Kirsi Ketola
Research Director
Cancer Cell Plasticity group leader, Adj.prof in Molecular Medicine
Director, Cell and Tissue Imaging Unit
Institute of Biomedicine, School of Medicine, Faculty of Health Sciences
kirsi.ketola@uef.fi | +358 50 329 9984
We study the molecular mechanisms of cancer cell plasticity and prostate cancer treatment resistance including neuroendocrine transdifferentiation and cellular neuroplasticity programs in prostate cancer. We aim at identifying novel therapeutic targets and biomarkers for neuroendocrine prostate cancer and ways to bring treatment resistant prostate cancer cells back to antiandrogen therapy sensitive state. We employ several genome-wide and cellular imaging methods such as RNA-seq, ATAC-seq, ChIP-seq and live-cell high-content and -throughput imaging and drug screening to understand and target through precision medicine approaches the cellular plasticity stages and epigenetic reprogramming in cancer treatment resistance. We also utilize patient-derived organoids of prostate and neuroendocrine prostate cancer patients as well as patient blood samples on different treatment stages to identify and validate our findings. Our recent identified novel players highly overexpressed after antiandrogen therapy include neuroplasticity protein DPYSL5, which regulates antiandrogen enzalutamide resistance, chromatin reprogramming and neuronal cell phenotype in prostate cancer, Fanconi anemia pathway and FANCI which plays a role in carboplatin resistance in prostate cancer as well as a stem cell transcription factor which turns on cancer stem cell and resistance program in androgen-independent prostate cancer. By inhibiting these cellular plasticity programs we believe we can target the development of aggressive forms of cancer.
Find Ketola Lab pages: https://uefconnect.uef.fi/en/group/cancer-cell-plasticity-ketola-lab/
Research groups
Projects
Publications
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DPYSL5 is highly expressed in treatment-induced neuroendocrine prostate cancer and promotes lineage plasticity via EZH2/PRC2
Kaarijärvi, Roosa; Kaljunen, Heidi; Nappi, Lucia; Fazli, Ladan; Kung, Sonia H. Y.; Hartikainen, Jaana M.; Paakinaho, Ville; Capra, Janne; Rilla, Kirsi; Malinen, Marjo; Mäkinen, Petri I.; Ylä-Herttuala, Seppo; Zoubeidi, Amina; Wang, Yuzhuo; Gleave, Martin E.; Hiltunen, Mikko; Ketola, Kirsi. 2024. Communications biology. 7: . 108 -
SIX2 promotes cell plasticity via Wnt/β-catenin signalling in androgen receptor independent prostate cancer
Leppänen, Noora; Kaljunen, Heidi; Takala, Eerika; Kaarijärvi, Roosa; Mäkinen, Petri I; Ylä-Herttuala, Seppo; Paatero, Ilkka; Paakinaho, Ville; Ketola, Kirsi. 2024. Nucleic acids research. 52: 5610-5623 -
Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, SOX2, and CD44 through NFκB-signaling
Kainulainen, Kirsi; Niskanen, Einari A; Kinnunen, Johanna; Mäki-Mantila, Kaisa; Hartikainen, Kiia; Paakinaho, Ville; Malinen, Marjo; Ketola, Kirsi; Pasonen-Seppänen, Sanna. 2024. Oncoimmunology. 13: . 2393442 -
Fanconi anemia pathway regulation by FANCI in prostate cancer
Kaljunen, Heidi; Taavitsainen, Sinja; Kaarijärvi, Roosa; Takala, Eerika; Paakinaho, Ville; Nykter, Matti; Bova, G Steven; Ketola, Kirsi. 2023. Frontiers in oncology. 13: . 1260826 -
M1 Macrophages Induce Protumor Inflammation in Melanoma Cells through TNFR–NF-κB Signaling
Kainulainen, Kirsi; Takabe, Piia; Heikkinen, Sami; Aaltonen, Niina; de la Motte, Carol; Rauhala, Leena; Durst, Franziska C; Oikari, Sanna; Hukkanen, Taija; Rahunen, Eija; Ikonen, Ella; Hartikainen, Jaana M; Ketola, Kirsi; Pasonen-Seppänen, Sanna. 2022. Journal of investigative dermatology. 1412: 3041-3051.e10 -
Microglial amyloid beta clearance is driven by PIEZO1 channels
Jäntti, Henna; Sitnikova, Valeriia; Ishchenko, Yevheniia; Shakirzyanova, Anastasia; Giudice, Luca; Ugidos, Irene F; Gómez-Budia, Mireia; Korvenlaita, Nea; Ohtonen, Sohvi; Belaya, Irina; Fazaludeen, Feroze; Mikhailov, Nikita; Gotkiewicz, Maria; Ketola, Kirsi; Lehtonen, Šárka; Koistinaho, Jari; Kanninen, Katja M; Hernández, Damian; Pébay, Alice; Giugno, Rosalba; Korhonen, Paula; Giniatullin, Rashid; Malm, Tarja. 2022. Journal of neuroinflammation. 19: . 147 -
Molecular and Functional Links between Neurodevelopmental Processes and Treatment-Induced Neuroendocrine Plasticity in Prostate Cancer Progression
Kaarijärvi, Roosa; Kaljunen, Heidi; Ketola, Kirsi. 2021. Cancers. 13: 692 -
Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse
Taavitsainen, S.; Engedal, N.; Cao, S.; Handle, F.; Erickson, A.; Prekovic, S.; Wetterskog, D.; Tolonen, T.; Vuorinen, E. M.; Kiviaho, A.; Nätkin, R.; Häkkinen, T.; Devlies, W.; Henttinen, S.; Kaarijärvi, R.; Lahnalampi, M.; Kaljunen, H.; Nowakowska, K.; Syvälä, H.; Bläuer, M. et al [incl. Ketola, K.]. 2021. Nature communications. 12: 5307 -
Subclone eradication analysis identifies targets for enhanced cancer therapy and reveals L1 retrotransposition as a dynamic source of cancer heterogeneity
Ketola, Kirsi; Kaljunen, Heidi; Taavitsainen, Sinja; Kaarijärvi, Roosa; Järvelä, Emmi; Rodriguez Martin, Bernardo; Haase, Kerstin; Woodcock, Dan J; Tubio, Jose; Wedge, David C; Nykter, Matti; Bova, G Steven. 2021. Cancer research. 81: 4901-4909 -
BCOR-coupled H2A monoubiquitination represses a subset of androgen receptor target genes regulating prostate cancer proliferation
Lempiäinen, JK; Manjur, ABMK; Malinen, M; Ketola, K; Niskanen, EA; Palvimo, JJ. 2020. Oncogene. 39: 2391-2407