Laboratory of Cell and Molecular Signaling

The Laboratory of Cell and Molecular Signaling was established in July 1998 through a collaborative effort of The Queen’s Medical Center and the University of Hawaii. The LCMS is headed by Andrea Fleig, Ph.D. and Reinhold Penner, M.D. Ph.D. and located within the University of Hawaii Tower on the campus of The Queen’s Medical Center.

The Science

Practically every cell type uses calcium to control a plethora of vital cellular responses. The LCMS focuses on various aspects of calcium signaling in electrically excitable as well as non-excitable cells using electrophysiology, fluorimetry, flow cytometry, molecular biology, and pharmacology.

Our approach to study signaling events is mainly at the single-cell level. The patch-clamp technique has revolutionized cellular physiology since its introduction in the early 1980’s (it earned its developers Erwin Neher and Bert Sakmann the Nobel Prize for Physiology or Medicine in 1991).

This electrophysiological technique allows investigators to assess important parameters such as ionic currents of a whole cell or even down to the molecular level of single ion channels, cell membrane potential, secretory mechanisms resolving even the fusion of a single secretory vesicle.

When combined with microfluorimetry and digital imaging techniques, the method can be used to measure the spatio-temporal aspects of intracellular levels and distribution of ions such as calcium, sodium, or chloride, changes in pH, and even production and movement of signaling molecules.

In the LCMS, these techniques are complemented by additional methods from areas such as biochemistry and genetics. Together, these techniques and tools provide the methodological framework to investigate signaling pathways at the cellular or molecular level in native systems (cell lines, primary and tissue cultures, brain slice preparations), in genetically modified systems (transient and/or stable transfections of cells), and in primary cells derived from transgenic animals.

General Overview

The laboratory’s work has concentrated on various aspects of calcium signaling in electrically excitable as well as non-excitable cells. Its mainstay is the elucidation of calcium signaling and Calcium-Release-Activated-Calcium channels (CRAC) in immune responses. This line of work has been expanded to microglia, the immune cells of the brain, which play an important role in neurodegenerative diseases. Another focus investigates the regulation of inositol-signaling pathways. We have also started to correlate calcium signaling and cell proliferation, which may lead to identify a central role of this ion in apoptotic cell death and tumorigenesis. Recently, we have initiated a project concerning the physiological function of four novel ion channels of the Transient-Receptor Potential (TRP)-family involved in calcium homeostasis, specifically TRPM2, TRPM4, TRPM5 and TRPM7.