01 - Cancer Biology & Immunology

01 - 癌症生物学

基本信息

批准号：
10411027
负责人：
SUNIL SUDARSHAN
金额：
$ 5.21万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-03-28 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10411027
关键词：
ATAC-seq Abbreviations Acarbose Achievement Acute Myelocytic Leukemia Alabama Basic Science Bioinformatics Shared Resource Biological Assay Biometry Bone Marrow CD4 Positive T Lymphocytes CXCL12 gene CXCR4 gene Cancer Biology Cancer Center Support Grant Cancer Control Cancer Prognosis Catchment Area Cell physiology Cells Cellular biology Chronic Myeloid Leukemia Clinical Sciences Clinical Trials Collaborations Community Outreach Comprehensive Cancer Center Doctor of Philosophy Epigenetic Process Exhibits Flow Cytometry Funding Future Gene Expression Genetic Genetic Engineering Genetic Transcription Genomics Shared Resource Goals Grant Heparanase inhibitors Histone Deacetylase Histone Deacetylase Inhibitor Imaging Techniques Immune Immune response Immunity Immunologist Immunology Immunology procedure Impairment In Situ Infrastructure Intestines Investigational Therapies Journals Knowledge Lead Leadership Link Location Malignant Neoplasms Malignant neoplasm of ovary Mediating Medicine Metabolic Metabolism Microscopy Modeling Multiple Myeloma Neuroendocrine Tumors Obesity Oxidative Stress Pathway interactions Peer Review Grants Pharmaceutical Preparations Phase I Clinical Trials Phenotype Population Sciences Positron-Emission Tomography Program Appropriateness Proteomics Shared Resource Publications Publishing Regulation Regulatory T-Lymphocyte Renal Cell Carcinoma Renal carcinoma Research Research Activity Research Personnel Resistance Resource Development Resource Sharing Role Services Site Strategic Planning Surgical Oncologist Sushi Domain Technology Testing Therapeutic Tissue Procurements Training Training and Education Transgenic Organisms Translational Research Tumor Biology Tumor Burden Tumor Cell Biology Tumor Immunity Tumor-Derived Tumor-Infiltrating Lymphocytes Tumor-infiltrating immune cells Tyrosine Kinase Inhibitor Urology alpha ketoglutarate animal imaging anti-tumor immune response anticancer research cancer cell cell type clinical center community engagement drug development drug discovery epigenome high throughput screening human imaging inhibitor interest leukemic stem cell malignant breast neoplasm meetings member microbiome mitochondrial metabolism neoplastic cell neuro-oncology novel strategies novel therapeutic intervention novel therapeutics nutrition patient derived xenograft model programs receptor single-cell RNA sequencing stem cells structural biology symposium therapy outcome tumor tumor behavior tumor growth tumor immunology tumor metabolism tumor microenvironment tumor progression urologic

项目摘要

ABSTRACT – CANCER BIOLOGY AND IMMUNOLOGY (CBI) PROGRAM Overview and Goals: The goals of the Cancer Biology and Immunology (CBI) program are to identify basic mechanisms of cancer cell biology and the immune response in order to develop novel therapeutic approaches to treat cancer. In particular, CBI members are interested in the transcriptional and epigenetic mechanisms controlling tumor and immune cell function, the impact of metabolism and metabolites on tumor and immune cell biology, and the role of the microenvironment in tumor biology and immune activity. Research Highlights: CBI investigators recently showed that the CXCL12/CXCR4 axis is an important target in both Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML). Targeting CXCR4 on AML promotes oxidative stress and terminal differentiation of leukemic stem cells (Cell Rep. 20201), whereas blockade of CXCL12 combined with tyrosine kinase inhibitors eliminates CML stem cells (Cell Stem Cell 20192). CBI investigators also defined how metabolites influence tumor and immune cell activities: tumor-derived L-2-hydroxyglutarate influences renal cancer progression and prognosis (Clin. Cancer Res. 20183), and alpha-ketoglutarate regulates the differentiation and function of CD4 T cells (Immunity 20174). Mechanistic discoveries by CBI investigators have led to therapeutics that are now being tested in clinical trials, including a heparanase inhibitor for multiple myeloma (Haematologica 20185) and a DNMT1 inhibitor for MDS and AML (NCT04167917). Program Activities: CBI catalyzes intra- and inter-programmatic interactions via monthly meetings, annual retreats, and seminars. Technology forums introduce members to new and existing capabilities of the Shared Resources, and members' discoveries are advanced from the bench to Phase I clinical trials through pilot funding from the Alabama Drug Discovery Alliance and the O'Neal Invests program. Members: CBI has 57 members from 16 Departments/Divisions who have a combined $5.2M in NCI funding and $10.1M in total cancer-relevant, peer- reviewed grants. In the current cycle, CBI members published 693 cancer-relevant publications, of which 39% were inter-programmatic and 23% were intra-programmatic collaborations and 18% of which are in journals with impact factor of 9 or greater. Future Directions: In line with the O'Neal strategic plan, CBI will focus on the role of obesity and metabolism in regulating cancer progression and the anti-tumor immune response. Of the 13 cancers linked with obesity, CBI investigators already have strength in tumor biology and anti-tumor immunity in multiple myeloma, renal, breast, and ovarian cancers, and we expect that these efforts will lead to collaborative, multi-PI grants in the next funding period. These cancers overlap with those being targeted by our Community Outreach and Engagement office, in part due to their relevance to the catchment area. Finally, CBI members will leverage imaging techniques developed by ET to follow tumor cell activity and immune cell reactivity in situ.

摘要 - 癌症生物学和免疫学（CBI）计划概述和目标：癌症生物学和免疫学（CBI）计划的目标是确定基本为了开发新型治疗方法，癌细胞生物学和免疫响应的机制治疗癌症。特别是，CBI成员对转录和表观遗传机制感兴趣控制肿瘤和免疫细胞功能，代谢和代谢物对肿瘤和免疫细胞的影响生物学以及微环境在肿瘤生物学和免疫反应性中的作用。研究亮点：CBI 研究人员最近表明，CXCL12/CXCR4轴是两个急性髓样的重要靶标白血病（AML）和慢性髓样白血病（CML）。将CXCR4靶向AML会促进氧化应激白血病干细胞的终末分化（细胞Rep。20201），而CXCL12的桶合并酪氨酸激酶抑制剂消除了CML干细胞（细胞干细胞20192）。 CBI调查人员也定义了代谢产物如何影响肿瘤和免疫细胞活性：肿瘤来源的L-2-羟基戊二酸肾脏会影响肾脏癌症的进展和预后（Clin。CancerRes。20183），α-酮戊二酸α-调节 CD4 T细胞的分化和功能（Immunity 20174）。 CBI调查人员的机械发现导致现在正在临床试验中测试的治疗，包括多个肝素酶抑制剂 MDS和AML的骨髓瘤（Haematologica 20185）和DNMT1抑制剂（NCT04167917）。程序活动：CBI通过每月会议，年度务虚会和半人物。技术论坛向成员介绍共享资源的新功能和现有功能，以及成员的发现是通过从板凳上到I期临床试验的。阿拉巴马州药物发现联盟和奥尼尔投资计划。成员：CBI有16名的57名成员总共有520万美元的NCI资金和1,010万美元与癌症相关的部门/部门审查的赠款。在当前周期中，CBI成员发表了693个与癌症相关的出版物，其中39％是程序间的，23％是策略内的合作，其中18％是在与影响因子9或更高。未来的方向：符合奥尼尔战略计划，CBI将重点关注该角色肥胖和代谢在控制癌症进展和抗肿瘤免疫反应方面。 13 与肥胖有关的癌症研究人员已经在肿瘤生物学和抗肿瘤免疫方面具有强度多发性骨髓瘤，肾脏，乳房和卵巢癌，我们希望这些努力将导致协作，在下一个资金期间，多PI赠款。这些癌症与我们社区所针对的癌症重叠外展与参与办公室，部分原因是它们与集水区有关。最后，CBI成员将 ET开发的利用成像技术遵循肿瘤细胞活性和原位免疫球反应性。