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The Department of Oncology at KU Leuven hosts over 500 researchers in nearly 30 research groups, making it a global leader in various fields of cancer research. The Laboratory for Computational Cancer Biology and Epigenomics is a newly established research group dedicated to developing computational methods and analyzing high-dimensional data to understand cancer epigenomics. Our primary focus is on epigenetic mechanisms and their role in tumorigenesis. The Skeletal Cell Biology and Physiology Lab, led by Prof. Christa Maes at the Center for Skeletal Biology and Engineering Research, is a premier group in the biology of quiescent stem cells, studying mechanisms of bone formation in development, growth, postnatal homeostasis, disease, aging, and fracture repair.
For more information about our group, please visit the link below.
Stem cells are crucial for the formation and maintenance of all tissues, including the skeletal system, which has multiple stem cell populations identified in bone and cartilage, primarily through mouse models [1]. Despite these advances, the specific functions, regulation, phylogeny, and relation to human stem cell populations of these skeletal stem cells are not well understood. Additionally, skeletal stem cells may give rise to aggressive bone tumors, such as giant cell tumor of bone (GCTB), driven by a hotspot mutation in a histone variant H3.3 [2], making them important therapeutic targets. This Ph.D. project will focus on omics-based characterization of stem cell populations in the mouse and human skeletal system and identify their contribution to epigenetically-driven skeletal tumors. We will generate single-cell and spatial multiomics data and integrate them with existing in-house and public skeletal cell atlases. The project aims to further develop computational methods for cross-species single-cell multiomics integration. Our previous deep learning methods have been successfully applied to various human single-cell multiomics data analyses [3, 4]. Therefore, we plan to extend these methods to find a joint landscape of human and mouse single-cell multiomes and conduct in-depth analyses on the single-cell skeletal multiomics data: integration of single-cell transcriptomes and epigenomes of human and mouse skeletal cell populations, trajectory inference for different populations, and identification of the most likely cell-of-origin for tumor cells.
[1] Lutsik et al. Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone. Nature Communications, 2020.
[2] Jeong et al. scMaui: a widely applicable deep learning framework for single-cell multiomics integration in the presence of batch effects and missing data. BMC Bioinformatics, 2024.
[3] Moeed et al. Identifying Effects of Disease on Single-Cells with Domain-Invariant Generative Modeling. NeurIPS workshop CRL, 2023.
[4] Trompet et al. Skeletal stem and progenitor cells in bone development and repair, Journal of Bone and Mineral Research, 2024.
We offer a full-time PhD position for 48 months, subject to positive evaluation by the doctoral committee at the end of the first year. A successful PhD candidate will join a vibrant and highly stimulating scientific environment within the Department of Oncology, VIB-KU Leuven Center for Cancer Biology, and the Skeletal Cell Biology and Engineering Research Center. The candidate will have access to cutting-edge datasets and computational infrastructure. The project will involve regular interactions with collaboration partners across Europe, presentations at scientific conferences, and meetings. Additionally, the candidate will have access to versatile options for personal growth and development, advanced qualification courses, and mentoring available via KU Leuven and affiliated institutions.
For more information, please contact Prof. Pavlo Lutsik, tel.: +32 16 32 30 09, email: pavlo.lutsik@kuleuven.be.
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