Research in my laboratory incorporates single-cell approaches to investigate the immune response, using the patch-clamp method to characterize ion channels and a variety of imaging techniques to monitor motility, Ca²⁺ signaling, and gene expression. There are two main directions of research: ion channels and their function in the immune response; and imaging cellular dynamics that underlie the immune response.

We are investigating ion channels that play vital roles in T cell activation, motility, and volume regulation. Five major classes of ion channels have been identified in T cells, including: voltage-gated K⁺ (KV) channels, calcium-activated K⁺ (KCa) channels, calcium-release-activated Ca²⁺ (CRAC) channels, Mg²⁺-inhibited cation (MIC) channels, and swelling-activated Cl- channels. Ongoing experiments are probing molecular and biophysical mechanisms of channel gating and ion permeation, and identifying selective channel blockers. In collaboration with Dr. George Chandy, novel targets and potentially useful therapeutic agents for immunosuppression have been identified. Recently, we identified STIM1 as an important component of the CRAC channel activation process. In addition, we are working on several TRP-related genes to understand their modes of activation.

A second major approach seeks to reveal dynamic interactions between T cells and antigen-presenting cells through imaging techniques. Recent advances in microscopy, development of novel fluorescent probes and labeling methods, and new experimental preparations have created exciting opportunities for the study of lymphocyte motility, chemotaxis, and antigen recognition in the physiological context of the tissue environment. In particular, two-photon laser microscopy has opened a new window to visualize the cellular dynamics of lymphocytes and dendritic cells deep within lymphoid organs. In collaboration with Dr. Ian Parker, members of Cahalan’s group have discovered that T and B cells are highly motile in their native habitat and migrate autonomously as part of their antigen-search strategy. Tissue explants and intravital imaging approaches are providing new insights into the choreography between dendritic cells and T cells during initation of an immune response in vivo. These studies open a new window to visualize the behaviors of individual immune cells within intact organs, and will ultimately lead to clinical applications.