{"id":61358,"date":"2013-08-27T00:00:00","date_gmt":"2013-08-27T00:00:00","guid":{"rendered":"https:\/\/www.uri.edu\/news-draft\/uncategorized\/uri-researcher-seeks-clues-to-rare-disease-that-killed-2-year-old-best-man\/"},"modified":"2013-08-27T00:00:00","modified_gmt":"2013-08-27T00:00:00","slug":"uri-researcher-seeks-clues-to-rare-disease-that-killed-2-year-old-best-man","status":"publish","type":"post","link":"https:\/\/www.uri.edu\/news\/2013\/08\/uri-researcher-seeks-clues-to-rare-disease-that-killed-2-year-old-best-man\/","title":{"rendered":"溏心vlog免费B站 researcher seeks clues to rare disease that killed 2-year-old best man"},"content":{"rendered":"
\n\t\tKINGSTON, R.I. \u2013 August 27, 2013 \u2013 When 2-year-old Logan Stevenson served as best man at his parents\u2019 wedding just days before he died of a rare genetic disorder, it drew international attention to a disease about which few people had ever heard. Hearing about Logan\u2019s story added another level of urgency to the research being conducted by 溏心vlog免费B站 Associate Professor Niall Howlett.<\/p>\n


\n\tLogan died from complications of Fanconi anemia, a rare hereditary disorder characterized by physical defects, bone marrow failure, and increased susceptibility to cancer. 溏心vlog免费B站 1 in 200,000 children in the United States are born with the disease, and treatment options are extremely limited. Howlett has been studying Fanconi anemia for 15 years, ever since he became interested in how cells recognize and repair DNA damage.<\/p>\n


\n\t\u201cPeople are continually being exposed to things that damage our DNA, like sunlight, chemicals and pollutants,\u201d he said. \u201cWe have evolved to have hundreds of proteins whose sole function is to fix damaged DNA. We have multiple specialized bDNA repair pathways that function continuously to repair damage accrued during our daily lives.\u201d<\/p>\n


\n\tAccording to Howlett, there are just a handful of diseases \u2013 all of them very rare \u2013 that are caused by mutations in DNA repair genes. Fanconi anemia is one of them.<\/p>\n


\n\t\u201cWe know that there are at least 16 genes that, when mutated, result in Fanconi anemia,\u201d said Howlett, who teaches in the 溏心vlog免费B站 Department of Cell and Molecular Biology. \u201cThese 16 genes encode for proteins that function together in a pathway to fix DNA damage. If you have a mutation in any one of these genes, the protein is defective and the repair pathway is broken.\u201d An inability to fix DNA damage can lead to the accumulation of additional mutations, ultimately leading to cancer, one of the characteristics of Fanconi anemia. \u201cWhy Fanconi anemia patients also develop physical defects and bone marrow failure remains a mystery,\u201d he added.<\/p>\n


\n\tHowlett\u2019s research focuses on two of the Fanconi anemia proteins \u2013 identified as FANCD2 and FANCI \u2013 that function together and are activated through a process called ubiquitination.<\/p>\n


\n\t\u201cUbiquitin is a small protein that is physically attached to other proteins after they are made,\u201d Howlett explained. \u201cIt\u2019s a molecular tag that provides instructions about the fate of a protein. In certain cases, ubiquitin can specify protein degradation, while in other cases it can signal that a protein needs to be moved from one place to another in the cell. In the case of FANCD2 and FANCI, ubiquitination targets these proteins to damaged DNA.\u201d<\/p>\n


\nHowlett said that the ubiquitination step is especially important because in 90 percent of Fanconi anemia patients, that step is broken.<\/p>\n


\n\t\u201cAn inability to attach ubiquitin to these proteins must be linked to why these kids get bone marrow failure and cancer,\u201d he said. \u201cWe want to learn as much as we can about this step \u2013 how it\u2019s regulated, how it works, and how can we fix this step when it\u2019s broken \u2013 so we can discover new ways to treat this disease.\u201d<\/p>\n


\nBased on the severity of Logan Stevenson\u2019s disease, Howlett speculates that he may have had mutations in one of the two BRCA genes, which are well known for their involvement in hereditary breast and ovarian cancer. <\/p>\n


\n\u201cFemales who inherit one bad BRCA gene – like actress Angelina Jolie – have a greatly increased risk for developing breast and ovarian cancer. If you inherit two bad BRCA genes you get Fanconi anemia,\u201d Howlett said. \u201cThe same is true for many Fanconi anemia genes. So while this disease is rare, the genes and proteins involved have major relevance for all of us in the fight against cancer. So it\u2019s really important that we figure out what these proteins do.\u201d<\/p>\n


\n\tHowlett\u2019s research is funded by the National Institutes of Health, the Department of Defense, and the Leukemia Research Foundation. He attends annual meetings of the Fanconi Anemia Research Fund, where he meets with patients, doctors and other researchers, and always returns re-energized to continue his research.<\/p>\n


\n\u201cStories like Logan\u2019s are heartbreaking,\u201d he said. \u201cThere are a lot of very challenging and important questions that need to be addressed to figure out how to fix this disease.\u201d Howlett\u2019s lab at 溏心vlog免费B站 is one of a small group of labs worldwide committed to addressing these challenges.<\/p>\n


\nPhoto by Joe GIblin<\/div>\n","protected":false},"excerpt":{"rendered":"

KINGSTON, R.I. \u2013 August 27, 2013 \u2013 When 2-year-old Logan Stevenson served as best man at his parents\u2019 wedding just days before he died of a rare genetic disorder, it drew international attention to a disease about which few people had ever heard. Hearing about Logan\u2019s story added another level of urgency to the research […]<\/p>\n","protected":false},"author":2,"featured_media":61360,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[],"class_list":["post-61358","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-archives"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/posts\/61358","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/comments?post=61358"}],"version-history":[{"count":0,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/posts\/61358\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/media\/61360"}],"wp:attachment":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/media?parent=61358"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/categories?post=61358"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/tags?post=61358"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}