Investigating CD56 signaling in multiple myeloma growth and immune escape

研究多发性骨髓瘤生长和免疫逃逸中的 CD56 信号传导

• 批准号: 10449807
• 负责人: Francesca Cottini
• 金额: $ 25.32万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10449807
• 关键词: Adult; Advisory Committees; Affect; American; Animal Model; Biology; CREB1 gene; Cell Adhesion; Cell Line; Cell physiology; Cell-Mediated Cytolysis; Cells; Characteristics; Clinical; Clinical Sciences; Clinical Trials; Committee Members; Complement; Comprehensive Cancer Center; Cyclic AMP-Responsive DNA-Binding Protein; Cytotoxic T-Lymphocytes; Data; Deubiquitinating Enzyme; Deubiquitination; Development Plans; Diagnosis; Dialysis procedure; Disease; Doctor of Philosophy; Elderly; Gene Expression; Genetic; Genomics; Goals; Grant; Growth; Health Care Costs; Hematology; Hospital Costs; Human; Immune; Immune response; Immune system; In Vitro; Internal Medicine; Knowledge; Leadership; Learning Skill; Length of Stay; MEKs; Malignant Neoplasms; Mediating; Mentors; Minority; Modeling; Molecular Abnormality; Morbidity - disease rate; Multiple Myeloma; Mus; NCAM1 gene; Names; Natural Killer Cells; Neurons; Ohio; Outcome; Oxidative Regulation; Oxidative Stress; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Physicians; Prognosis; Proteins; Quality of life; Recurrence; Recycling; Rehabilitation therapy; Reporting; Research; Resistance; Role; Science; Scientist; Signal Transduction; Surface; Testing; Therapeutic; Toxic effect; Translational Research; Tumor Escape; UCHL1 gene; Universities; Writing; Yang; base; career; career development; cell growth; cell type; cytotoxicity; design; drug development; experience; genomic data; high risk; improved; improved outcome; in vivo Model; individualized medicine; loss of function; overexpression; predictive marker; professor; programs; protein degradation; response biomarker; skills; therapeutically effective; transcription factor; treatment response; tumor; tumor immunology; tumor microenvironment; ubiquitin C-terminal hydrolase

PROJECT SUMMARY/ABSTRACT Francesca Cottini, MD, is a Tenure-eligible Assistant Professor in the Division of Hematology, Department of Internal Medicine (70% research, 30% clinical) at The Ohio State University Comprehensive Cancer Center. Dr. Cottini’s career goal is to become an independent and productive physician scientist whose research will combine aspects of multiple myeloma (MM) pathogenesis and tumor immunology to develop tailored therapies for MM patients. MM is an incurable disease that affects vulnerable adults causing high healthcare costs and poor quality of life. No tailored therapies exist to treat patients with MM, despite major differences in terms of genetic abnormalities, gene expression profiles, or immune signatures. To fill this gap, Dr. Cottini has identified a surface marker, named CD56, which is present in 70 percent of patients and is associated with poor prognosis. Thus far, Dr. Cottini has demonstrated the feasibility of her project with strong preliminary data, showing that CD56 promotes MM growth and tumor escape from the immune system. The main objective of Dr. Cottini’s K08 proposal is to characterize the mechanisms associated with CD56 protumoral phenotype in terms of: 1. MM growth; 2. resistance to anti-MM therapies; 3. regulation of oxidative stress; and 4. escape from natural killer (NK) cell-mediated cytotoxicity. The final step of Dr. Cottini’s proposal is to find strategies to promote CD56 degradation in MM and induce tumor regression. This knowledge will lead to science-driven clinical trials and improve outcomes in high-risk CD56 positive MM patients. To support her pathway to independence, Dr. Cottini has established a mentoring committee consisting of: Drs. Don Benson MD, PhD (Primary Mentor: expertise in MM biology, tumor immunology, and translational and clinical science), Yiping Yang MD, PhD (co-Mentor: expertise in tumor immunology, grant writing, and leadership skills), Bei Liu, PhD (Advisory Committee Member: expertise in MM murine animal models), and Natarajan Muthusamy, DVM, PhD (Advisory Committee Member: expertise in signaling and translational science). She will also take advantages of two additional collaborators, with experience in genomics (Dr. Pearlly Yan) and drug development (Dr. Gerard Hilinski). She formulated a career development plan with objectives of (1) learning skills in tumor immunology, drug development, and animal models; (2) developing knowledge in the analysis and interpretation of genomic data and design of correlatives for clinical trials; (3) improving expertise in leadership, grant writing, and team management. These objectives will complement Dr. Cottini’s current knowledge to help achieving independence as a physician scientist in the field of MM. To conclude, Dr. Cottini’s studies have the potential to identify therapeutic options based on disease characteristics and hence improve outcomes and reduce toxicities in patients.

项目摘要/摘要 医学博士Francesca Cottini是符合任期资格的血液学助理教授， 俄亥俄州立大学的内科学系（70％的研究，30％临床） 癌症中心。 研究将结合多发性骨髓瘤（MM）发病机理和肿瘤免疫学的各个方面 针对MM患者的量身定制疗法。 MM是一种无法治愈的疾病，会影响脆弱的成年人，导致较高的医疗保健成本和质量差 生活。 异常，基因表达谱或免疫特征。 标记为CD56，它存在于70％的患者中，并且预后不良。 远处，库奇蒂尼（Cottini 促进MM生长和肿瘤从免疫系统逃脱。 建议是表征与CD56杂种表型相关的机制：1。mm 生长；抗MM疗法的抗性； 3。 （NK）细胞介导的细胞毒性。 MM的降解并诱导肿瘤回归。 改善高危CD56阳性MM患者的预后。 为了支持她的独立途径，D。Cottini成立了一个指导委员会， ：Drs。 和临床科学），Yiping Yang MD，博士学位（Co-Centor：肿瘤免疫学专业知识，赠款写作和和 领导技能），Bei Liu，博士学位（咨询委员会成员：MM Murine Animal Models的专业知识）和 Natarajan Muthusamy，DVM博士（咨询委员会成员：信号和翻译专业知识 科学）。 Yan）和毒品开发（Gerard Hilinski博士）。 （1）肿瘤免疫学，药物开发和动物模型方面的学习技能； 基因组数据的分析和解释以及临床试验的相关性设计； 在领导力，赠款写作和团队管理中。 知识帮助实现独立 研究有可能根据疾病特征鉴定治疗选择，从而改善 结果并降低患者的毒性。