BAFF Pathology: Novel Therapeutic Targets in Chronic Graft versus Host Disease

描述（由申请人提供）：摘要本提案的主要目标是发展候选人在骨髓移植后发展的免疫病理学实验室研究方面的学术生涯。该候选人在哈佛癌症中心获得Paul Calebrisi K12 Grant（布鲁斯查布纳博士，PI）资助2.5年，在Dana-Farber癌症研究所的杰罗姆里茨博士实验室担任博士后。候选人现在提出了一个导师计划，在北卡罗来纳州（北），查佩尔山，她开始了终身教职的位置在2009年6月1日大学。该项目将由阿尔伯特·鲍德温博士领导，他将作为候选人的主要导师Baldwin博士是NFkB信号传导领域的领先专家，在成功指导年轻研究人员方面有着悠久的历史。他为候选人制定了一个全面的导师计划，主要集中在发展她在TNF家族成员受体信号传导方面的知识和实验专业知识。候选人的共同导师将是Serody博士，他是医学、微生物学和免疫学的教授，也是Lineberger癌症中心免疫学部门的共同负责人。Serody博士被公认为移植物抗宿主病（GVHD）领域的领导者，他领导了几项NIH资助的实验室研究，重点是趋化因子受体和免疫调节细胞在GVHD中的作用。由候选人的主要合作者之一托马斯谢伊博士开发的综合临床数据库，连同在亚特兰大的IRB组织采购方案，将允许Sarantopoulos博士从接受异基因造血干细胞移植（HSCT）的患者中收集和表征样本。此外，Dana-Farber癌症中心的杰罗姆里兹博士、杜克大学的纳尔逊赵博士和弗雷德哈钦森癌症中心的斯蒂芬妮李博士将合作，为候选人提供新鲜和冷冻保存的HSCT患者样本。最后，Sarantopoulos博士组建了一个由Stephen Clarke博士和Barbara Vilen博士组成的当地生物医学专家科学咨询委员会，他们都是B细胞病理学方面的专家。她的导师和专家咨询委员会将使候选人联合收割机结合她以前学到的东西，并在TNF家族成员受体信号传导的详细，具体的学徒培训完成。研究将集中在异基因造血干细胞移植（HSCT）治疗癌症后患者发生的显著免疫病理学研究。本研究项目的长期目标是了解TNF家族B细胞活化因子（BAFF）及其相关信号通路的作用。拟议的实验将允许未来开发用于慢性GVHD的新型靶向治疗剂和改善癌症患者的总体生存率。导师，教学法和研究建议沿着学术和研究基础设施提供的研究中心和Lineberger综合癌症中心将确保候选人的成功过渡到NIH资助的独立研究者。

DESCRIPTION (provided by applicant): ABSTRACT The major objective of this proposal is the development of the candidate's academic career in laboratory research of immune pathology that develops after bone marrow transplantation. For 2.5 years, the candidate was funded by a Paul Calebrisi K12 Grant (Dr. Bruce Chabner, PI) at the Harvard Cancer Center as a post- doctoral in Dr. Jerome Ritz' laboratory at Dana-Farber Cancer Institute. The candidate now proposes a mentorship plan at the University of North Carolina (UNC), Chapel Hill where she began a tenure-track faculty position on June 1st, 2009. The UNC K08 mentorship program will be headed by Albert Baldwin, Ph.D., who will serve as the candidate's primary mentor. Dr. Baldwin is a leading expert in NFkB signaling with a long track record of successfully mentoring young investigators. He has developed a comprehensive mentorship plan for the candidate primarily focused on developing her knowledge and experimental expertise in TNF family member receptor signaling. The candidate's co-mentor will be Dr. Serody who is an endowed Professor of Medicine, Microbiology and Immunology and co-leader of the Immunology Section in the Lineberger Cancer Center. Dr. Serody is recognized as a leader in the field of Graft versus Host Disease (GVHD) having led several NIH-funded laboratory studies focused on the role of chemokine receptors and immune regulatory cells in GVHD. A comprehensive clinical data base developed by one of the candidate's key collaborators, Dr. Thomas Shea, in conjunction with an IRB tissue procurement protocol at UNC will allow Dr. Sarantopoulos to collect and characterize samples from patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). In addition, Dr. Jerome Ritz from Dana-Farber Cancer Center, Dr. Nelson Chao from Duke University and Dr. Stephanie Lee from Fred Hutchinson Cancer Center will collaborate and supply the candidate with fresh and cryopreserved HSCT patient samples. Finally, Dr. Sarantopoulos has assembled a local UNC expert scientific advisory committee comprised of Dr. Stephen Clarke and Dr. Barbara Vilen in the, Department Microbiology & Immunology at UNC, both experts in B cell pathobiology. Her mentors and expert advisory committee will enable the candidate to combine what she has previously learned and accomplished with detailed, specific apprenticeship training in TNF family member receptor signaling. Research will focus on studies of significant immune pathology that develops in patients after treatment for cancer with allogeneic hematopoietic stem cell transplantation (HSCT). The long-term goal of this research project is to understand the role of B cell Activating Factor of the TNF family (BAFF) and its associated signaling pathways. The proposed experiments will allow for future development of novel targeted therapeutic agents for chronic GVHD and improved overall survival of cancer patients. The mentorship, didactics, and research proposal along with the academic and research infrastructure provided by UNC and the Lineberger Comprehensive Cancer Center will ensure the candidate's successful transition to an NIH-funded independent investigator.