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Leukemia Stem Cell Antigen Discovery Using Advanced Genomic and Proteomic Methods

使用先进的基因组和蛋白质组方法发现白血病干细胞抗原

基本信息

批准号：
8617862
负责人：
Paul Michael Armistead
金额：
$ 13.21万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8617862
关键词：
Acute Myelocytic Leukemia Algorithms Allogenic American Antigen Targeting Antigens Applications Grants Award Bioinformatics Biological Biology Cells Chemistry Code Complication Comprehensive Cancer Center Computational Biology Computing Methodologies Data Detection Development Disease Doctor of Philosophy Funding Genetic Genomics Goals Grant High Pressure Liquid Chromatography Human Immune response Immunity Immunologics Immunology Immunotherapy In complete remission Investigation Ions Laboratories Lead Learning Manuals Mass Spectrum Analysis Massive Parallel Sequencing Mediating Medicine Mentored Clinical Scientist Development Award (K08)Mentors Mentorship Methods Minor Histocompatibility Antigens Normal tissue morphology North Carolina Organ Outcome Patients Peptides Physicians Play Population Positioning Attribute Postdoctoral Fellow Principal Investigator Process Production Proteomics RNA Sequence Analysis RNA Sequences Recommendation Recurrent disease Research Research Infrastructure Research Personnel Research Project Grants Research Proposals Research Training Resolution Risk Role Sampling Scientist Single Nucleotide Polymorphism Societies Spectrometry Stem cell transplant Structure Surface T-Lymphocyte The Cancer Genome Atlas Time Tissues Training Transplantation Universities cancer genomics career clinically relevant doctoral student genome analysis graduate student high risk immunogenic immunogenicity improved in vivo ion mobility leukemia leukemic stem cell mass spectrometer novel novel strategies professor protein aminoacid sequence prototype skills standard of care theories therapeutic development therapeutic target

项目摘要

DESCRIPTION (provided by applicant): The major objective of this Mentored Clinical Scientist Development Award (K08) proposal is the development of the candidate's academic career in the field of leukemia biology and stem cell transplantation. The candidate proposes in this application to learn new skills in genome analysis and mass spectrometry in order to complete a novel research investigation to discover leukemia stem cell-associated minor histocompatibility antigens. Since moving to the University of North Carolina in 2009, the candidate has been funded by a UNC Department of Medicine KL2 Award to develop bioinformatic and immunologic methods for minor histocompatibility antigen discovery. In this K08 proposal, the candidate has identified Dr. Chuck Perou, PhD, as his primary mentor and advisor in the application of RNA sequencing analysis aimed at the computational predication of leukemia stem cell associated minor histocompatibility antigens (LSC-associated mHA). Dr. Perou is a leader in the field of cancer genomics, and the leader of the UNC contribution to The Cancer Genome Atlas. He has mentored many graduate and post-doctoral students and has developed a comprehensive training and mentorship plan for the candidate so that he can develop new skills in genome analysis. The candidate has also identified Dr. Gary Glish PhD as a co-mentor to provide training and mentorship in mass spectrometry. The candidate has a PhD in Chemistry, but has no specific formal training in mass spectrometry. Because mass spectrometry plays a crucial role in antigen discovery research the candidate is proposing training and research in this field as part of the overall K08 project. Dr. Glish is a professor of Chemistry at UNC and the Past President of the American Society of Mass Spectrometry. He has mentored numerous graduate students through his very successful career, and will provide training in the theory and practice of mass spectrometry in the detection of biomolecules. Additionally, Dr. Glish's laboratory has developed and built a prototype high-field asymmetric waveform ion mobility spectrometry (FAIMS) mass spectrometer that will be used for the first time to probe for specifically predicted peptides in a biological sample. In addition to the mentorship provided by Dr. Perou and Dr. Glish, the candidate will receive advice and recommendations from an advisory panel consisting of Dr. Jon Serody and Dr. D. Neil Hayes in human T cell immunology and computational biology. The candidate's research will closely follow his mentorship plan as he will use his training in genomics and computational biology to predict LSC-associated mHA, and then confirm their production in leukemia using HPLC-FAIMS mass spectrometry. The long-term goal of this project is to predict and confirm common, immunogenic, LSC-associated mHA, as described in this K08 proposal, and to then develop them as targets for LSC-directed immune therapy. From the research conducted in this proposal, the training, mentorship and academic research infrastructure provided through UNC and its Lineberger Comprehensive Cancer Center the candidate will be able to successfully transition to become in independent NID-funded investigator.

描述（由申请人提供）：本指导临床科学家发展奖（K08）提案的主要目标是发展候选人在白血病生物学和干细胞移植领域的学术生涯。候选人在此申请中建议学习基因组分析和质谱分析的新技能，以便完成一项新的研究调查，以发现白血病干细胞相关的次要组织相容性抗原。自 2009 年转到北卡罗来纳大学以来，该候选人一直受到北卡罗来纳大学医学部 KL2 奖的资助，用于开发用于发现次要组织相容性抗原的生物信息学和免疫学方法。在这项 K08 提案中，候选人指定 Chuck Perou 博士作为他应用 RNA 测序分析的主要导师和顾问，旨在对白血病干细胞相关次要组织相容性抗原（LSC 相关 mHA）进行计算预测。 Perou 博士是癌症基因组学领域的领导者，也是北卡罗来纳大学癌症基因组图谱贡献的领导者。他指导了许多研究生和博士后，并为候选人制定了全面的培训和指导计划，以便他能够发展基因组分析方面的新技能。该候选人还指定 Gary Glish 博士作为共同导师，提供质谱方面的培训和指导。该候选人拥有化学博士学位，但没有接受过质谱方面的专门正规培训。由于质谱分析在抗原发现研究中发挥着至关重要的作用，因此候选人提议将这一领域的培训和研究作为整个 K08 项目的一部分。 Glish 博士是以下大学的教授北卡罗来纳大学化学系和美国质谱学会前任主席。他在其非常成功的职业生涯中指导了众多研究生，并将提供生物分子检测中质谱理论和实践的培训。此外，Glish 博士的实验室还开发并建造了原型高场不对称波形离子迁移谱 (FAIMS) 质谱仪，该质谱仪将首次用于探测生物样品中专门预测的肽。除了 Perou 博士和 Glish 博士提供的指导外，候选人还将获得由 Jon Serody 博士和 D. Neil Hayes 博士组成的顾问小组在人类 T 细胞免疫学和计算生物学方面的意见和建议。该候选人的研究将密切遵循他的指导计划，因为他将利用他在基因组学和计算生物学方面的培训来预测 LSC 相关的 mHA，然后使用 HPLC-FAIMS 质谱法确认它们在白血病中的产生。该项目的长期目标是预测和确认常见的、免疫原性的、LSC 相关的 mHA，如本 K08 提案中所述，然后将它们开发为 LSC 定向免疫治疗的靶点。根据该提案中进行的研究，北卡罗来纳大学及其 Lineberger 综合癌症中心提供的培训、指导和学术研究基础设施，候选人将能够成功过渡成为 NID 资助的独立调查员。