CYTOKINE EXPRESSION AND SIGNALLING IN AGED EPIDERMIS

候选人：Ghadially博士是一位富有成效的年轻科学家， 确定了一个新的临床相关研究领域。 她有 她的赞助商，埃利亚斯博士，在博士的杰出顾问的全力支持。 法因戈尔德，还有她系主任的大力支持。 具有 描述了重要的结构、功能和脂质生化 Ghadially博士现在计划， 探索异常细胞因子信号传导的潜在作用， 这些异常的原因。 这个项目对她来说是顺理成章的下一步 以前的工作在表皮老化，并补充她的赞助商的项目， 皮肤老化 在她的皮肤病基金会临床 作为研究者，Ghadially博士将与她的赞助商密切合作， 将引导她在皮肤科学术上走向独立。 博士 Ghadially还将参加科学小组的会议 在皮肤病学和代谢中研究屏障和/或细胞因子。 在这段任期结束时，Ghadially博士将能够 维持一个独立的皮肤老化实验室研究项目。 项目：CA表皮，即使没有光老化，显示 渗透屏障稳态的异常， 只有压力。 申请方将检查CA中的细胞因子表达 皮肤，以及异常细胞因子信号传导的可能性， 这些异常。 表皮产生丰富的，复杂的 细胞因子对各种外源性损伤的反应。 此外，细胞因子 在几种皮外组织中，产量随年龄而变化。 此外，细胞因子如TNF和IL-1 α已被证明可以调节 角质形成细胞中的DNA合成以及组织中的脂质代谢 如肝脏和脂肪组织，随着年龄增长，它们合成脂质减少。 申请人首先将评估CA表皮是否显示 一个或多个关键调节因子的表达异常， 细胞因子、IL-1a、TNF、IL-1ra和/或它们的受体， 条件 第二，她将评估表皮是否安装了一个 对各种外部损伤的异常细胞因子反应。 三是 申请人将确定异常的表皮细胞因子表达是否 单独解释了屏障功能的改变，或者皮肤 和/或系统性因素起作用。 最后，申请人将尝试 通过给药来纠正CA表皮的异常， 外源性细胞因子和复制衰老表型通过操纵 年轻表皮细胞因子表达。 老年人抱怨各种各样的 的问题，包括干燥，瘙痒，和规模，这涉及到 屏障功能的改变。 然而，表皮的后果 衰老可能更重要，包括改变吸收 局部治疗产品和对外源性 促炎性/感染性损伤。 这些研究可以提供新的 改善老年人表皮功能的治疗策略。

Candidate: Dr. Ghadially is a productive young scientist who has identified a new, clinically relevant area of investigation. She has the full support of her sponsor, Dr. Elias, an outstanding consultant in Dr. Feingold, and strong backing from her department chairman. Having described important structural, functional, and lipid biochemical abnormalities in chronically aged (CA) epidermis, Dr. Ghadially now plans to explore the potential role of aberrant cytokine signalling as a key cause of these abnormalities. This project is a logical next step to her prior work in epidermal aging and complements her sponsor's project on skin aging. As during her Dermatology Foundation Clinical Investigatorship, Dr. Ghadially will work closely with her sponsor, who will direct her growth toward independence in academic dermatology. Dr. Ghadially also will participate in the meetings of the scientific team working on the barrier and/or cytokines in Dermatology and Metabolism. By the end of this investigatorship, Dr. Ghadially will be able to sustain an independent laboratory research program on skin aging. Project: CA epidermis, even in the absence of photoaging, displays abnormalities in permeability barrier homeostasis, which become apparent only with stress. The applicant will examine cytokine expression in CA skin, and the possibility that aberrant cytokine signalling underlies these abnormalities. The epidermis generates an abundant, complex cytokine response to a variety of exogenous insults. Moreover, cytokine production changes with age in several extracutaneous tissues. Furthermore, cytokines such as TNF and IL-1a have been shown to regulate DNA synthesis in keratinocytes, as well as lipid metabolism in tissues such as liver and adipose tissue, which synthesize less lipid with age. The applicant first will assess whether CA epidermis displays abnormalities in the expression of one or more of the key regulatory cytokines, IL-1a, TNF, IL-1ra, and/or their receptors under basal conditions. Second, she will assess whether the epidermis mounts an aberrant cytokine response to various external insults. Third, the applicant will ascertain whether aberrant epidermal cytokine expression alone explains the alterations in barrier function, or whether dermal and/or systemic factors play a role. Finally, the applicant will attempt to correct the abnormalities in CA epidermis through administration of exogenous cytokines and to reproduce the aging phenotype by manipulating cytokine expression in young epidermis. The aged complain of a variety of problems, including dryness, pruritus, and scaling, that relate to alterations in barrier function. Yet, the consequences of epidermal aging are potentially of greater importance, including altered absorption of topical therapeutic products and abnormal susceptibility to exogenous pro-inflammatory/infectious insults. These studies could provide new therapeutic strategies to improve epidermal function in the aged.