Kaisa Irene Lehti
About
Norwegian Cancer Society project: Strategies for combinatorial tumour microenvironment targeting and ex vivo tissue-based drug testing to eradicate metastatic cancers
With background in developing and applying cutting-edge techniques of primary cell isolation, ex vivo 3D cell & tissue culture and in vivo tumour models, the Lehti group at NTNU will focus on translational ovarian cancer research, microenvironment-dependent cell signalling and phenotypic plasticity in tumor growth, invasion and drug resistance. The group has established ovarian cancer organoids & orthotopic metastasis model and collaborates on different aspects of clinical ovarian cancer therapy development.
Previous research
Since graduate studies, Lehti’s scientific interest has been in the general and context-dependent mechanisms of cell invasion and tissue remodeling, with particular focus on the underlying proteolytic effectors and signals in cancer and pathological angiogenesis.
The observations in her PhD thesis established fundamental regulatory features of the transmembrane proteinase, MT1-MMP in cancer cells. Her postdoctoral research with Stephen J Weiss revealed the first physical and functional interaction of this protease, earlier considered mainly as a downstream effector of pro-invasive signaling, with receptor tyrosine kinase signaling complexes.
With her research group, Lehti has focused on uncovering the molecular mechanisms of cancer invasion, growth control and apoptosis evasion in varying extracellular matrices and tumor microenvironments (TME). The results have revealed various mechanisms of 1) coordination between collagen degradation, migrations signaling and cytoskeletal dynamics in collective invasion or epithelial-to-mesenchymal transition-induced invasion and metastasis in carcinomas and 2) collagen assembly, cell aggregation and lymphatic invasion associated with poor cancer prognosis.
Recently, the group identified a clinically relevant, co-targetable mechanism of FGFR4 oncogenic activity via evasion from cell stress-associated Hippo MST1/2 kinase-induced apoptosis. Using an oncology drug library and FGFR4 inhibitor, they showed that FGFR4 encompasses co-targetable vulnerabilities with intrinsic apoptosis or EGFR, AKT & mTORC1 pathways. Moreover, they revealed a robust mechanism, whereby ovarian cancer cells develop TME-dependent chemotherapy resistance via an adaptive RSK-EphA2-GPRC5A signalling switch.
Coupled with collaborative studies on for example cytoskeletal signaling in cancer-associated fibroblasts and carcinomas as well as fibrosis and immuno-microenvironment in aggressive uterine tumors, Lehti’s results add to the comprehensive understanding of tumor invasion, growth, apoptosis as well as the related drug responses & treatment options in different cancers.
Education and degrees
1995 MSc, Biochemistry, University of Helsinki, Finland
2002 PhD, Biochemistry & Cancer cell biology, University of Helsinki
2002-2004 Postdoctoral training, Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, USA
2009 Docent, Cell and molecular biology, University of Helsinki
Academic positions
2005-2009 Researcher, Molecular Cancer Biology Program, University of Helsinki
2010-2015 Academy of Finland Researcher and Independent Research Group Leader, Genome-scale Biology Program, University of Helsinki
2015-2017 K. Albin Johansson Senior Cancer Researcher, Finnish Cancer Institute
2015-2020 Research Director University of Helsinki, Finland (2019-20 Individualized Drug Therapy / 2015-18 Genome-Scale Biology Research Program)
2015- (continues part-time) Group Leader, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Sweden
2020- Professor of Cell and molecular biology, Department of Biomedical Laboratory Science, Norwegian University of Science and Technology NTNU, Trondheim, Norway
Publications
2023
-
Closset, Lara;
Gultekin, Okan;
Salehi, Sahar;
Sarhan, Dhifaf;
Lehti, Kaisa Irene;
Gonzalez-Molina, Jordi.
(2023)
The extracellular matrix – immune microenvironment crosstalk in cancer therapy: Challenges and opportunities.
Matrix Biology
Academic literature review
-
Bugaeva, Olga;
Maliniemi, Pilvi;
Prestvik, Wenche Slettahjell;
Leivo, Eeva;
Kluger, Nicolas;
Salava, Alexander.
(2023)
Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but Downregulated in Thick Tumours.
Acta Dermato-Venereologica
Academic article
-
Gonzalez-Molina, Jordi;
Hahn, Paula;
Falcão, Raul Maia;
Gultekin, Okan;
Kokaraki, Georgia;
Zanfagnin, Valentina.
(2023)
MMP14 expression and collagen remodelling support uterine leiomyosarcoma aggressiveness.
Molecular Oncology
Academic article
-
Åkerlund, Emma;
Gudoityte, Greta;
Moussaud-Lamodière, Elisabeth;
Lind, Olina;
Bwanika, Henri Colyn;
Lehti, Kaisa Irene.
(2023)
The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients.
NPJ precision oncology
Academic article
-
Monzo, Hector J.;
Kalander, Kerttu;
Hyytiäinen, Marko M.;
Elbasani, Endrit;
Wall, Johanna;
Moyano-Galceran, Lidia.
(2023)
Efficacy and Safety of Glycosphingolipid SSEA-4 Targeting CAR-T Cells in an Ovarian Carcinoma Model.
Molecular Cancer Therapeutics
Academic article
2022
-
Gizaw, Nebeyu Yosef;
Kallio, Pauliina;
Punger, Tatjana;
Gucciardo, Erika;
Haglund, Caj;
Böhling, Tom.
(2022)
PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets.
Proceedings of the National Academy of Sciences of the United States of America
Academic article
-
Gonzalez-Molina, Jordi;
Kirchhof, Katharina Miria;
Rathod, Bhavik;
Moyano-Galceran, Lidia;
Calvo-Noriega, Maria;
Kokaraki, Georgia.
(2022)
Mechanical Confinement and DDR1 Signaling Synergize to Regulate Collagen-Induced Apoptosis in Rhabdomyosarcoma Cells.
Advanced Science
Academic article
-
Schoutrop, Esther;
Moyano-Galceran, Lidia;
Lheureux, Stephanie;
Mattsson, Jonas;
Lehti, Kaisa;
Dahlstrand, Hanna.
(2022)
Molecular, cellular and systemic aspects of epithelial ovarian cancer and its tumor microenvironment.
Seminars in Cancer Biology
Academic literature review
-
Gonzalez-Molina, Jordi;
Moyano-Galceran, Lidia;
Single, Andrew;
Gultekin, Okan;
Alsalhi, Shno;
Lehti, Kaisa.
(2022)
Chemotherapy as a regulator of extracellular matrix-cell communication: Implications in therapy resistance.
Seminars in Cancer Biology
Academic literature review
2021
-
Jukonen, Joonas;
Moyano-Galceran, Lidia;
Höpfner, Katrin;
Pietilä, Elina A.;
Lehtinen, Laura;
Huhtinen, Kaisa.
(2021)
Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality.
Scientific Reports
Academic article
-
Pietilä, Elina A.;
Gonzalez-Molina, Jordi.;
Moyano-Galceran, Lidia;
Jamalzadeh, Sanaz;
Zhang, Kaiyang;
Lehtinen, Laura.
(2021)
Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance.
Nature Communications
Academic article
-
Korhonen, Ani;
Gucciardo, Erika;
Lehti, Kaisa;
Loukovaara, Sirpa.
(2021)
Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement.
Scientific Reports
Academic article
-
Korhonen, Ani;
Gucciardo, Erika;
Lehti, Kaisa;
Lehti, Kaisa;
Loukovaara, Sirpa.
(2021)
Phosphodiesterase type 5 inhibitor (sildenafil) – impact in proliferative diabetic retinopathy?.
Acta Ophthalmologica
Letter to the editor
-
Jaiswal, Alok;
Gautam, Prson;
Pietilä, Elina A;
Timonen, Sanna;
Nordström, Nora;
Akimov, Yevhen.
(2021)
Multi-modal meta-analysis of cancer cell line omics profiles identifies ECHDC1 as a novel breast tumor suppressor.
Molecular Systems Biology
Academic article
-
Su, Yanhong;
Tsagozis, Panagiotis;
Papakonstantinou, Andri;
Tobin, Nicholas P.;
Gultekin, Okan;
Malmerfelt, Anna.
(2021)
Cd11c‐cd8 spatial cross presentation: A novel approach to link immune surveillance and patient survival in soft tissue sarcoma.
Cancers
Academic article
-
Schoutrop, Esther;
El-Serafi, Ibrahim;
Poiret, Thomas;
Zhao, Ying;
Gultekin, Okan;
He, Rui.
(2021)
Mesothelin-specific CAR T cells target ovarian cancer.
Cancer Research
Academic article
-
Gultekin, Okan;
Gonzalez-Molina, Jordi;
Hardell, Elin;
Moyano-Galceran, Lidia;
Mitsios, Nicholas;
Mulder, Jan.
(2021)
FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation.
NPJ precision oncology
Academic article
-
Filppu, Paulinna;
Ramanathan, Jayendrakishore;
Granberg, Kirsi J.;
Gucciardo, Erika;
Haapasalo, Hannu;
Lehti, Kaisa.
(2021)
CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity.
JCI Insight
Academic article
2020
-
Miki, Yuichiro;
Yashiro, Masakazu;
Moyano-Galceran, Lidia;
Sugimoto, Atsushi;
Ohira, Masaichi;
Lehti, Kaisa.
(2020)
Crosstalk Between Cancer Associated Fibroblasts and Cancer Cells in Scirrhous Type Gastric Cancer.
Frontiers in Oncology
Academic literature review
-
Peuget, Sylvain;
Zhu, J;
Sanz, Gema;
Singh, Madhurendra;
Gaetani, Massimiliano;
Chen, Xinsong.
(2020)
Thermal proteome profiling identifies oxidative-dependent inhibition of the transcription of major oncogenes as a new therapeutic mechanism for select anticancer compounds.
Cancer Research
Academic article
2019
-
Binzer-Panchal, Amrei;
Hardell, Elin;
Viklund, Björn;
Ghaderi, Mehran;
Bosse, Tjalling;
Nucci, Marisa R..
(2019)
Integrated molecular analysis of undifferentiated uterine sarcomas reveals clinically relevant molecular subtypes.
Clinical Cancer Research
Academic article
Journal publications
-
Closset, Lara;
Gultekin, Okan;
Salehi, Sahar;
Sarhan, Dhifaf;
Lehti, Kaisa Irene;
Gonzalez-Molina, Jordi.
(2023)
The extracellular matrix – immune microenvironment crosstalk in cancer therapy: Challenges and opportunities.
Matrix Biology
Academic literature review
-
Bugaeva, Olga;
Maliniemi, Pilvi;
Prestvik, Wenche Slettahjell;
Leivo, Eeva;
Kluger, Nicolas;
Salava, Alexander.
(2023)
Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but Downregulated in Thick Tumours.
Acta Dermato-Venereologica
Academic article
-
Gonzalez-Molina, Jordi;
Hahn, Paula;
Falcão, Raul Maia;
Gultekin, Okan;
Kokaraki, Georgia;
Zanfagnin, Valentina.
(2023)
MMP14 expression and collagen remodelling support uterine leiomyosarcoma aggressiveness.
Molecular Oncology
Academic article
-
Åkerlund, Emma;
Gudoityte, Greta;
Moussaud-Lamodière, Elisabeth;
Lind, Olina;
Bwanika, Henri Colyn;
Lehti, Kaisa Irene.
(2023)
The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients.
NPJ precision oncology
Academic article
-
Monzo, Hector J.;
Kalander, Kerttu;
Hyytiäinen, Marko M.;
Elbasani, Endrit;
Wall, Johanna;
Moyano-Galceran, Lidia.
(2023)
Efficacy and Safety of Glycosphingolipid SSEA-4 Targeting CAR-T Cells in an Ovarian Carcinoma Model.
Molecular Cancer Therapeutics
Academic article
-
Gizaw, Nebeyu Yosef;
Kallio, Pauliina;
Punger, Tatjana;
Gucciardo, Erika;
Haglund, Caj;
Böhling, Tom.
(2022)
PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets.
Proceedings of the National Academy of Sciences of the United States of America
Academic article
-
Gonzalez-Molina, Jordi;
Kirchhof, Katharina Miria;
Rathod, Bhavik;
Moyano-Galceran, Lidia;
Calvo-Noriega, Maria;
Kokaraki, Georgia.
(2022)
Mechanical Confinement and DDR1 Signaling Synergize to Regulate Collagen-Induced Apoptosis in Rhabdomyosarcoma Cells.
Advanced Science
Academic article
-
Schoutrop, Esther;
Moyano-Galceran, Lidia;
Lheureux, Stephanie;
Mattsson, Jonas;
Lehti, Kaisa;
Dahlstrand, Hanna.
(2022)
Molecular, cellular and systemic aspects of epithelial ovarian cancer and its tumor microenvironment.
Seminars in Cancer Biology
Academic literature review
-
Gonzalez-Molina, Jordi;
Moyano-Galceran, Lidia;
Single, Andrew;
Gultekin, Okan;
Alsalhi, Shno;
Lehti, Kaisa.
(2022)
Chemotherapy as a regulator of extracellular matrix-cell communication: Implications in therapy resistance.
Seminars in Cancer Biology
Academic literature review
-
Jukonen, Joonas;
Moyano-Galceran, Lidia;
Höpfner, Katrin;
Pietilä, Elina A.;
Lehtinen, Laura;
Huhtinen, Kaisa.
(2021)
Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality.
Scientific Reports
Academic article
-
Pietilä, Elina A.;
Gonzalez-Molina, Jordi.;
Moyano-Galceran, Lidia;
Jamalzadeh, Sanaz;
Zhang, Kaiyang;
Lehtinen, Laura.
(2021)
Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance.
Nature Communications
Academic article
-
Korhonen, Ani;
Gucciardo, Erika;
Lehti, Kaisa;
Loukovaara, Sirpa.
(2021)
Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement.
Scientific Reports
Academic article
-
Korhonen, Ani;
Gucciardo, Erika;
Lehti, Kaisa;
Lehti, Kaisa;
Loukovaara, Sirpa.
(2021)
Phosphodiesterase type 5 inhibitor (sildenafil) – impact in proliferative diabetic retinopathy?.
Acta Ophthalmologica
Letter to the editor
-
Jaiswal, Alok;
Gautam, Prson;
Pietilä, Elina A;
Timonen, Sanna;
Nordström, Nora;
Akimov, Yevhen.
(2021)
Multi-modal meta-analysis of cancer cell line omics profiles identifies ECHDC1 as a novel breast tumor suppressor.
Molecular Systems Biology
Academic article
-
Su, Yanhong;
Tsagozis, Panagiotis;
Papakonstantinou, Andri;
Tobin, Nicholas P.;
Gultekin, Okan;
Malmerfelt, Anna.
(2021)
Cd11c‐cd8 spatial cross presentation: A novel approach to link immune surveillance and patient survival in soft tissue sarcoma.
Cancers
Academic article
-
Schoutrop, Esther;
El-Serafi, Ibrahim;
Poiret, Thomas;
Zhao, Ying;
Gultekin, Okan;
He, Rui.
(2021)
Mesothelin-specific CAR T cells target ovarian cancer.
Cancer Research
Academic article
-
Gultekin, Okan;
Gonzalez-Molina, Jordi;
Hardell, Elin;
Moyano-Galceran, Lidia;
Mitsios, Nicholas;
Mulder, Jan.
(2021)
FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation.
NPJ precision oncology
Academic article
-
Filppu, Paulinna;
Ramanathan, Jayendrakishore;
Granberg, Kirsi J.;
Gucciardo, Erika;
Haapasalo, Hannu;
Lehti, Kaisa.
(2021)
CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity.
JCI Insight
Academic article
-
Miki, Yuichiro;
Yashiro, Masakazu;
Moyano-Galceran, Lidia;
Sugimoto, Atsushi;
Ohira, Masaichi;
Lehti, Kaisa.
(2020)
Crosstalk Between Cancer Associated Fibroblasts and Cancer Cells in Scirrhous Type Gastric Cancer.
Frontiers in Oncology
Academic literature review
-
Peuget, Sylvain;
Zhu, J;
Sanz, Gema;
Singh, Madhurendra;
Gaetani, Massimiliano;
Chen, Xinsong.
(2020)
Thermal proteome profiling identifies oxidative-dependent inhibition of the transcription of major oncogenes as a new therapeutic mechanism for select anticancer compounds.
Cancer Research
Academic article
-
Binzer-Panchal, Amrei;
Hardell, Elin;
Viklund, Björn;
Ghaderi, Mehran;
Bosse, Tjalling;
Nucci, Marisa R..
(2019)
Integrated molecular analysis of undifferentiated uterine sarcomas reveals clinically relevant molecular subtypes.
Clinical Cancer Research
Academic article
Teaching
Courses
Media
2022
-
PosterGjerde, Christiane Helgestad; Langer, Anika; Ruiz de Garibay, Gorka; Kleinmanns, Katrin; Dongre, Harsh Nitin; Elnour, Rammah. (2022) Establishment of peritoneal dECM scaffolds for 3D culture of ovarian cancer organoids. ESGO 2022 European Congress on Gynaecological Oncology 2022-10-27 - 2022-10-30