Leukocyte Immunoglobulin-like Receptors in Cutaneous Host Defense

该提案描述了一个为期5年的培训计划，以发展学术生涯， 皮肤科主要研究者已完成了90%以上的结构化住院医师培训， 她目前正在通过一个致力于提高她的科学技能的项目， 通过将皮肤科住院医师培训与为期两年的 受保护的博士后研究奖学金。该计划将促进细胞免疫学的掌握， 用于皮肤传染病，麻风病。罗伯特·莫德林博士将指导校长 研究者的科学发展，是麻风病领域公认的领导者，目前正在 在他的实验室中进行的研究涉及皮肤中宿主防御和先天免疫的机制， 与这项提议有关。首席研究员的长期职业目标是成为一名独立的 她是皮肤科学术研究员，拥有自己的实验室。 研究将集中在使用麻风病，一种疾病的临床结果取决于 宿主免疫反应，研究一个新的受体家族的作用，白细胞免疫球蛋白样 受体（LILR）在免疫失调中的作用。莫德林博士实验室最近的研究发现， LILR家族成员在进行性麻风瘤型中的表达与自身免疫缺陷型相比， 通过基因图谱研究治愈类结核病。拟议的实验将需要进一步分析 LILR在麻风中的表达以及LILR家族成员的功能研究。的 具体目的包括：1）鉴定麻风病损中表达特定LILR家族的细胞类型 成员，2）评估LILR在先天免疫调节中的作用，以及3）调查LILR是否 激活影响适应性免疫应答。 多种药物疗法仍然没有根除麻风病，全世界大约有100万人受到影响， 仍然给发展中国家造成重大的健康和经济负担。从《经济学人》中获得的见解 对LILR的研究，发现在麻风瘤型麻风中的水平增加，将有助于扩大我们对 免疫调节的先天性和适应性免疫系统，并可能导致发展 免疫疗法来治疗这种疾病和其他传染病。

This proposal describes a 5 year training program for the development of an academic career in Dermatology. The principal investigator has completed over 90% of her structured residency training in Dermatology at UCLA, and is currently expanding her scientific skills through a program committed to promoting careers in academic medicine by integrating dermatology residency training with a two-year protected postdoctoral research fellowship. This program will promote the command of cellular immunology, as applied to the dermatologic infectious disease, leprosy. Dr. Robert Modlin will mentor the principal investigator's scientific development and is a recognized leader in the field of leprosy, with current ongoing studies in his laboratory involving the mechanisms of host defense and innate immunity in skin, both of which are relevant to this proposal. The principal investigator's long-term career goal is to be an independent investigator in academic dermatology with her own laboratory. Research will focus on using leprosy, a disease with a spectrum of clinical outcomes depending on the host immune response, to study the role of a novel family of receptors, the leukocyte immunoglobulin-like receptors (LILRs) in immune dysregulation. Recent work in Dr. Modlin's laboratory identified an increased expression of LILR family members in the progressive lepromatous form of leprosy compared to the self- healing tuberculoid form by gene profiling studies. The proposed experiments will entail further analysis of the expression of LILRs in leprosy as well as investigation of the function of the LILR family members. The specific aims include: 1) identifying the cell type(s) in leprosy lesions that express particular LILR family members, 2) evaluating the roles of LILRs in regulation of innate immunity, and 3) investigating whether LILR activation affects adaptive immune responses. Multidrug therapy still has not eradicated leprosy, affecting approximately one million people worldwide, still poses a significant health and economic burden on developing countries. The insights gained from the study of LILRs, found at increased levels in lepromatous leprosy, will help broaden our understanding of immunoregulation of the innate and adaptive immune systems and may lead to the development of immunotherapies to treat this and other infectious diseases.