AACR Gertrude B. Elion Cancer Research Award
The AACR Gertrude B. Elion Cancer Research Award represents a joint effort to encourage and support tenure-eligible junior faculty. The research proposed for funding must focus on research in cancer etiology, diagnosis, treatment, or prevention and may be basic, translational, or clinical in nature.
Esther Obeng, MD, PhD
St. Jude Children’s Research Hospital
Targeting SF3B1 in myeloid malignancies
Scientific Statement of Research
RNA splicing factor mutations are the most common acquired mutations in myelodysplastic syndrome (MDS), a hematopoietic stem cell (HSC) disorder with a high risk of progression to acute myeloid leukemia (AML). MDS and AML are inherently resistant to conventional chemotherapy. Understanding how splicing factor mutations transform HSCs into pre-leukemic cells will enable the development of less toxic, targeted therapies. SF3B1 is the most commonly mutated splicing factor, and SF3B1 mutations frequently co-occur with mutations in the epigenetic regulator, TET2. Dr. Obeng previously demonstrated that mutant SF3B1 is sufficient to cause MDS, that SF3B1 and TET2 mutations cooperate to cause more aggressive MDS, and that SF3B1-mutant cells are selectively killed by spliceosome-inhibitors. She will use isogenic cell lines, mouse models, and patient samples to determine how splicing factor and epigenetic modifier mutations cooperate to cause MDS and to identify synergistic pathways that cooperate with spliceosome inhibition to target splicing factor-mutant cells.
Dr. Obeng is an assistant member in the oncology department and a stem cell transplant attending at St. Jude Children’s Research Hospital. She obtained a BS and PhD (mentor, Dr. Lawrence Boise) from the University of Miami (Coral Gables, FL), and an MD from the University of Miami School of Medicine. She completed a pediatrics residency at Boston Children’s Hospital/Boston Medical Center and a pediatric hematology/oncology fellowship at the Dana-Farber Cancer Institute. Her postdoctoral training with Dr. Benjamin Ebert examined the pathobiology of splicing factor mutations in myelodysplastic syndromes. The Obeng laboratory focuses on identifying novel treatments for myeloid malignancies.
Acknowledgement of Support
It is a great honor to accept the 2019 AACR Gertrude B. Elion Cancer Research Award, which will help me establish my career. This award will support talented personnel and enable cutting-edge experiments designed to identify novel, targeted therapies that will cure myelodysplastic syndromes and prevent secondary acute myeloid leukemia.
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