Alban Gaultier

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Primary Appointment

Associate Professor, Neuroscience

Education

  • PhD, University of Pierre and Marie Curie

Research Disciplines

Biochemistry, Biotechnology, Immunology, Microbiology, Neuroimmunology, Neuroscience

Research Interests

Exploring new therapeutics avenues to treat Multiple Sclerosis.

Research Description

Multiple Sclerosis is a currently incurable autoimmune disease that affects 400,000 Americans and millions worldwide. The disease is characterized by destruction of myelin, the protective coat that wraps neuronal axons in the brain, thereby impairing the function of these âdenudedâ neurons. Depending on the position of the MS lesion(s) in the brain, the symptoms associated with the disease are very diverse and often debilitating. The main destructive force in MS is caused through the activation of T cells, which initiate myelin degradation and the development of autoimmunity. Although the etiology of MS is poorly understood, it is now clear that both genetic and environmental factors are involved.
The long-term goal of the laboratory is to discover novel therapeutic avenues for the treatment of Multiple Sclerosis. To achieve the ambitious goal of finding effective treatments for MS, it is critical to first unravel the mechanisms that drive disease pathology.
Project #1: Discovering new interventions that control the immune system during MS.
Current immunomodulatory treatments for MS mostly act by blocking the migration of immune cells into the brain. While this strategy is protective, it comes with two major drawbacks; first, the immune-surveillance of the CNS is inhibited, opening the way for opportunistic infections, and second, these therapies are not effective against pathological immune cells that are already âon-siteâ in the brain. To bypass these pitfalls of first generation therapeutics, we are exploring cellular metabolic states and specific functions of the endoplasmic reticulum during the immunological response and pathology in MS.
Project #2: Promoting myelin repair to increase neuroprotection.
Chronic demyelination is a major reason for disease progression and increased disability in MS patients, as exposed neurons become prone to neurodegeneration. Unfortunately, currently approved therapies are only aimed at dampening the immune response and do not address the critical need for stimulating myelin repair during/following an MS attack. Understanding the mechanisms of remyelination is critical in preventing neuronal loss, and is paramount to improving the quality of life of MS patients. We are using a combination of bioinformatics and animal studies to further our understanding of remyelination with the hope to develop new therapeutic options.
Project #3: Understanding the contribution of the gut microbiome to mental health.
Major depressive disorder is the most common group of symptoms observed in MS patients (20%) and affects 5% of the total US population. Current therapies for depression are marred with severe side effects and incomplete efficacy. We have demonstrated that the gut microbiome is an active participant in initiation and progression of depression. In particular, we have demonstrated that Lactobacillus species of bacteria influence the host biology and control the production of pro-depressive compounds. We are currently further exploring the connection between the microbiome and mental health.

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Interdisciplinary Training Program in Immunology
  • Predoctoral Training in Neuroscience
  • Training in the Pharmacological Sciences

Selected Publications

2024

Kharel, Y., Huang, T., Dunnavant, K., Foster, D., Souza, G., Nimchuk, K. E., . . . Lynch, K. R. (2024). Assessing Spns2-dependent S1P Transport as a Prospective Therapeutic Target.. bioRxiv. doi:10.1101/2024.03.26.586765

Rivet-Noor, C. R., Merchak, A. R., Render, C., Gay, N. M., Beiter, R. M., Brown, R. M., . . . Gaultier, A. (2024). Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors. BRAIN BEHAVIOR AND IMMUNITY, 119, 665-680. doi:10.1016/j.bbi.2024.03.028

2023

Merchak, A. R., Wachamo, S., Brown, L. C., Thakur, A., Moreau, B., Brown, R. M., . . . Gaultier, A. (2024). Lactobacillus from the Altered Schaedler Flora maintain IFNγ homeostasis to promote behavioral stress resilience. BRAIN BEHAVIOR AND IMMUNITY, 115, 458-469. doi:10.1016/j.bbi.2023.11.001

Merchak, A. R., Wachamo, S., Brown, L. C., Thakur, A., Moreau, B., Brown, R. M., . . . Gaultier, A. (2023). Lactobacillus maintains IFNγ homeostasis to promote behavioral stress resilience.. bioRxiv. doi:10.1101/2023.05.10.540223

Merchak, A., Cahill, H. M., Brown, L. R., Brown, R. G., Rivet-Noor, C., Beiter, R., . . . Gaultier, A. (2023). The activity of the aryl hydrocarbon receptor in T cells tunes the gut microenvironment to sustain autoimmunity and neuroinflammation. PLOS BIOLOGY, 21(2). doi:10.1371/journal.pbio.3002000

2022

Beiter, R. M., Rivet-Noor, C., Merchak, A. R., Bai, R., Johanson, D. M., Slogar, E., . . . Gaultier, A. (2022). Evidence for oligodendrocyte progenitor cell heterogeneity in the adult mouse brain. SCIENTIFIC REPORTS, 12(1). doi:10.1038/s41598-022-17081-7

Rivet-Noor, C. R., Merchak, A. R., Li, S., Beiter, R. M., Lee, S., Thomas, J. A., . . . Gaultier, A. (2022). Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4+cells. SCIENTIFIC REPORTS, 12(1). doi:10.1038/s41598-022-12464-2

2020

Min, H., Xu, L., Parrott, R., Overall, C. C., Lillich, M., Rabjohns, E. M., . . . Filiano, A. J. (2021). Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies. STEM CELLS, 39(1), 115-128. doi:10.1002/stem.3292

Merchak, A., & Gaultier, A. (2020). Microbial metabolites and immune regulation: New targets for major depressive disorder. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, 9. doi:10.1016/j.bbih.2020.100169

Seki, S. M., Posyniak, K., McCloud, R., Rosen, D. A., Fernandez-Castaneda, A., Beiter, R. M., . . . Gaultier, A. (2020). Modulation of PKM activity affects the differentiation of TH17 cells. SCIENCE SIGNALING, 13(655). doi:10.1126/scisignal.aay9217

Johanson, D. M., Goertz, J. E., Marin, I. A., Costello, J., Overall, C. C., & Gaultier, A. (2020). Experimental autoimmune encephalomyelitis is associated with changes of the microbiota composition in the gastrointestinal tract. SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-72197-y

Min, H., Xu, L., Parrott, R., Overall, C., Lillich, M., Meadows, N., . . . Filiano, A. (2020). Cord Blood Connect: The International Congress for Cord Blood and Perinatal Tissue Research 2020.. Stem cells translational medicine, 9 Suppl 1, S2-S18. doi:10.1002/sctm.12807

Rivet-Noor, C., & Gaultier, A. (2020). The Role of Gut Mucins in the Etiology of Depression. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 14. doi:10.3389/fnbeh.2020.592388

Min, H., Xu, L., Parrott, R., Overall, C., Lillich, M., Meadows, N., . . . Filiano, A. (2020). Targeting Neuroinflammation with Human Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells. STEM CELLS TRANSLATIONAL MEDICINE, 9. Retrieved from https://www.webofscience.com/

2019

Fernandez-Castaneda, A., Chappell, M. S., Rosen, D. A., Seki, S. M., Beiter, R. M., Johanson, D. M., . . . Gaultier, A. (2020). The active contribution of OPCs to neuroinflammation is mediated by LRP1. ACTA NEUROPATHOLOGICA, 139(2), 365-382. doi:10.1007/s00401-019-02073-1

Rosen, D. A., Seki, S. M., Fernandez-Castaneda, A., Beiter, R. M., Eccles, J. D., Woodfolk, J. A., & Gaultier, A. (2019). Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. SCIENCE TRANSLATIONAL MEDICINE, 11(478). doi:10.1126/scitranslmed.aau5266

Arandjelovic, S., Perry, J. S. A., Lucas, C. D., Penberthy, K. K., Kim, T. -H., Zhou, M., . . . Ravichandran, K. S. (2019). A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammatory arthritis. NATURE IMMUNOLOGY, 20(2), 141-+. doi:10.1038/s41590-018-0293-x

2018

Uchiyama, R., Kupkova, K., Shetty, S. J., Linford, A. S., Pray-Grant, M. G., Wagar, L. E., . . . Auble, D. T. (2018). Histone H3 lysine 4 methylation signature associated with human undernutrition. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 115(48), E11264-E11273. doi:10.1073/pnas.1722125115

Louveau, A., Herz, J., Alme, M. N., Salvador, A. F., Dong, M. Q., Viar, K. E., . . . Kipnis, J. (2018). CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. NATURE NEUROSCIENCE, 21(10), 1380-+. doi:10.1038/s41593-018-0227-9

Norris, G. T., Smirnov, I., Filiano, A. J., Shadowen, H. M., Cody, K. R., Thompson, J. A., . . . Kipnis, J. (2018). Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury. JOURNAL OF EXPERIMENTAL MEDICINE, 215(7), 1789-1801. doi:10.1084/jem.20172244

2017

Seki, S. M., Stevenson, M., Rosen, A. M., Arandjelovic, S., Gemta, L., Bullock, T. N. J., & Gaultier, A. (2017). Lineage-Specific Metabolic Properties and Vulnerabilities of T Cells in the Demyelinating Central Nervous System. JOURNAL OF IMMUNOLOGY, 198(12), 4607-4617. doi:10.4049/jimmunol.1600825

Marin, I. A., Goertz, J. E., Ren, T., Rich, S. S., Onengut-Gumuscu, S., Farber, E., . . . Gaultier, A. (2017). Microbiota alteration is associated with the development of stress-induced despair behavior. SCIENTIFIC REPORTS, 7. doi:10.1038/srep43859

2016

Chuang, T. -Y., Guo, Y., Seki, S. M., Rosen, A. M., Johanson, D. M., Mandell, J. W., . . . Gaultier, A. (2016). LRP1 expression in microglia is protective during CNS autoimmunity. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 4. doi:10.1186/s40478-016-0343-2

Fernandez-Castaneda, A., & Gaultier, A. (2016). Adult oligodendrocyte progenitor cells - Multifaceted regulators of the CNS in health and disease. BRAIN BEHAVIOR AND IMMUNITY, 57, 1-7. doi:10.1016/j.bbi.2016.01.005

2015

Walsh, J. T., Hendrix, S., Boato, F., Smirnov, I., Zheng, J., Lukens, J. R., . . . Kipnis, J. (2015). MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. JOURNAL OF CLINICAL INVESTIGATION, 125(2), 699-714. doi:10.1172/JCI176210

2013

Staudt, N. D., Jo, M., Hu, J., Bristow, J. M., Pizzo, D. P., Gaultier, A., . . . Gonias, S. L. (2013). Myeloid Cell Receptor LRP1/CD91 Regulates Monocyte Recruitment and Angiogenesis in Tumors. CANCER RESEARCH, 73(13), 3902-3912. doi:10.1158/0008-5472.CAN-12-4233

Orita, S., Henry, K., Mantuano, E., Yamauchi, K., De Corato, A., Ishikawa, T., . . . Campana, W. M. (2013). Schwann Cell LRP1 Regulates Remak Bundle Ultrastructure and Axonal Interactions to Prevent Neuropathic Pain. JOURNAL OF NEUROSCIENCE, 33(13), 5590-5602. doi:10.1523/JNEUROSCI.3342-12.2013

2012

Fernandez-Castaneda, A., Arandjelovic, S., Stiles, T. L., Schlobach, R. K., Mowen, K. A., Gonias, S. L., & Gaultier, A. (2013). Identification of the Low Density Lipoprotein (LDL) Receptor-related Protein-1 Interactome in Central Nervous System Myelin Suggests a Role in the Clearance of Necrotic Cell Debris. JOURNAL OF BIOLOGICAL CHEMISTRY, 288(7), 4538-4548. doi:10.1074/jbc.M112.384693

Stiles, T. L., Dickendesher, T. L., Gaultier, A., Fernandez-Castaneda, A., Mantuano, E., Giger, R. J., & Gonias, S. L. (2013). LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin-associated glycoprotein that functions in neurite outgrowth inhibition by MAG and CNS myelin. JOURNAL OF CELL SCIENCE, 126(1), 209-220. doi:10.1242/jcs.113191

2011

Cousin, H., Abbruzzese, G., Kerdavid, E., Gaultier, A., & Alfandari, D. (2011). Translocation of the Cytoplasmic Domain of ADAM13 to the Nucleus Is Essential for Calpain8-a Expression and Cranial Neural Crest Cell Migration. DEVELOPMENTAL CELL, 20(2), 256-263. doi:10.1016/j.devcel.2010.12.009

Shi, Y., Yamauchi, T., Gaultier, A., Takimoto, S., Campana, W. M., & Gonias, S. L. (2011). Regulation of Cytokine Expression by Schwann Cells in Response to α2-Macroglobulin Binding to LRP1. JOURNAL OF NEUROSCIENCE RESEARCH, 89(4), 544-551. doi:10.1002/jnr.22576

Mantuano, E., Henry, K., Yamauchi, K., Yamauchi, T., DeCorato, A., Gaultier, A., . . . Campana, W. M. (2011). LRP1 GENE DELETION LINKS MYELINATING SCHWANN CELL SURVIVAL TO THE PREVENTION OF CHRONIC NEUROPATHIC PAIN. JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, 16, S82. Retrieved from https://www.webofscience.com/

Gonias, S. L., Gaultier, A., & Jo, M. (2011). Regulation of the Urokinase Receptor (uPAR) by LDL Receptor-related Protein-1 (LRP1). CURRENT PHARMACEUTICAL DESIGN, 17(19), 1962-1969. Retrieved from https://www.webofscience.com/

2010

Gaultier, A., Simon, G., Niessen, S., Dix, M., Takimoto, S., Cravatt, B. F. I. I. I., & Gonias, S. L. (2010). LDL Receptor-Related Protein 1 Regulates the Abundance of Diverse Cell-Signaling Proteins in the Plasma Membrane Proteome. JOURNAL OF PROTEOME RESEARCH, 9(12), 6689-6695. doi:10.1021/pr1008288

Gorovoy, M., Gaultier, A., Campana, W. M., Firestein, G. S., & Gonias, S. L. (2010). Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages. JOURNAL OF LEUKOCYTE BIOLOGY, 88(4), 769-778. doi:10.1189/jlb.0410220