Henri Leinonen (henri.leinonen@uef.fi)
My laboratory´s research focuses on two projects: (1) Homeostatic plasticity in the retina, its molecular mechanisms and implications for functional adaptation; (2) investigation of a novel drug repurposing-strategy for the treatment of retinal degenerations (RD). We use the retina as a model tissue for plasticity, pharmacology and drug discovery research for several reasons, such as amenability for noninvasive imaging due to eye’s transparency, finely layered structure and well-characterized structure-function relationships, functional similarity to that of brain due to same neurodevelopmental origin. Arguably, the retina is the best-characterized neuronal system in the body.
I detected retinal adaptability to sensory defect in year 2013 and our first paper related to this was published in 2020 (Leinonen et al., eLife). Next, we aim to solve the molecular pathways enabling retinal homeostatic plasticity. This knowledge will help to find mechanisms how the CNS adapts to injury and malfunction and can guide pharmacotherapies.
Our drug discovery program uses repurposed GPCR drugs. We have shown that a treatment with a combination therapy comprised of three GPCR-drugs slows progressive RD. The next crucial task is to uncover the therapeutic mechanisms of our therapy. This will facilitate further development of the treatment concept and can launch innovative drug development pipelines.
Jorma Palvimo (jorma.palvimo@uef.fi)
Our research builds on our firm expertise in the steroid signaling and transcriptional regulation and our pioneering work on the SUMOylation of transcription factors and chromatin. Our current major goals are to:
– Identify the chromatin-bound proteins associated with the androgen receptor (AR) and the glucocorticoid receptor (GR) and reveal the role of SUMOylation in these associations.
– Discover novel means to target the AR and GR in castration resistant prostate cancer.
– Reveal the chromatin targets and mechanisms by which SUMOylation regulates gene networks and chromatin structure in cellular plasticity.
To address these aims, we will use cutting-edge genome- and proteome-wide tools, including GRO-seq, ChIP-seq, ChIP-SICAP and Turbo-ID proximity labeling, with human prostate cancer cell lines, mesenchymal stem cells and reprogrammable somatic cells as our main model systems.
We anticipate that our systemic studies and studies will provide us with novel leads for targeting steroid receptors. We also believe that our innovative and systematic approaches with multitalented research collaboration will provide us with novel SUMOylation targets and significant discoveries of the mechanisms by which SUMOylation regulates cellular plasticity and homeostasis. The results are likely to have translational potential in regenerative medicine and drug discovery for diseases, such as cancer.
Ketola lab: Cancer Cell Plasticity
Kirsi Ketola (kirsi.ketola@uef.fi)
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/
Petro Julkunen (petro.julkunen@uef.fi)
I am a part-time professor 50% of time. I am working as a chief physicist (50%) at the Diagnostic Imaging Center, Kuopio University hospital.
My research profile consists presently of neuromodulation of muscle activity and neuroplasticity.
Sareh Yaripour (sareh.yaripour@uef.fi)
My PhD project focuses on environment-induced plasticity in reproduction and survival-related traits of fishes under the supervision of Prof. Raine Kortet.
As a junior researcher, my overall goal is to understand how environment-induced plasticity can generally operate and modify traits like sperm motility and juvenile survival. This information is needed to follow the impact of changing environment on fish reproductive success, and to predict how the performance of fish populations in the future may change as a response to increasing environmental issues.