{"311191":{"#nid":"311191","#data":{"type":"news","title":"Altered States - New Study Sheds Light on Sickle Cell Disease and Offers New Hope for Patients","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EEd Botchwey\u0027s research takes sharp turn as they explore possible new causes for the disease.\u003Cbr \/\u003E\u003Cbr \/\u003E\u003C\/strong\u003EEd Botchwey is not a hematologist. He\u2019s very clear about that. Botchwey runs a tissue-engineering lab at the Parker H. Petit Institute for Bioengineering and Bioscience, with a focus on regenerative medicine. \u003Cbr \/\u003E\u003Cbr \/\u003EThat\u2019s been his professional history \u2013 tissue engineering and regenerative medicine. But there\u2019s a piece of personal history that carries a bit more influence, and that, perhaps more than anything else, is what led Botchwey and his research team to publish in the journal Blood, the most cited peer-reviewed publication in the field of hematology. \u003Cbr \/\u003E\u003Cbr \/\u003ETheir research and paper, with the running title, \u201cSphingolipid Metabolism in Sickle Cell Disease,\u201d represents a sharp turn for Botchwey and his colleagues, who shed new light on causes for some of the disease\u2019s pervasive and devastating symptoms, while offering new hope for patients who struggle with the disease, people like his sister. \u003Cbr \/\u003E\u003Cbr \/\u003E\u201cAs it turns out, my sister has sickle cell disease, and I have a student, the first author of this paper, Anthony Awojoodu \u2013 his sister has it. So this is something we felt very passionate about,\u201d says Botchwey, associate professor in the Wallace H. Coulter Department of Biomedical Engineering (Coulter Department), who didn\u2019t set out to research sickle cell disease (SCD). It just sort of happened. He was just following a logical trail of research. \u003Cbr \/\u003E\u003Cbr \/\u003E\u201cWe\u2019d been looking at certain classes of signaling lipids and how they regulate inflammation. Part of our goal was, and still is, exploiting certain inflammatory responses to help in tissue regeneration,\u201d Botchwey says. \u201cBut along the way, we recognized that some of the enzymes that are central components in the metabolism and production of these signaling lipids were responsive to stresses in cell membranes.\u201d \u003Cbr \/\u003E\u003Cbr \/\u003ELike, for example, the stresses that cause the telltale geometric distortion of red blood cell (RBC) membranes in sickle cell disease (SCD). It occurred to Botchwey that SCD would make a great model system in which to observe the relationship between membrane stresses, inflammation and the metabolism of these sphingolipids. Turns out, there\u2019s a very close relationship. \u003Cbr \/\u003E\u003Cbr \/\u003ETheir findings reveal for the first time that sphingolipid metabolism is indeed dysregulated, or altered in SCD. Membrane stresses associated with SCD activate sphingomyelinase (SMase), an enzyme that contributes to progression of the disease (SMase has been implicated in vascular inflammation). SMase, in concert with other enzymes, also causes elevated production of microparticles, which contribute to what Botchwey calls, \u201cthis chronic inflammatory state that underlies so much of the pathology of sickle cell disease.\u201d \u003Cbr \/\u003E\u003Cbr \/\u003EWhat encourages Botchwey is the research also illuminates potential new strategies to regulate inflammation through modulating sphingolipid metabolism \u2013 results that may also be applicable to other red blood cell disorders, not just SCD. What\u2019s more, a promising therapeutic solution is already close at hand \u2013 the antidepressant, amitriptyline. \u003Cbr \/\u003E\u003Cbr \/\u003E\u201cWe wanted to know, can you pharmacologically inhibit SMase in order to reduce these pro-inflammatory microparticles. And we found that, in fact, we can, and we\u2019re excited about it. If you can cut off one of the primary means whereby sickled red blood cells are perpetuating a chronic inflammatory state in the patient, then you may be cutting off a wide range of the disease consequences associated with SCD,\u201d says Botchwey. \u201cAmytriptyline happened to factor quite highly in our survey of potential inhibitors of SMase. You can find certain papers that will make an indirect association to what we\u2019ve shown.\u201d \u003Cbr \/\u003E\u003Cbr \/\u003ESure enough, there are 30-plus year-old research papers that explore the inhibitive effects of tricyclic antidepressants on SMase in various contexts, and Botchwey\u2019s team connected the complicated dots. But there has been next to no research on the role of SMase and sphingolipid dysregulation in SCD (a disease that affects millions worldwide), and that surprises Botchwey. \u003Cbr \/\u003E\u003Cbr \/\u003E\u201cIt\u2019s a mystery to me.\u201d says Botchwey. \u201cWhen you think about a disease as prevalent as this one, as well understood as it is, in terms of what the underlying genetic mutation is, and you consider all the tools we have at our disposal for correcting such mutations, you would think this would be a curable disease. I\u2019ve lamented the fact that it\u2019s not cured, but never considered that I might be part of the research that might lead to a cure.\u201d \u003Cbr \/\u003E\u003Cbr \/\u003EBotchwey, whose work is supported by the NIH and NSF, as well as the Petit Institute and Coulter Department, led a research team that included Awojoodu, a native Nigerian who was responsible for recruiting Petit Scholar, Alicia Lane, to the team. \u003Cbr \/\u003E\u003Cbr \/\u003E\u201cThey struck up a very productive working and mentoring relationship, and this paper is partly the culmination of that,\u201d says Botchwey, whose collaborators in the study also include Phillip Keegan, Yuying Zhang, Kevin Lynch from the University of Virginia, and BME assistant professor Manu Platt. \u003Cbr \/\u003E\u003Cbr \/\u003EBotchwey, not a blood guy, says this research represents a new direction for him, one he might not have taken if he didn\u2019t make the move several years ago from the University of Virginia to the Georgia Institute of Technology, and the Petit Institute. \u003Cbr \/\u003E\u003Cbr \/\u003E\u201cLike I said, I\u2019m not a hematology researcher, but the opportunity to take risks resonated with me. It\u2019s a risk to go in new directions, and Georgia Tech enabled me to take that risk,\u201d he says. \u201cThe multidisciplinary, interdisciplinary environment here is one in which I felt comfortable asking what I perceived to be a frontier question that impacted a disease I felt passionately about. I don\u2019t know if that would have happened if I\u2019d stayed where I was.\u201d\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cbr \/\u003E\u003Cem\u003EThis study was supported in part by NIH Grants 1R01DE019935-01, 1R01AR056445-01A2 and R01GM067958, and 1DP2OD007433-01 and NSF Grant NSF#0933643.\u003C\/em\u003E\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Ed Botchwey\u0027s research takes sharp turn as they explore possible new causes for the disease."}],"field_summary":[{"value":"\u003Cp\u003EEd Botchwey\u0027s research takes sharp turn as they explore possible new causes for the disease.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Ed Botchwey\u0027s research takes sharp turn as they explore possible new causes for the disease."}],"uid":"27195","created_gmt":"2014-07-28 13:57:53","changed_gmt":"2016-10-08 03:16:48","author":"Colly Mitchell","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2014-07-28T00:00:00-04:00","iso_date":"2014-07-28T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"311171":{"id":"311171","type":"image","title":"Ed Botchwey, PhD - Associate professor in the Wallace H. Coulter Department of Biomedical Engineering","body":null,"created":"1449244726","gmt_created":"2015-12-04 15:58:46","changed":"1475895020","gmt_changed":"2016-10-08 02:50:20","alt":"Ed Botchwey, PhD - Associate professor in the Wallace H. Coulter Department of Biomedical Engineering","file":{"fid":"199854","name":"botchwey_ed_-_july_2014.jpg","image_path":"\/sites\/default\/files\/images\/botchwey_ed_-_july_2014_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/botchwey_ed_-_july_2014_0.jpg","mime":"image\/jpeg","size":661178,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/botchwey_ed_-_july_2014_0.jpg?itok=Mf7zlVNm"}},"311181":{"id":"311181","type":"image","title":"Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body.","body":null,"created":"1449244726","gmt_created":"2015-12-04 15:58:46","changed":"1475895020","gmt_changed":"2016-10-08 02:50:20","alt":"Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body.","file":{"fid":"199855","name":"sickle_cell.jpg","image_path":"\/sites\/default\/files\/images\/sickle_cell_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/sickle_cell_0.jpg","mime":"image\/jpeg","size":270785,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/sickle_cell_0.jpg?itok=OyK6Jqab"}}},"media_ids":["311171","311181"],"related_links":[{"url":"http:\/\/botchweylab.gatech.edu\/","title":"Botchwey lab website"},{"url":"http:\/\/www.ibb.gatech.edu\/","title":"Petit Institute for Bioengineering and Bioscience"}],"groups":[{"id":"1254","name":"Wallace H. Coulter Dept. of Biomedical Engineering"}],"categories":[{"id":"135","name":"Research"}],"keywords":[],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u0026nbsp;\u003Cbr \/\u003EBioengineering \u0026amp; Bioscience\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}