Our laboratory studies the organization, assembly, and dynamics of membrane-delimited signal transduction pathways. We presently study this in the context of two very important systems: (1) voltage-gated K+ channels (Kv) channels in the cardiovascular system, and (2) odorant signaling proteins in olfactory system.
In the cardiovascular system, Kv channels are essential for the control of resting membrane potential and the shaping of action potentials. The steady-state expression levels of Kv channels in cardiovascular tissues modulate cellular excitability and are altered in pathophysiological states such as chronic atrial fibrillation. Although much is known about the structure and function of these important proteins, surprisingly little is known regarding the regulation and mechanisms that control trafficking into and out of the plasma membrane. We combine molecular biology, electrophysiology and state-of-the-art fluorescence microscopy to study the molecular machinery and the modulatory mechanisms regulating the surface density of Kv channels in cardiac myocytes.
A second focus in our laboratory is the olfactory system. Olfactory dysfunction in the general population is frequent, affecting at least 2.5 million people in the U.S. alone. In at least 20% of the cases the etiology of the chemosensory disturbance cannot be identified. Recently, we were one of the first to demonstrate olfactory dysfunction as a clinical manifestation of an emerging class of human genetic disorders, termed ciliopathies, which involve defects in ciliary assembly and/or protein transport. Given the plasticity of the olfactory system and its regenerative properties, olfactory sensory neurons (OSNs) undergo a continual process of ciliogenesis and protein transport that is critical for olfactory function. Remarkably, the mechanisms and molecular machinery necessary for ciliary transport in OSNs are virtually unexplored. Therefore, current projects in the laboratory seek to elucidate the mechanisms underlying the transport of odorant signaling proteins into mammalian olfactory cilia and their alterations in cilia-related disorders.