Cancer, Autoantigens, and Scleroderma Investigating the Connection

描述（由申请人提供）：本提案的主要目标是获得临床和转化研究技能，成为一名优秀的，独立的风湿病学研究者，重点是硬皮病。系统性硬化症（硬皮病）是一种复杂的多系统疾病，涉及组织纤维化，免疫紊乱和血管异常。先前的流行病学研究提供了令人信服的证据，即硬皮病患者与普通人群相比患癌症的风险增加。癌症诊断和硬皮病发作之间的密切时间关系的观察，以及癌症治疗停止硬皮病进展的报告，表明硬皮病可能是一些患者的副肿瘤综合征。在这项提案中，候选人将探索硬皮病和癌症之间的时间关系，检查硬皮病中癌症的风险因素，并评估肿瘤中硬皮病自身抗原表达是否与免疫反应相关。这项研究将定义可能从靶向恶性肿瘤筛查中受益的患者亚群，深入了解硬皮病发病机制，并为候选人提供在指导环境中建立强大的临床和转化研究计划的机会。通过参加约翰霍普金斯临床研究生培训计划的培训，以及她发起和完成硬皮病临床相关问题研究的能力，该候选人已经证明了对学术风湿病学事业的承诺。这个指导以患者为导向的研究职业发展奖将为候选人提供继续发展这些技能的机会，部分通过计划在约翰霍普金斯彭博公共卫生学院的课程。专门的导师团队，流变学部门的多样化临床和研究环境，以及公共卫生学院的资源是这个指导以患者为导向的研究职业发展奖的理想基础。该提案的大型导师和合作者团队在研究硬皮病和癌症的流行病学和基本免疫学基础方面提供了重要的专业知识。此外，约翰霍普金斯硬皮病中心（JHSC）的资源;超过4800名受试者的大型JHSC和皇家自由医院硬皮病数据库; Bayview生物统计学，流行病学和数据管理（BEAD）核心;约翰霍普金斯肿瘤学部;和风湿病研究核心中心（RDRCC）都可以充分利用，使该项目取得成功。

DESCRIPTION (provided by applicant): The major goal of this proposal is to attain clinical and translational research skills to become an excellent, independent investigator in rheumatology, with a focus in scleroderma. Systemic sclerosis (scleroderma) is a complex, multisystem disease involving tissue fibrosis, immunological derangements and vascular abnormalities. Previous epidemiological studies provide compelling evidence that patients with scleroderma have an increased risk of cancer compared to the general population. Observations of a close temporal relationship between cancer diagnosis and scleroderma onset, and reports of cancer therapy halting scleroderma progression, suggest that scleroderma may be a paraneoplastic syndrome in some patients. In this proposal, the candidate will probe the temporal relationship between scleroderma and cancer, examine risk factors for cancer in scleroderma, and assess whether scleroderma autoantigen expression in tumors is associated with the immune response. This research will define patient subsets that may benefit from targeted malignancy screening, provide insight into mechanisms relevant in scleroderma pathogenesis, and offer the candidate an opportunity to build a strong clinical and translational research program in a mentored environment. The candidate has demonstrated a commitment to a career in academic rheumatology through her training in Johns Hopkins' Graduate Training Program in Clinical Investigation and her ability to initiate and complete investigations of clinically relevant questins in scleroderma. This Mentored Patient-Oriented Research Career Development Award will afford the candidate the opportunity to continue building on these skills, in part through planned coursework at the Johns Hopkins Bloomberg School of Public Health. The dedicated mentorship team, diverse clinical and research environment in the Division of Rheumatology, and resources of the School of Public Health are an ideal foundation for this mentored patient-oriented research career development award. The large team of mentors and collaborators for this proposal provide significant expertise in studying the epidemiology and basic immunologic underpinnings of scleroderma and cancer. In addition, the resources of the Johns Hopkins Scleroderma Center (JHSC); the large JHSC and Royal Free Hospital scleroderma databases of over 4800 subjects; the Bayview Biostatistics, Epidemiology and Data Management (BEAD) Core; the Johns Hopkins Division of Oncology; and the Rheumatic Diseases Research Core Center (RDRCC) are fully available to make this project a success.