A recurring motif in cellular physiology and biology is that external chemical or physical stimuli induce changes in the concentration of small molecules that function as “second messengers” within the cell. Cyclic AMP is one such ubiquitous second messenger used by most cells to translate extracellular cues into adaptive changes in cell function.

The regulation of cAMP levels within the cell requires sophisticated molecular structures that continuously gauge its production and degradation. Synthesis of cAMP is mediated by adenylyl cyclases whereas its inactivation is catalyzed by phosphodiesterases (PDEs). The focus of our laboratory is to understand the properties of this signaling machinery and its function during different physiological processes.

This laboratory has contributed to the understanding of the complexity of the cyclase and phosphodiesterase system by identifying and characterizing several genes coding for these enzymes. The overall strategy pursued now is to identify a regulatory module involving cyclases and PDEs, to understand its function within a signaling circuit, and to explore how this circuit mediates physiological processes. 

A wide array of approaches ranging from the enzymology of isolated proteins to genetic inactivation of genes in laboratory animals is used to understand how cyclases and PDEs are regulated and assembled in macromolecular complexes. Efforts are underway to define the role of these signaling modules during activation of inflammatory cells, during differentiation of somatic cells of the gonads, and in the differentiation of germ cells until they fuse during fertilization.