BLR&D Research Career Scientist Award Application

我们研究的主要领域是帮助理解和发展的原因 治疗神经退行性疾病和状况，特别是阿尔茨海默氏症 疾病(AD)和多发性硬化症(MS)。这项工作包括改变药物的用途，这些药物 FDA批准用于其他适应症，但我们表明可以在动物模型中提供益处 AD和MS，使他们更容易带到诊所。更好地了解如何 这些疾病开始和发展，确定干预措施将有助于减少 疾病症状，以及社会和经济负担。我们目前的MS研究 已经扩展到遗传风险因素领域，这些因素可能 基于我们对一种新的核苷酸变异的发现，易患多发性硬化症 一种特殊的基因。我们现在正在使用cell来确定该变体如何增加风险 培养和我们开发的复制人类变体的小鼠模型，并进行测试 看看它们是否能将其影响降至最低。我们还在测试这个变种，或者其他变种 在某些退伍军人群体中出现的频率更高，包括在非洲 美国人、西班牙人和高加索人。同时在由政府资助的工作中 全国多发性硬化症协会，我们正在多发性硬化症小鼠模型上测试一种新的化合物 Believe将减少神经元损伤，并增加周围的髓鞘 并保护神经细胞。 我们还在开展一个项目，以评估过量饮酒的后果 消费对AD发展的影响。我们发现暴露在大脑中的“支持”细胞(胶质细胞 乙醇降低了它们清除淀粉样斑块的能力；我们计划扩大这些 细胞对阿尔茨海默病小鼠模型的研究。我们还得到资助进行研究， 可能对我们的现役军人和退伍军人特别重要， 即对常用抗病毒药物可能引起的神经损伤的研究 凝血剂(例如华法林)，以及更有效的用于 杀鼠剂，但不幸的是，也被用于军事情况。我们是 开发使用FDA批准的药物的方法，我们希望能防止 这些药物以及长期后果。

The major area of our research is to help understand the causes of, and development treatments for neurodegenerative diseases and conditions, in particular Alzheimer’s Disease (AD) and Multiple Sclerosis (MS). This work includes repurposing drugs that are FDA-approved for other indications but we show can provide benefit in animal models of AD and MS, making it easier to bring them to the clinic. A better understanding of how these diseases start and evolve, and identification of interventions will help reduce disease symptoms, as well as social and economic burdens. Our MS studies currently funded by a Merit grant have expanded into the area of genetic risk factors that may predispose one to developing MS, based on our findings of a novel nucleotide variant in one particular gene. We are now determining how the variant increases risk using cell cultures and a mouse model that we developed to replicate the human variant, and testing drugs to see if they can minimize its effects. We are also testing if this variant, or others, is present at higher frequency in certain veteran populations, including in African American, Hispanic, and Caucasian cohorts. At the same time in work funded by the National MS society, we are testing a novel compound in a mouse model of MS we believe will reduce neuronal damage and also increase the myelin sheath that surrounds and protections nerve cells. We are also working on a project to evaluate the consequences of excessive alcohol consumption on the development of AD. We found that exposing brain ‘support’ cells (glial cells) to ethanol reduces their ability to clear amyloid plaques; we plan to extend those cell studies to a mouse model of AD. We have also been funded to carry out studies that may have particular importance to our active military as well as veteran population, namely studies on possible neurological damage caused by commonly used anti- coagulants (e.g.warfarin), and also more potent ‘superwarfarins’ that are used as rodenticides, but unfortunately have also been used in military situations. We are developing methods using FDA-approved drugs, we hope will prevent the toxic effects of these drugs as well as long term consequences.