Juha Klefstrom, MSc, PhD
Professor
Cell and Tissue Biology
School of Dentistry

Klefstrom laboratory strives to advance basic cancer research toward early clinical development, focusing on therapeutic strategies that exploit oncogene-induced vulnerabilities in cancer. Our research focuses on therapeutically intervenable metabolic vulnerabilities caused by the oncogenic MYC protein, synthetic lethal approaches to treat breast cancer and, several strategies to enhance immunotherapies through immunogenic cell death. Moreover, Klefstrom Lab develops and tests chemical compounds to explore synthetic lethal therapeutic opportunities and novel biological mechanisms. Klefstrom Lab has established three-dimensional culture systems and patient tumor-derived breast explant cultures for ex vivo target validation, drug testing and for studies of breast cancer development. Klefstrom has special expertise in breast cancer biology, translational oncology, cancer metabolism, oncogenes, synthetic lethal strategies, combination immune therapies, preclinical genetically engineered mouse models, ex vivo organoid cultures and recombinant viral gene/shRNA/CRISPR gRNA transfer methods.

• Fibrin Stiffness Regulates Phenotypic Plasticity of Metastatic Breast Cancer Cells.
  Advanced healthcare materials 2023 Heilala M, Lehtonen A, Arasalo O, Peura A, Pokki J, Ikkala O, Klefström J, Munne PM
• MYC-an emerging player in mitochondrial diseases.
  Frontiers in cell and developmental biology 2023 Purhonen J, Klefström J, Kallijärvi J
• Laminin matrix adhesion regulates basal mammary epithelial cell identity.
  Journal of cell science 2022 Englund JI, Bui H, Dinç DD, Paavolainen O, McKenna T, Laitinen S, Munne P, Klefström J, Peuhu E, Katajisto P
• Author Correction: Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer.
  Nature communications 2022 Lee JV, Housley F, Yau C, Nakagawa R, Winkler J, Anttila JM, Munne PM, Savelius M, Houlahan KE, Van de Mark D, Hemmati G, Hernandez GA, Zhang Y, Samson S, Baas C, Kok M, Esserman LJ, van 't Veer LJ, …
• Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer.
  Nature communications 2022 Lee JV, Housley F, Yau C, Nakagawa R, Winkler J, Anttila JM, Munne PM, Savelius M, Houlahan KE, Van de Mark D, Hemmati G, Hernandez GA, Zhang Y, Samson S, Baas C, Kok M, Esserman LJ, van 't Veer LJ, …
• Compressive stress-mediated p38 activation required for ERa?+?phenotype in breast cancer.
  Nature communications 2021 Munne PM, Martikainen L, Räty I, Bertula K, Ruuska J, Ala-Hongisto H, Peura A, Hollmann B, Euro L, Yavuz K, Patrikainen L, Salmela M, Pokki J, Kivento M, Väänänen J, Suomi T, Nevalaita L, Mutka M, …
• Sortilin-related receptor is a druggable therapeutic target in breast cancer.
  Molecular oncology 2021 Al-Akhrass H, Pietilä M, Lilja J, Vesilahti EM, Anttila JM, Haikala HM, Munne PM, Klefström J, Peuhu E, Ivaska J
• Hepsin regulates TGFß signaling via fibronectin proteolysis.
  EMBO reports 2021 Belitškin D, Pant SM, Munne P, Suleymanova I, Belitškina K, Hongisto HA, Englund J, Raatikainen T, Klezovitch O, Vasioukhin V, Li S, Wu Q, Monni O, Kuure S, Laakkonen P, Pouwels J, Tervonen TA, …
• ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma.
  Cancers 2021 Filippou A, Pehkonen H, Karhemo PR, Väänänen J, Nieminen AI, Klefström J, Grénman R, Mäkitie AA, Joensuu H, Monni O
• Oncogenic Ras Disrupts Epithelial Integrity by Activating the Transmembrane Serine Protease Hepsin.
  Cancer research 2021 Tervonen TA, Pant SM, Belitškin D, Englund JI, Närhi K, Haglund C, Kovanen PE, Verschuren EW, Klefström J
• Assessment of the WAP-Myc mouse mammary tumor model for spontaneous metastasis.
  Scientific reports 2020 Utz B, Turpin R, Lampe J, Pouwels J, Klefström J
• UBR5 Is Coamplified with MYC in Breast Tumors and Encodes an Ubiquitin Ligase That Limits MYC-Dependent Apoptosis.
  Cancer research 2020 Qiao X, Liu Y, Prada ML, 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, …
• Strain-Stiffening of Agarose Gels.
  ACS macro letters 2019 Bertula K, Martikainen L, Munne P, Hietala S, Klefström J, Ikkala O
• Publisher Correction: Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy.
  Nature communications 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, …
• Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy.
  Nature communications 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, …
• Discovery of Selective Matriptase and Hepsin Serine Protease Inhibitors: Useful Chemical Tools for Cancer Cell Biology.
  Journal of medicinal chemistry 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
• Design, Synthesis, and Testing of Potent, Selective Hepsin Inhibitors via Application of an Automated Closed-Loop Optimization Platform.
  Journal of medicinal chemistry 2018 Pant SM, Mukonoweshuro A, Desai B, Ramjee MK, Selway CN, Tarver GJ, Wright AG, Birchall K, Chapman TM, Tervonen TA, Klefström J
• Phenotype-driven identification of epithelial signalling clusters.
  Scientific reports 2018 Marques E, Peltola T, Kaski S, Klefström J
• Analyzing the Type II Transmembrane Serine Protease Hepsin-Dependent Basement Membrane Remodeling in 3D Cell Culture.
  Methods in molecular biology (Clifton, N.J.) 2018 Pant SM, Belitskin D, Ala-Hongisto H, Klefström J, Tervonen TA
• Virtual Screening of Transmembrane Serine Protease Inhibitors.
  Bio-protocol 2017 Poso A, Tervonen T, Klefström J
• MYC and AMPK-Save Energy or Die!
  Frontiers in cell and developmental biology 2017 Haikala HM, Anttila JM, Klefström J
• Myc requires RhoA/SRF to reprogram glutamine metabolism.
  Small GTPases 2016 Haikala HM, Marques E, Turunen M, Klefström J
• Data integration to prioritize drugs using genomics and curated data.
  BioData mining 2016 Louhimo R, Laakso M, Belitskin D, Klefström J, Lehtonen R, Hautaniemi S
• MYC-induced apoptosis in mammary epithelial cells is associated with repression of lineage-specific gene signatures.
  Cell cycle (Georgetown, Tex.) 2016 Haikala HM, Klefström J, Eilers M, Wiese KE
• Par6 family proteins in cancer.
  Oncoscience 2015 Marques E, Klefström J
• Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation.
  Cell reports 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
• Deregulated hepsin protease activity confers oncogenicity by concomitantly augmenting HGF/MET signalling and disrupting epithelial cohesion.
  Oncogene 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…
• Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers.
  Oncogene 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
• Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells.
  The EMBO journal 2015 Wiese KE, Haikala HM, von Eyss B, Wolf E, Esnault C, Rosenwald A, Treisman R, Klefström J, Eilers M
• Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic Acid-induced 2.
  Cancer discovery 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, …
• Chk1 targeting reactivates PP2A tumor suppressor activity in cancer cells.
  Cancer research 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,…
• 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 2013 Partanen JI, Tervonen TA, 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 2013 Nieminen AI, Eskelinen VM, Haikala HM, Tervonen TA, Yan Y, Partanen JI, Klefström J
• Impact of epithelial organization on Myc expression and activity--letter.
  Cancer research 2012 Partanen JI, Klefstrom 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 2012 Partanen JI, Tervonen TA, Myllynen M, Lind E, Imai M, Katajisto P, Dijkgraaf GJ, Kovanen PE, Mäkelä TP, Werb Z, Klefström J
• Faulty epithelial polarity genes and cancer.
  Advances in cancer research 2011 Tervonen TA, Partanen JI, Saarikoski ST, Myllynen M, Marques E, Paasonen K, Moilanen A, Wohlfahrt G, Kovanen PE, Klefstrom J
• Regulation of cell death in human fetal and adult ovaries--role of Bok and Bcl-X(L).
  Molecular and cellular endocrinology 2010 Jääskeläinen M, Nieminen A, Pökkylä RM, Kauppinen M, Liakka A, Heikinheimo M, Vaskivuo TE, Klefström J, Tapanainen JS
• GATA4 protects granulosa cell tumors from TRAIL-induced apoptosis.
  Endocrine-related cancer 2010 Kyrönlahti A, Kauppinen M, Lind E, Unkila-Kallio L, Butzow R, Klefström J, Wilson DB, Anttonen M, Heikinheimo M
• Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation.
  International journal of cancer 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…
• 3D view to tumor suppression: Lkb1, polarity and the arrest of oncogenic c-Myc.
  Cell cycle (Georgetown, Tex.) 2009 Partanen JI, Nieminen AI, Klefstrom J
• Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer.
  BMC genomics 2008 Heinonen H, Nieminen A, Saarela M, Kallioniemi A, Klefström J, Hautaniemi S, Monni O
• 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 2007 Partanen JI, Nieminen AI, Mäkelä TP, 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.) 2007 Nieminen AI, Partanen JI, Klefstrom J
• c-Myc primed mitochondria determine cellular sensitivity to TRAIL-induced apoptosis.
  The EMBO journal 2007 Nieminen AI, Partanen JI, Hau A, Klefstrom J
• [Lentiviruses to use].
  Duodecim; laaketieteellinen aikakauskirja 2003 Klefström J, Alitalo K
• The oncogenic potential of Kaposi's sarcoma-associated herpesvirus cyclin is exposed by p53 loss in vitro and in vivo.
  Cancer cell 2002 Verschuren EW, Klefstrom J, Evan GI, Jones N
• c-Myc augments the apoptotic activity of cytosolic death receptor signaling proteins by engaging the mitochondrial apoptotic pathway.
  The Journal of biological chemistry 2002 Klefstrom J, Verschuren EW, Evan G
• c-Myc and E1A induced cellular sensitivity to activated NK cells involves cytotoxic granules as death effectors.
  Oncogene 1999 Klefstrom J, Kovanen PE, Somersalo K, Hueber AO, Littlewood T, Evan GI, Greenberg AH, Saksela E, Timonen T, Alitalo K
• Similarities between TNF and exogenous oxidants on the cytotoxic response of c-Myc-expressing fibroblasts in vitro.
  Cancer letters 1998 Kinnula VL, Aito H, Klefstrom J, Alitalo K, Raivio KO
• Induction of TNF-sensitive cellular phenotype by c-Myc involves p53 and impaired NF-kappaB activation.
  The EMBO journal 1997 Klefstrom J, Arighi E, Littlewood T, Jäättelä M, Saksela E, Evan GI, Alitalo K
• BCL2 overexpression associated with chromosomal amplification in diffuse large B-cell lymphoma.
  Blood 1997 Monni O, Joensuu H, Franssila K, Klefstrom J, Alitalo K, Knuutila S
• Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia.
  Oncogene 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
• c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha.
  The EMBO journal 1994 Klefstrom J, Västrik I, Saksela E, Valle J, Eilers M, Alitalo K
• Major and minor breakpoint sites of chromosomal translocation t(14;18) in subtypes of non-Hodgkin's lymphomas.
  Leukemia research 1994 Klefstrom J, Franssila K, Peltomäki P, Kaartinen M, Solin ML, Knuutila S
• Two novel human B-cell lymphoma lines of lymphatic follicle origin: cytogenetic, molecular genetic and histopathological characterisation.
  European journal of haematology 1994 Knuutila S, Klefström J, Szymanska J, Lakkala T, Peltomäki P, Eray M, Teerenhovi L, Elonen E, Franssila KO, Kaartinen M
• Myc protein: partners and antagonists.
  Critical reviews in oncogenesis 1994 Västrik I, Mäkelä TP, Koskinen PJ, Klefstrom J, 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 1993 Klefstrom J, Koskinen PJ, Saksela E, Jäättelä M, Bravo R, Alitalo K
• [Complex mechanics of tumor-necrosis-factor-induced cell death].
  Duodecim; laaketieteellinen aikakauskirja 1992 Klefström J, Saksela E, Alitalo K
• [The use of polymerase chain reaction in the diagnosis of non-Hodgkin's lymphoma].
  Duodecim; laaketieteellinen aikakauskirja 1990 Klefström J, Kaartinen M, Peltomäki P, Solin ML, Franssila K, Knuutila S