Julio Cordero-Morales

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. Members of the transient receptor potential (TRP) ion channel subfamily, such as TRPV1, TRPV4, and TRPC3, are involved in numerous physiological processes, including temperature, chemical, and noxious stimuli detection, as well as osmoregulation and neuronal and vascular function. 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 side effects. We envision that new strategies that fine-tune TRP channel function, while maintaining their physiological roles, might circumvent drug side these effects. Accordingly, membrane lipid manipulation has the potential to regulate channel function and bypass side effects. To determine the mechanisms whereby polyunsaturated fatty acids, phosphoinositides, and diacylglycerol fine-tune TRP channel activity, 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, cryo-EM, site-directed mutagenesis, membrane protein biochemistry, and mouse behavior among others. We are also working to provide the molecular basis for understanding the mechanism by which the lack of a ubiquitin-protein ligase modulates the function of mechanosensitive ion channels (like PIEZO2) in the context of Angelman syndrome (a neurogenetic disorder characterized by intellectual disability and sensory ataxia).