Dr. Michael X. Zhu
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Integrative Biology and Pharmacology
Calcium ions (Ca2+) play a critical role in cell functions ranging from secretion, contraction, to gene expression and programmed cell death. Our research focuses on understanding mechanisms regulating stimulus-evoked intracellular Ca2+ increases and their physiological implications. One area of our research includes functional characterizations of Transient Receptor Potential (TRP) channels. This novel family of ion channels includes ~28 members with diverse functions in mammalian species and they generally serve as sensors for environmental changes inside and outside cells. We focus on studying the roles of TRP channels in Ca2+ signaling and their regulation by Ca2+. We also study the mechanism of regulation and physiological functions of a number of TRP channels including TRPCs, TRPV1, TRPV3, TRPA1, and TRPM8. Some of these channels are involved in pain sensing, especially inflammatory pain. In addition, we aim to identify chemical ligands of therapeutic values for some TRP channels. In a separate study, we investigate molecular mechanism of Ca2+ release from acidic organelles (endosomes and lysosomes). We recently identified two-pore channels (TPC1, TPC2, and TPC3) as receptors for the potent Ca2+ mobilizing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP), expressed in membranes of endolysosomes. We aim to illustrate the roles of two-pore channels and NAADP signaling in overall Ca2+ handling and of endolysosomal Ca2+ regulation in animal cells.
Current projects in my lab include Molecular mechanism of regulation of TRPC channels, high throughput screening of TRPC ligands, and two-pore channels and NAADP receptors in integrative Ca2+ signaling. We use molecular biology, electrophysiology, biochemistry, cell biology, fluorescence imaging, pharmacology, and transgenic animals in our studies. Students will learn basic experimental skills working with ion channels and cell signaling using state-of-the-art technology and become familiarized with mechanisms of signal transduction involving receptors and channels. Students with interests in drug discovery will learn basic skills and knowledge for this area of research.