Our lab focuses on the prototypical second messenger cyclic AMP (cAMP). Adenylyl cyclases produce cAMP, and in mammalian cells there are two distinct classes of adenylyl cyclase, a family of heterotrimeric G-protein responsive, transmembrane adenylyl cyclases (tmACs; ADCY1-9) and the bicarbonate-regulated soluble adenylyl cyclase (sAC; ADCY10). Our combined laboratory purified and cloned sAC. Despite its more recent discovery, sAC represents the primordial cyclase in mammals. In contrast to tmACs, which are modulated by heterotrimeric G proteins in response to extracellular signals acting through seven-transmembrane spanning, G protein-coupled receptors, sAC is directly regulated by intracellular signals such as bicarbonate and calcium ions. In biological systems, carbonic anhydrases equilibrate bicarbonate ions with carbon dioxide and pH nearly instantaneously. Via this equilibrium, sAC and sAC-like cyclases throughout all kingdoms of life serve as “Natures carbon dioxide/bicarbonate/pH sensors.”
Our laboratory studies sAC-dependent physiologic processes using genetically modified knockout and knock-in mouse models, cell-lines, antibodies, and multiple selective pharmacologic inhibitors developed in the lab. Current projects can be separated into to two broad categories: discovery of sAC physiologic functions and drug discovery efforts.
In mammals, sAC is most abundantly expressed in male germ cells, and it is proven to be essential for male fertility in mice and men. sAC is responsible for generating the cAMP which is required for sperm motility and the maturation processes that occur after ejaculation during transit through the female reproduction tract. In addition to studying these sAC-dependent, cAMP mediated processes, we are attempting to develop sAC specific inhibitors into novel, non-hormonal contraceptives for men and women. (See Figure)
Updated June 25, 2026