The sympathetic nervous system, 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 bioactive agents, including opioid peptides, and stress hormones. By design, the secretion process is mutable so that release can be rapidly tuned to match physiological demands. These demands have the potential to vary tremendously, depending on a variety of environmental or metabolic factors, including stress, pain, and diet. Unfortunately, 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 primary research goal is to understand how systems-level and local (molecular/cellular) control over adrenomedullary secretion is achieved. Within this context, projects are designed to: 1) Understand how excitation/inhibition balance in sympathetic nerves projecting to the adrenal medulla is determined; 2) Define how stress modifies activity of the adrenal gland, in vivo; 3) Understand how hormone/peptide secretion and signaling are regulated (and dysregulated by stress) at the sympatho-adrenal synapse; and, 4) Define the role of molecules responsible for activity-dependent control over the exocytotic process in cells.
We exploit a variety of state-of-the-art experimental approaches including optical imaging (TIRF, super-resolution, and lightsheet microscopy), electrophysiology, mass spectrometry, molecular biology, and genetic animal models.
In addition to our work on the sympatho-adrenal synapse, we collaborate with several other labs (Jefferson Knight, UC Denver; Edwin Chapman, U Wisconsin; Patrick Mueller, Wayne State University; David Castle, UVA) on both basic and more clinically-oriented research projects. The unifying theme in all of these studies is our use of sophisticated imaging and analytical tools to understand the mechanisms of intracellular trafficking in physiological and pathophysiological contexts.