Regulation of Antitumor Immunity by DC Subsets

这个K01指导职业发展奖的广泛目标是在肿瘤免疫学和树突状细胞（DC）生物学领域获得深入的研究培训和经验，最终目标是成为开发新型抗肿瘤治疗模式的独立研究者。该研究方案基于DC亚群在抗肿瘤免疫应答的启动和调节中起着非常重要的作用，其功能会受到肿瘤微环境和肿瘤源性因子的影响这一假设。为了检验这一假设，我们将研究两个具体目标，即，(1)髓系和淋巴系DC亚群的功能分析与比较：（2）肿瘤源性因子对不同亚群DC抗原提呈功能的影响。该建议的重要性在于，由于难以获得纯DC亚群，并且可以从hFlex基因处理的小鼠中分离出高纯度的DC亚群，这是本实验室新开发的方法，因此DC亚群很少被研究。候选人非常适合进行研究。贺博士在医学、分子生物学和基因传递方面训练有素，这在他的17篇同行评审的出版物和三篇提交的手稿中有记载。该候选人致力于利用基因递送和分子生物学的知识和技术来研究DC生物学并开发新的癌症治疗模式。这两个目标涉及现代免疫学和生物学的所有基础知识和技术。候选人在分子生物学方面的强大背景已经与肿瘤免疫学和DC生物学的培训，因为他将通过拟议的研究接收。他将通过利用分子生物学、肿瘤免疫学和DC生物学的知识和技术，在开发新的抗肿瘤方法领域成为一名独立的研究者。这个奖项的候选人选择的环境是杰出的。导师路易斯·D博士小法洛在肿瘤免疫学和DC生物学领域建立良好，资金充足。匹兹堡大学癌症研究所（UPCI）在罗纳德·赫伯曼（Ronald Herberman）、特里萨·怀特塞德（Theresa Whiteside）和奥利维拉·芬恩（Olivera Finn）博士的领导下，以其在肿瘤免疫学和DC应用方面的实力而闻名。UPCI拥有最大的DC生物学和应用研究团队。部门和机构资源是优秀的，知识环境是一流的，因为有三个完善的研讨会系列在癌症生物学，肿瘤免疫学和DC生物学领域和一个期刊俱乐部。此外，医学院其他学系亦提供其他与癌症有关的讲座。研究所致力于通过提供所有资源来全力支持候选人。候选人、研究提案和环境共同为该奖项提供了强有力的申请。

The broad objective of this K01 mentored career development award is to obtain in depth research training and experience in the field of tumor immunology and dendritic cell (DC) biology, with the ultimate goal of becoming an independent investigator for developing novel anti-tumor treatment modalities. The research proposal is based on the hypothesis that DC subsets play a very important role in the initiation and regulation of anti-tumor immune response and their function will be affected by the tumor microenvironment and tumor-derived factors. For testing this hypothesis, we will study two specific aims, i.e., (1) Functional analysis and comparison of myeloid and lymphoid DC subsets; (2) Influence of the tumor derived factors on the antigen presentation function of different subsets of DC. The importance of this proposal lies in the fact that DC subsets are scarcely studied due to the difficulty of obtaining pure DC subsets and on the ground that highly pure DC subsets can be isolated from hFlex gene treated mice, which is a newly developed approach in this lab. The candidate is highly suited to perform the research. Dr. He is well trained in medicine, molecular biology, and gene delivery as documented in his 17 peer-reviewed publications and three submitted manuscripts. The candidate is committed to using the knowledge and techniques of gene delivery and molecular biology to study the DC biology and develop novel cancer treatment modalities. The two aims involve all the basic knowledge and techniques of modern immunology and biology. Incorporating the strong background in molecular biology the candidate already has with the training in tumor immunology and DC biology as he will receive through the proposed research., he will be positioned very well in the path towards an independent investigator in the field of developing new anti-tumor approaches by harnessing the knowledge and techniques of molecular biology, tumor immunology and DC biology. The environment the candidate chosen for this award is outstanding. The mentor, Dr. Louis D. Falo Jr., is well established and well funded in the field of tumor immunology and DC biology. The University of Pittsburgh Cancer Institute (UPCI) is well known for its strength in tumor immunology and DC application under the leadership of Drs. Ronald Herberman, Theresa Whiteside and Olivera Finn. The UPCI has the largest research team on DC biology and application. The departmental and institutional resources are excellent and the intellectual environment is superb as there are three well-established seminar series in the area of cancer biology, tumor immunology and DC biology and one journal club. In addition, other cancer related seminars are also available from other departments in the school of medicine. The institute is committed to fully support the candidate by providing access to all of the resources. Together, the candidate, research proposal, and the environment provide a strong application for this award.