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Coorens group

Somatic evolution and phylogenetics

We study how normal cells in different tissues acquire somatic mutations, use mutations as inherent barcodes to study human development and the origins of cancer, and develop computational tools to analyse mutations in novel single-cell and spatial data.

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Cells in the human body continuously acquire mutations, either due to errors in DNA replication or damage due to exposures. This process generates an enormous amount genetic diversity within the human body and enables natural selection within tissues. Until recently, our understanding of the somatic mutation landscape of normal cells has been limited compared to that of cancer cells. In our group, we develop new tools to study many different aspects of somatic mutations across human cells. Our research activities are articulated around 3 main areas:

Lineage tracing and phylogenetics. Somatic mutations are reliably passed on to daughter cells, so that by tracing their presence, we can assess the ancestral relationships between different cells in the body. In essence, somatic mutations can connect all cells of an organism into a phylogenetic tree, with all currently existing cells at the tips, nodes representing ancestral cells, and the zygote as the root. As novel methods of sequencing normal cells enable new scales of generating data on many cells, the group develops approaches for fast and robust methods to produce high-quality somatic mutation calls, reconstruct phylogenetic trees of cells and trace the ancestry of cells, clones and tissues within the human body.

Patterns of somatic mutation across human tissues. The stepwise accumulation of key somatic mutations drives the emergence of cancer, but insights into the difference in mutation rate, mutational processes and critical cancer-driver genes have been limited across normal tissues. As our methods of mutation detection become scalable, our group aims to further elucidate the different patterns of somatic mutations across various human tissues and research the effects of lifestyle choices, exposures, and inflammation to somatic mutation patterns and investigate their links to the origins of cancers. We are part of the NIH-funded Somatic Mosaicism across Human Tissues (SMaHT) Network.

Development and childhood cancer. By using large phylogenetic trees of normal cells, we can study early human embryogenesis without the need to sample embryonic tissue. The group studies cell decision making in early embryogenesis, mosaic patterning, and cell differentiation through somatic mutations. Furthermore, by comparing lineages of cancers and normal cells, we can deduce the origins of childhood cancers and assess the role of abnormal developmental processes. The group is part of the NIH-funded developmental Genotype Tissue-Expression (dGTEx) Consortium, with the aim to better understand the normal transcriptional state against which to compare childhood cancers.

We are a highly collaborative group and enjoy working with committed collaborators with complementary expertise to ours. Much of our work is developed in close collaboration with experimental biologists and clinical collaborators, on campus, within the SMaHT and dGTEx consortia, and beyond. We are always happy to discuss potential collaborations aligned with the goals of the group outlined above.

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