Nutrient Sensing, Gut/Brain Communication in Health and Diseases

Our lab uses advanced technologies, genetically engineered models, ex-vivo cultures and human-derived cell lines to unmask pathways regulating bodyweight, glucose and brain functions. Sensing by the peripheral nerve system (PNS) is altered in states such as obesity, aging, or even neurodegenerative diseases (neuropathic pain, Parkinson etc.). We strive to translate our research to human to develop therapies. This spring 2022, our lab relocated from Chicago to Lausanne.

mansuyaubertlab
The specific research directions
of our laboratory include

Project 1

Role of nuclear receptors (LXRs and PPARs) in sensory neurons (vagal and non-vagal).

How lipids are sensed by neurons and impact nerve function ?

the lab

Recent data comparing dysregulated pathways in the peripheral nervous system (PNS) of type II diabetic neuropathic individuals have highlighted alterations in lipid nuclear receptors, which may provide insight into the physiological basis of diabetic neuropathy. Liver X Receptors (LXR) α and β are nuclear transcription factors that respond to cholesterol or fatty acid metabolites. LXRs interact with PPAR (peroxisome proliferator activated receptor) or RXR (retinoid X receptor) in liver cells, adipocytes, and macrophages to regulate complex intracellular lipid metabolism, though the physiological and molecular roles of LXRs in nerve system is understudied and obscure. We try to clarify the role of nuclear lipid sensors expressed in the PNS in model of diabetes and in aging model.

the lab

Project 2

Role of microbiome derived-short chain fatty acid and their receptors in diet-induced neuropathies.

How gut microbiome can impact the peripheral nerve system and associated diseases such as pain?

Over 70 million Americans are obese, pre-diabetic and 10 -30% of them develop neuropathic pain, a condition that severely impacts quality of life for which there is no disease modifying therapy.

Research using diabetic rodents shows that high circulating glucose and/or dyslipidemia disrupts the peripheral nerve system (PNS) secondary to mitochondrial disruption, impaired calcium homeostasis and neurotransmitter secretion and altered neuroimmune function. Novel mechanism-based treatment is necessary to produce non addictive and individualized therapies for obese and early diabetic patients. Recently, we published that fecal microbiota transplantation (FMT) from lean mice to Western-diet (WD) fed obese mice reduced indices of pain and neuropathy concomitant with an increase in circulating butyrate, PNS immune cell reprogramming and change in calcium homeostasis in PNS neurons. Our data shows that FFAR (Free fatty acid receptor 3), a Gi-coupled receptor that binds butyrate and expressed in sensory neurons and immune cells of WD-fed mice may mediate efficacy, we used novel cell specific tools to test this hypothesis.

Project 3

Role of gut-brain communication involving vagal innervation in glucose homeostasis, cognitive functions and pain behavior.

the lab

The prevalence of obesity and its associated comorbidities such as type 2 diabetes (T2D) continues to rise, and innovative interventions are needed1. Recent studies have identified the vagus nerve (VN) as a promising target for the treatment of obesity and T2D. The vagus nerve consists primarily of sensory neurons, many of which relay information from the alimentary tract to the brain to regulate behavior, energy balance and glucose homeostasis5. More recently, attention has been drawn to the VN because of its role in communicating information from gut microbiome metabolites to the brain. Gut bacteria ferment non-digestible dietary fiber to produce the short-chain fatty acids (SCFA’s) acetate, propionate, butyrate6 which can serve as potent signals regulating host physiology7. Dietary supplementation of fiber or SCFA’s has been shown to improve glucose tolerance and appetite, and studies suggest that the vagus nerve is required, but the neurobiology underlying this effect is unknown, using vagal genetically modified models we are testing the hypothesis that SCFA are sensed to regulate energy balance and glucose homeostasis.

the lab

Project 4

Role of C2CD5, neuronal trafficking proteins, in hypothalamic mitochondria function.

How metabolic cues modifies neuronal receptor trafficking for proper sensing ?

Previous whole-body knockout studies showed that loss of C2CD5 induced pronounced obesity by modifying food intake behavior or even energy expenditure14. Our studies demonstrates that C2CD5 is associated with mitochondria and regulates mitochondrial trafficking in neurons and likely other cell types. We are testing the hypothesis that C2CD5 could represent the first protein regulated by metabolic cues and involved in mitochondria trafficking in the brain. C2CD5 may link neuronal dysfunction and metabolic diseases such as obesity and diabetes.

Meet the team

Virginie Mansuy-Aubert

Principal investigator

Virginie is from France where she got her PhD in Biochemistry and Molecular Biology then moved to Switzerland and to the USA in 2010. First at the Sanford-Burnham Institute where she focused on insulin sensitivity and obesity in peripheral metabolic tissues(liver, heart, muscle, adipose tissues). In 2013, she got an instructor position at UTSW, Dallas in the Division of Hypothalamic Research to develop projects aiming at understand better neural control of peripheral metabolism and pain. In september 2015, she started her independent lab at Loyola Chicago Stritch Medical School in the Cell and Molecular Physiology Dpt. She is the director of the Loyola Metabolic and Behavior Phenotyping User Groups (MetBug). ORCID number : https://orcid.org/0000-0002-9976-446X

Chaitanya Gavini

Senior Post-doctoral fellow

Chaitanya Gavini is a postdoctoral researcher in Mansuy-Aubert lab. He graduated “first class with distinction” with a B-Tech in Biotechnology from JNTU, Hyderabad, India and his Ph.D in Cell and Molecular Biology from Kent State University, USA. His Ph.D research focused on central neural mechanisms regulating body weight. His emphasis was on how peripheral tissues particularly, skeletal muscle adapt to signals originating from both periphery and the hypothalamus in regulation of metabolism. Following his doctoral degree, he joined Mansuy-Aubert lab, working on neural regulation of metabolism. Current work includes understanding, 1) the role of neuronal lipid sensors in modulation of energy balance and Obesity-related peripheral neuropathy, and, 2) the role of neuronal trafficking proteins in regulation of cellular metabolism.

Gwenaël Labouèbe

Senior scientist

After a master’s degree in computational science achieved in France, I joined the University of Geneva where I obtained my PhD (2004-2008) under the supervision of the Pr. Lüscher working on the cellular and molecular mechanisms underlying addictive properties of drugs of abuse. In 2009, I started a post-doctoral position with the Pr. Borgland in Canada (UBC) where I investigated appetitive motivation disorders such as obesity and addiction. For 11 years (2011-2022), I worked as a research associate in the Pr. Thorens laboratory at the University of Lausanne where I studied the interaction between neuronal circuits involved in glucose-sensing and motivated feeding behaviors. I am now delighted to join the Pr. Mansuy-Aubert’s group and contribute with my expertise in Neuroscience, Metabolism, and Electrophysiology to the challenging scientific projects carried out in the lab.

Emily Gornick

PHD student

Emily grew up in the Chicagoland suburbs and attended Benedictine University in Lisle, Illinois where she gained experience as an undergraduate researcher. She earned her Bachelor of Science degree in Biochemistry and Molecular Biology in 2018, and in 2019 she joined the Integrated Program in Biomedical Sciences at Loyola University Chicago for her PhD. In the Mansuy-Aubert lab, Emily is studying the short chain fatty acid receptor free fatty acid receptor 2 (FFAR2) and its role in obesity. She is particularly interested in the function of FFAR2 in immune cells and how its activation or deletion in these cells might affect the inflammatory and metabolic phenotypes associated with obesity. She is eager to see where her research takes her during her PhD, and she is excited at the prospect of continuing to make scientific discoveries long after receiving her degree.

Nadia Elshareif

PHD student

Nadia grew up in South Elgin,IL. She attended the University of Wisconsin-Madison where, in December 2018, she earned a Bachelor of Science in Molecular Biology with a minor in Global Health. After graduation, Nadia matriculated into the Loyola University Chicago Integrative Cell Biology Graduate Program, and obtained her Master's in the summer of 2021. Nadia is now continuing her studies at Loyola in pursuit of her Ph.D., investigating how neuronal lipid metabolism affects neuropathic pain. She will join Virginie's lab in Lausanne to work on prebiotics and gut/brain recommendation

In the MALab, we believe that ...

Science

Science

is real

Teamwork

Teamwork

makes the dream work

Love

Love

is life

Sensory neurons

Sensory neurons

are cool

Feminism

Feminism

is for everyone

Food

Food

is all

Lab Alumni

Tyler Cook, PhD student 2017-2022, currently pos-doc at Colorado University Anshutz

Raiza Bonomo, PhD student 2016-2020 currently post-doc at the NIH
Hollie Schaffer, Year 1, STAR medical student
Robin Wang, Loyola summer research program (2 months), Cornell College
Ryan Parnell, Case Western, Pharmadiscovery student
Shaima Patangia, MS Neurosciences, September 2018 – February 2018
Isabelle Brown, Year 3 Loyola U. Chicago, summer then one day per week
Trisha Cabrera, Year 2 Loyola U. Chicago, summer then one day per week
Sergio Escobar, Northeastern University, Summer PharmaDiscovery student
Shaima Patangia, Jan 2019 – June 2019
Robin Wang, Loyola summer research STAR program (2 months), Cornell College
Neha Jihian, SPARK high school program (2 months)
Nabihaa Khan, SPARK high school program (2 months)
Emilie Verran, Pre-med at Augustana college
Alisa Wang, SPARK high school program
Allan Sherman, SPARK high school program

logo alumni