Background and activities
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.
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
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