{"id":47610,"date":"2023-04-22T17:47:47","date_gmt":"2023-04-22T22:47:47","guid":{"rendered":"https:\/\/www.erdheim-chester.org\/?p=47610"},"modified":"2026-07-08T16:32:36","modified_gmt":"2026-07-08T21:32:36","slug":"award-2023-inferring-origin-of-erdheim","status":"publish","type":"post","link":"https:\/\/www.erdheim-chester.org\/pt\/award-2023-inferring-origin-of-erdheim\/","title":{"rendered":"Inferring the origin of Erdheim-Chester Disease from phylogenetic mapping"},"content":{"rendered":"[et_pb_section global_module=\"47611\"][\/et_pb_section]\n<h4><strong>Year Awarded:<\/strong> 2023<br \/>\n<strong>Amount:\u00a0 <\/strong>200,000 USD in partnership with the Leukemia &amp; Lymphoma Society<\/h4>\n<p>Dr. Matthew Collin is a clinician-scientist at Newcastle University in Newcastle upon Tyne, UK. He was awarded a 2023 research grant to conduct the study Inferring the Origin of Erdheim\u2013Chester Disease from Phylogenetic Mapping, which aims to trace the genetic mutations responsible for ECD and better understand how the disease develops at the cellular level.<\/p>\n<p>Erdheim Chester Disease (ECD) is caused by mutations in the DNA of blood cells. Blood cells are formed in the bone marrow from stem cells that can live for many years producing many generations of new stem cells. The frequent questions that patients ask about ECD include: where did it come from? how long have I had it? couldn\u2019t anything have been done sooner? why does my disease affect a particular site? Our research aims to shed new light on these important questions. The technique we will use is called \u2018phylogenetic mapping\u2019. This approach allows us to go back in time and \u2018date-stamp\u2019 the origin of mutations that cause ECD, to within a few years of a patient\u2019s past life. The way that this works is by growing many clones of single stem cells in the laboratory and sequencing the whole genome of each clone. Each clone differs from the next by a few mutations in its DNA. Some of these mutations arose a very long time ago in the ancestors of the stem cell when the patient was younger. By sequencing about one hundred clones it is possible to reconstruct the life history of the stem cells within a person and so create a timeline of mutations as they appear over the years. Among these mutations will be the mutation that caused ECD in the patient. If we know the timeline of all of the mutations, we can \u2018datestamp\u2019 the ECD mutation. We can then estimate how long the ECD mutation lay dormant in the body, how quickly it grew to a size that could cause disease, and whether it was assisted by any other mutations on the way. These are fundamental issues. In other related diseases called myeloproliferative neoplasms, mutations arise in childhood and evolve into different types of disease depending on other events in the life of a patient, over decades. When we apply this analysis to ECD, we should be able to answer the questions about its origin. The potential benefits also include the possibility to detect ECD at an early stage before it has evolved to cause disease; to determine why there is a spectrum of affected organs in different patients; and, why some patients have higher risk disease that progresses more quickly. Finally, unraveling the \u2018personal life history\u2019 of ECD may help us in the future with personalized therapy for better outcomes.<\/p>\n<h3>Final Report<\/h3>\n<p>Erdheim\u202fChester Disease (ECD) is caused by mutations in the DNA of blood cells. Blood cells are formed in the bone marrow from stem cells that can live for many\u202fyears\u202fproducing many generations of new stem cells.\u202f\u202fThe frequent questions that patients ask about ECD include: where did it come from?\u202f\u202fhow\u202flong have I had it?\u202f\u202fcouldn\u2019t anything\u202fhave\u202fbeen done sooner?\u202f\u202fwhy\u202fdoes my disease affect a particular site?\u202f\u202fOur research aims to shed new light on these important questions.\u202f\u202fThe technique we will use is called \u2018phylogenetic mapping\u2019.\u202f This approach allows us to go back in time and \u2018date-stamp\u2019 the origin of mutations that cause ECD, to\u202fwithin a few years of a patient\u2019s past life.\u202f\u202fThe way that this works is by growing many clones of single stem cells in the laboratory and sequencing the whole genome of each clone.\u202f\u202fEach clone differs from the next by a few mutations in its DNA.\u202f\u202fSome of these mutations arose\u202fa very long\u202ftime ago in the ancestors of the stem cell, when the patient was younger.\u202f\u202fBy sequencing about one hundred\u202fclones\u202fit is possible to reconstruct the life history of the stem cells within a person and so create a\u202ftime line\u202fof mutations as they appear over the years.\u202f\u202fThis is like drawing a family tree of how\u202fall of\u202fthe cells are related\u202fto one another\u202fand\u202fis\u202fknown as the \u2018phylogeny\u2019.\u202f\u202fAmong these mutations will be the mutation that caused ECD in the patient.\u202f\u202fIf we know the timeline of\u202fall of\u202fthe mutations, we can \u2018date-stamp\u2019 the ECD mutation.\u202f\u202fWe can then estimate how long the ECD mutation lay dormant in the body, how quickly it grew to a size that could cause disease and whether it was\u202fassisted\u202fby any other mutations on the way.\u202f\u202fThese are fundamental issues.\u202f\u202fIn other related diseases called myeloproliferative neoplasms, mutations arise in childhood and evolve into\u202fdifferent types\u202fof disease depending on other events in the life of a patient, over decades.\u202f\u202fWhen we apply this analysis to ECD, we should be able to answer\u202fthe questions\u202fabout its origin.\u202f\u202fThe potential benefits also include: a possibility to detect ECD at an early stage before it has evolved to cause disease; to determine why there is a spectrum of affected organs in different patients; and, why some patients have higher risk disease that progresses more quickly.\u202f\u202fFinally, unravelling the \u2018personal life history\u2019 of ECD may help us in the future to\u202fpersonalized\u202ftherapy for better outcomes.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Researchers are pioneering a unique approach to understand Erdheim Chester Disease (ECD) through phylogenetic mapping of blood stem cell mutations. By reconstructing the genetic timeline of the disease, scientists aim to uncover its origins and progression. The study seeks to answer critical patient questions about disease onset, mutation development, and potential early detection strategies.<\/p>","protected":false},"author":20,"featured_media":92309,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","cybocfi_hide_featured_image":"","wds_primary_category":0,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[306],"tags":[338],"class_list":["post-47610","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-past-awards","tag-338"],"_links":{"self":[{"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/posts\/47610","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/users\/20"}],"replies":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/comments?post=47610"}],"version-history":[{"count":3,"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/posts\/47610\/revisions"}],"predecessor-version":[{"id":173991,"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/posts\/47610\/revisions\/173991"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/media\/92309"}],"wp:attachment":[{"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/media?parent=47610"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/categories?post=47610"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/pt\/wp-json\/wp\/v2\/tags?post=47610"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}