CREB is a transcription factor that is overexpressed in AML cells and is associated with a worse prognosis. CREB requires association with it’s binding partner and histone deacetylase, CBP (CREB Binding Partner). We are developing novel inhibitors that disrupt CREB:CBP interaction in collaboration with experts in medicinal chemistry, structural biology, and computational modeling. The goal is to develop these inhibitors into drugs for patients with AML.

Pediatric CML has unique clinical features that are distinct from adult CML. To study the molecular differences, RNA-seq was performed and identified distinct signaling pathways that differentiate the two diseases. Future studies will focus on the role of these pathways in the pathogenesis of pediatric CML.

One of the known kinases that phosphorylates and activates CREB is pp90RSK (ribosomal S6 kinase). Our laboratory has shown that different RSK isoforms play unique roles during blood cell development and leukemia. Current work focuses on characterizing signaling pathways downstream of RSK isoforms during normal hematopoiesis and AML pathogenesis. In the future, we plan to develop novel inhibitors or RSK.

Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome that results in anemia, congenital abnormalities, and predisposition to cancer. Our laboratory identified that Nemo-like kinase (NLK) is hyperactivated in DBA bone marrow cells. Current work focuses on characterizing signaling pathways downstream of NLK and identifying inhibitors of this kinase for future clinical application.