iCAN Science seminar
Dr Anniina Färkkilä
Wihuri Research Institute Special Seminar by Dr. Elina Ikonen
Dr. Elina Ikonen ’s lab focuses on lipids that are stored in excessive amounts in human lipid storage diseases. The regulated metabolism and exchange of lipids between these storage organelles, membrane bilayers and the extracellular environment is of key importance for several physiological functions of cells. In turn, their disturbances are associated with the most common diseases globally, including cardiovascular disease, metabolic syndrome and fatty liver. Her research team employs novel techniques to visualize lipids in living cells and tissues, and develops assays to quantitatively analyze lipid trafficking and metabolism. Besides unraveling basic lipid transport mechanisms, these methods are employed to monitor subtle changes in lipid handling mechanisms at the cellular level between individuals. In the long run, these methods will assist in personalized assessment, monitoring and prevention of lipid related pathological conditions in man.
Pirhonen J, Szkalisity Á, Hagström J, Kim Y, Migh E, Kovács M, Hölttä M, Peränen J, Seppänen H, Haglund C, Gil J, Rezeli M, Malm J, Horvath P, Markó- Varga G, Puolakkainen P, Ikonen E. Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer. Cancer Res. 2022 Nov 2;82(21):3932-3949.
Pfisterer SG, Brock I, Kanerva K, Hlushchenko I, Paavolainen L, Ripatti P, Islam MM, Kyttälä A, Di Taranto MD, Scotto di Frega A, Fortunato G, Kuusisto J, Horvath P, Ripatti S, Laakso M, Ikonen E. Multiparametric platform for profiling lipid trafficking in human leukocytes. Cell Rep Methods. 2022 Feb 8;2(2):100166
Long M, Sanchez-Martinez A, Longo M, Suomi F, Stenlund H, Johansson AI, Ehsan H, Salo VT, Montava-Garriga L, Naddafi S, Ikonen E, Ganley IG, Whitworth AJ, McWilliams TG. DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion. EMBO J. 2022 May 16;41(10):e109390.
Combot Y, Salo VT, Chadeuf G, Hölttä M, Ven K, Pulli I, Ducheix S, Pecqueur C, Renoult O, Lak B, Li S, Karhinen L, Belevich I, Le May C, Rieusset J, Le Lay S, Croyal M, Tayeb KS, Vihinen H, Jokitalo E, Törnquist K, Vigouroux C, Cariou B, Magré J, Larhlimi A, Ikonen E, Prieur X. Seipin localizes at endoplasmic- reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes. Cell Rep. 2022 Jan 11;38(2):110213.
Special Seminar by Merja Heinäniemi
Speaker’s synopsis of seminar
Progression of malignancy to overt disease requires multiple genetic hits. Lymphoid precursor cells have a unique vulnerability that arises through the expression of recombination activating genes (RAG) complexes and Activation-induced deaminase (AID) complexes that can drive leukemo- and lymphomagenesis, respectively, by generating off-target DNA breaks. In the first part of the talk, I will discuss the unique transcriptional features that characterise recurrent DNA breakpoints in these cancers, uncovered through genomics.
Typically, AID and RAG activity is tightly controlled and their expression limited to non-dividing cells. I will next discuss the role of cell fate-regulating transcription factors and how their diminished activity creates a subtle, yet significant predisposition to progression to overt leukemia that we have recently explored at single cell resolution.
At the final part of this talk, I will address the deficient cell cycle entry and DNA repair control at overt leukemia as a potential targetable, focusing on the kinase WEE1 that supports genome integrity by suppressing CDK activities during DNA replication. Inhibition of WEE1 removes the negative phosphorylation on CDK1/2 (in concert with CDC25) resulting in deregulation of CDKs, increased origin firing and replication fork degradation leading to fork collapse, DNA damage and unscheduled mitosis. Recently, we uncovered a previously unrecognized selectivity for KMT2A-rearranged acute lymphoblastic leukemia cells, compared to other leukemia subgroups. Time-resolved genomics revealed complex cellular dynamics in response to cell cycle checkpoint targeting, with distinct cell fates emerging. The disruption of a core RUNX1-MYC regulatory network was mutually exclusive with a pro-survival response. Based on the results, we devised a strategy to counteract this route to resistance through novel sequential drug administration.
Selected recent publications:
Laukkanen S, Veloso A… Heinäniemi M, Kelliher M, Heckman CA, Lohi O, Langenau DM (2022) Therapeutic targeting of LCK tyrosine kinase and mTOR signaling in T-cell acute lymphoblastic leukemia. Blood 140:1891-1906
Turunen T, Hernández de Sande A, Pölönen P, Heinäniemi M (2021) Genome-wide analysis of primary microRNA expression using H3K36me3 ChIP-seq data. Comput Struct Biotechnol J 19:1944-1955
Mehtonen J, Teppo S… Heinäniemi M (2020) Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1-positive pediatric leukemia identifies drug-targetable transcription factor activities. Genome Med 12:99
Dissertation: Elli-Mari Aska
Afternoon in the Science Basement: Mattia Retta
The Science Basement would like to invite you to listen and interact during an Afternoon in the Science Basement. The first speaker of the monthly spring series, Mattia Retta, will present their work, ‘Did they mean it? Implicit forms of hate speech in politics’
Description: Hate speech incites violence and intolerance, but is unfortunately a common feature of political debates. However, explicit hate speech is not tolerated in most modern societies. To overcome this, some politicians utilize more implicit hate speech – something that cannot directly be disputed, but is obviously polarizing based on how the public reacts. The echo chamber effect on social media provides an effective platform for the spread of hate speech without the repercussions to the original instigator. By challenging the understanding of hate speech only as an explicitly derogatory act, we can better understand the linguistic properties of hate speech and shed light on the crucial role that a sensibilisation to implicitness plays in educating inclusive and aware digital citizens. Mattia investigates implicit forms of hate speech in the Italian political debate, that manage to convey derogatory contents while overcoming any form of censorship or automatic detection of offensive contents in social networks.
P.S. Any PhD student from University of Helsinki or Aalto can give a talk (any topic), contact the email above to find out more ;)