Hematologic Malignancies

血液系统恶性肿瘤

基本信息

批准号：
10666390
负责人：
Thomas J Kipps
金额：
$ 3.26万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10666390
关键词：
ADAR1 Acceleration Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Address Area Biological Assay Biological Response Modifier Therapy Biology Blood California Cancer Center Cancer Center Support Grant Cancer Relapse Catchment Area Cell Culture Techniques Cell Therapy Cells Clinic Clinical Clinical Research Clinical Trials Clonal Evolution Code Cryopreservation DNA DNA Sequence Alteration Development Disease Dissection Dysmyelopoietic Syndromes Epigenetic Process Erinaceidae Funding Genes Genetic Goals Hematologic Neoplasms Hematopoiesis Hispanic Populations Human Impairment Innate Immune Response JAK2 gene Lymphoma Malignant Neoplasms Malignant lymphoid neoplasm Marrow Medicine Mission Modeling Molecular Target Monoclonal Antibodies Multiple Myeloma Myeloproliferative disease Pathogenesis Pathway interactions Patient-Focused Outcomes Patients Peer Review Phase Phase I Clinical Trials Phase II Clinical Trials Phenotype Preleukemia Property Proteomics Publications RNA Editing RNA Processing RNA Splicing ROR1 gene Regenerative Medicine Regulation Relapse Research Research Institute Research Personnel Resistance Resource Sharing Ribosomes Sampling Schools Scientist Signal Pathway Signal Transduction Somatic Mutation Source Spliceosomes Stem Cell Research Strategic Planning Surrogate Endpoint T-Lymphocyte Technology Testing Therapeutic Therapeutic Index Transgenic Organisms Translating Translational Research Transplantation Treatment Side Effects United States National Institutes of Health Untranslated RNA adaptive immune response biobank cancer stem cell carcinogenesis clinical development clinical translation diagnostic assay epigenome functional genomics hip replacement arthroplasty humanized mouse improved improved outcome inhibitor insight leukemia leukemia/lymphoma lymphoid neoplasm member mouse model mutant nanoproteomic neoantigens novel novel strategies novel therapeutic intervention novel therapeutics pharmacokinetics and pharmacodynamics phase I trial pre-clinical precision medicine premalignant prevent professor programs relapse risk risk mitigation self-renewal small molecule stem cell biology stem cells therapeutic target therapy resistant transcriptome transcriptomics tumor progression whole genome

项目摘要

HEMATOLOGIC MALIGNANCIES PROGRAM ABSTRACT The overarching goal of the Hematologic Malignancies Program (HEM) is to advance the treatment of hematologic malignancies and reduce the side effects of treatment through the conduct of translational and clinical research performed by HEM members and collaborators. This will be accomplished by providing a clinically tractable understanding of somatic mutational, epigenetic, and proteomic drivers of myeloid and lymphoid neoplasm pathogenesis, using whole genome, epigenome, whole transcriptome and Nano- proteomic assays, and developing effective small molecule, biologic, and/or cellular therapies for patients that mitigate the risk of relapse. The program is led by Thomas Kipps (Professor, Medicine) a nationally recognized investigator in lymphoid malignancies, who founded the program, and Catriona Jamieson (Professor, Medicine) a cancer-stem-cell biologist focused on myeloid malignancies who joined Kipps in 2013 to broaden the program’s research scope and capabilities. HEM received an outstanding rating during the last CCSG renewal. The program’s scientific aims are to 1) use functional genomics, single cell transcriptomics, epigenetics, and proteomics to identify somatic DNA mutations, coding and non-coding RNA processing and ribosomal alterations in myeloproliferative neoplasms, myelodysplastic syndrome, leukemia, multiple myeloma, and lymphoma that promote therapeutic resistance and/or relapse, with a particular emphasis on cancer-stem- cell biology; 2) generate niche-relevant cell culture, transgenic, and/or humanized mouse models of pre- leukemia, leukemia, lymphoma, or myeloma to improve our understanding of the pathogenesis of disease, and validate somatic DNA, RNA processing alterations and aberrant signaling pathways as therapeutic targets; and 3) test promising new approaches in Phase l/ll clinical trials with pharmacokinetic and pharmacodynamics studies that examine whether the targeted molecular pathways are inhibited by therapy and establish surrogate endpoints for activity of novel therapeutic strategies for patients with myeloid or lymphoid malignancies, providing information for later-stage clinical trials. These aims align with the mission of the MCC, which is to mitigate the risk of developing cancer and improve the outcomes of patients with cancer within and beyond the catchment area; this represents a major focus of the strategic plan. The program’s 39 members represent 10 departments and 2 schools at UCSD, and 2 institutes: the La Jolla Institute (LJI) and The Scripps Research Institute (TSRI). In 2017, members had $15.4M (annual DC) in cancer-focused peer-reviewed funding of which $2.4M was from NCI; $13.0M was from other peer-reviewed agencies including other NIH sources and the California Institute for Regenerative Medicine (CIRM). During the project period, members have been involved in clinical translation of 5 Moores Cancer Center discoveries, authored 390 cancer-relevant publications, of which 63 (16%) were intra- programmatic, 76 (19%) were inter-programmatic, and 146 (37%) were collaborative with investigators from other NCI Cancer Centers.

血液系统恶性肿瘤项目摘要血液恶性肿瘤计划 (HEM) 的总体目标是推进以下疾病的治疗：血液恶性肿瘤并通过进行转化和减少治疗的副作用 HEM 成员和合作者进行的临床研究将通过提供对骨髓和骨髓细胞的体细胞突变、表观遗传和蛋白质组驱动因素的临床易于理解淋巴肿瘤发病机制，利用全基因组、表观基因组、全转录组和纳米蛋白质组学测定，并为患者开发有效的小分子、生物和/或细胞疗法该计划由托马斯·基普斯（Thomas Kipps）（医学教授）领导，是一个全国性的项目。公认的淋巴恶性肿瘤研究人员，他创立了该项目，Catriona Jamieson（教授，医学）一位癌症干细胞生物学家，专注于骨髓恶性肿瘤，于 2013 年加入 Kipps，以拓宽研究领域该项目的研究范围和能力在上届 CCSG 中获得了出色的评价。该计划的科学目标是 1) 使用功能基因组学、单细胞转录组学、表观遗传学和蛋白质组学，用于识别体细胞 DNA 突变、编码和非编码 RNA 加工和骨髓增生性肿瘤、骨髓增生异常综合征、白血病、多发性骨髓瘤中的核糖体改变和促进治疗耐药和/或复发的淋巴瘤，特别强调癌症干细胞细胞生物学；2)生成预-相关的细胞培养物、转基因和/或人源化小鼠模型白血病、白血病、淋巴瘤或骨髓瘤，以提高我们对疾病发病机制的了解，以及验证体细胞 DNA、RNA 加工改变和异常信号通路作为治疗靶点； 3) 通过药代动力学和药效学研究在 l/ll 期临床试验中测试有前景的新方法检查靶向分子途径是否被治疗抑制并建立替代骨髓或淋巴恶性肿瘤患者新治疗策略活动的终点，提供这些目标与 MCC 的使命一致，即减轻患癌症的风险并改善学区内外癌症患者的治疗结果领域；这代表了该计划的 39 名成员代表 10 个部门。加州大学圣地亚哥分校 (UCSD) 的 2 所学校以及 2 个研究所：拉霍亚研究所 (LJI) 和斯克里普斯研究所 (TSRI)。 2017 年，成员获得了 1540 万美元（年度 DC）的癌症同行评审资金，其中 240 万美元来自 NCI；1300 万美元来自其他同行评审机构，包括其他 NIH 来源和加州研究所再生医学（CIRM）项目期间，成员参与了再生医学的临床翻译。 5 摩尔癌症中心的发现，撰写了 390 篇与癌症相关的出版物，其中 63 篇 (16%) 是内部发表的程序性的，76 例 (19%) 是程序间的，146 例 (37%) 与来自以下国家的研究人员合作：其他 NCI 癌症中心。