Tapahtumakalenteri
FICAN Science Webinar: De novo cholesterol biosynthesis as a metabolic vulnerability in rhabdomyosarcoma – implications for novel treatment options
This time the seminar is hosted by FICAN East and chaired by Prof. Arto Mannermaa.
These nationwide webinars provide a platform to share new scientific findings, highlight recent advances in cancer research, and foster collaboration among cancer researchers and clinicians across Finland.
Abstract
Rhabdomyosarcoma (RMS) is an aggressive pediatric soft-tissue cancer. Identification of RMS precursor cells and models has been a challenge due to unknown molecular mechanisms that drive the common proliferative myogenic phenotype. Our studies have revealed that the PROX1 transcription factor is essential for the growth and myogenic features of RMS, and its downregulation reverts RD cells to a phenotype resembling benign mesenchymal stem cells. Our findings demonstrate that the effects of PROX1 on RMS cell growth are mediated by FGFR, predominantly by FGFR1 and FGFR4, which were found to compensate for each other. Our findings place PROX1 as a major mediator of RMS characteristics and development and suggests that pan-FGFR inhibitors provide a promising option for the treatment of RMS. We have also identified de novo cholesterol biosynthesis as a key metabolic vulnerability in rhabdomyosarcoma, regulated by PROX1. Cholesterol synthesis inhibition halts RMS cell proliferation and triggers ER stress-induced apoptosis, offering a promising therapeutic strategy. The findings highlight a potential therapeutic strategy for rhabdomyosarcoma by targeting de novo cholesterol biosynthesis, as statins are already widely used and well tolerated.
Relevat references from the speaker for this talk:
- Gizaw NY, Kallio P, Punger T, Gucciardo E, Haglund C, Böhling T, Lehti K, Sampo M, Alitalo K, Kivelä R. PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2116220119. doi: 10.1073/pnas.2116220119.
- Gizaw NY, Kolari K, Kallio P, Alitalo K, Kivelä R. Inhibiting cholesterol synthesis halts rhabdomyosarcoma growth via ER stress and cell cycle arrest. EMBO Mol Med. 2025 Dec;17(12):3586-3606. doi: 10.1038/s44321-025-00336-x.
For more information on the FICAN science webinar series, please contact Finnish Cancer Center FICAN info@fican.fi
CAMM Special seminar by Assoc Prof Marcel Den Hoed
Welcome to the Clinical and Molecular Metabolism (CAMM) Special Seminar titled “Zebrafish larvae towards target identification and precision medicine in cardiometabolic disease”.
Marcel den Hoed, PhD, is Associate Professor at Uppsala University, Sweden
Marcel den Hoed leads a research group on Molecular epidemiology and translational genomics. His research aims to identify and characterise causal genes for human disease, with a focus on cardiovascular and metabolic disorders.
Already in 2012, Marcel recognized the emerging gap between discovery of variants associated with complex cardiometabolic disease in genome-wide association studies on the one hand, and functional understanding of how causal genes drive these associations on the other hand. To overcome this pending bottle neck, he transitioned from using a genetic epidemiological approach in humans towards an experimental functional genomics approach with zebrafish model systems. Since joining Uppsala University in 2013, Marcel has built a physical infrastructure and developed and validated a series of experimental pipelines for meaningful, systematic functional characterization of the role of candidate genes in traits related to obesity, type-2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, atherosclerosis, and sudden cardiac death. Studies proposed by Marcel have been enabled by grants from Vetenskapsrådet, the Swedish Heart-Lung Foundation, The Beijer Foundation, NIH/NIDDK, the NIH-funded Accelerating Medicines Partnership for Complex Metabolic Diseases, as well as by partners in industry. By systematically characterising the role of >100 genes using CRISPR/Cas9, automated in vivo fluorescence microscopy, and deep learning-based image analysis, Marcel and his team have recently identified 23 genes that affect diabetes traits (9 novel), 21 genes that affect early-stage atherosclerosis (8 novel), and 14 genes that affect liver fat content (8 novel). These genes are enriched for rare variant associations with the disease they were prioritized for in humans. Some findings are currently taken forward on the path towards drug development or precision medicine applications.
To date, Marcel has been awarded 17 oral presentations at international conferences – of which eight invited (one keynote) – and has given numerous invited seminar presentations globally.
Striving to make the model systems available to a larger audience for the benefit of patients, Marcel co-founded a service organisation (Veyviser A/B) in 2022, which offers tailored target validation and drug screens for common cardiometabolic diseases as a service to e.g. pharmaceutical and biotech companies.
Read more: https://www.uu.se/en/department/immunology-genetics-and-pathology/research/molecular-tools-and-functional-genomics/marcel-den-hoed
Kliinisen mikrobiologian perjantaisarja
Ilkka Helanterä, nefrologian erikoislääkäri, osastonylilääkäri, HUS Vatsakeskus
Dissertation: Weikaixin Kong
Opponent: Professor Riccardo De Bin, University of Oslo
HiLIFE / Biomedicum Helsinki seminar by Bryan Traynor
Bryan J. Traynor, MD, PhD, is a neurologist and Senior Investigator at the National Institutes of Health. His work has revolutionized our understanding of the genetic basis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). He led an international team identified pathogenic repeat expansions in C9orf72, a major cause of both disorders. His lab has also discovered several other genes linked to these conditions, including VCP, MATR3, KIF5A, SPTLC1, and HTT.
Dr. Traynor has published over 200 articles in leading journals such as Neuron, the New England Journal of Medicine, Nature Genetics, Nature Neuroscience, and Nature Medicine. His honors include the NIH Director’s Award, the Sheila Essey Award, the Potamkin Prize, the F.E. Bennett Lectureship, and the Sean Healey Prize.
He obtained his medical degree and Doctor of Philosophy (PhD) from University College Dublin, as well as an MMSc from the Harvard–MIT HST program. His training includes a neurology residency and fellowship at Massachusetts General Hospital and Brigham and Women’s Hospital. He was part of the faculty at Harvard Medical School and Massachusetts General Hospital before joining the NIH in 2005. He is also Professor at Johns Hopkins University.
Welcome to this exciting seminar!
Pentti Tienari
Selected publications
A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis. Chia R, Moaddel R, Kwan JY, Rasheed M, Ruffo P, Landeck N, Reho P, Vasta R, Calvo A, Moglia C, Canosa A, Manera U, Snyder A, Saez-Atienzar S, Egan JM, Candia J, Tanaka T, Ferrucci L, Dalgard CL, Scholz SW, Chiò A, Traynor BJ. Nat Med 2025 Oct;31(10):3440-3450.
Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data. Saez-Atienzar S, Souza CDS, Chia R, Beal SN, Lorenzini I, Huang R, Levy J, Burciu C, Ding J, Gibbs JR, Jones A, Dewan R, Pensato V, Peverelli S, Corrado L, van Vugt JJFA, van Rheenen W, Tunca C, Bayraktar E, Xia M; Ratti A, Gellera C, Johnson K, Doucet-O'Hare T, Pasternack N, Wang T, Nath A, Siciliano G, Silani V, Başak AN, Veldink JH, Camu W, Glass JD, Landers J, Traynor BJ. Cell Genom 2024 Nov 13;4(11):100679.
New antisense oligonucleotide therapies reach first base in ALS. Lopez ER, Borschel WF, Traynor BJ. Nat Med. 2022 Jan;28(1):25-27.
Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types Saez-Atienzar S, Bandres-Ciga S, Langston RG, Kim JJ, Choi SW, Reynolds RH; International ALS Genomics Consortium; ITALSGEN; Abramzon Y, Dewan R, Ahmed S, Landers JE, Chia R, Ryten M, Cookson MR, Nalls MA, Chiò A, Traynor BJ. Sci Adv. 2021 Jan 15;7(3):eabd9036
A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Remes AM, Scholz SW, Duckworth J, Harmer DW, Hernandez DG, Neal J, Murray A, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Hölttä-Vuori M, Ikonen E, Sulkava R, Benatar M, Chiò A, Restagno G, Borghero G, Sabatelli M; Heckerman D, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ. Neuron. 2011 Oct 20;72(2):257-68.