{"id":15,"date":"2022-05-06T12:30:00","date_gmt":"2022-05-06T12:30:00","guid":{"rendered":"https:\/\/www.embl.org\/groups\/dayton\/home\/"},"modified":"2025-07-02T10:01:16","modified_gmt":"2025-07-02T10:01:16","slug":"home","status":"publish","type":"page","link":"https:\/\/www.embl.org\/groups\/dayton\/","title":{"rendered":"Home"},"content":{"rendered":"<div class=\"vf-grid vf-grid__col-3 | vf-u-margin__bottom--800\">\n      <div class=\"vf-grid__col--span-2\">\n      <div class=\"vf-content-hub-html\">\n  <!-- Generated by: http:\/\/content.embl.org\/api\/v1\/pattern.html?filter-content-type=profiles&amp;filter-uuid=a9225fde-7cf7-41e0-beaa-fad9c007b7ed&amp;pattern=node-teaser -->\n      <div data-embl-js-conditional-edit=\"162169\">\n              <h1 class=\"vf-lede\">The Dayton group leverages novel organoid models of neuroendocrine (NE) cells and tumours to recapitulate and dissect mechanisms of human disease including cancer initiation, progression, and drug response.<\/p>\r\n\n            <a class=\"vf-text vf-text--body-r vf-link embl-conditional-edit\" rel=\"noopener noreferrer nofollow\" href=\"\/node\/162169\" target=\"_blank\">Edit<\/a>\n    <\/div>\n  <\/div>\n    <\/div>\n      <div >\n\n<!-- <style>\n  .vf-content-hub-html {\n    --vf-stack-margin--custom: unset !important;\n  }\n<\/style> -->\n\n    <div class=\"vf-content-hub-html vf-stack vf-stack--600\" data-cache=\"bc9b52e0\">\n      <!-- Generated by: http:\/\/content.embl.org\/api\/v1\/pattern.html?filter-content-type=person&amp;filter-field-value%5Bfield_person_positions.entity.field_position_membership%5D=leader&amp;filter-field-value%5Bfield_person_positions.entity.field_position_team.entity.field_foreignid%5D=584&amp;filter-ref-entity%5Bfield_person_positions%5D%5Btitle%5D=&amp;filter-ref-entity%5Bfield_person_positions%5D%5Bfield_position_primary%5D=1&amp;hide%5Bteam%2Cmobile%2Cphones%5D=1&amp;limit=5&amp;pattern=vf-profile-inline&amp;sort-field-value%5Bchanged%5D=DESC -->\n                \n                            <article class=\"vf-profile vf-profile--very-easy vf-profile--medium vf-profile--inline\" data-embl-js-conditional-edit=\"162191\">\n              <img decoding=\"async\" class=\"vf-profile__image\" src=\"https:\/\/content.embl.org\/\/sites\/default\/files\/styles\/medium\/public\/persons\/CP-60039127.jpg?itok=AiRc8tYK\" alt=\"image of Talya Dayton\" \/>\n      \n              <h3 class=\"vf-profile__title\">\n                      <a href=\"https:\/\/www.embl.org\/people\/person\/talya-dayton\" class=\"vf-profile__link\">Talya Dayton<\/a>\n                  <\/h3>\n      \n              <p class=\"vf-profile__job-title\">\n          Group Leader\n        <\/p>\n      \n      \n      \n      \n      \n      \n              <p class=\"vf-profile__uuid\">\n          <span>ORCID:<\/span>\n          <a class=\"vf-profile__link vf-profile__link--secondary\" href=\"https:\/\/europepmc.org\/authors\/0000-0002-7994-7963\">\n            0000-0002-7994-7963\n          <\/a>\n        <\/p>\n            <a class=\"vf-text vf-text--body-r vf-link embl-conditional-edit\" rel=\"noopener noreferrer nofollow\" href=\"\/node\/162191\/162191\" target=\"_blank\">\n        Edit\n      <\/a>\n    <\/article>\n  <\/div>\n\n  <\/div>\n<\/div>\n\n\n\n<div class=\"vf-grid | vf-grid__col-3\"><div class=\"vf-grid__col--span-2\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<h3 class=\"wp-block-heading\">Previous and current research<\/h3>\n\n\n\n<p>Our group uses organoids to understand: (1) differentiation and plasticity of NE cells, and (2) the biology of NE cancers (Figure 1).<\/p>\n\n\n\n<p><strong>Differentiation and plasticity of NE cells<\/strong><\/p>\n\n\n\n<p>Pulmonary NE cells account for only 0.5% of the lung epithelium. They secrete hormones and neuropeptides that influence lung physiology, and multiple studies show increased pulmonary NE cell numbers in human diseases, suggesting an important function. These cells are also a cell of origin for pulmonary NE neoplasms, a tumour type that constitutes 20-25% of invasive primary lung cancers.<\/p>\n\n\n\n<p>We have pioneered a tractable and robust model system for the study and manipulation of human pulmonary NE cells and their progenitors in multicellular organoids that also contain all of the major airway cell types (Figure 2).<\/p>\n\n\n\n<p><strong>Biology of NE cancers<\/strong><\/p>\n\n\n\n<p>NE neoplasms comprise NE tumours (NETs) and NE carcinomas (NECs). While NETs generally proliferate and progress slowly, NECs are associated with a very poor prognosis. Irrespective of subtype, the treatment options for patients with unresectable, relapsed, or metastasized NE neoplasms are limited. We have developed novel patient-derived tumour organoids (PDTOs) of pulmonary NETs and of large cell NEC (LCNEC) that conserve and maintain the intratumoral heterogeneity and major gene expression patterns observed in matched tumour tissue. Using these PDTO models we:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Identified a subset of pulmonary NETs that expresses high levels of EGFR and depends on EGF for its growth in culture.<\/li>\n\n\n\n<li>Identified a biomarker potentially predictive of therapeutic response of NE cancers to BCL2 inhibitors.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Future projects and goals<\/h3>\n\n\n\n<p>Broadly, we aim to tackle several outstanding questions:&nbsp;<\/p>\n\n\n\n<p>(1) Does heterogeneity in the molecular states that lie along the differentiation trajectories for NE cells influence genomic and phenotypic intratumour and inter-tumour heterogeneity in NE cancers?&nbsp;<\/p>\n\n\n\n<p>(2) How do NE cells respond to acute and chronic injury and how do these responses change when they acquire cancer-associated mutations?&nbsp;<\/p>\n\n\n\n<p>(3) How do cancer-associated mutations influence cell state and differentiation in NE cells and NE cell progenitors?<\/p>\n\n\n\n<p>More specific goals include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Development of genetic tools to manipulate and label NE cells and their progenitors<\/li>\n\n\n\n<li>Define the NE cell response to environmental stimuli<\/li>\n\n\n\n<li>Apply CRISPR-Cas9 gene editing to model NE tumour progression<\/li>\n\n\n\n<li>Engineer organoid models of NE cancer initiation that enable natural evolution of a tumour in an <em>in vitro <\/em>system<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Online presentations<\/h3>\n\n\n\n<p><a href=\"https:\/\/www.youtube.com\/watch?v=aWgw4QYncok\">Seminario Frontiers in Genomics 2025<\/a> &#8211; <a href=\"https:\/\/www.lcg.unam.mx\/frontiers-in-genomics\/\">Frontiers in Genomics<\/a> <\/p>\n\n\n\n<p><a href=\"https:\/\/www.youtube.com\/watch?v=aakPXh8WFzE\">June 2020 London Stem Cell Network Stem Cell Forum<\/a><\/p>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large is-style-default\"><a href=\"https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig1.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"717\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig1-1024x717.jpg\" alt=\"ingfographic showing the schematic of media impact on neuroendocrine lung organoids and tumor\/neoplasm organoids\" class=\"wp-image-61\" srcset=\"https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig1-1024x717.jpg 1024w, https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig1-300x210.jpg 300w, https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig1-768x538.jpg 768w, https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig1.jpg 1200w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a><figcaption class=\"vf-figure__caption\">Figure 1: Schematic outline of novel organoid models of human NE cells and NE cancers that recapitulate features of NE cell growth, differentiation, and transformation. Figure made with Biorender. <\/figcaption><\/figure>\n\n\n\n<figure class=\"vf-figure wp-block-image size-large is-style-default\"><a href=\"https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig2.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"579\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig2-1024x579.jpg\" alt=\"ingfographic showing IF staining for neuroendocrine cells in human lung\/airway organoids after differentiation\" class=\"wp-image-62\" srcset=\"https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig2-1024x579.jpg 1024w, https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig2-300x170.jpg 300w, https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig2-768x435.jpg 768w, https:\/\/www.embl.org\/groups\/dayton\/wp-content\/uploads\/2022\/05\/dayton-group-fig2.jpg 1200w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a><figcaption class=\"vf-figure__caption\">Figure 2: Airway organoids containing NE cells and all major airway cell types were generated from human lung tissue and NE cell differentiation was recapitulated in vitro by addition of NE differentiation medium: whole-mount immunofluorescence of organoids for the NE marker, UCHL1 (green). Figure made with some images from Biorender. <\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"embl_taxonomy":[],"class_list":["post-15","page","type-page","status-publish","hentry"],"acf":[],"embl_taxonomy_terms":[],"_links":{"self":[{"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/pages\/15","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/comments?post=15"}],"version-history":[{"count":13,"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/pages\/15\/revisions"}],"predecessor-version":[{"id":19219,"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/pages\/15\/revisions\/19219"}],"wp:attachment":[{"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/media?parent=15"}],"wp:term":[{"taxonomy":"embl_taxonomy","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/dayton\/wp-json\/wp\/v2\/embl_taxonomy?post=15"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}