Areas of Interest

Research Interests

Structure and function of sensory receptors

Our laboratory is centered on understanding the structural and molecular bases underlying the function and modulation of ion channels involved in somatosensation and blood pressure regulation. These ion channels are remarkable because they respond to a broad range of physical (e.g., heat and pressure) and chemical (e.g., acid, irritants, and inflammatory mediators) stimuli that depolarize sensory neurons to elicit environmental perception and increase the intracellular calcium concentration in vascular cells to regulate arterial blood pressure. We focus our research on the transient receptor potential (TRP) channel family, which is a diverse group of cation channels that mediate a variety of physiological processes such as electrical activity, signal transduction, sensory perception, nociception, cardiac excitability, and blood pressure regulation.

TRP channel dysfunction underlies various pathophysiological conditions such as pain hypersensitivity (e.g., after injury), peripheral neuropathies (e.g., diabetes), inflammation, hypertension, and neurological disorders (e.g., ataxia). Because TRP channels play critical roles in health and disease, there are many challenges that agonists or antagonists must overcome during clinical trials due to their potential side effects. We envision that new strategies for fine-tuning TRP channel function, while maintaining their physiological roles, might circumvent these responses. Accordingly, membrane lipid manipulation has the potential to regulate channel function and bypass potential side effects. The long-term objective of my group is to uncover the mechanism(s) by which bioactive lipids modulate the function of vascular and sensory ion channels in vitro and in vivo. Genetically inherited mutations in sensory ion channels could underlie numerous pathological conditions. Hence, the biophysical characterization of these membrane proteins represents a major goal in developing therapeutic agents to target them. Together with TRP channel gating mechanisms, we are motivated to study how disease-associated mutants alter the biophysical properties of TRP channels to provide insight into the molecular mechanisms underlying normal and pathophysiology.

We combine multiple in vitro and in vivo techniques, such as tissue culture (cell lines, murine and human cultured primary cells, and human iPSC-derived sensory neurons), electrophysiology (patch-clamp), calcium imaging, lipidomics, cryoEM, site-directed mutagenesis, electron paramagnetic spectroscopy, membrane protein biochemistry, and mouse and C. elegans behavior, among others.

Selected Publications:

Romero LO, Caires R, Kaitlyn Victor A, Ramirez J, Sierra-Valdez FJ, Walsh P, Truong V, Lee J, Mayor U, Reiter LT, Vásquez V, Cordero-Morales JF. Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome. Nat Communications. 2023 Mar 1;14(1):1167.

Caires R, Garrud TAC, Romero LO, Fernández-Peña C, Vásquez V, Jaggar JH, Cordero-Morales JF. Genetic- and diet-induced ω-3 fatty acid enrichment enhances TRPV4-mediated vasodilation in mice. Cell Reports. 2022 Sep 6;40(10):111306.

Caires R, Bell B, Lee J, Romero LO, Vásquez V, Cordero-Morales JF. 2021. Deficiency of inositol monophosphatase activity decreases phosphoinositide lipids and enhances TRPV1 function in vivo. J Neurosci. 2021 Jan 20;41(3):408-423.