Omar I. Abdel-Wahab, MD

As a postdoctoral fellow in Ross Levine’s lab (also part of HOPP), Dr. Abdel-Wahab was instrumental in identifying the clinical, prognostic, and biological significance of mutations in a number of epigenetic modifiers newly identified in patients with acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasms. For instance, he identified that mutations in the gene ASXL1 are loss-of-function mutations that are correlated with genome-wide abundance of the transcriptionally repressive histone H3 lysine 27 methylation. This discovery then led to the identification of ASXL1 as a critical mediator of Polycomb-mediated repression in hematopoietic cells. Further creation of a novel conditional knockout model of ASXL1 in mice revealed a number of important functions of ASXL1 in development and hematopoiesis. Current areas of investigation include:

• Functional characterization of ASXL2 in development and cancer through use of a novel conditional knockout mouse model, and biochemical and epigenomic studies
• Creation of genetically accurate mouse models of MDS for biological and preclinical therapeutic studies using the ASXL1conditional knockout mouse model
• Functional characterization of mutations in spliceosome through use of novel conditional mouse models
• Genomic and epigenomic studies in clinically annotated chronic lymphocytic leukemia patient cohorts
• Pharmacodynamic, pharmacokinetic, and biochemical studies of RAS-RAF-MEK inhibition in primary samples from patients with hairy cell leukemia