Murine models to test parasite products as cures for Inflammatory Bowel Disease

描述（由申请人提供）：投资增强曼斯菲尔德博士的小鼠模型活动，将在理解和治疗肠道病原体引起的肠道炎症性疾病方面取得进展，并培养兽医进入研究领域。Mansfield博士于1990年毕业于宾夕法尼亚大学（University of Pennsylvania）生物医学研究生项目的医学博士学位，并于1994年在the Animal Parasite Institute完成博士后培训。目前，她已经完成了11年的培训，因此，她有资格成为一名职业中期调查员。她的培训和研究生涯主要用于开发人类和动物感染性肠道疾病的动物模型。从1990年到2003年，她专注于寻找天然存在的空肠弯曲杆菌和囊肿形成球虫（神经肌囊虫等）的动物模型，并将其转化为小鼠模型。2002- 2004年，她成功地获得了实施这些病原体的小鼠模型的资金，从而将她在比较医学领域的重点从这些人类和动物肠道疾病的大型动物模型转移到小鼠模型。最近资助的和未决的小鼠病理生物学资助记录了这一职业转变。同时，她要求免除在人口和动物健康诊断中心临床寄生虫科的行政职责。在她的领导下，案件量从每年1500起迅速增长到每年100万起，这对研究和指导的时间要求越来越高。曼斯菲尔德博士寻求职业奖基金，以加强她在小鼠病理生物学方面的项目，特别是在NIH资助的合同“密歇根州立大学微生物研究单位：食品和水传播综合研究网络”中进行项目。这些职业奖资金将支持新的小鼠模型，包括：1)“空肠梭菌定植和肠炎小鼠模型”，以确定空肠梭菌和其他肠道细菌刺激肠道慢性炎症的机制；2)“蠕虫介导的炎症性肠病控制”，以确定毛滴虫寄生产物对结肠炎症（自发和病原体介导）的免疫调节特性。这些小鼠模型将作为测试选定寄生虫及其分子在下调慢性炎症中的功效的第一种模式。曼斯菲尔德博士在指导研究生方面取得了成功，并寻求扩大她在小鼠病理生物学方面对d.v.m.的指导。

DESCRIPTION (provided by applicant): Investing in enhancement of Dr. Mansfield's mouse model activities will result in progress in understanding and treating inflammatory disease of the bowel resulting from enteric pathogens and in fostering veterinarians to enter the research arena. Dr. Mansfield graduated from a V.M.D., Ph.D. program in Biomedical Graduate Studies at the University of Pennsylvania in 1990 and finished postdoctoral training at the Animal Parasite Institute in 1994. Currently, she is 11 years from her training, thus, qualifying as a Mid-Career investigator. Her training and research career were spent developing animal models of human and animal infectious enteric diseases. From 1990-2003, she focused on finding naturally occurring animal models for Campylobacter jejuni and Cyst forming coccidia (Sarcocystis neurona, etc.) with the long-term goal to convert these to mouse models. In 2002-04, she successfully achieved funding to implement mouse models for these pathogens and, thus, shifted her focus within comparative medicine from large animal models of these human and animal enteric diseases to murine models. Recent funded and pending grants on mouse pathobiology document this career shift. Simultaneously, she requested relief from administrative duties running the Clinical Parasitology Section of the Diagnostic Center for Population and Animal Health. Caseloads had burgeoned under her leadership from 1500 to >10,000/year placing increasing demands on time for research and mentoring. Dr. Mansfield seeks Career Award funds to enhance her program in mouse pathobiology especially to pursue projects in the funded NIH contract "Michigan State University Microbiology Research Unit: Food and Waterborne Integrated Research Network". These Career Award funds would enable new mouse models including, 1)"Murine models of C. jejuni colonization and enteritis" to determine mechanisms by which C. jejuni and other enteric bacteria stimulate chronic inflammation in the gut, and 2)"Worm mediated control of inflammatory Bowel Disease" to determine immunomodulatory properties of defined parasitic products from Trichuris on colonic inflammation (spontaneous and pathogenmediated). These mouse models will serve as the first modality for testing select parasites and their molecules for efficacy in down modulating chronic inflammation. Dr. Mansfield has documented success mentoring graduate students and seeks to expand her mentoring of D.V.M.s in mouse pathobiology.