Khaled Machaca   Associate Dean for Research

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 becoming 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 interfering with the function of the dual specificity phosphatase Cdc25C, a central player in the regulation of meiotic progression.

Publications

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Funding awarded

  • Interplay Between Ca2+ Release and Ca2+ Entry Pathways in Hypertension-Induced Vascular Remodeling  awarded by Qatar National Research Fund Principal Investigator 2015 - 2018

Background

Contact

Primary Email

  • khm2002@qatar-med.cornell.edu