CYTOKINE EXPRESSION AND SIGNALLING IN AGED EPIDERMIS

候选人：加迪亚利博士是一位多产的年轻科学家 确定了一个新的、与临床相关的研究领域。她有一种 她的赞助商伊莱亚斯博士全力支持她，伊莱亚斯博士是医学博士的杰出顾问。 Feingold，以及她所在部门负责人的大力支持。拥有 描述了重要的结构、功能和脂类生化 慢性衰老(CA)表皮的异常，Ghadially博士现在计划 探索异常细胞因子信号转导作为关键信号的潜在作用 造成这些异常的原因。这个项目对她来说是合乎逻辑的下一步 之前在表皮老化方面的工作，补充了她的赞助商关于 皮肤老化。在她的皮肤科基金会临床期间 Ghadially博士将与她的赞助商密切合作，后者 将引导她在皮肤科学术领域走向独立。Dr。 Ghadially还将参加科学团队的会议 研究皮肤病和新陈代谢中的屏障和/或细胞因子。 在这次调查结束时，加迪亚利博士将能够 维持独立的皮肤老化实验室研究计划。 项目：CA表皮，即使在没有光老化的情况下，也会显示 通透性屏障动态平衡异常，变得明显 只是有压力。申请者将检查CA中细胞因子的表达 皮肤，以及异常细胞因子信号传递的可能性 这些反常现象。表皮产生丰富的、复杂的 细胞因子对各种外源性侮辱的反应。此外，细胞因子 几种皮外组织的产量随年龄变化。 此外，细胞因子，如肿瘤坏死因子和白介素1α已被证明是调节 角质形成细胞的DNA合成以及组织中的脂肪代谢 如肝脏和脂肪组织，随着年龄的增长，它们合成的脂肪较少。 申请者首先将评估CA表皮是否显示 一个或多个关键调控因子的表达异常 细胞因子、IL-1a、肿瘤坏死因子、IL-1ra和/或其受体 条件。其次，她将评估表皮是否安装了 细胞因子对各种外界侮辱的异常反应。第三， 申请者将确定表皮细胞因子的异常表达 仅仅解释了屏障功能的变化，或者皮肤 和/或系统性因素发挥了作用。最后，申请者将尝试 用药矫治尖锐湿疣表皮异常 外源性细胞因子和通过操纵复制衰老表型 细胞因子在幼年表皮中的表达。老年人抱怨千姿百态 一系列问题，包括干燥、瘙痒和鳞屑，与 屏障功能的改变。然而，表皮的后果 衰老可能更重要，包括吸收改变。 局部治疗产品和对外源性药物的异常敏感性 支持炎症性/传染性的侮辱。这些研究可能会提供新的 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.