Eduardo A. Perozo, Ph.D.

Research

Most membrane proteins contain moving elements that enable their specific functions, often in response to external stimuli. Our research seeks to elucidate the molecular principles by which different forms of energy are transduced into protein motion—with a particular emphasis on voltage sensing and mechanotransduction, the process through which physical forces regulate ion channel gating. Mechanical cues drive essential physiological processes across all forms of life, making this a fundamental question in biology.

We are equally interested in protein structure as in protein dynamics, for it is the dynamic behavior of a molecule that links structure to function. To this end, we combine structural approaches—such as cryo-electron microscopy—with spectroscopic and high-resolution functional techniques, including single-channel, macroscopic, and gating-current electrophysiology. These complementary methods allow us to study ion channels and other membrane proteins in the context of a native-like lipid bilayer environment.

Our long-term goals center on answering several key questions: What is the molecular basis of mechanosensitivity? How does mechanotransduction contribute to fundamental sensory systems such as touch, hearing, and balance? How did these systems evolve? Mechanosensitive ion channels are now recognized as the primary molecular transducers of mechanical force in a wide array of physiological contexts, including touch, hearing, blood pressure regulation, and embryonic development. Moreover, dysfunction of these channels is increasingly linked to human disease, including hearing loss, cardiac disorders, and cancer.

By uncovering the molecular mechanisms of mechanotransduction, we aim to establish foundational knowledge that could help in the development of therapeutic strategies. A deeper understanding of these processes holds the potential to revolutionize treatments for hearing loss, heart disease, and cancer—enabling the development of pharmacological and gene-based strategies not yet conceptualized.

As an Innovation Fund investigator, Eduardo Perozo, Ph.D., is teaming up with Juan-Pablo Castillo, Ph.D., to elucidate the molecular principles that underlie mechanotransduction, the process by which mechanical stimuli are translated into electrical signals that can be decoded by the brain. The intricate biochemistry and structural components of the mechanoelectric systems are only partially known and difficult to study. Together, the investigators will leverage recent experimental advances in electrophysiology, force spectroscopy, functional measurements, and cellular engineering to examine this critical process in mechanically active cells, with the goal of visualizing—atom by atom—how transduction occurs. In addition to their shared background in electrophysiology and molecular biophysics, the pair will combine Perozo’s expertise in ion channel structural biology and biochemistry with Castillo’s extensive experience in force spectroscopy and optical instrumentation for this work. They hope these findings will help launch a transformative new period in the field of sensory physiology and lead to deeper understanding of mechanotransduction-based pathologies.