I am the UVA 2012-2014 Hartwell Foundation Postdoctoral
My work is focused on the amazing ability of immune cells and molecules to modulate higher brain functions like learning and memory, to mediate CNS pathology, and serve as therapeutic targets in the amelioration of CNS disease. Specifically, I am interested in the ability of innate immune cells—e.g. monocytes, macrophages, microglia, and dendritic cells—to exert effects in the CNS.
I employ a wide variety of techniques aimed at (a) modifying immune function, including bone marrow transplant, ex-vivo manipulation and reintroduction of monocytes, in-vivo gene therapy targeting tissue-resident macrophages including microglia; (b) analyzing immune phenotype, including 16-color flow cytometry, and two-photon live imaging of the brain parenchyma, meningeal spaces, and skull bone marrow niche; and (c) measuring behavior, including Morris water maze, elevated plus maze, rotorod motor learning, and unrestrained breathing by plethysmography.
In terms of specific pathologies, of keen interest to me are meningitis—particularly in the setting of immune deficiency—and the devastating CNS developmental disease Rett syndrome. Rett syndrome was long thought to be caused solely by neuronal dysfunction. We recently showed that bone marrow transplant from wild type mice into Mecp2-null mutant mice (a model for the disease) leads to engraftment of bone marrow cells in the brain that function as microglia, and are associated with striking arrest of the disease.
These and other findings will hopefully open new avenues for understanding the basic mechanisms underlying nero-immune interactions in CNS health, homeostasis, and disease, and reveal novel treatment options for CNS pathologies.
Derecki NC, Cronk JC, Kipnis J. The role of microglia in brain maintenance: implications for Rett syndrome. Trends Immunol. 2012 Oct 30. S1471-4906(12)00177-9.
Kipnis J, Gadani S, and Derecki NC. Pro-cognitive
properties of T cells. Nat Rev Immunol. 2012
Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB, Guyenet PG, Kipnis J. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature. 2012 Mar 18;484(7392):105-9.
Derecki NC, Quinnies KM, Kipnis J. Alternatively
activated myeloid (M2) cells enhance cognitive function in immune
compromised mice. Brain Behav Immun. 2010 Nov
Derecki NC, Cardani AN, Yang CH, Quinnies KM, Crihfield A, Lynch KR, Kipnis J. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med. 2010 May 10;207(5):1067-80.
Derecki NC, Privman E, Kipnis J. Rett syndrome and other autism spectrum disorders--brain diseases of immune malfunction? Mol Psychiatry. 2010 Apr;15(4):355-63.
Kipnis J, Derecki NC, Yang C, Scrable H. Immunity and cognition: what do age-related dementia, HIV-dementia and 'chemo-brain' have in common? Trends Immunol. 2008 Oct;29(10):455-63.