The Means Laboratory is interested in the study of cell signaling cascades that regulate cell proliferation, differentiation, or function and how alterations in these pathways contribute to oncogenesis.

It is hoped that an understanding of these pathways may provide clues to novel targets that may be amenable to the drug-discovery process.

Current Major Projects Under Investigation 

• The cellular mechanisms that govern regulation of the “CaM kinase cascade” that includes CaMKKß, CaMKIV, and CaMKI. CaMKK and CaMKIV modify the activities of transcriptional components such as CREB and CBP, and these calcium-mediated signaling cascades affect cell fate decisions. Examples of such decisions include apoptosis, differentiation, and self-renewal of hematopoietic stem cells. On the other hand, CaMKK and CaMKI regulate the G1/S transition of the cell cycle by activating the cyclin D/Cdk4 complex.
• Evaluating the pathways that are involved in regulating cell migration and invasiveness. One project investigates the protein kinase MLK3 and how it is involved in the cascade of events by which small G proteins such as Rac and Rho control directed cell movements via changes in the cytoskeleton.
• Examining the role of the prolyl isomerase Pin1 in oncogenesis. Studies are focused on the Ras-mediated pathways involving Pin1 that control accumulation of oncoproteins such as Myc and cyclin E and how these pathways participate in mouse and human cell transformation and tumorigenesis.