Research

We study the neural circuits, physiological mechanisms and neuroimmune pathways by which the nervous system senses and regulates immune and metabolic processes and cardiopulmonary functions. To answer such fundamental questions, we have developed implants for chronic stimulation and chronic recording of the vagus nerve in anesthetized and freely moving mice and characterized the chronic cardiopulmonary effects of VNS in rats. We found that stimulation of the vagus and abdominal autonomic nerves elicits transient release of norepinephrine in the spleen, producing anti-inflammatory effects via splenic macrophages. In response to the release of NE in the speen, VNS also modulates B-cell function and antibody production, through specific noradrenergic and cholinergic receptors on immune cells. Stimulation of the sensory innervation of the liver normalizes glucose homeostasis in animal models of diabetes.

Selected papers:

• Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response (Science Advances 2024)
• Voltammetry in the spleen assesses real-time anti-inflammatory norepinephrine release elicited by autonomic neurostimulation (J Neuroinflammation 2024)
• A fully implantable wireless bidirectional neuromodulation system for mice (Biosensors Bioelectronics 2022)
• Development and characterization of a chronic implant mouse model for vagus nerve stimulation (eLife 2021)
• Implant- and anesthesia-related factors affecting cardiopulmonary threshold intensities for vagus nerve stimulation (J Neural Engineering 2021)
• Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine (Nature Biomedical Engineering 2022)

VNS is used clinically in the treatment of epilepsy, depression, stroke rehabilitation and rheumatoid arthritis and explored as therapeutic option in several other neurological, inflammatory, metabolic, gastrointestinal and cardiovascular diseases. As VNS increases its therapeutic footprint, there is need for more organ- and function-selective devices that target mechanisms specific to the affected organ(s), often delivered in closed-loop mode. We developed methods to quantify VNS-engagement of fibers regulating cardiopulmonary functions, and used those to show that stimulus polarity permits directional (afferent or efferent) VNS. We found that kHz-frequency VNS engages small sensory vagal fibers in a current intensity- and frequency-dependent manner. More recently, we characterized the microscopic, functional anatomy of the vagus nerve in swine and, based on that, developed a novel device for fascicular VNS. Furthermore, we showed that using such a device and delivering interferential VNS, we can modulate specific vagal fibers in a precise, temporally and spatially, manner.

Selected papers:

• Control of spatiotemporal activation of organ-specific fibers in the swine vagus nerve by intermittent interferential current stimulation (Nature Communications 2025)
• Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation (Brain Stimulation 2023)
• kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents (Brain Stimulation 2022)
• Strategies for precision vagus neuromodulation (Bioelectronic Medicine 2022)
• Cortical responses to vagus nerve stimulation are modulated by brain state in nonhuman primates (Cerebral Cortex 2021)
• Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers (Brain Stimulation 2020)
• Anodal block permits directional vagus nerve stimulation (Scientific Reports 2020)
• Closed-loop neuromodulation in physiological and translational research (Cold Spring Harbor Perspectives Medicine 2018)

We investigate neuroimmune dysfunction in the context of diseases with autonomic, immune and metabolic dysfunction, with a focus on cardiovascular diseases like pulmonary hypertension and heart failure. Furthermore, we test neuroimmune modulation therapies in preclinical disease models and in early-stage clinical studies.

For more details:

• Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury (Bioelectronic Medicine 2025)
• Ultrasound neuromodulation of an anti-inflammatory pathway at the spleen improves experimental pulmonary hypertension (Circulation Research 2024)
• Vagus nerve stimulation for cardiovascular diseases: Is there light at the end of the tunnel? (Trends Cardiovascular Medicine 2023)
• Trans-spinal focused ultrasound suppresses spinal reflexes in healthy rats (Neuromodulation 2023)
• Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans (Brain Stimulation 2023)
• Autonomic neuromodulation for atrial fibrillation following cardiac surgery (J American College Cardiology 2022)
• Pulmonary arterial hypertension: the case for a bioelectronic treatment (Bioelectronic Medicine 2019)
• Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation (Nature Communications 2019)