Research Program

项目总结研究方案 JAX癌症中心(JAXCC)研究计划的首要目标是建立精确的遗传模型 癌症医学，是通过基础研究发现推进精确肿瘤学的愿景 潜在的翻译和临床影响。成员使用不同的、多尺度的策略来解开谜团 复杂的癌症系统的主要成分并调查癌细胞复杂性的驱动因素， 肿瘤进化和肿瘤适应。阐明这些基本的生物过程是 对癌症治疗的不利影响和治疗耐药性的原则性、机械性理解。 在目前的资助期间，我们已经扩大并重塑了日本宇宙航空研究开发中心，使其成为一个新的癌症研究中心 力量，重点是复杂遗传学和功能基因组学。研究围绕三个方面展开 互补的具体目标。目标1试图开发新的生物、细胞和计算模型 癌症，利用日本宇宙航空研究开发机构在模型开发方面的长期优势。AIM 2检查基因组 癌症的不稳定性和遗传复杂性决定了它们在癌细胞中的功能后果。 使用先进的计算方法和基因组技术，我们将询问开发的动物模型 在目标1和患者样本中。目标3研究肿瘤的关键成分和宿主是如何起作用的 对于癌症生物学，研究恶性肿瘤的癌细胞的内在和外在成分。结果 从目标3中的研究，结合目标2中确定的基因改变和目标1中开发的模型， 将使我们能够解开肿瘤和宿主微环境之间的复杂相互作用。53个满贯 JAXCC的项目成员包括巴尔港校区的33名和法明顿校区的20名。 通过强调基础研究、独特的模式开发和技术创新，该计划 利用来自多个NIH IC的资金支持以癌症为重点的研究。最近，我们带来了我们的 通过与SWOG、缅因州癌症基因组学倡议、 希望之城、贝丝以色列女执事医疗中心、康涅狄格大学健康中心和 康涅狄格州儿童医院。该计划由NCI和其他同行的10,401,511美元直接成本支持- 审查了上一预算年度与癌症有关的赠款。在上一个赠款周期中，CCSG基金支持 379份出版物，其中30%是计划内合作，72%是与外部合作。这个 联合项目负责人Karolina Palucka博士和Roel Verhaak博士以及JAXCC领导层的努力 通过定期研究计划会议、补贴旅行等方式促进日本宇宙航空研究开发中心成员之间的互动 在校园和JAXCC年度务虚会之间。JAXCC年度务虚会和每月项目会议 是将来自两个校区的癌症中心成员聚集在一起以开发内部- 方案协作，并参与资源开发和教师招聘的规划。

PROJECT SUMMARY RESEARCH PROGRAM The overarching goal of the JAX Cancer Center (JAXCC) Research Program, Genetic Models for Precision Cancer Medicine, is to advance the vision of precision oncology through basic research discoveries with potential for translational and clinical impact. Members use diverse, multi-scale strategies to deconvolute complex cancer systems to their principal components and to investigate the drivers of cancer cell complexity, tumor evolution, and tumor adaptation. Elucidating these fundamental biological processes are key to a principled, mechanistic understanding of the adverse effects of cancer therapy and of treatment resistance. During the current funding period we have expanded, and reshaped, the JAXCC into a new cancer research force with a focus on complex genetics and functional genomics. Research is organized around three complementary Specific Aims. Aim 1 seeks to develop novel organismal, cellular, and computational models of cancer, drawing on the JAXCC's longstanding strengths in model development. Aim 2 examines the genomic instability and genetic complexity of cancer and determines their functional consequences in the cancer cell. Using advanced computational methods and genomic technologies we will interrogate animal models developed in Aim 1 as well as patient samples. Aim 3 investigates how key components of a tumor and the host contribute to cancer biology, examining the cancer cell intrinsic and extrinsic components of a malignant tumor. Results from studies in Aim 3, integrated with the genetic alterations identified in Aim 2 with models developed in Aim 1, will allow us to deconvolute the complex interactions of the tumor and host microenvironments. The 53 full program members of the JAXCC include 33 on the Bar Harbor campus and 20 on the Farmington campus. Through its emphasis on basic research, unique model development, and technological innovation, the program leverages funding from multiple NIH ICs in support of cancer-focused research. More recently, we brought our technologies into the clinical arena through collaborations with SWOG, the Maine Cancer Genomics Initiative, City of Hope, Beth Israel Deaconess Medical Center, University of Connecticut Health Center, and the Connecticut Children's Hospital. The program is supported by $10,401,511 direct costs in NCI and other peer- reviewed cancer-related grants in the last budget year. Over the last grant cycle, CCSG funds have supported 379 publications including 30% intra-programmatic collaborations and 72% with external collaborators. The efforts of the Co-Program Leaders, Drs. Karolina Palucka and Roel Verhaak, and JAXCC leadership have fostered interactivity among JAXCC members through regular Research Program meetings, subsidized travel between campuses, and the JAXCC Annual Retreat. The annual JAXCC Retreat and monthly program meetings are the primary forums that bring together Cancer Center members from both campuses to develop intra- programmatic collaborations and to participate in the planning for resource development and faculty recruitment.