Kwame Ohene-Frempong Chair on Sickle Cell Anemia and Professor of Pediatrics – Children’s Hospital of Philadelphia (CHOP).

Personal Statement

I have a long-term expertise in the pathophysiology and genetics of several murine models of hematopoiesis-, inflammation-, and iron-related disorders as well as in the use of lentiviral vectors for modulation of gene expression and gene transfer for the cure of hemoglobinopathies as indicated by several publications (see specific sections) and reviews (at the end of this section). I characterized the role of seminal factors contributing to the morbidity and mortality in ß-thalassemia, sickle cell anemia, Polycythemia vera, hemochromatosis and in anemia of inflammation, such as such hepcidin, intereleukin-6 and ferroportin (see Iron metabolism and inflammation), the phosphokinase Jak2 and macrophages (see Erythropoiesis). Based on some of these studies, I have developed or contributed to the characterization of novel therapeutics (see Development of novel therapeutics for hemoglobinopathies and iron disorders). I generated the first lentiviral vector that corrected the hemoglobin synthesis in ß-thalassemia animals (May C et al, Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin, Nature, 2000), the first murine model of adult ß-thalassemia major and establish a system to characterize lentiviral vectors expressing the normal ß-globin gene in mice and patient cells (see section “Gene therapy for hemoglobinopathies”). I’m currently working on getting approval from the FDA to use our lentiviral vector for the cure of beta-globinopathies and establishing international relationships to potentially extend this cure outside USA and Europe. For my research, I have been awarded the New Investigator Award at the International Society of Experimental Hematology, the Sultan bin Khalifa International Thalassemia Federation Award, the Marcel Simon Award from the International BioIron Society (IBIS), numerous travel and fellowship awards from several international scientific societies, grants from the Cooley’s Anemia Foundation, Roche Foundation for Anemia Research (RoFAR) and 8 grants from the National Institutes of Health (NIH) as a PI. The successful completion of these grants taught me to efficiently administer the corresponding projects (e.g. staffing, research protections, budget) and allowed me to establish several international scientific relationships. I am presently holding one RO1 grant from the NIH and additional international and research sponsored grants to advance my work. As a result of these previous experiences, I am aware of the importance of frequent communication among project members and of constructing a realistic research plan, timeline, and budget. I am presently an active member of the International BioIron Society (IBIS), American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Gene and Cell Therapy (ASGCT).

I am very committed to pre-doctoral and post-doctoral training since, in the last 10 years, I have trained 10 and 9 pre- and post-doctoral fellows. Some of them have been supported by T32 programs. Many of them (>80%) transitioned into careers in the biomedical research workforce, consistent with trainees’ skills, interests, and values. In the last several years, I have been the Discussion Leader on “Peer Review” for our Responsible Conduct of Research sessions and CHOP and Penn to PhD, MD and MD-PhD students where unbiased experimental design, methodology, analysis, interpretation, and reporting of results are discussed. In addition, I revise these topics every with members of my laboratory. I have been a permanent member for F study session for many years. With respect to this application I can provide training in the areas of erythropoiesis, iron metabolism, hemoglobinopathies and novel therapeutic approaches (novel drugs and gene therapy techniques) that are associated with benign hematological disorders such as beta- and alpha-thalassemia and sickle cell disease. In addition, I can provide training the analysis of in the interaction between abnormal red cells (like in sickle cell anemia), hemolysis, iron, oxidative stress and other hematopoietic cells associated with hemostasis and thrombosis. In addition, in the last decade, I have been teaching the subject of normal and aberrant erythropoiesis and iron metabolism to PhD, MD and MD/PhD students (in US and foreign countries), using our models and results to explain the pathophysiology of many human diseases and the emerging new therapies.

• Rivella S. (2015) β-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies. Haematologica. PMID: 25828088; PMCID: PMC4380714
• Dong AC, and Rivella S. (2017). Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia. Advances in Experimental Medicine and Biology. PMID: 29127680; PMCID: PMC5718882
• Muckenthaler MU, Rivella S, Hentze MW, Galy B. (2017) A Red Carpet for Iron Metabolism. Cell. PMID: 28129536; PMCID: PMC5706455
• Crielaard BJ, Lammers T, and Rivella S. (2017) Targeting iron metabolism in drug discovery and delivery. Nature Reviews Drug Discovery. PMID: 28154410; PMCID: PMC5455971