Kaisa Irene Lehti

About

With background in biochemistry and cell biology, as well as in developing and applying cutting-edge technologies of tissue profiling, primary cell isolation, and 3D in vitro, ex vivo & in vivo experimental models, the Lehti group at NTNU focuses on basic and translational cancer research, tumor/tissue microenvironment (TME)-dependent cell signalling and phenotypic plasticity in cell growth, invasion, and drug resistance. The group collaborates actively on different aspects of clinical cancer diagnosis and therapy development particularly in (but not limited to) ovarian cancer.

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 Title of 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 Research Program; 2015-18 Genome-Scale Biology Research Program)

2015- (continues part-time) Researcher, 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

Research

Previous research

Since graduate studies at the University of Helsinki, 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 membrane-type matrix metalloproteinase, MT1-MMP in cancer cells. Her postdoctoral research with Stephen J Weiss at the University of Michigan 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 complexes.

With her research groups at the University of Helsinki, Karolinska Institutet, and NTNU, Lehti has focused on uncovering the molecular mechanisms of cancer invasion, growth control, and apoptosis evasion in varying extracellular matrices (ECM) and TMEs. The results have revealed unique mechanisms of 1) coordination between ECM degradation, adhesion, and signaling connected with cytoskeletal dynamics in collective invasion as well as epithelial-to-mesenchymal transition-induced invasion and metastasis, and 2) collagen assembly, cell aggregation and lymphatic involvement associated with poor cancer prognosis as well as proliferative diabetic retinopathy.

The group has also 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, their results 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 sarcomas and proliferative diabetic retinopathy, Lehti’s results add to the comprehensive understanding of cell invasion, growth, and apoptosis, as well as the related drug responses & treatment options in different cancers and other fibro-inflammatory conditions.

Current major projects:

Norwegian Cancer Society (Kreftforeningen, Norway), Strategies for combinatorial tumour microenvironment targeting and ex vivo tissue-based drug testing to eradicate metastatic cancers, 2021-25, PI.

Novo Nordisk Fonden SYNERGY grant, Understanding and overcoming cancer drug resistance through experimental-computational studies of cancer cell lineage dynamics, 2022-26, co-PI.

Swedish Cancer Society (Cancerfonden, Sweden), Signals and proteolytic
effectors of invasion, metastasis and anticancer drug resistance in ovarian cancer, 2022-25, PI.

NTNU Health and Central Norway Regional Health Authority (Helse Midt-Norge), Inflammation “the fuel for cancer” -adding precision to patient stratification and therapy, 2023-26, co-PI.

Publications

2023

Liao, Zehuan; Lim, Joseph Jing Heng; Lee, Jeannie Xue Ting; Chua, Damien; Vos, Marcus Ivan Gerard; Yip, Yun Sheng. (2023) Attenuating Epithelial-to-Mesenchymal Transition in Cancer through Angiopoietin-Like 4 Inhibition in a 3D Tumor Microenvironment Model. Advanced Healthcare Materials
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
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
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
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
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

2022

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
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
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 (PNAS)
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

2021

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
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
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
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
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
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
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
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

2020

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
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

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

Liao, Zehuan; Lim, Joseph Jing Heng; Lee, Jeannie Xue Ting; Chua, Damien; Vos, Marcus Ivan Gerard; Yip, Yun Sheng. (2023) Attenuating Epithelial-to-Mesenchymal Transition in Cancer through Angiopoietin-Like 4 Inhibition in a 3D Tumor Microenvironment Model. Advanced Healthcare Materials
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
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
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
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
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
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
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
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 (PNAS)
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
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
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
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
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
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
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
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
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
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
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
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

Outreach

2024

Poster

Singh, Mithlesh Prasad; Wess, Maximilian; Rye, Morten Beck; Lehti, Kaisa Irene; Tessem, May-Britt; Andersen, Maria K.. (2024) Unveiling Spatial Metabolism in Prostate Cancer Tissue: Applying Explainable Machine Learning to Mass Spectrometry Imaging Data. Biomarker Discovery with MSI and Explainable Machine Learning. VIB-KU Leuven Spatial Omics 2024 a VIB Tools and Technologies conference , Ghent 2024-06-13 - 2024-06-14

2022

Poster

Gjerde, 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

Språkvelger

Kaisa Irene Lehti