- PhD, University of Pierre and Marie Curie
- Associate Professor, Neuroscience
Exploring new therapeutics avenues to treat Multiple Sclerosis.
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 “denuded” 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 “on-site” 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.
- Marin I, Goertz J, Ren T, Rich S, Onengut-Gumuscu S, Farber E, Wu M, Overall C, Kipnis J, Gaultier A. Microbiota alteration is associated with the development of stress-induced despair behavior. Scientific reports. 2017;7 43859. PMID: 28266612 | PMCID: PMC5339726
- Seki S, Gaultier A. Exploring Non-Metabolic Functions of Glycolytic Enzymes in Immunity. Frontiers in immunology. 2017;8 1549. PMID: 29213268 | PMCID: PMC5702622
- Seki S, Stevenson M, Rosen A, Arandjelovic S, Gemta L, Bullock T, Gaultier A. Lineage-Specific Metabolic Properties and Vulnerabilities of T Cells in the Demyelinating Central Nervous System. Journal of immunology (Baltimore, Md. : 1950). 2017;198(12): 4607-4617. PMID: 28507026 | PMCID: PMC5485845
- Chuang T, Guo Y, Seki S, Rosen A, Johanson D, Mandell J, Lucchinetti C, Gaultier A. LRP1 expression in microglia is protective during CNS autoimmunity. Acta neuropathologica communications. 2016;4(1): 68. PMID: 27400748 | PMCID: PMC4940960
- Fernandez-Castaneda A, Gaultier A. Adult oligodendrocyte progenitor cells - Multifaceted regulators of the CNS in health and disease. Brain, behavior, and immunity. 2016;57 1-7. PMID: 26796621 | PMCID: PMC4940337
- Walsh J, Hendrix S, Boato F, Smirnov I, Zheng J, Lukens J, Gadani S, Hechler D, Gölz G, Rosenberger K, Kammertöns T, Vogt J, Vogelaar C, Siffrin V, Radjavi A, Fernandez-Castaneda A, Gaultier A, Gold R, Kanneganti T, Nitsch R, Zipp F, Kipnis J. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. The Journal of clinical investigation. 2015;125(6): 2547. PMID: 25938785
- Orita S, Henry K, Mantuano E, Yamauchi K, De Corato A, Ishikawa T, Feltri M, Wrabetz L, Gaultier A, Pollack M, Ellisman M, Takahashi K, Gonias S, Campana W. Schwann cell LRP1 regulates remak bundle ultrastructure and axonal interactions to prevent neuropathic pain. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013;33(13): 5590-602. PMID: 23536074 | PMCID: PMC3837698
- Staudt N, Jo M, Hu J, Bristow J, Pizzo D, Gaultier A, VandenBerg S, Gonias S. Myeloid cell receptor LRP1/CD91 regulates monocyte recruitment and angiogenesis in tumors. Cancer research. 2013;73(13): 3902-12. PMID: 23633492 | PMCID: PMC3702673
- Fernandez-Castaneda A, Arandjelovic S, Stiles T, Schlobach R, Mowen K, Gonias S, Gaultier A. 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. The Journal of biological chemistry. 2012;288(7): 4538-48. PMID: 23264627 | PMCID: PMC3576060
- Stiles T, Dickendesher T, Gaultier A, Fernandez-Castaneda A, Mantuano E, Giger R, Gonias S. 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. 2012;126 209-20. PMID: 23132925 | PMCID: PMC3603516
- Cousin H, Abbruzzese G, Kerdavid E, Gaultier A, Alfandari D. Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration. Developmental cell. 2011;20(2): 256-63. PMID: 21316592 | PMCID: PMC3074609
- Gonias S, Gaultier A, Jo M. Regulation of the urokinase receptor (uPAR) by LDL receptor-related protein-1 (LRP1). Current pharmaceutical design. 2011;17(19): 1962-9. PMID: 21711236
- Shi Y, Yamauchi T, Gaultier A, Takimoto S, Campana W, Gonias S. Regulation of cytokine expression by Schwann cells in response to α2-macroglobulin binding to LRP1. Journal of neuroscience research. 2011;89(4): 544-51. PMID: 21290408 | PMCID: PMC3560970
- Gaultier A, Simon G, Niessen S, Dix M, Takimoto S, Cravatt B, Gonias S. LDL receptor-related protein 1 regulates the abundance of diverse cell-signaling proteins in the plasma membrane proteome. Journal of proteome research. 2010;9(12): 6689-95. PMID: 20919742 | PMCID: PMC2997161
- Gorovoy M, Gaultier A, Campana W, Firestein G, Gonias S. Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages. Journal of leukocyte biology. 2010;88(4): 769-78. PMID: 20610799 | PMCID: PMC2974427
- Gaultier A, Hollister M, Reynolds I, Hsieh E, Gonias S. LRP1 regulates remodeling of the extracellular matrix by fibroblasts. Matrix biology : journal of the International Society for Matrix Biology. 2009;29(1): 22-30. PMID: 19699300 | PMCID: PMC2818094
- Gaultier A, Wu X, Le Moan N, Takimoto S, Mukandala G, Akassoglou K, Campana W, Gonias S. Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis. Journal of cell science. 2009;122 1155-62. PMID: 19299462 | PMCID: PMC2714439
- Inoue G, Gaultier A, Li X, Mantuano E, Richardson G, Takahashi K, Campana W. Erythropoietin promotes Schwann cell migration and assembly of the provisional extracellular matrix by recruiting beta1 integrin to the cell surface. Glia. 2009;58(4): 399-409. PMID: 19705458 | PMCID: PMC2807473
- Gaultier A, Arandjelovic S, Niessen S, Overton C, Linton M, Fazio S, Campana W, Cravatt B, Gonias S. Regulation of tumor necrosis factor receptor-1 and the IKK-NF-kappaB pathway by LDL receptor-related protein explains the antiinflammatory activity of this receptor. Blood. 2008;111(11): 5316-25. PMID: 18369152 | PMCID: PMC2396725
- Mantuano E, Inoue G, Li X, Takahashi K, Gaultier A, Gonias S, Campana W. The hemopexin domain of matrix metalloproteinase-9 activates cell signaling and promotes migration of schwann cells by binding to low-density lipoprotein receptor-related protein. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008;28(45): 11571-82. PMID: 18987193 | PMCID: PMC3837707
- Gaultier A, Arandjelovic S, Li X, Janes J, Dragojlovic N, Zhou G, Dolkas J, Myers R, Gonias S, Campana W. A shed form of LDL receptor-related protein-1 regulates peripheral nerve injury and neuropathic pain in rodents. The Journal of clinical investigation. 2007;118(1): 161-72. PMID: 18060043 | PMCID: PMC2104478
- Montel V, Gaultier A, Lester R, Campana W, Gonias S. The low-density lipoprotein receptor-related protein regulates cancer cell survival and metastasis development. Cancer research. 2007;67(20): 9817-24. PMID: 17942912
- Campana W, Li X, Dragojlovic N, Janes J, Gaultier A, Gonias S. The low-density lipoprotein receptor-related protein is a pro-survival receptor in Schwann cells: possible implications in peripheral nerve injury. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(43): 11197-207. PMID: 17065459
- Gaultier A, Salicioni A, Arandjelovic S, Gonias S. Regulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1: activities based on regulation of mRNA expression. The Journal of biological chemistry. 2006;281(11): 7332-40. PMID: 16407289
- Jo M, Thomas K, Takimoto S, Gaultier A, Hsieh E, Lester R, Gonias S. Urokinase receptor primes cells to proliferate in response to epidermal growth factor. Oncogene. 2006;26(18): 2585-94. PMID: 17043637
- Alfandari D, Cousin H, Gaultier A, Hoffstrom B, DeSimone D. Integrin alpha5beta1 supports the migration of Xenopus cranial neural crest on fibronectin. Developmental biology. 2003;260(2): 449-64. PMID: 12921745
- Moreau N, Alfandari D, Gaultier A, Cousin H, Darribère T. Cloning and expression patterns of dystroglycan during the early development of Xenopus laevis. Development genes and evolution. 2003;213(7): 355-9. PMID: 12739143
- Salicioni A, Gaultier A, Brownlee C, Cheezum M, Gonias S. Low density lipoprotein receptor-related protein-1 promotes beta1 integrin maturation and transport to the cell surface. The Journal of biological chemistry. 2003;279(11): 10005-12. PMID: 14699139
- Gaultier A, Cousin H, Darribère T, Alfandari D. ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin. The Journal of biological chemistry. 2002;277(26): 23336-44. PMID: 11967265
- Smith K, Gaultier A, Cousin H, Alfandari D, White J, DeSimone D. The cysteine-rich domain regulates ADAM protease function in vivo. The Journal of cell biology. 2002;159(5): 893-902. PMID: 12460986 | PMCID: PMC2173380
- Alfandari D, Cousin H, Gaultier A, Smith K, White J, Darribère T, DeSimone D. Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration. Current biology : CB. 2001;11(12): 918-30. PMID: 11448768
- Cousin H, Gaultier A, Bleux C, Darribère T, Alfandari D. PACSIN2 is a regulator of the metalloprotease/disintegrin ADAM13. Developmental biology. 2000;227(1): 197-210. PMID: 11076687
- Darribère T, Skalski M, Cousin H, Gaultier A, Montmory C, Alfandari D. Integrins: regulators of embryogenesis. Biology of the cell / under the auspices of the European Cell Biology Organization. 2000;92(1): 5-25. PMID: 10761694