University of Helsinki
Lab home parent page
For organizing pages more neatly. Isn’t shown on the site.
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.
Juha Klefström
Juha Klefström, PhD, is a FICAN Research Professor in Finnish Cancer Institute, a part time Professor in FICAN-South (HUS) and a part time Research Director in the Translational Cancer Medicine Program, Medical Faculty, University of Helsinki. FICAN is the National Cancer Center Finland, a new operating model to promote current and high quality cancer care and research in Finland. 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 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
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.
Pharmacological intervention of SARS-CoV-2 entry mechanisms by blockade of TMPRSS activity
“Hepsin/TMPRSS family members do not only promote cancer invasion, but they also help the coronavirus SARS-CoV-2 to infect cells”
Normally, epithelial cells are separated from neighboring tissues by a blanket- or sheet-like basement membrane. However, when cancer arises the overactive cell surface serine proteases damage the basement membrane. This enables cancerous epithelial cells to invade neighboring tissues, and ultimately metastasize to distant sites. Many cancer-promoting cell surface serine proteases belong to the Hepsin/TMPRSS family.
Interestingly, recent evidence suggests that the hepsin/TMPRSS family members not only promote cancer invasion, but they also help the coronavirus SARS-CoV-2 to infect cells. This may lead to the life-threatening COVID-19 coronavirus disease. 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 the cells, potentially offering a fast-track treatment option for the COVID-19 disease. We are currently testing a number of hepsin/TMPRSS family-targeting drug-like molecules and drugs as potential antivirals as weapons in the battle against coronavirus.
Damalanka VC, Han Z, Karmakar P, O’Donoghue AJ, La Greca F, Kim T, Pant SM, Helander J, Klefström J, Craik CS, Janetka JW.
J Med Chem. 2019 Jan 24;62(2):480-490. doi: 10.1021/acs.jmedchem.8b01536. Epub 2019 Jan 4.
Pant SM, Mukonoweshuro A, Desai B, Ramjee MK, Selway CN, Tarver GJ, Wright AG, Birchall K, Chapman TM, Tervonen TA, Klefström J.
J Med Chem. 2018 May 24;61(10):4335-4347. doi: 10.1021/acs.jmedchem.7b01698. Epub 2018 May 14.
Pant SM, Belitskin D, Ala-Hongisto H, Klefström J, Tervonen TA.
Methods Mol Biol. 2018;1731:169-178. doi: 10.1007/978-1-4939-7595-2_16.
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.
Oncogene. 2016 Apr 7;35(14):1832-46. doi: 10.1038/onc.2015.248. Epub 2015 Jul 13.
Immunogenic Cell Death (ICD) in Breast Cancer
Immune checkpoint (IC) inhibitors have revolutionized cancer treatment by offering treatment options for previously incurable forms of cancer. However, IC inhibitor monotherapy is not effective against so-called ‘non-immunogenic’ cancers, such as breast cancer. Thus, a clear unmet medical need exists to increase effectiveness of immunotherapy in such cancers. One way to trigger an immune reaction against “non-immunogenic” tumours is induction of immunogenic cell death (ICD), which activates the innate immune system through release of danger-associated molecular patterns (DAMPS). For example, some types of chemotherapy induce ICD through cytotoxic effects, which elicits an immune response that is subsequentially often dampened through upregulation of checkpoint ligands. However, chemotherapy often has quite severe adverse effects that negatively impact quality of life. Therefore, a major opportunity in cancer treatment is to identify more cancer-specific, less toxic alternatives to induce ICD, which is the aim of this project.
Now we will screen a library of candidate cancer drugs in several breast cancer ICD-reporter cell lines we created. To shorten the time to clinical application, a chemical libraries containing approved and emerging investigational drugs will be used. The most promising candidates will be studied in vitro (in cell lines and in monocyte-derived dendritic cells (MDDCs)), ex vivo (in PDEC) and in vivo.
Targeting MYC-dependent metabolic vulnerabilities
MYC is an oncogene and a transcription factor that is overexpressed in over 40% of breast cancers (Haikala et al., 2017). MYC supports cancer cell division by promoting cell cycle progression, and by switching cell metabolism to serve growth-promoting metabolism. MYC activation induces a metabolic switch characterized by enhanced glucose and glutamine utilization as well as by instructing the normally ATP- generating citric acid cycle to serve biosynthetic reactions. We found that the metabolic changes induced by MYC lead to decreased production of ATP and the consequent activation of a key cellular energy sensor protein AMP-activated kinase (AMPK) (Nieminen et al., 2013). We also found, that MYC-induced AMPK activity makes the cells more sensitive to apoptotic cell death, providing important new insight into the close connections between the MYC oncogene, cell death sensitivity and cancer metabolism.
Furthermore, we study how the altered metabolism-derived sensitivity to apoptosis could be exploited as a potential therapeutic strategy to kill cancer cells. We have discovered novel synthetic lethal and combination therapy- based approaches to harness MYC’s full apoptotic potential to pharmacologically activate apoptotic cell death in cancer cells (Haikala et al., 2016, Haikala et al., 2017).
Save
How loss of epithelial Integrity promotes cancer?
In order to properly perform their function, epithelial tissues need to maintain a pre-defined architecture. This structure is built via the localization and polarized orientation of the cells that constitute the tissue. Classical examples of epithelial tissues include skin with important barrier function and secretion glands, for example, milk producing mammary gland.
If the structurally organized epithelial cells lose contact with the rest of the structure or polarized orientation, this will affect to their ability control proliferation or cell death regulation. These defects in epithelial integrity can lead to tissue malfunction and development of epithelial pre-cancerous lesions or full-blown cancer.
Specific cell signaling circuitries are responsible for providing cues that help epithelial cells to organize into tissue structures. We aim to understand how cancer gene mutations affect to these signaling pathways in a way that predisposes the epithelial tissues to development of breast cancer.
For more information about this resaerach line, see
Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4
Microenvironmental management of mammary cell fate determination
Cancer cell lines have been proven to be a valuable source of information for drug discovery process, but their limitations have been increasingly recognized. Culturing cells in 2D conditions will cause a lack of original complexity and heterogeneity of the tumor in situ. Chemicophysical cues from the surrounding stroma and cell- cell /cell- ECM interactions are also lacking from 2D cultures. This tumor-stroma interaction is particularly important since it affects cell signaling, proliferation, cell survival, and therefore has an impact on drug sensitivity and responses. For these reasons there has been an increasing interest in creating artificial models by implanting malignant tissues in three-dimensional culture systems and bioreactors. The advantage of these systems (patient derived ex vivo, pdex) is that the conditions are more controllable, they allow higher throughput studies, shorter time to achieve results with lower costs, and free of experimental animal use. In the past several years, a tremendous effort has been put into a development of 3D culture systems and adopting them in drug discovery, cancer cell biology, and stem cell studies. The biggest challenges of 3D models are to maintain the viability of tumor samples in long term cultures and preventing them for changing their cellular identity, and the overall heterogeneity of the original tumor during culture period. We have developed in collaboration with molecular material specialists from Aalto University a novel cellular identity preserving 3D model, which we are using to reveal those fundamental molecular mechanisms regulating cellular identity in mammary gland and in breast cancer. Realizing both the chemical and mechanical properties of microenvironment, which are constantly been altered through tissue remodeling (proliferation, apoptosis, migration), affects directly gene expression profiles, opens up new research directions to design new approaches in cancer research but also for regenerative medicine, developmental, and cell biology.
Targeting protelytic activity that alters tumor microenvironment and cell autonomously promotes tumor growth
Our recent investigations have exposed a role for tumor suppressor LKB1 in maintenance of cell junction integrity in mammary epithelial cells. Loss of LKB1 damages tight junctions and desmosomes, which leads to redistribution of proteins that normally reside in desmosomes, including a transmembrane serine protease hepsin. The redistributed hepsin inflicts damage to basement membranes, thus paving a way to dissemination of cancerous cells (Partanen et al PNAS 2012).
Type II transmembrane serine protease hepsin is overexpressed and redistributed in clinical breast cancer samples, although the HPN gene is not a frequent target of cancer-specific genetic alterations. Our aim is to identify cancer relevant upstream factors responsible for oncogenic deregulation of hepsin and cancer promoting downstream consequences of uninhibited hepsin action. We are also currently investigating different therapeutic approaches to inhibit hepsin as a possible strategy to limit cancer growth and invasion (Tervonen et al. Adv. Cancer Res 2011; Partanen et al. Philos Trans R Soc Lond B Biol Sci 2013; Tervonen et al. Oncogene 2016).
Publications
Selected publications
Please follow our latest publications in TUHAT or PubMed
Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer Nature Communications :, 2021.
Oncogenic Ras disrupts epithelial integrity by activating the transmembrane serine protease hepsin Cancer Research :, 2021.
Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy. Nature communications 1:620, 2019.
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.
Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic Acid-induced 2. Cancer discovery 5:506-19, 2015.
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.
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.
MYC-induced apoptosis in mammary epithelial cells is associated with repression of lineage-specific gene signatures. Cell cycle (Georgetown, Tex.) 3:316-23, 2016.
Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation. Cell reports 6:1019-31, 2015.
Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers. Oncogene 11:1386-98, 2016.
Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells. The EMBO journal 11:1554-71, 2015.
Full list of publications
Please follow our latest publications in TUHAT or PubMed
2021
Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer Nature Communications :, 2021.
ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma. Cancers 5:, 2021.
Oncogenic Ras disrupts epithelial integrity by activating the transmembrane serine protease hepsin Cancer Research :, 2021.
2020
Assessment of the WAP-Myc mouse mammary tumor model for spontaneous metastasis Scientific Reports :, 2020.
2019
Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy. Nature communications 1:620, 2019.
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
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.
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
2016
MYC-induced apoptosis in mammary epithelial cells is associated with repression of lineage-specific gene signatures. Cell cycle (Georgetown, Tex.) 3:316-23, 2016.
Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers. Oncogene 11:1386-98, 2016.
2015
Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic Acid-induced 2. Cancer discovery 5:506-19, 2015.
Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation. Cell reports 6:1019-31, 2015.
Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells. The EMBO journal 11:1554-71, 2015.
2014
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
Chk1 targeting reactivates PP2A tumor suppressor activity in cancer cells. Cancer research 22:6757-69, 2013.
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.
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
Impact of epithelial organization on Myc expression and activity–letter. Cancer research 4:1035; author reply 1036, 2012.
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
2010
GATA4 protects granulosa cell tumors from TRAIL-induced apoptosis. Endocrine-related cancer 3:709-17, 2010.
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
Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation. International journal of cancer 10:2441-9, 2009.
3D view to tumor suppression: Lkb1, polarity and the arrest of oncogenic c-Myc. Cell cycle (Georgetown, Tex.) 5:716-24, 2009.
2008
Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer. BMC genomics :348, 2008.
2007
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.
c-Myc primed mitochondria determine cellular sensitivity to TRAIL-induced apoptosis. The EMBO journal 4:1055-67, 2007.
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
2002
The oncogenic potential of Kaposi’s sarcoma-associated herpesvirus cyclin is exposed by p53 loss in vitro and in vivo. Cancer cell 3:229-41, 2002.
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
1998
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
Induction of TNF-sensitive cellular phenotype by c-Myc involves p53 and impaired NF-kappaB activation. The EMBO journal 24:7382-92, 1997.
1994
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.
Major and minor breakpoint sites of chromosomal translocation t(14;18) in subtypes of non-Hodgkin’s lymphomas. Leukemia research 4:245-50, 1994.
c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha. The EMBO journal 22:5442-50, 1994.
1993
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
[Complex mechanics of tumor-necrosis-factor-induced cell death]. Duodecim; laaketieteellinen aikakauskirja 17:1449-55, 1992.
1990
[The use of polymerase chain reaction in the diagnosis of non-Hodgkin’s lymphoma]. Duodecim; laaketieteellinen aikakauskirja 23-24:1645-53, 1990.
For open positions in the lab, click here.
Research Coordinator
TOPI TERVONEN
Adjunct ProfessorTopi Tervonen received his PhD in 2008, in the field of neural stem cells at the Neuroscience Center, University of Helsinki. For his post-doctoral training he chose to study molecular cancer biology in Dr. Juha Klefström’s group at the 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. Related to the topic, Topi has supervised 2 MSc theses, one engineer thesis, one lab analyst thesis and 2 PhD theses thus far. Topi has served as a research coordinator since 2014 and, in 2020, he obtained the title of docent (adjunct professor) from the University of Helsinki in the field of cell and molecular biology. During recent years, Topi has been actively bringing in genome-scale genome editing resources and services in University of Helsinki and also nationally. He was named the vice chair of Stem Cells and Genome Editing technology platform of Biocenter Finland in 2020. He has also taken a position as principal investigator in Finnish Genome Editing Center (FinGEEC) core unit of GoEditStem HiLIFE infra platform in University of Helsinki 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
PhDPauliina 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.
Daniel Nicorici
PhD, Senior BioinformaticianDaniel has a Doctor of Technology on data processing and bioinformatics from Tampere University of Technology (nowadays Tampere University).
He has experience with omics data analysis, next generation sequencing, drug discovery, and biomarker discovery. In his free time, Daniel enjoys jogging and dancing.
Ruixian Liu (Mars)
PhDMars 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
Johanna Anttila
MScJohanna 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.
Mariel Savelius
MScMariel Savelius recently completed 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.
Iiris Räty
MD PhD StudentIiris has started her medical studies in the MD PhD programme in 2016 and she joined Klefström lab in 2017. Her research focuses on the interaction between the tumor microenvironment and ER-positive breast cancer cells and new potential therapeutic targets related to ER-signaling. In her free time Iiris enjoys reading, spending time outdoors and various sports such as skiing, running and dancing.
Aino Peura
MD PhD StudentAino 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
July Aung
MScJuly recently completed her Master’s degree in Genetics and Molecular Biosciences at the University of Helsinki, specialising in Cell and Developmental Biology. She is keen on learning how cancer and the tumour microenvironment interact with the immune system. Her interests in cancer, immunology and translational research have brought her to Klefa lab where she investigates MYC synthetic lethal targets in enhancing cancer immunotherapy. She is motivated by and looks forward to the day where her research can benefit patients battling with breast cancer.
When not at her bench, July can be found either enjoying the beautiful Finnish nature, cooking up a storm for close friends and family, attempting to grow a new plant or trying to pick up a new language. On dark winter days, she avidly watches movies and hopes to be lucky enough to see the Aurora Borealis one day.
Linda Id
MScLinda completed her Master’s degree at the University of Helsinki in Genetics and Molecular Biosciences program with a major in Genetics and Genomics. Her project in Klefström lab focuses on finding oncogene MYC driving metabolic vulnerabilities in TNBC. In addition to cancer metabolism, Linda is interested in immune-oncology and combining these two for future cancer therapies.
Outside of the lab Linda enjoys a great variety of sports, board games and knitting, as well as taking care of her plant babies.
Antti Hiltunen
MScAntti Hiltunen received his Master’s degree in Genetics and Molecular Biosciences from the University of Helsinki with a focus on genetics and genomics. His master’s thesis focused on the function of serine protease hepsin in the immune landscape of triple negative breast cancer. Antti is now switching gears and has started his PhD studies with a focus on exploiting the vulnerabilities caused by the oncogene Myc. He is keen on understanding how Myc regulates the mitochondrial metabolism and how Myc-driven cancers may be susceptible to drugs targeting the electron transport chain.
In his free time, Antti is an avid climber, outdoorsman, and a gamer.
Masters Students
Emmie Salmelin
BScEmmie 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.
Technical Staff
Babette Hollmann
Babette has finished her job training 2007 in Marburg/Lahn. She joined Klefström lab 2021 where she’s providing a pair of helping hands for the “Munne-Klubi”.
Outside of work, Babette is rarely spotted alone. Usually accompanied by her dog, she enjoys various outdoor activities. As a passionate couch potato, she’s happily handicrafting the evenings away or solving jigsaw puzzles.
Klefalab alumni
-
Rita Turpin
-
MSc, RN
-
Jeroen Pouwels
-
Shishir Pant
-
Denis Belitskin
-
Linda Patrikainen
-
Elina Hurskainen
-
Maria Salmela
-
Ilida Suleymanova
-
Tiina Raatikainen
-
Katariina Karjalainen Laboratory coordinator
-
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
-
Mari Urb
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.
FINNISH TRANSLATIONAL BREAST CANCER RESEARCH PROGRAM IS LOOKING FOR A SCIENTIFIC COORDINATOR
We are hiring an ambitious and talented
Scientific Coordinator
to coordinate a large and well-funded breast cancer research program, which aims to translate preclinical laboratory-based breast cancer research to new clinically viable treatment modalities for breast cancer. The program is seeking new ways to sensitize breast cancer to immune checkpoint inhibitors via synthetic lethal and immunogenic cell death concepts, which are integrated with computational predictions.
One key investigational platform in this approach is a novel method to grow 3D cultures of intact fragments of patient-derived tissue (Patient-Derived Explant Cultures/PDECs) for analysis of tumor cell and tumor infiltrated lymphocyte responses (Haikala et al., Nature Comm. 2019; PMID: 30728358, Munne et al., Nature Comm. in press; Al-Akhrass et al., Mol. Oncol. 2021, PMID: 34564954). The program is funded by significant long-term grants from the US Department of Defense Breast Cancer Research Program, Business Finland, The Jane and Aatos Erkko Foundation, EU Horizon 2020, The Juselius Foundation, The Academy of Finland, the Finnish Cancer Organizations, and others.
The Finnish Translational Breast Cancer Research Program is led by FICAN Professor Juha Klefström, with his team located in the Faculty of Medicine* at the University of Helsinki. The program closely interacts with a number of leading translational breast cancer research teams in Finland, the EU and the USA, as well as with clinical oncologists in the HUS Comprehensive Cancer Center and the Finnish National Cancer Centre (FICAN) network.
The candidate will join a translational research group (https://klefstromlab.com) that is part of the Translational Cancer Medicine Research Program of the Medical Faculty’s Research Programs Unit (RPU; link). A list of publications from the host laboratory can be found at PubMed, search for Klefstrom+j. Highlights include publications in Nat. Comms (in press and 2019), Cancer Research, J. Med. Chem, Cancer Discovery, PNAS, Oncogene and EMBO J.
Candidate requirements:
- PhD degree and several years of Principal Investigator, Scientific Coordinator or strong Post Doc experience in a relevant field
- Highly motivated and scientifically knowledgeable with strong interest in translational cancer research and working for cancer patients’ benefit
- Documented experience in translational cancer research
- Strong team player with outstanding communication and leadership skills
- Experience in grant writing, management and reporting
- Experience in supervising students and postdocs, working in expert teams and writing manuscripts
- As the working language of the research group and associated teams is English, the chosen candidate must be able to communicate fluently in English
The candidate’s tasks include, but are not limited to:
- As part of the coordination team, you will coordinate interdisciplinary academic and entrepreneurial programs
- You will supervise both scientific and non-scientific personnel in Klefström’s research team and through collaborations in partner teams
- You will participate in writing, managing and reporting research grants
- You will participate in managing health related data, ethical and research permits, as well as a variety of contracts and agreements
- You will take responsibility of scientific communication within the programs and carry out general operational duties and implementation in various related research programs
- You will participate in planning of the translational research projects, oversee implementation of the projects and contribute to writing manuscripts
What we offer:
- A challenging international research-oriented position within a well-funded, ambitious and ground-breaking cancer research program
- Every day is different. You will perform a large set of diverse tasks, ensuring your professional development.
- Tight involvement in several multi-disciplinary translational research projects with broad national and international (EU and USA) exposure and multi-stakeholder involvement (academics, Pharma and other companies, oncologists, patient organizations)
- Opportunity to develop your leadership, communications and management skills through appointment in the strategic management team
- Opportunity to travel and develop networks nationally and internationally
- Opportunity to develop your publications list through co-authorship
The initial contract will be for one year, starting at your earliest convenience. Total program funding covers 5-years and contract extension is possible. The salary is in accordance with the University salary system (for teaching and research personnel).
Applications must include a CV and an application letter clearly describing how your profile matches the candidate requirements and other previous achievements in the field. Also include names and contact information of two or three references. The application, together with the required attachments, must be submitted via email to cancerio-office (at) helsinki.fi. Deadline for applications is November 12 2021, but the position will be closed once a suitable candidate has been identified. For further inquiries, please contact cancerio-office (at) helsinki.fi.
*The Faculty of Medicine of the University of Helsinki promotes scientific research of a high standard and is responsible for providing research-based undergraduate and postgraduate education in medicine, dentistry, psychology and logopedics, as well as for the English-language Master’s Programme in Translational Medicine. In addition to teaching and research activities, the Faculty serves as a significant expert organisation in the healthcare sector and contributes to the discourse on ethics in the field. In terms of research, the Faculty aims for a place among the best medical faculties in the world, while consolidating and strengthening its status as a top-level institution of medical education. Together with the Helsinki University Hospital (HUS) and the Helsinki Institute of Life Sciences (HiLIFE), the Faculty of Medicine constitutes the Academic Medical Center Helsinki (AMCH). This medical center has been ranked among the top 10 medical campuses in Europe and among the top 50 globally.
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.
