Bio


Postdoctoral fellow in the laboratory of Dr. Carla Shatz.

Boards, Advisory Committees, Professional Organizations


  • Communications Director (previously Co-Chair and Advocacy Coordinator), Stanford University Postdoctoral Association - SURPAS (2017 - Present)

Professional Education


  • Bachelor of Science, Lafayette College (2011)
  • Doctor of Philosophy, University of Virginia (2017)

Lab Affiliations


All Publications


  • Microbiota alteration is associated with the development of stress-induced despair behavior SCIENTIFIC REPORTS Marin, I. A., Goertz, J. E., Ren, T., Rich, S. S., Onengut-Gumuscu, S., Farber, E., Wu, M., Overall, C. C., Kipnis, J., Gaultier, A. 2017; 7: 43859

    Abstract

    Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.

    View details for DOI 10.1038/srep43859

    View details for Web of Science ID 000395636300001

    View details for PubMedID 28266612

    View details for PubMedCentralID PMC5339726

  • Experimental autoimmune encephalomyelitis is associated with changes of the microbiota composition in the gastrointestinal tract. Scientific reports Johanson, D. M., Goertz, J. E., Marin, I. A., Costello, J., Overall, C. C., Gaultier, A. 2020; 10 (1): 15183

    Abstract

    The gut microbiome is known to be sensitive to changes in the immune system, especially during autoimmune diseases such as Multiple Sclerosis (MS). Our study examines the changes to the gut microbiome that occur during experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We collected fecal samples at key stages of EAE progression and quantified microbial abundances with 16S V3-V4 amplicon sequencing. Our analysis of the data suggests that the abundance of commensal Lactobacillaceae decreases during EAE while other commensal populations belonging to the Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae families expand. Community analysis with microbial co-occurrence networks points to these three expanding taxa as potential mediators of gut microbiome dysbiosis. We also employed PICRUSt2 to impute MetaCyc Enzyme Consortium (EC) pathway abundances from the original microbial abundance data. From this analysis, we found that a number of imputed EC pathways responsible for the production of immunomodulatory compounds appear to be enriched in mice undergoing EAE. Our analysis and interpretation of results provides a detailed picture of the changes to the gut microbiome that are occurring throughout the course of EAE disease progression and helps to evaluate EAE as a viable model for gut dysbiosis in MS patients.

    View details for DOI 10.1038/s41598-020-72197-y

    View details for PubMedID 32938979

  • Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia JOURNAL OF EXPERIMENTAL MEDICINE Cronk, J. C., Filiano, A. J., Louveau, A., Marin, I., Marsh, R., Ji, E., Goldman, D. H., Smirnov, I., Geraci, N., Acton, S., Overall, C. C., Kipnis, J. 2018; 215 (6): 1627–47

    Abstract

    Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.

    View details for DOI 10.1084/jem.20180247

    View details for Web of Science ID 000440821300010

    View details for PubMedID 29643186

    View details for PubMedCentralID PMC5987928

  • Central Nervous System: (Immunological) Ivory Tower or Not? NEUROPSYCHOPHARMACOLOGY Marin, I. A., Kipnis, J. 2017; 42 (1): 28–35

    Abstract

    The view of the nervous system being the victim of destructive inflammation during autoimmunity, degeneration, or injury has been rapidly changing. Recent studies are supporting the idea that the immune system provides support for the nervous system at various levels. Though cell patrolling through the nervous system parenchyma is limited compared with other tissues, immune cell presence within the central nervous system (CNS; microglia), as well as around it (in the meningeal spaces and choroid plexus) has been shown to be important for brain tissue maintenance and function. This review primarily explores recent findings concerning neuroimmune interactions and their mechanisms under homeostatic conditions.

    View details for DOI 10.1038/npp.2016.122

    View details for Web of Science ID 000390083300003

    View details for PubMedID 27402496

    View details for PubMedCentralID PMC5143482

  • Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli IMMUNITY Cronk, J. C., Derecki, N. C., Ji, E., Xu, Y., Lampano, A. E., Smirnov, I., Baker, W., Norris, G. T., Marin, I., Coddington, N., Wolf, Y., Turner, S. D., Aderem, A., Klibanov, A. L., Harris, T. H., Jung, S., Litvak, V., Kipnis, J. 2015; 42 (4): 679–91

    Abstract

    Mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2, are the predominant cause of Rett syndrome, a disease characterized by both neurological symptoms and systemic abnormalities. Microglial dysfunction is thought to contribute to disease pathogenesis, and here we found microglia become activated and subsequently lost with disease progression in Mecp2-null mice. Mecp2 was found to be expressed in peripheral macrophage and monocyte populations, several of which also became depleted in Mecp2-null mice. RNA-seq revealed increased expression of glucocorticoid- and hypoxia-induced transcripts in Mecp2-deficient microglia and peritoneal macrophages. Furthermore, Mecp2 was found to regulate inflammatory gene transcription in response to TNF stimulation. Postnatal re-expression of Mecp2 using Cx3cr1(creER) increased the lifespan of otherwise Mecp2-null mice. These data suggest that Mecp2 regulates microglia and macrophage responsiveness to environmental stimuli to promote homeostasis. Dysfunction of tissue-resident macrophages might contribute to the systemic pathologies observed in Rett syndrome.

    View details for DOI 10.1016/j.immuni.2015.03.013

    View details for Web of Science ID 000353347500014

    View details for PubMedID 25902482

    View details for PubMedCentralID PMC4407145

  • Learning and memory ... and the immune system LEARNING & MEMORY Marin, I., Kipnis, J. 2013; 20 (10): 601–6

    Abstract

    The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS), microglia constantly monitor synapses and participate in their pruning during development and possibly also throughout life. Classical inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF), are released during neuronal activity and play a crucial role in regulating the strength of synaptic transmission. Systemically, proper functioning of the immune system is critical for maintaining normal nervous system function. Disruption of the immune system functioning leads to impairments in cognition and in neurogenesis. In this review we provide examples of the communication between the nervous and the immune systems in the interest of normal CNS development and function.

    View details for DOI 10.1101/lm.028357.112

    View details for Web of Science ID 000325860600010

    View details for PubMedID 24051097

    View details for PubMedCentralID PMC3768198

  • Mutation of the dyslexia-associated gene Dcdc2 impairs LTM and visuo-spatial performance in mice GENES BRAIN AND BEHAVIOR Gabel, L. A., Marin, I., LoTurco, J. J., Che, A., Murphy, C., Manglani, M., Kass, S. 2011; 10 (8): 868–75

    Abstract

    Developmental reading disorder (RD) affects 5-10% of school aged children, with a heritability of approximately 60%. Genetic association studies have identified several candidate RD susceptibility genes, including DCDC2; however, a direct connection between the function of these genes and cognitive or learning impairments remains unclear. Variants in DCDC2, a member of the doublecortin family of genes, have been associated in humans with RD and ADHD and Dcdc2 may play a role in neuronal migration in rats. In this study, we examined the effect of Dcdc2 mutation on cognitive abilities in mice using a visual attention and visuo-spatial learning and memory task. We show that both heterozygous and homozygous mutations of Dcdc2 result in persistent visuo-spatial memory deficits, as well as visual discrimination and long-term memory deficits. These behavioral deficits occur in the absence of neuronal migration disruption in the mutant mice, and may be comorbid with an anxiety phenotype. These are the first results to suggest a direct relationship between induced mutation in Dcdc2 and changes in behavioral measures. Dcdc2 mutant mice should prove useful in future studies designed to further dissect the underlying neural mechanisms that are impaired following Dcdc2 mutation.

    View details for DOI 10.1111/j.1601-183X.2011.00727.x

    View details for Web of Science ID 000297209900007

    View details for PubMedID 21883923

    View details for PubMedCentralID PMC3212622