Investigating CD56 signaling in multiple myeloma growth and immune escape

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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.