Training in the Molecular Basis of Skin/Mucosa Parthobiology

描述(由申请人提供)：俄勒冈健康与科学大学(OHSU)皮肤病学系建议继续其“皮肤病理生物学分子基础培训”计划，目的是培养高素质的博士后和博士后研究人员，从事皮肤病实验和相关上皮疾病，特别是癌症和炎症性疾病的学术生涯。我们的具体目标是：1.让受训者进一步了解粘膜和皮肤疾病背后的分子途径，发展和使用推进该领域所需的专门方法，并提供洞察力并最终应用于临床问题；2，促进我们的导师/实习实验室之间的互动，以丰富皮肤病领域，并扩大其范围和对疾病的理解和治疗的影响。拟议的计划提供了一个核心导师，包括国际公认的教师，皮肤病研究部的研究人员和5个基础科学系，他们通过这个计划互动和合作，形成对上皮癌变和炎症性疾病的关注。该培训计划旨在通过以下方式实现这些目标：1)让学员和导师参与讨论、互动/合作，分享关于上皮癌和表面上皮炎性疾病多个领域的想法和方法(通过每月轮换学员和导师参加的数据演示、共同指导和共享专业资源)，以及2)通过与临床皮肤科医生和肿瘤学家的密切互动(通过我们的每月翻译主题论坛和杂志俱乐部以及住院医师和科学家的联合演示来促进学员接受基础科学到临床治疗的转换)。该计划涵盖皮肤和粘膜癌变、稳态、致癌和肿瘤抑制机制(Trim32、Wnt、TGF？1/SMAD、c-Myc、RAS和B-Raf、胰岛素样生长因子、COX2、Piasy、p73、抑制性Smads)，以及癌症和炎症疾病中的细胞因子，并促进专业研究资源的共享，供学员项目使用(皮肤、结肠癌、头颈部癌症和炎症疾病的上皮靶向基因开关模型；非侵入性光学成像；上皮和免疫人群的专业细胞分离；以及我们包含新鲜冷冻的人类肿瘤标本和正常黏膜和皮肤对照的分子图谱资源)。每年任命两名博士后和三名博士后候选人，根据他们的能力、他们给该领域带来的特殊经验以及他们开展具有很强临床翻译成分的皮肤/粘膜研究的愿望，选择他们对癌症和炎症领域的皮肤病研究产生影响。 相关性：该项目研究身体表面器官(皮肤、口腔和肠道粘膜)的癌症和炎症性疾病，从组织、细胞、分子和生化水平了解它们是如何引起的，并发现新的治疗方法。皮肤是一个很好的模型，因为我们可以看到癌症和炎症性疾病从早期发展起来，并很容易看到新治疗方法的反应；然而，我们的团队正在开发非侵入性成像，使我们能够同时看到口腔和肠道疾病，并将病理与这些器官部位成人干细胞、癌症基因表达和促炎分子的变化联系起来。这些和相关上皮癌构成了人类癌症的大多数，其中最致命的癌症在美国每年影响超过68万人，近30万人死亡，而仅牛皮癣(一种皮肤炎性疾病)在美国每年就影响约750万人。

DESCRIPTION (provided by applicant): The Oregon Health & Science University (OHSU) Department of Dermatology proposes continuation of its "Training in the Molecular Basis of Skin Pathobiology" program with objectives to train highly qualified predoctoral and postdoctoral researchers for academic careers in experimental dermatology and related epithelial disorders, in particular cancer and inflammatory disease. Specifically we aim: 1. to engage trainees in furthering an understanding of the molecular pathways that underlie mucosal and skin disease, in evolving and using specialized approaches needed to advance the field, and in providing insight and ultimately application to clinical problems; and 2, to foster interactions among our mentor/trainee laboratories that enrich the dermatology field and increase its scope and impact on understanding and treating disease. The proposed program offers a core of mentors including internationally recognized faculty researchers from the Dermatology research division and 5 basic science departments who through this program interact and collaborate to form a focus on epithelial carcinogenesis and inflammatory disease. The training program is designed to achieve these aims by 1) engaging trainees and mentors in discussion, interaction/collaboration and sharing ideas and approaches in multiple areas of epithelial carcinogenesis and inflammatory disease of surface epithelia (facilitated through monthly rotation of trainee presentations of data attended by all trainees and mentors, co-mentoring, and sharing specialized resources) and 2) exposing trainees to translation of basic science to clinical treatment through close interaction with clinical dermatologists and oncologists (facilitated through our monthly translational topics forum and journal clubs with joint presentations of residents and scientists). This program spans skin and mucosal carcinogenesis, homeostatic, oncogenic and tumor suppressor mechanisms (Trim32, Wnt, TGF¿1/SMAD, c-Myc, Ras and B-Raf, insulin-like growth factors, Cox2, Piasy, p73, inhibitory SMADs), and cytokines in cancer and inflammatory disorders, and fosters sharing of specialized research resources for use in trainee projects (epithelial-targeted gene-switch models of skin, colon, and head and neck cancer and inflammatory disease; non-invasive optical imaging; specialized cell isolation of epithelial and immune populations; and our Molecular Profiling Resource containing freshly cryopreserved human tumor specimens and normal mucosa and skin controls). Two predoctoral and three postdoctoral MD, PhD or MD/PhD candidates are appointed each year, selected for their aptitude, the special experience they bring to the field and their desire to carry out skin/mucosa research with a strong clinical translational component and potential for impact on investigative dermatology in the areas of cancer and inflammation. RELEVANCE: This program studies cancer and inflammatory diseases of surface organs of the body (skin, oral and intestinal mucosa), to understand how they are caused at the tissue, cellular, molecular and biochemical levels, and to discover new treatments. Skin is a good model because we can see cancer and inflammatory diseases develop from their earliest stages and easily see responses to new treatments; however our group is developing non-invasive imaging that allows us to see oral and intestinal disease as well and to connect the pathology with changes in adult stem cells, cancer gene expression and inflammation-promoting molecules at these organ sites. Cancers of these and related epithelia make up the majority of human cancers, the most deadly of these affecting over 680,000 people a year in the US, with nearly 300,000 deaths, while psoriasis alone (a skin inflammatory disease) affects ~ 7.5 million people in the US annually,