The sympatho-adrenal synapse, stress, and stress hormone secretion
Calcium-triggered exocytosis underlies cell-to-cell communication in a variety of critical contexts, including synaptic transmission and endocrine signaling. For the past several decades, the adrenomedullary chromaffin cell – a key component of the sympathetic nervous system – has served as a veritable "Rosetta Stone" for our understanding of this process.
Chromaffin cells synthesize, store, and secrete a complex cocktail of powerful neuropeptides and hormones. By design, the secretion process is mutable so that release can be rapidly tuned to match physiological demands. However, the mechanisms by which this tuning is achieved remain unclear. Because the sympatho-adrenal system is known to modify the function of nearly every organ in the human body, this conceptual gap is a significant issue.
Our research goals are twofold: 1) To understand how hormone/peptide secretion and signaling are regulated by stress at the sympatho-adrenal synapse; and, 2) To identify the molecules responsible for transducing stress into secretion. To achieve our goals, we utilize state-of-the-art optical tools (TIRF and super-resolution microscopy), electrophysiology, and genetic animal models.
In addition to our work on the sympatho-adrenal synapse, we collaborate with others on both basic and more clinically-oriented research projects. For example, we work with Dr. Jefferson Knight (Department of Chemistry, UC Denver) to explore the nanoscale interaction of proteins and membranes using synthetic bilayer systems. We also work with Dr. Krishnan Raghavendran (Department of Surgery, UM) to investigate mechanisms of bactericidal activity in immune cells. Specifically, we would like to know how Klebsiella pneumoniae co-opts intracellular trafficking pathways to avoid macrophage killing in a genetic animal model. The unifying theme in all of these studies is our use of high resolution imaging tools to understand the mechanisms of intracellular trafficking in physiological and pathophysiological contexts.