Department of Neuroscience
Director, Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program
Assistant Professor, Department of Neuroscience and Neurology
Research Interests: The molecular basis for the responses of neural stem cells (NSCs) to injury and chronic neuroinflammation is unknown. In mouse models of multiple sclerosis, chronic neuroinflammation has deleterious effects in NSCs (Imitola et. al., 2011) by decreasing their self-renewal capacity.
The goal of the Imitola laboratory is to identify and validate genes that mediate the responses of neural stem cells (NSCs) to central nervous system (CNS) injury in multiple sclerosis and brain cancer in the so-called injury-induced stem cell niches.
Few candidate genes have been validated for NSCs function in CNS pathology such as the chemokine receptor CXCR4 that mediates the migration of human NSCs to sites of injury and brain tumors. (Imitola et al, 2004) Imitola's team hopes to translate novel molecular targets on NSCs to enhance human central nervous system repair and regeneration.
- Inflammation transcriptional control of NSCs and brain cancer stem cell intrinsic properties
- Modeling inflammation-induced neurodegeneration and repair with iPSCs
Research Techniques: iPSCs, cell culture, isolation of neural stem cells from multiple sclerosis models, confocal microscopy, organotypical slices, RNA isolation and gene expression analysis with computational biology tools
Selected Publications:Imitola J*, Rasmussen S*, et al. Reversible neural stem cell niche dysfunction in a model of multiple sclerosis. Ann Neurol. 2011 May; 69(5):878-91. (Co-first) (Cover).
Imitola J, et al. Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice. J Biomed Opt. 2011 Feb; 16(2):021109.
Starossom SC*, Imitola J*, et al. Subventricular zone microglia transcriptional networks. Brain Behav Immun. 2011 Jul; 25(5):991-9 (Co-first)
Wang Y, Imitola J, et al. Paradoxycal dysregulation of the neural stem cell pathway sonic hedgehog-Gli1 in autoimmune encephalomyelitis and multiple sclerosis. Ann Neurol. 2008 Oct; 64(4):417-27.
Esposito G, Imitola J, et al. Genomic and functional profiling of human Down syndrome neural progenitors implicates S100B and aquaporin 4 in cell injury. Hum Mol Genet. 2008 Feb 1; 17(3):440-57.
Rasmussen S, Wang Y, Kivisäkk P, Bronson RT, Meyer M, Imitola J*, Khoury SJ*. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing-remitting experimental autoimmune encephalomyelitis. Brain. 2007 Nov; 130(Pt 11):2816-29. (Co-correspondent authors).
Imitola J, et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18117-22. (Cited 545 times).
Imitola J, et al. Am J. Neural stem/progenitor cells express costimulatory molecules that are differentially regulated by inflammatory and apoptotic stimuli. Am J. Pathol. 2004 May;164(5):1615-25.
Sheen VL, Ganesh VS, Topcu M, Sebire G, Bodell A, Hill RS, Grant PE, Shugart YY, Imitola J, Khoury SJ, Guerrini R, Walsh CA. Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Nat Genet. 2004 Jan; 36(1):69-76.
MD: University of Cartagena
Center for Neurologic Diseases, Harvard Stem Cell Institute, Harvard Medical School