Leukemia Stem Cell Antigen Discovery Using Advanced Genomic and Proteomic Methods

描述（由申请人提供）：本临床科学家导师发展奖（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。候选人在本申请中提出学习基因组分析和质谱分析的新技能，以完成一项新的研究，发现白血病干细胞相关的次要组织相容性抗原。自2009年进入北卡罗来纳大学以来，该候选人获得了北卡罗来纳大学医学部KL2奖的资助，致力于开发用于次要组织相容性抗原发现的生物信息学和免疫学方法。在这个K08提案中，候选人已经确定Chuck Perou博士作为他的主要导师和顾问，在RNA测序分析的应用中，旨在计算预测白血病干细胞相关次要组织相容性抗原（LSC-associated mHA）。他是癌症基因组学领域的领导者，也是UNC对癌症基因组图谱的贡献的领导者。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，使他能够在基因组分析方面发展新的技能。候选人还确定了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正式培训。由于质谱法在抗原发现研究中起着至关重要的作用，候选人建议将该领域的培训和研究作为整个K08项目的一部分。格里什博士是……的教授

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.