Associate Professor, Neuroscience
- PhD, University of Pierre and Marie Curie
Biotechnology, Immunology, Neuroimmunology, Neuroscience
Exploring new therapeutics avenues to treat Multiple Sclerosis.
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.
- 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
Arandjelovic S, Perry JSA, Lucas CD, Penberthy KK, Kim TH, Zhou M, Rosen DA, Chuang TY, Bettina AM, Shankman LS, Cohen AH, Gaultier A, Conrads TP, Kim M, Elliott MR, Ravichandran KS, A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammatory arthritis., 2019; Nature immunology. 20(2) 141-151. PMID: 30643265 | PMCID: PMC6402828
Rosen DA, Seki SM, FernÃ¡ndez-CastaÃ±eda A, Beiter RM, Eccles JD, Woodfolk JA, Gaultier A, Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis., 2019; Science translational medicine. 11(478) . PMID: 30728287
Uchiyama R, Kupkova K, Shetty SJ, Linford AS, Pray-Grant MG, Wagar LE, Davis MM, Haque R, Gaultier A, Mayo MW, Grant PA, Petri WA, Bekiranov S, Auble DT, Histone H3 lysine 4 methylation signature associated with human undernutrition., 2018; Proceedings of the National Academy of Sciences of the United States of America. 115(48) E11264-E11273. PMID: 30420518 | PMCID: PMC6275549
Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J, CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature., 2018; Nature neuroscience. 21(10) 1380-1391. PMID: 30224810 | PMCID: PMC6214619
Norris GT, Smirnov I, Filiano AJ, Shadowen HM, Cody KR, Thompson JA, Harris TH, Gaultier A, Overall CC, Kipnis J, Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury., 2018; The Journal of experimental medicine. 215(7) 1789-1801. PMID: 29941548 | PMCID: PMC6028515
Seki SM, Stevenson M, Rosen AM, Arandjelovic S, Gemta L, Bullock TNJ, Gaultier A, Lineage-Specific Metabolic Properties and Vulnerabilities of T Cells in the Demyelinating Central Nervous System., 2017; Journal of immunology (Baltimore, Md. : 1950). 198(12) 4607-4617. PMID: 28507026 | PMCID: PMC5485845
Marin IA, Goertz JE, Ren T, Rich SS, Onengut-Gumuscu S, Farber E, Wu M, Overall CC, Kipnis J, Gaultier A, Microbiota alteration is associated with the development of stress-induced despair behavior., 2017; Scientific reports. 7() 43859. PMID: 28266612 | PMCID: PMC5339726
Chuang TY, Guo Y, Seki SM, Rosen AM, Johanson DM, Mandell JW, Lucchinetti CF, Gaultier A, LRP1 expression in microglia is protective during CNS autoimmunity., 2016; Acta neuropathologica communications. 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., 2016; Brain, behavior, and immunity. 57() 1-7. PMID: 26796621 | PMCID: PMC4940337
Walsh JT, Hendrix S, Boato F, Smirnov I, Zheng J, Lukens JR, Gadani S, Hechler D, GÃ¶lz G, Rosenberger K, KammertÃ¶ns T, Vogt J, Vogelaar C, Siffrin V, Radjavi A, Fernandez-Castaneda A, Gaultier A, Gold R, Kanneganti TD, Nitsch R, Zipp F, Kipnis J, MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4., 2015; The Journal of clinical investigation. 125(6) 2547. PMID: 25938785
Fernandez-Castaneda A, Arandjelovic S, Stiles TL, Schlobach RK, Mowen KA, Gonias SL, 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., 2012; The Journal of biological chemistry. 288(7) 4538-48. PMID: 23264627 | PMCID: PMC3576060
Stiles TL, Dickendesher TL, Gaultier A, Fernandez-Castaneda A, Mantuano E, Giger RJ, Gonias SL, 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., 2012; Journal of cell science. 126(0) 209-20. PMID: 23132925 | PMCID: PMC3603516