Dr. Yu Shin Kim was the first to develop in vivo genetically encoded calcium indicator (GCaMP) imaging in primary sensory neurons in 2010. During his postdoctoral training in Dr. Xinzhong Dong’s laboratory at Johns Hopkins University School of Medicine after his PhD taining for learning and memory mechanism study using electrophysiological recordings from Dr. David Linden in Neuroscience department in Johns Hopkins University School of Medicine, he conceived a novel approach to image primary sensory neurons—such as dorsal root ganglion (DRG) and trigeminal ganglion (TG)—in vitro and in vivo without perturbing the ganglia themselves. Recognizing the challenges of exposing and imaging DRG and TG neurons, Dr. Kim realized the potential of newly developed GCaMP indicators to overcome these limitations. By creating a Pirt-GCaMP3 knock-in mouse line, he successfully established in vitro explant TG imaging methods using nerve injury models in the craniofacial system. He later advanced the field further by pioneering in vivo intact DRG imaging techniques using this genetic tool.
DRG and TG neurons are remarkably diverse in terms of cell size, gene expression, electrophysiological properties, axonal targets, and sensory modalities (pain, itch, mechanosensation, and thermosensation). Their axons innervate peripheral tissues such as skin, muscle, and visceral organs, transmitting signals to central terminals in the spinal cord or trigeminal nuclei. These neurons undergo profound changes under pathological conditions such as nerve injury and inflammation. Historically, studies of their activity have relied heavily on electrophysiology, which provides high precision but is limited to single cells or nerves. Population-level studies have largely been restricted to dissociated cultures, which alter native neuronal properties and disrupt axonal connections.
To overcome these limitations, Dr. Kim generated the Pirt-GCaMP3 mouse line in which the calcium sensor GCaMP3 is expressed robustly and specifically in nearly all primary sensory neurons under the control of the Pirt promoter. This innovation has several unique advantages: broad expression in DRG/TG neurons but not in satellite glia or peripheral tissues; exceptionally strong promoter activity (Pirt ranks in the top 0.3% of DRG-expressed genes); and compatibility with genetic crosses for labeling or knockout studies. Imaging with Pirt-GCaMP3 provides simple preparation, excellent spatial resolution, simultaneous visualization of multiple neurons and fibers, and preservation of somatotopic organization. These advances enabled Dr. Kim and colleagues to pioneer functional imaging of intact DRG and TG in vitro and in vivo, a development that has transformed the field and is now used by more than 100 laboratories worldwide.
After securing his first faculty position, Dr. Kim rapidly expanded these techniques to in vivo TG imaging, applying them to models of temporomandibular joint disorder, tooth pain, headache, migraine, and craniofacial nerve injury. His work has been supported by multiple NIH R01 grants and published in leading journals including Neuron, Pain, and Journal of Neuroscience.
Building on these successes, Dr. Kim has pushed the field into voltage imaging. He pioneered the use of state-of-the-art, positively tuned genetically encoded voltage sensors (e.g., ASAP4, Marina, pAce) in sensory neurons, developing Pirt-Marina and Pirt-pAce knock-in lines. These tools now allow dynamic imaging of voltage fluctuations in peripheral fibers and DRG/TG cell bodies in vivo. His voltage imaging work has been published in leading journals including Nature Communications, and PNAS.
In his laboratory, Dr. Kim has also established two complementary in vivo imaging systems for freely moving animals: the Mightex fiber-optic system, for imaging deep structures such as DRG, TG, vagal ganglia, and spinal cord, and the Miniscope system, for brain and brainstem imaging. His ability to overcome major technical barriers is impressive—for example, designing a custom stabilizer to minimize motion artifacts from breathing and heartbeat during DRG imaging. His persistence, creativity, and collaborative skills in working with engineers and industry partners underscore his exceptional technical leadership.
Dr. Kim’s most recent innovations involve simultaneous, high-speed imaging of voltage and signaling events across multiple sites. These techniques enable physiologically relevant monitoring of neural and non-neural interactions with millisecond precision. His work opens entirely new avenues to study coding mechanisms underlying communication between neurons, satellite glia, Schwann cells, immune cells, and fibroblasts in vivo. This capacity provides a transformative advance over existing preclinical approaches.
His methods also allow the application of diverse somatosensory stimuli (mechanical, thermal, chemical, electrical, optogenetic) with quantitative voltage readouts, independent of behavioral interpretation. This platform will allow unprecedented exploration of how signals are gated at the DRG level and how non-neuronal cells shape somatosensory processing. Ultimately, these studies will reveal how peripheral coding determines the quality and intensity of sensory input to the CNS and open new opportunities for peripherally targeted therapies that avoid central opioid side effects.
In addition, Dr. Kim has extended his expertise to imaging second messengers and neurotransmitters (cAMP, cGMP, others), visualizing their dynamic changes in vivo. These tools have broad utility and are already advancing neuroscience research worldwide.