Abby Green, MD

Assistant Professor of Pediatrics
Assistant Professor of Pathology and Immunology

Keywords:

pediatric cancer, genome instability, endogenous DNA damage in leukemia

Research:

Cancer develops through accumulation of DNA mutations and structural aberrations collectively known as genome instability. Genome damage in adult-onset malignancies can be traced to exogenous carcinogens or simply the process of aging. However, pediatric cancers do not arise as a result of aging or exogenous genotoxic agents. We are interested in the etiology of genome instability in pediatric cancers and the resulting genome-protective responses, also called DNA damage responses, that are activated. Our long-term goal is to identify factors within DNA damage response signaling pathways that represent therapeutic vulnerabilities in order to develop new treatment options for children with cancer. Our current investigations are centered around two etiologies of endogenous DNA damage in leukemia: (1) APOBEC3 enzymes, DNA cytosine deaminases that are expressed at high levels in acute myeloid leukemia, and (2) MLL (KMT2A) gene rearrangements that drive infant acute lymphoblastic leukemia. Projects: 1. Functional whole-genome knock out screen to evaluate synthetic lethality with APOBEC3A expression in leukemia. 2. Impact of APOBEC3A on DNA replication. 3. DNA damage responses elicited by MLL gene rearrangements in infant leukemia. 4. Impact of APOBEC3 enzymes on normal and malignant hematopoiesis.

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