Willy is in the Dept of Developmental Biology (EMC) and currently supervises 5 PhD students, one technician, and a MSc student. Her group has made major contributions to the understanding of the mechanism of XY body (special chromatin configuration of the sex chromosomes) formation during male meiotic prophase. She identified the role of persistent meiotic DNA double-strand breaks (DSBs) in the mediation of meiotic transcriptional silencing which is key to formation of the XY body. Subsequently she has broadened this research question towards trying to unravel how meiotic DSB repair and chromosome pairing are mechanistically connected. Her group was the first to use two-colour super-resolution (dSTORM) technology to study the repair foci in meiotic prophase to show that two key proteins involved in the repair process form complicated structures in a much more variable fashion than would be expected and predicted based on genetic data and ‘omics’ approaches. Using her microscopy expertise she also developed a useful phenotyping protocol to assess meiotic defects in men suffering from nonobstructive azoospermia, and could classify the most frequent meiotic arrest stages. She has sequenced the genome of Ellobius lutescens as a first step towards unravelling the sex determination pathway in this enigmatic species with karyotype 17,X in both sexes.
Relevant publications
• Boers R, Boers J, Tan B, van Leeuwen ME, Wassenaar E, Sanchez EG, Sleddens E, Tenhagen Y, Mulugeta E, Laven J, Creyghton M, Baarends WM, van IJcken WFJ, Gribnau J (2023). Retrospective analysis of enhancer activity and transcriptome history. Nat Biotechnol. doi: 10.1038/s41587-023-01683-1. Epub ahead of print. PMID: 36823354.
• Koornneef L, Slotman JA, Sleddens-Linkels E, van Cappellen WA, Barchi M, Tóth A, Gribnau J, Houtsmuller AB, Baarends WM (2022). Multi-color dSTORM microscopy in Hormad1-/- spermatocytes reveals alterations in meiotic recombination intermediates and synaptonemal complex structure (2022). PLoS Genet. 18(7):e1010046.
• Ghouil R, Miron S, Koornneef L, Veerman J, Paul MW, Le Du MH, Sleddens-Linkels E, van Rossum-Fikkert SE, van Loon Y, Felipe-Medina N, Pendas AM, Maas A, Essers J, Legrand P, Baarends WM, Kanaar R, Zinn-Justin S, Zelensky AN (2021) BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination. Nature Commun 12(1): 4605
• Krausz C, Riera-Escamilla A, Moreno-Mendoza D, Holleman K, Cioppi C, Algaba F, Pybus M, Friedrich C, Wyrwoll MJ, Casamonti E, Pietroforte S, Nagirnaja L, Lopes AM, Kliesch S, Pilatz A, Carrell DT, Conrad DF, Ars E, Ruiz-Castañé E, Aston,KI, Baarends WM*, Tüttelmann F* (2020). Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men. Genet Med 22:1956-1966
Slotman JA, Paul MW, Carofiglio F, Vergroesen T, Koornneef L, van Cappellen WA, Houtsmuller AB, Baarends WM (2020). Super-resolution imaging of RAD51 and DMC1 in DNA repair foci reveals dynamic distribution patterns in meiotic prophase. Plos Genet 16:e1008595
• Enguita-Marruedo A, Sleddens-Linkels E, Ooms M, de Geus V, Wilke M, Blom E, Dohle GR, Looijenga LHJ, van Cappellen W, Baart EB, Baarends WM (2019). Meiotic arrest occurs most frequently at metaphase and is often incomplete in azoospermic men. Fertil Steril 112:1059-1070.e3
• Enguita-Marruedo A, van Cappellen WA, Hoogerbrugge J, Carofiglio F, Wassenaar E, Slotman JA, Houtsmuller AB, Baarends WM (2018). Live cell analyses of synaptonemal complex dynamics and chromosome movements in cultured mouse testis tubules and embryonic ovaries. Chromosoma 127:341-359
• Carofiglio F, Inagaki A, de Vries S, Wassenaar E, Schoenmakers S, Vermeulen C, van Cappellen WA, Sleddens-Linkels E, Grootegoed JA, te Riele H, de Massy B, Baarends WM (2013). SPO11-independent DNA repair foci and their role in meiotic silencing. Plos Genet 9:e1003538