研究概况:布莱恩P. 迪莱尔,Ph值.D.
研究很少是一条有明确目的地的直路. 但随着布莱恩·P. 迪莱尔,Ph值.D., has discovered are vital to understanding why certain gene mutations impact individual patients the way they do.
迪莱尔, associate professor of physiology at the Saha Cardiovascular Research Center, 肯塔基大学医学院, 研究长QT综合征, a hereditary heart disorder that can present in children or young adults without warning as sudden death. What makes long QT syndrome an interesting area of study for 迪莱尔 and others is that sudden death in patients can be prevented with commonly prescribed drugs like beta blockers.
The key--the heart of 迪莱尔’s research--is how to find children and young adults in the population who need treatment despite having no signs or symptoms of disease.
“如果我们能识别出潜在的患者, 我们实际上可以干预并预防危及生命的线上娱乐电子游戏网站,迪莱尔说.
关于长QT综合征我们已经知道了很多. Scientists uncovered the syndrome’s genetics in the mid-1990s, according to 迪莱尔.
“This is one of the first heart diseases for which commercial genetic screening and patient-specific cell models were developed. Critical advances in both basic science and clinical research early on helped transition us to where we are today,迪莱尔说.
One of the twists in studying long QT syndrome is not all mutations identified in genes linked to long QT syndrome cause the disease. 大多数是中性变异，不会导致疾病. So, 近年来, 迪莱尔 and colleagues secured 美国心脏协会 Institute of Precision Cardiovascular Medicine funding to develop screening approaches to differentiate which long QT syndrome-associated gene variants, 或突变, are neutral and don’t result in the syndrome versus those that might cause it.
University of Kentucky researchers partnered with Geisinger Health System, which provided genetic and clinical data to help validate the screening approaches.
“Dr. Tooraj Mirshahi and his colleagues provided data on the genetic variants already suspected of causing long QT syndrome, 我们用我们的功能屏幕说ok, 这个看起来是中性的，这个看起来可能是坏的,他说. “That was the point of our work with the Institute—to help improve the clinical value of a genetic test that might identify patients with this disease.”
This type of screening would help doctors identify those children and young adults that need to be clinically evaluated for the disease and treated appropriately. It also helps to avoid unnecessary treatment of patients who have neutral variants but not the disease.
That individual approach is part of the goal of precision medicine, according to 迪莱尔.
还有更多的东西要学，还有更多的曲折. 迪莱尔 and colleagues noticed that even when they could predict if a variant was likely bad, some patients with these variants didn’t seem to actually get the disease.
“精准医学的一部分不仅仅是研究基因变异, but also taken into account the gene and environment interactions that may also contribute to the risk for this disease,他说.
The National Institutes of Health recently awarded 迪莱尔 and colleagues an R01 grant to take their research on long QT syndrome to the next level, by looking at how circadian rhythms--the body’s internal clock—might influence the expressivity of the disease using genetic mouse models.
迪莱尔 said the importance of his work became more personal in the 1990s when he was lobbying with the 美国心脏协会 to increase federal funding for the National Institutes of Health. He and colleagues would work with survivors and meet with their congressional representatives in Washington, DC, 告诉他们投资研究的重要性.
“When I was there, I got to meet one survivor whose child had died from long QT syndrome. 可悲的是, she felt responsible because she found out she carried the mutation that likely contributed to the child’s death,他说. “这是悲剧。. It became clear to me that we need to know as much as we can about this disease, 这样我们就可以识别和治疗有风险的人, as well as help educate parents who lost children to know they are not responsible. 我可以毫无疑问地说，如果没有美国心脏协会的支持, the NIH grant and the opportunity to reach that goal would not have happened.”
