Research

Our research laboratory is focused on unraveling the complex molecular mechanisms that underlie the establishment of chronic pain states, with the ultimate goal of developing non-addictive pain therapeutics.

RNA control in pain

Utilizing a multifaceted approach in understanding translational regulation in pain-sensing neurons, a key driver of pain plasticity.

My research in the field of Pain leverages an interdisciplinary approach to comprehensively understand translational regulation in peripheral sensory neurons, a key driver of pain plasticity. Combining high-throughput next-generation sequencing with advanced molecular biology techniques, pharmacology, and animal models, my work has unveiled novel and pivotal roles played by RNA control mechanisms in dorsal root ganglion neurons, contributing significantly to pain plasticity. These mechanisms encompass Nonsense-Mediated Decay, the translation of uORFs, and the functions of emerging RNA-binding proteins (e.g., HuR). These findings represent a burgeoning area in pain research, providing critical insights into new mechanisms and potential therapeutic targets. Notable publications arising from this research include:

de la Peña et al., 2019

Novel pain targets

Employing unbiased, high-throughput approaches to identify Arc and Fos, as key targets.

A significant outcome of our work employing unbiased high-throughput next-generation sequencing in peripheral nociceptors has been the identification of immediate early gene, Activity Regulated Cytoskeleton Associated Protein (Arc), and the transcription factor, Fos proto-oncogene (Fos), as key targets. While these genes have been implicated in central nervous system plasticity, their roles in the peripheral nervous system remained unclear. Our research was the first to demonstrate the pivotal roles of these plasticity-related genes in the PNS. We found that Arc forms extracellular vesicles that mediate intercellular communication and neurogenic inflammation, while Fos orchestrates behavioral pain sensitization through an S6K1-mediated mechanism. Our findings have stimulated further investigations into these plasticity-related genes as potential pain therapeutics, with several research groups corroborating our discoveries.

de la Peña et al., 2021

Addiction

In addition to my work in the pain field, I have made significant contributions in the field of drug addiction, an issue of paramount importance, particularly in the context of the opioid epidemic. As a research professor and graduate student in South Korea, I delineated the long-term neuronal consequences of adolescent-onset cigarette smoking, evaluated the abuse potential of anesthetic drugs, and devised an efficient abuse liability screening platform for novel psychoactive substances (a.k.a. designer drugs), which the World Health Organization and South Korean government used as scientific evidence for control and regulation.

Neurodevelopmental disorders

I have harnessed high-throughput next-generation sequencing to elucidate transcriptional changes in the brains of mice exhibiting hyperactive, inattentive, and impulsive phenotypes and their response to stimulant treatment. This endeavor has yielded novel animal models for ADHD, contributing significantly to our understanding of the disorder's underlying molecular mechanisms.

Natural product-based therapeutics

I also maintain a strong interest in the discovery and screening of natural product-based substances for the treatment of various neurological disorders. My research has led to the discovery and demonstration of the efficacy of various compounds derived from natural products in alleviating symptoms associated with insomnia, anxiety, depression, learning and memory problems, ADHD, and autism. A current international collaborative project with the University of the Philippines seeks to identify marine natural product-based compounds (e.g., conotoxins) with analgesic properties, further diversifying our contributions to the field.

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