Faculty
Guillaume de Lartigue, PhD

Adjunct Assistant Professor of Neuroscience
Department: Neuroscience
Contact information
3500 Market Street
Philadelphia, PA 19104
Philadelphia, PA 19104
Office: 14752018057
Email:
gdelartigue@monell.org
gdelartigue@monell.org
Publications
Education:
BSc (Medical Biochemistry)
Royal Holloway, University of London, 2002.
PhD (Molecular and Cellular Physiology)
University of Liverpool, 2007.
Permanent linkBSc (Medical Biochemistry)
Royal Holloway, University of London, 2002.
PhD (Molecular and Cellular Physiology)
University of Liverpool, 2007.
Description of Research Expertise
My expertise lies at the intersection between neuroscience and physiology. I study how internal physiological state is communicated and integrated by the brain. Disruption in how internal information is sensed and perceived has been implicated with impaired cognition, depression, metabolic disorders, autism, and anxiety. My lab has pioneered innovative approaches that combine peripheral and central manipulations and recordings which have revolutionized our ability to gain mechanistic understanding of the neural circuits involved in this novel research field. My lab focuses on the vagus nerve, as a gut-brain neural relay, to address questions about interoception in live animals. We have made numerous unexpected findings highlighting the extraordinary impact gut-brain signaling has on health and disease.A key focus of my lab has been on treating obesity, a major global health problem. Despite decades of research, effective therapies for obesity remain elusive and the physical, emotional and economic costs of obesity continue to rise. The dogmatic belief that calories-in equals calories-out, has led to ineffective strategies that are over-reliant on exercise and reducing food intake. This view has stigmatized individuals with obesity as being lazy and lacking will power, while ignoring the complex pathophysiology of obesity that defends against weight loss by altering brain circuits associated with reward, learning, memory, and fullness. Current drugs targeting the central nervous system are plagued by aversive side effects. Thus, there is an urgent need to identify peripheral cellular and molecular targets for treating obesity.
The vagus nerve is a key component of the gut-brain axis that inhibits food intake, yet this neural pathway has been largely overlooked as a therapeutic target for treating chronic metabolic diseases. The textbook understanding is that the vagus nerve controls short-term food intake with little impact on long-term regulation of body weight. This dogmatic view is based on literature using vagotomy, a flawed technique which abolishes bidirectional vagal communication between abdominal organs and the brain. The lack of organ specificity, and confounds caused by damaging motor branches of the vagus nerve that control organ function, makes it difficult to interpret the outcomes from these experiments. My lab is developing new tools to study precise populations of vagal sensory neurons that selectively innervate the gut. I pioneered the application of molecular and genetic tools to deconstruct the sensory vagus nerve into cellular components based on genetic markers, projection patterns, and functional responses. I subsequently adapted viral technology for connectivity mapping, in vivo imaging, cell ablation and control of neural activity to study the role of these previously intractable neurons in the control of eating. Using these tools, we have identified previously unsuspected roles of the sensory vagus nerve in many aspects of higher order feeding behavior, including reward, memory, anxiety, and fullness.
Selected Publications
Scott KA, Tan Y, Johnson DN, Elsaafien K, Baumer-Harrison C, Méndez-Hernández R, Kirchner MK, Eikenberry SA, Sa JM, Stern JE, de Lartigue G*, de Kloet AD*, Krause EG*.: Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice. Nat Metab. January 2025.Yang M, Singh A, de Araujo A, McDougle M, Ellis H, Décarie-Spain L, Kanoski SE, de Lartigue G.: Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation. Nat Metab. January 2025.
Woodie LN, Melink LC, Midha M, de Araújo AM, Geisler CE, Alberto AJ, Krusen BM, Zundell DM, de Lartigue G, Hayes MR, Lazar MA.: Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake. Science November 2024
Zuarth Gonzalez JD, Mottinelli M, McCurdy CR, de Lartigue G, McMahon LR, Wilkerson JL.: Mitragynine and morphine produce dose-dependent bimodal action on food but not water intake in rats. Am J Physiol Regul Integr Comp Physiol. December 2024.
de Araujo A, Sree Kumar H, Yang T, Plata AA, Dirr EW, Bearss N, Baekey DM, Miller DS, Donertas-Ayaz B, Ahmari N, Singh A, Kalinoski AL, Garrett TJ, Martyniuk CJ, de Lartigue G*, Zubcevic J*.: Intestinal serotonergic vagal signaling as a mediator of microbiota-induced hypertension. BioRxiv September 2024.
Minaya DM, Kim JS, Kirkland R, Allen J, Cullinan S, Maclang N, de Lartigue G, de La Serre CB. : Transfer with microbiota from lean donors prevents excessive weight gain and restores gut-brain vagal signaling in obese rats maintained on a high fat diet. Res Sq May 2024.
Baumer-Harrison C, Elsaafien K, Johnson DN, Peñaloza Aponte JD, de Araujo A, Patel S, Bruce EB, Harden SW, Frazier CJ, Scott KA, de Lartigue G, Krause EG, de Kloet AD.: Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons. J Neurosci 44: e1154232023, Feb 2024.
Baumer-Harrison C, Elsaafien K, Johnson DN, Peñaloza Aponte JD, de Araujo A, Patel S, Bruce EB, Harden SW, Frazier CJ, Scott KA, de Lartigue G, Krause EG, de Kloet AD.: Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons. J Neurosci. 28;(44(9)), February 2024.
McDougle M, de Araujo A, Singh A, Yang M, Braga I, Paille V, Mendez-Hernandez R, Vergara M, Woodie LN, Gour A, Sharma A, Urs N, Warren B, de Lartigue G.: Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab 36: 393-407, Feb 2024.
Minaya DM, Kim JS, Kirkland R, Allen J, Cullinan S, Maclang N, de Lartigue G, de La Serre C. : Transfer of microbiota from lean donors in combination with prebiotics prevents excessive weight gain and improves gut-brain vagal signaling in obese rats. Gut Microbes. 2024.
© The Trustees of the University of Pennsylvania | Site best viewed in a supported browser. | Site Design: PMACS Web Team.