Mark P. Kamps, Ph.D.

Research

My laboratory is interested in the molecular mechanisms used by human oncogenes to prevent differentiation of hemopoietic stem cells and cause progenitor cell leukemias. We are particularly interested in how coexpression of the HoxA9 and Meis1 homeodomain transcription factors causes acute myeloid leukemia (AML) and how the human oncoprotein Nup98-Nsd1 activates transcription of HoxA9 and Meis1 in AML. To evaluate the myeloid transforming ability of oncoproteins, we use a well-characterized mouse model in which mice are transfused with marrow stem cells infected by retrovirus-expressing oncoproteins, such as HoxA9 and Meis1. These mice acquire AML within 5 months. We model myeloid transformation using a novel myeloid progenitor assay that employs conditional oncoproteins, allowing us to control differentiation at the morphologic and genetic level by turning the oncoprotein on or off. We use genomic approaches to identify important target genes, transcription/promoter assays to deduce biochemical mechanisms of oncoprotein-mediated gene activation, and mutational analysis to interrelate transcription activities with myeloid leukemogenesis activity. Our long-term goal is to identify oncoprotein activities required for leukemogenesis, which then represent new drug targets for human AML therapies.