J.
Phenotype-driven identification of epithelial signalling clusters. Scientific reports 1:4034, 2018.
Pant SM, Mukonoweshuro A, Desai B, Ramjee MK, Selway CN, Tarver GJ, Wright AG, Birchall K, Chapman TM, Tervonen TA, Klefström J.
Design, Synthesis, and Testing of Potent, Selective Hepsin Inhibitors via Application of an Automated Closed-Loop Optimization Platform. Journal of medicinal chemistry 10:4335-4347, 2018.
Pant SM, Belitskin D, Ala-Hongisto H, Klefström J, Tervonen TA.
Analyzing the Type II Transmembrane Serine Protease Hepsin-Dependent Basement Membrane Remodeling in 3D Cell Culture. Methods in molecular biology (Clifton, N.J.) :169-178, 2018.

2017

Haikala HM, Anttila JM, Klefström J.
MYC and AMPK-Save Energy or Die! Frontiers in cell and developmental biology :38, 2017.

2016

Haikala HM, Klefström J, Eilers M, Wiese KE.
MYC-induced apoptosis in mammary epithelial cells is associated with repression of lineage-specific gene signatures. Cell cycle (Georgetown, Tex.) 3:316-23, 2016.
Marques E, Englund JI, Tervonen TA, Virkunen E, Laakso M, Myllynen M, Mäkelä A, Ahvenainen M, Lepikhova T, Monni O, Hautaniemi S, Klefström J.
Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers. Oncogene 11:1386-98, 2016.
Tervonen TA, Belitškin D, Pant SM, Englund JI, Marques E, Ala-Hongisto H, Nevalaita L, Sihto H, Heikkilä P, Leidenius M, Hewitson K, Ramachandra M, Moilanen A, Joensuu H, Kovanen PE, Poso A, Klefström J.
Deregulated hepsin protease activity confers oncogenicity by concomitantly augmenting HGF/MET signalling and disrupting epithelial cohesion. Oncogene 14:1832-46, 2016.
Haikala HM, Marques E, Turunen M, Klefström J.
Myc requires RhoA/SRF to reprogram glutamine metabolism. Small GTPases :1-9, 2016.
Louhimo R, Laakso M, Belitskin D, Klefström J, Lehtonen R, Hautaniemi S.
Data integration to prioritize drugs using genomics and curated data. BioData mining :21, 2016.

2015

Werner S, Brors B, Eick J, Marques E, Pogenberg V, Parret A, Kemming D, Wood AW, Edgren H, Neubauer H, Streichert T, Riethdorf S, Bedi U, Baccelli I, Jücker M, Eils R, Fehm T, Trumpp A, Johnsen SA, Klefström J, Wilmanns M, Müller V, Pantel K, Wikman H.
Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic Acid-induced 2. Cancer discovery 5:506-19, 2015.
Marques E, Klefström J.
Par6 family proteins in cancer. Oncoscience 11:894-5, 2015.
Myant K, Qiao X, Halonen T, Come C, Laine A, Janghorban M, Partanen JI, Cassidy J, Ogg EL, Cammareri P, Laiterä T, Okkeri J, Klefström J, Sears RC, Sansom OJ, Westermarck J.
Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation. Cell reports 6:1019-31, 2015.
Wiese KE, Haikala HM, von Eyss B, Wolf E, Esnault C, Rosenwald A, Treisman R, Klefström J, Eilers M.
Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells. The EMBO journal 11:1554-71, 2015.

2014

Hickman JA, Graeser R, de Hoogt R, Vidic S, Brito C, Gutekunst M, van der Kuip H, IMI PREDECT Consortium..
Three-dimensional models of cancer for pharmacology and cancer cell biology: capturing tumor complexity in vitro/ex vivo. Biotechnology journal 9:1115-28, 2014.

2013

Khanna A, Kauko O, Böckelman C, Laine A, Schreck I, Partanen JI, Szwajda A, Bormann S, Bilgen T, Helenius M, Pokharel YR, Pimanda J, Russel MR, Haglund C, Cole KA, Klefström J, Aittokallio T, Weiss C, Ristimäki A, Visakorpi T, Westermarck J.
Chk1 targeting reactivates PP2A tumor suppressor activity in cancer cells. Cancer research 22:6757-69, 2013.
Partanen JI, Tervonen TA, Klefström J.
Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 1629:20130111, 2013.
Nieminen AI, Eskelinen VM, Haikala HM, Tervonen TA, Yan Y, Partanen JI, Klefström J.
Myc-induced AMPK-phospho p53 pathway activates Bak to sensitize mitochondrial apoptosis. Proceedings of the National Academy of Sciences of the United States of America 20:E1839-48, 2013.

2012

Partanen JI, Klefstrom J.
Impact of epithelial organization on Myc expression and activity–letter. Cancer research 4:1035; author reply 1036, 2012.
Partanen JI, Tervonen TA, Myllynen M, Lind E, Imai M, Katajisto P, Dijkgraaf GJ, Kovanen PE, Mäkelä TP, Werb Z, Klefström J.
Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity. Proceedings of the National Academy of Sciences of the United States of America 7:E388-97, 2012.

2011

Tervonen TA, Partanen JI, Saarikoski ST, Myllynen M, Marques E, Paasonen K, Moilanen A, Wohlfahrt G, Kovanen PE, Klefstrom J.
Faulty epithelial polarity genes and cancer. Advances in cancer research :97-161, 2011.

2010

Kyrönlahti A, Kauppinen M, Lind E, Unkila-Kallio L, Butzow R, Klefström J, Wilson DB, Anttonen M, Heikinheimo M.
GATA4 protects granulosa cell tumors from TRAIL-induced apoptosis. Endocrine-related cancer 3:709-17, 2010.
Jääskeläinen M, Nieminen A, Pökkylä RM, Kauppinen M, Liakka A, Heikinheimo M, Vaskivuo TE, Klefström J, Tapanainen JS.
Regulation of cell death in human fetal and adult ovaries–role of Bok and Bcl-X(L). Molecular and cellular endocrinology 1-2:17-24, 2010.

2009

Rajecki M, af Hällström T, Hakkarainen T, Nokisalmi P, Hautaniemi S, Nieminen AI, Tenhunen M, Rantanen V, Desmond RA, Chen DT, Guse K, Stenman UH, Gargini R, Kapanen M, Klefström J, Kanerva A, Pesonen S, Ahtiainen L, Hemminki A.
Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation. International journal of cancer 10:2441-9, 2009.
Partanen JI, Nieminen AI, Klefstrom J.
3D view to tumor suppression: Lkb1, polarity and the arrest of oncogenic c-Myc. Cell cycle (Georgetown, Tex.) 5:716-24, 2009.

2008

Heinonen H, Nieminen A, Saarela M, Kallioniemi A, Klefström J, Hautaniemi S, Monni O.
Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer. BMC genomics :348, 2008.

2007

Partanen JI, Nieminen AI, Mäkelä TP, Klefstrom J.
Suppression of oncogenic properties of c-Myc by LKB1-controlled epithelial organization. Proceedings of the National Academy of Sciences of the United States of America 37:14694-9, 2007.
Nieminen AI, Partanen JI, Hau A, Klefstrom J.
c-Myc primed mitochondria determine cellular sensitivity to TRAIL-induced apoptosis. The EMBO journal 4:1055-67, 2007.
Nieminen AI, Partanen JI, Klefstrom J.
c-Myc blazing a trail of death: coupling of the mitochondrial and death receptor apoptosis pathways by c-Myc. Cell cycle (Georgetown, Tex.) 20:2464-72, 2007.

2003

Klefström J, Alitalo K.
[Lentiviruses to use]. Duodecim; laaketieteellinen aikakauskirja 20:1917-9, 2003.

2002

Klefstrom J, Verschuren EW, Evan G.
c-Myc augments the apoptotic activity of cytosolic death receptor signaling proteins by engaging the mitochondrial apoptotic pathway. The Journal of biological chemistry 45:43224-32, 2002.

1999

Klefstrom J, Kovanen PE, Somersalo K, Hueber AO, Littlewood T, Evan GI, Greenberg AH, Saksela E, Timonen T, Alitalo K.
c-Myc and E1A induced cellular sensitivity to activated NK cells involves cytotoxic granules as death effectors. Oncogene 13:2181-8, 1999.

1998

Kinnula VL, Aito H, Klefstrom J, Alitalo K, Raivio KO.
Similarities between TNF and exogenous oxidants on the cytotoxic response of c-Myc-expressing fibroblasts in vitro. Cancer letters 1-2:191-8, 1998.

1997

Klefstrom J, Arighi E, Littlewood T, Jäättelä M, Saksela E, Evan GI, Alitalo K.
Induction of TNF-sensitive cellular phenotype by c-Myc involves p53 and impaired NF-kappaB activation. The EMBO journal 24:7382-92, 1997.
Enholm B, Paavonen K, Ristimäki A, Kumar V, Gunji Y, Klefstrom J, Kivinen L, Laiho M, Olofsson B, Joukov V, Eriksson U, Alitalo K.
Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene 20:2475-83, 1997.
Monni O, Joensuu H, Franssila K, Klefstrom J, Alitalo K, Knuutila S.
BCL2 overexpression associated with chromosomal amplification in diffuse large B-cell lymphoma. Blood 3:1168-74, 1997.

1994

Knuutila S, Klefström J, Szymanska J, Lakkala T, Peltomäki P, Eray M, Teerenhovi L, Elonen E, Franssila KO, Kaartinen M.
Two novel human B-cell lymphoma lines of lymphatic follicle origin: cytogenetic, molecular genetic and histopathological characterisation. European journal of haematology 2:65-72, 1994.
Klefstrom J, Franssila K, Peltomäki P, Kaartinen M, Solin ML, Knuutila S.
Major and minor breakpoint sites of chromosomal translocation t(14;18) in subtypes of non-Hodgkin’s lymphomas. Leukemia research 4:245-50, 1994.
Klefstrom J, Västrik I, Saksela E, Valle J, Eilers M, Alitalo K.
c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha. The EMBO journal 22:5442-50, 1994.
Västrik I, Mäkelä TP, Koskinen PJ, Klefstrom J, Alitalo K.
Myc protein: partners and antagonists. Critical reviews in oncogenesis 1:59-68, 1994.

1993

Klefstrom J, Koskinen PJ, Saksela E, Jäättelä M, Bravo R, Alitalo K.
A sub-set of immediate early mRNAs induced by tumor necrosis factor-alpha during cellular cytotoxic and non-cytotoxic responses. International journal of cancer 4:655-9, 1993.

1992

Klefström J, Saksela E, Alitalo K.
[Complex mechanics of tumor-necrosis-factor-induced cell death]. Duodecim; laaketieteellinen aikakauskirja 17:1449-55, 1992.

1990

Klefström J, Kaartinen M, Peltomäki P, Solin ML, Franssila K, Knuutila S.
[The use of polymerase chain reaction in the diagnosis of non-Hodgkin’s lymphoma]. Duodecim; laaketieteellinen aikakauskirja 23-24:1645-53, 1990.
  • Klefström lab

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  • Lab life

For open positions in the lab, click here.

Research Coordinator

Jeroen Pouwels


Adjunct Professor

Jeroen Pouwels obtained his PhD in 2004 from the University of Wageningen in the Netherlands, after which he did two postdocs in Turku, one at VTT Biotechnology and one at the Turku Centre for Biotechnology. From 2013-2018, Jeroen has run his own research team at the Turku Centre for Biotechnology, which focused on the characterization of the multifunctional adaptor protein Sharpin.

Since August 2017, Jeroen works as research coordinator in the Klefström research group, initially as coordinator of the TEHO project, a Challenge Finland (TEKES) awarded project focusing on adaptive clinical trial design. Jeroen has obtained independent research funding from the Academy of Finland (research project) and K. Albin Johansson Foundation to develop patient-derived tumor explant cultures as a predictive preclinical model for breast cancer and to identify treatments that sensitize breast cancer to immunotherapies. Lastly, Jeroen is involved in the preparation of an investigator-initiated phase I clinical trial in metastatic breast cancer and in spinning out a diagnostic company that utilizes tumour explant cultures.

In his free time Jeroen likes to spend time with his family, he loves traveling all around the globe, and he is a very active stock market investor.

LinkedIn

TOPI TERVONEN


Adjunct Professor

Topi Tervonen received his PhD in 2008, in the field of neural stem cells at Neuroscience Center, University of Helsinki. For his post-doctoral training he chose to study molecular cancer biology in Dr. Juha Kleftröm’s group at University of Helsinki. Topi’s work on membrane-anchored serine proteases and cancer has revealed new up- and downstream mechanisms regulating these microenvironment modifying and tumor promoting enzymes. Topi has served as research coordinator since 2014 and also works in Biomedicum Functional Genomics Unit (FuGU) as head of virus services and principal investigator of FuGU/libraries life science infrastructure of GoEditStem infrastructure platform of HiLIFE, University of Helsinki. During recent years, Topi has been actively bringing genome-scale genome editing resources and services into University of Helsinki and he was named the chair of Genome Editing technology platform of Biocenter Finland in 2020. He will also take position as principal investigator in Finnish Genome Editing Center (FinGEEC) core unit of GoEditStem HiLIFE infra platform in 2021. Topi has also worked as part time contractor in Biomedicum Genomics Oy (partially owned by University of Helsinki). Outside work Topi loves sports, music, movies, scientific books, and spending time with his wife and two children.

Post Docs

Pauliina Munne


PhD

Pauliina Munne received her PhD in 2010, in the field of developmental biology and physiology at the Institute of Biotechnology, University of Helsinki and continued her post-doctoral training in breast cancer and mammary gland biology at the Institute for Molecular Medicine Finland (FIMM) at University of Helsinki. After that she worked as a head of genome profiling in Biomedicum Functional Genomics Unit (FuGU), where she gained expertise in next generation sequencing and microarrays. Her current position as a post-doctoral researcher focuses on understanding molecular mechanisms regulated by the microenvironment in mammary gland and in breast cancer, where she is particularly interested in the regulation of cellular identity. She is also involved as a part time contract researcher in BMGen Oy coordinating projects in genome profiling. She is keen on all beauties and wonders of nature and science.

LinkedIn

Ruixian Liu (Mars)


PhD

Mars received his PhD in 2017 from the Sun Yat-sen University, China, where his research interest focused on tumor-infiltrating B cells. After that he continued his post-doctoral training about biomarker discovery and cancer immunotherapy in Sun Yat-sen University.
Mars joined the lab in November 2019. He is now working on developing new combination strategies to improve efficacy of immunotherapy in breast cancer. Outside of lab, he likes cooking, hiking, and swimming.

Doctoral students

Shishir Pant


MSc

Shishir completed his Master’s degree in Molecular biotechnology from University of Helsinki. Currently he is a graduate student in doctoral program in biomedicine and his research focuses on deciphering the oncogenic role of serine protease hepsin in breast cancer. He is particularly interested in how the cancer cell interact with the microenvironment and development of novel therapeutic agents to prevent this cross-talk.  Shishir is also an active board member of biomedical and clinical student council and has been organizing several courses, conferences and various science outreach events. When not in lab, Shishir is either on a football field, hiking or traveling around Europe.
LinkedIn 

Denis Belitskin


MSc

I received my BSc and MSc in Gene Technology from The University of Tartu (Estonia), where I started in the field of applied virology, and later went on, to study the role of stem cells in liver cancer for my Master`s thesis. My research is focused on novel biological roles of the serine protease hepsin in breast cancer, discovery of mechanisms through which hepsin is providing advantages to cancer cells in growth and survival. I`m working in close collaboration with other members of the team (Topi Tervonen, Shishir M. Pant) and international collaborators in the attempt to target extracellular and intracellular functions of hepsin by using small molecules, which will provide proof of principle that hepsin is an attractive target for breast cancer therapy.

Outside of the lab I`m a great husband, cool father, stock market investor and a beekeeper.

Johanna Anttila


MSc

Johanna Anttila received her MSc degree in Biochemistry from the Molecular and Cellular Biology Programme in University of Oulu and did her Master’s thesis in Klefström lab in 2017. After graduating she has continued her work in the lab as a doctoral student. Johanna aspires to harness oncogene MYC-dependent cancer cell vulnerabilities in the objective of translating our research into benefit of cancer patients. Besides science, Johanna is into various sports including frisbee golf and tennis as well as loves to spend time enjoying music and photography.

LinkedIn

 

Rita Turpin


MSc

Rita Turpin finished her MSc with a major in Human Genetics and a minor in Molecular Biology at the University of Helsinki, and is continuing her work throughout her doctoral studies. Her project focuses on determining the immunocontexture of a novel 3D ex vivo breast cancer model in hopes of opening doors for future immune-relevant synthetic lethal drug combination and biomarker studies. In addition to her own work, Rita has been collaborating with CancerIO.

Rita’s hobbies include singing, board games, and hosting parties.

LinkedIn

Iiris Räty


MD PhD Student
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Aino Peura


MD PhD Student

Aino Peura is a MD-PhD-student who joined Klefsröm lab in 2018. Her thesis is focused on understanding the immunological interactions between the breast cancer microenvironment and immune cells.

In her free time she enjoys reading and is a keen long distance runner

Masters Students

Mariel Savelius


Mariel Savelius is currently doing her Master’s degree in Molecular Biotechnology from University of Helsinki. She is interested in translational research and how people can benefit from the applications that it creates. Mariel is keen on learning more about the molecular mechanisms of cancer and now she is working in the project about linking oncogene MYC metabolism to cancer cell apoptosis. She is also interested in how cancer cells apoptosis effects on immune system and how that could be used to create new therapies against cancer. In her free time she likes to travel, enjoys good food and doing different activities with her friends.

 

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Linda Patrikainen


BSc

Linda Patrikainen is a Masters student in the Genetics and Molecular Biosciences -Master’s program at the University of Helsinki. Her research project focuses on the interaction between the tumor microenvironment and ER-positive breast cancer cells. When she is not studying, she enjoys good music, nature and jogs.

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Linda Id


Bsc

Linda Id is doing her Master’s degree at the University of Helsinki in the Genetics and Molecular Biosciences program. Linda’s research project is focused on finding new treatments that specifically kill MYC-overexpressed breast cancer cells.

Emmie Salmelin


BSc

Emmie Salmelin is a master’s student in Genetics and Molecular Biosciences at University of Helsinki. Her research project focuses on activating NK cell cytotoxicity towards Myc-driven breast cancer. When she isn’t at work or at school, she enjoys sports, the outdoors and spending time with her friends.

Lab Management

Elina Hurskainen


Laboratory Manager

Elina is remotely finishing her Master´s Degree in Cell and Molecular Biology at the University of Jyväskylä Spring 2020. She works as a laboratory manager with versatile tasks from coordinating and integrating lab resources to technical experimental support. Additionally, she manages the Biomedicum Virus Core (BVC) which falls under the Finnish Helsinki Institute of Life Sciences (HiLIFE) infrastructure aimed to promote quality research across campuses. Her BVC responsibilities include facility management, user training and support, virus titer testing for clients (RCV, p24) among others.

Outside the lab Elina is a live music-enthusiast, animal (esp. cat) lover, green-thumb, and a superb home chef. She is also a licensed swim instructor, lifeguard and cocktail bartender in case there is a need.

Mari Urb


Laboratory Manager

Mari is finalizing her doctoral studies in Neurosciences in University of Tartu (Estonia), where her research interest focused on the epigenetic mechanisms of psychostimulant addiction. In 2019, she worked for Protobios LCC, a life science company to study the molecular mechanisms of schizophrenia for possible biomarker identification.

Mari joined the lab in Jan 2020 and is now involved in management of recombinant virus services in Biomedicum Functional Genomics Unit (FuGU), the development of genome editing resources and assisting in research. Outside of lab, she enjoys hiking, singing and is enthused of sports.

Functional genomics unit (FuGu)

Maria Salmela


PhD, Laboratory Coordinator

Maria Salmela received her PhD in 2017, in the field of biochemistry and cell biology at the University of Turku, where she studied integrin mediated cell adhesion and signalling pathways. Her current position as a laboratory coordinator in HiLIFE affiliated GoEditStem platform (including Biomedicum Functional Genomics Unit (FuGU) and Finnish Genome editing Center (FinGEEC)) involves management of recombinant virus services and platform development. The main goal of the platform is to educate researches and facilitate the use of different genome editing tools. Other geek stuff in Maria’s life include playing computer games and reading fantasy and science fiction novels. The natural habitats for her, outside the lab, are dance floor and forest, where she likes to shake-shake-shake or pick mushrooms, respectively.

LinkedIn

Computer/data Consultant

Ilida Suleymanova


Ilida has a Master’s degree in computational mathematics, and cybernetics from Kazan Federal University (KFU), Kazan, Russia. During her Masters, she focused on solving mathematical equations using Matlab software. To further enhance her skills, she decided to focus on its implementation in clinical studies, and joined the Neurobiology research group led by Dr. Rustem Khazipov’s at KFU. During her work in this lab, she was involved in developing Matlab-based algorithms for automatized analysis of brain activity in neonatal rats, and the clusterization of spikes of multiunit activity in the immature cortex.
Currently, she is completing her Ph.D. studies at the University of Helsinki. During her Ph.D. study, she quickly learned the necessary skills to perform biological experiments and on the other hand utilized her expertise in programming to develop novel algorithms to quantify large-scale images generated during the experiments.
As part of her long term goal, she wishes to contribute and pursue her career in the field involving mathematical and computational approaches to analyze biological data.

Klefalab alumni

  • Katariina Karjalainen Laboratory coordinator
  • Tiina Raatikainen
  • Janika Ruuska
  • Johanna Lampe
  • Begüm Erdoğan
  • Heidi Haikala
  • Elina Pörsti
  • Hanna Ala-Hongisto
  • Tarja Välimäki
  • Annika Hau
  • Anni Viheriäranta
  • Ekaterina Virkunen
  • Johanna Englund
  • Liina Nevalaita
  • Vilja Eskelinen
  • Katriina Muona
  • Mikko Myllynen
  • Sirkku Saarikoski
  • Heini Natri
  • Misa Imai
  • Yan Yan
  • Essi Havula
  • Sauli Toikka
  • Anne Mäkelä
  • Katja Suomi
  • Elina Enlund
  • Harriet Gullsten
  • Marjukka
  • Jaakko
  • Amit Cohen
  • Juho
  • Kaisu
  • Niklas Ekman
  • Elsa Marques
  • Iiris Juopperi

Open positions

OPEN POSITIONS 

Feel free to contact us if you are interested in joining our lab. Specific job roles will appear here as they come.

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Want to join us?

Want to join us? We are about 16 researchers, including postdocs, graduate students and skilled research assisting personnel. The lab is dedicated to translate high-impact laboratory discoveries to the benefit of breast cancer patients and our strengths are in versatile use of genetic and pharmacological approaches together with sophisticated in vitro, ex vivo and in vivo models of breast cancer.

What do we expect from a new lab member? Your incentive to carry out research has to be scientific curiosity. You keep on asking why and how things happen? We are a translational science lab and for that type of environment we invite not only your experimental skills but also your ideas, brains and personal creativity. Once your hypotheses mature, you will have high degree of freedom to pursue own scientific ideas and projects. At this stage, you will find collaborators from inside and outside of the lab, no-one works alone. We expect you to show determination and commitment to your projects. You have to believe in your vision and prove it. That means hard work, but this is for the benefit of yourself.

What do we offer for you? You will learn many state-of-art molecular research technologies, from CRISPR mediated gene editing to modern 3D culture technology of cells and patient-derived breast cancer explants. You will learn molecular cloning, protein techniques, confocal microscopy and methods pertaining to transgenic, knock-out and syngrafted mouse models of cancer. In addition, you will develop your skills in reasoning and scientific argumentation. We discuss and argue a lot in our weekly lab meetings, journal clubs as well as in our annual lab retreat. In addition to the training offered by the lab, you will be exposed to vivid scientific atmosphere of the Research Programs Unit (RPU) of Medical Faculty. RPU groups include both basic researchers and clinical scientists working with patients and the program offers weekly seminars and symposia, Science days as well as social program.

Contact

Research Programs Unit/Translational Cancer Biology
& Medicum, Biomedicum Helsinki 1,
Medical Faculty, University of Helsinki

Haartmaninkatu 8
00290 Helsinki
FINLAND

University of Helsinki internal mailing address
P.O. Box 63
FI-00014 University of Helsinki
Finland

Tel. Lab +358 2 941 25494 (room B509)
Office +358 2 941 25493 (room B507b)
Junior office (room B503)
Fax +358 2 941 25610

firstname.surname@helsinki.fi

 

How to find us in Biomedicum 1 building:
Take the main lifts to 5th floor, turn left and find the signpost “Translational Cancer Biology”. Follow the corridor about 20 meters.

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Research Programs Unit/Translational Cancer Biology
& Medicum, Biomedicum Helsinki 1,
Medical Faculty, University of Helsinki

Haartmaninkatu 8
00290 Helsinki
FINLAND

University of Helsinki internal mailing address
P.O. Box 63
FI-00014 University of Helsinki
Finland

Tel. Lab +358 2 941 25494 (room B509)
Office +358 2 941 25493 (room B507b)
Junior office (room B503)
Fax +358 2 941 25610

firstname.surname@helsinki.fi