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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结/文摘