The study of leukemia has often been at the leading edge of technology advances. Since 2009, and the first characterization of an acute myeloid leukemia (AML) genome, there has been an incredible rise in deep genomic characterization of childhood leukemias, AML and acute lymphoblastic leukemia (ALL). We are still learning about the feasibility of applying the genomic discoveries to the clinical care of pediatric patients with acute leukemia. We are interested in the implementation of clinical genomics, characterization and validation of novel genomic findings, development of biomarkers and correlative biology studies, and development of combination drug approaches for pediatric patients with acute leukemia.
Projects in the laboratory are focused on: 1) Validating novel mutations/alterations in pediatric AML and ALL models 2) Targeting Ras signaling pathway in pediatric acute leukemia, where Ras pathway mutations are the most common somatic mutations 3) Developing combination therapies with MAPK pathway-targeting drugs |
Using a genomic approach, we have identified enzymes of the mitochondrial one-carbon folate pathway as being differentially suppressed with therapy in acute myeloid leukemia (AML). We are now studying the role of this pathway in AML and ALL, using both genetic and chemical approaches. Working with primary patient samples, we are interested in identifying targetable metabolic alterations that can be used for therapy. We are profiling plasma samples from patients with acute leukemia and studying the metabolic alteration of bone marrow microenvironment as it relates to leukemia genomics and response to therapy. We are interested in how metabolic alterations occur in response to chemotherapy and may contribute to chemotherapy resistance. |