Ashlee and the Organ Mountains

Ashlee Rowe

          I am a broadly trained neurobiologist and my research program integrates venom biochemistry with genetics, sensory physiology and animal behavior to address the overarching question – how do animals detect, process and respond appropriately to noxious stimuli? My lab aims to understand the molecular and physiological mechanisms underlying sensory processing and behavior. The challenge is to show how changes in gene structure and expression alter protein structure and function, and how those changes impact physiology and behavior. To overcome these challenges, I developed a predator-prey model for studying sensory processes and behavior across multiple levels of analyses (i.e., molecules, genes, proteins, behavior). I focus on predator-prey behavior because these interactions rely on fast, specialized sensory inputs and motor responses, and because the ion channels that encode sensory information and regulate motor responses to stimuli are genetically and physiologically tractable. Moreover, because ion channels are crucial for all physiological processes, they are targets of venom-derived toxins produced by diverse taxa. I use scorpion neurotoxins (polypeptides) that reversibly modify the activation and inactivation gates of voltage-dependent sodium and potassium ion channels to probe these targets in the nerve and muscle tissue of predatory mice. Interactions between venom peptides and target channels enable the examination of the molecular mechanisms by which animals transduce sensory stimuli, interpret signals, and generate motor responses. The strength of this system is that differential sensory phenotypes (e.g., inter-individual variation in pain sensitivity) expressed in natural populations of mammals can be linked to genetic variation in ion-channel encoding genes, laying the foundation for contributions to translational medicine. For example, my system highlighted the potential for the sensory voltage-gated sodium channel Nav1.8 to serve as a target for pain drugs (Rowe et al., Science, 2013). In 2017, I was recruited by the University of Oklahoma to fill a Molecular Neurobiology position as part of a cluster hire in The Biology of Behavior. This transition enabled me to advance my research on the biophysical interactions between venom peptides and their ion channel targets via collaborations with researchers in the NIH-funded Oklahoma Center of Biomedical Research Excellence (COBRE) in Structural Biology. I am currently working with proteomics and structural biology researchers to elucidate the mechanisms of peptide-mediated ion channel inhibition. A better understanding of the biophysical interactions between venom peptides and Nav1.8 will provide a structural guide for developing novel pain therapeutics.

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