Khaled Machaca

Calcium Signaling Pathways

Research Summary:

The Machaca Lab is interested in the regulation of Ca2+ signaling pathways under both physiological and pathological conditions. Ca2+ signals are ubiquitous and are involved in a plethora of cell physiological processes including fertilization, cell proliferation, and gene expression. Our interest in the basic cellular and molecular mechanisms of Ca2+ signaling is framed in the context of several projects that the Lab is presently focused on.

We have a long standing interest in the regulation and remodeling of Ca2+ signaling pathways during the meiotic cell cycle. Before fertilization competent oocytes undergo a maturation period - oocyte maturation - which encompasses entry into meiosis and dramatic remodeling of Ca2+ signaling pathways. This is a physiologically attractive model because a Ca2+ signal at fertilization is the universal trigger to induce egg activation in all sexually reproducing species tested to date. We are interested in the mechanisms mediating this molecular remodeling of Ca2+ signals during meiotic maturation. Such remodeling includes the IP3-dependent Ca2+ release, the plasma membrane Ca2+-ATPase at the cell membrane, and store-operated Ca2+ entry (see Figure). Ongoing projects in the Lab are focused on understanding the regulation of IP3-dependent Ca2+ release and store-operated Ca2+ entry (SOCE) during the meiotic cell cycle. This includes the basic molecular regulation of the two key molecules in SOCE, STIM1 and Orai1. STIM1 is the ER Ca2+ sensor that detects Ca2+ store depletion and activates the plasma membrane channel Orai1. We are further interested in the regulation of the IP3 receptor during hypertension in vascular smooth cells in a collaborative project with the Rusch Lab.

We are also interested in the regulation of the cell division phase by transition metals. We have discovered that transition metal chelation arrests the meiotic cell cycle through i with the function of the dual specificity phosphatase Cdc25C, a central player in the regulation of meiotic progression.