Regenerative Neuroimmunology Research
The Imitola Lab has maintained a focus in developing translational human models of neuroinflammation and education of trainees in the field of regenerative neuroimmunology. We have contributed with the understanding of the immune signals that facilitate migration of neural stem cells to areas of injury (Proc Natl Acad Sci U S A. 2004.) The intrinsic capacity of neural progenitor to respond to immune cytokines and being target in inflammation in vitro. In vivo effects of inflammation in neural stem cell niches, Oligodendrocyte progenitors cells in models of Multiple Sclerosis. (Ann Neurol. 2011 May;69(5):878-91). In addition, the generation of a new model of microglia from patient monocytes, (Sci Transl Med. 2017 Dec 20;9:421) as well as tools to analyze phenotype-genotype relationships of iPSCs models of neurological diseases (EMBO Mol Med. 2017 Dec;9(12):1742).
Our work aims for translational solutions with regenerative neuroimmunology principles for neurodegeneration in progressive MS.
The Imitola Lab has maintained a focus in developing translational human models of neuroinflammation and education of trainees in the field of regenerative neuroimmunology. We have contributed with the understanding of the immune signals that facilitate migration of neural stem cells to areas of injury (Proc Natl Acad Sci U S A. 2004.) The intrinsic capacity of neural progenitor to respond to immune cytokines and being target in inflammation in vitro. In vivo effects of inflammation in neural stem cell niches, Oligodendrocyte progenitors cells in models of Multiple Sclerosis. (Ann Neurol. 2011 May;69(5):878-91). In addition, the generation of a new model of microglia from patient monocytes, (Sci Transl Med. 2017 Dec 20;9:421) as well as tools to analyze phenotype-genotype relationships of iPSCs models of neurological diseases (EMBO Mol Med. 2017 Dec;9(12):1742).
Our work aims for translational solutions with regenerative neuroimmunology principles for neurodegeneration in progressive MS.
|
Impact of immunity on NSCs in models of Multiple Sclerosis (MS).
The mechanisms of progression and lack of repair in MS are unknown. Our early studies demonstrated the NSC, OPCs and neurons harbours an intrinsic inducible program of inflammation that leads to changes in self-renewal and differentiation. Our lab studies the effects of inflammation on mouse and human NSCs to validate potential pathways to prevent transcriptional changes in NSCs, OPCs and neurons. Front Cell Neurosci. 2023 Aug 16;17:1156802 J Neuroimmunol. 2019 Jun 15;331:1-3. Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):8646-8648 Human models of inflammatory-induced neurodegeneration
There is a lack of human-based translational models for neurodegenerative diseases. In order to study the genetics that underlie the phenotypic functions of human NSCs in the context of neuroinflammation. Our lab studies the effects of inflammation on human-derived in vitro induced pluripotent stem cell (iPSC)-derived cerebral organoids. These models can help identify human-specific mechanisms and validate targets for repair that can be applicable to MS. Semin Cell Dev Biol. 2019 Aug 16 Cell Stem Cell. 2017 Feb 2;20(2):157 Curr Protoc. 2021 Feb;1(2):e15 |
 Confocal imaging of the SVZ during EAE upregulating STAT1, an inducible transcription factor that mediates the effect of Th1 cytokine IFN-g in NSCs.
 Confocal imaging of radial glia transcription factor PAX6 and the newborn neurons marker (DCX) doublecortin in human cerebral organoids
|
|
Influence of the immune system on the Glioma stem cells programs
We investigate the mechanisms of glioma stem cells (GSC) responses to an immune microenvironment using deep sequencing, gene expression analysis and functional studies in Glioblastoma Organoids (GBMO). J Neurooncol. 2023 Jan;161(1):67-76. doi: 10.1007/s11060-022-04205-2 https://www.biorxiv.org/content/10.1101/2021.10.06.463228v1 https://www.biorxiv.org/content/10.1101/2022.03.17.484756v1 |
Confocal imaging of migratory cancer progenitors in human glioblastoma organoids
|
|
Clinical real-world Integrative MS research
The Imitola Lab is interested in how social determinants and environmental exposures operate as catalysts to accelerate molecular progression in MS. As such, the lab has embarked in the last four years in efforts to investigate social determinants in at risk populations. Our team has achieved that at multiple levels: 1) We created and directed the first AAN annual meeting course for diagnosis and treatment of MS in diverse populations in 2023 targeting general neurologists. 2) We created an educational tool, “the 4-square MS educational matrix” to help neurology residents, general neurologists, and patients learn about the modern proactive goals of care and the No evidence of disease activity (NEDA) visit Coban et al, 2021 Mult Scler Relat Disord. 2021 Jan;47:102631 (PMID: 33296855). 3) Our team defined the real-world impact of Ocrelizumab initiation in a diverse population. Coban et al, 2021 Mult Scler Relat Disord. 2021 Aug;53:103021.(PMID: 34077828). 4) Our team investigated new ways to decrease barriers to early diagnosis by utilizing DIR imaging in MS. Patel et al, 2023 (PMID: 36978252). J Neuroimaging. 2023 Jul-Aug;33(4):521-526. One of the most important barriers is understanding clinical phenotypes and awareness of early MS, we are developing strategies to fill this gap. |
Annual Meeting Course for MS in Diverse population in 2023
"4-square education matrix" to educate patients and trainees about the NEDA visit and goals of care in MS.
First real-world Ocrelizumab initiation study in diverse population in the US.
Study demonstrating the DIR-sequence in the brain is able to detect spinal cord lesions in MS patients
|