The contribution of the immune system to homeostatic brain function is a growing field that is still not well understood; however, neuroinflammation is increasingly associated with neurocognitive disorders including Alzheimer’s disease (AD) and post-infectious West Nile virus (WNV) encephalitis, illustrating a need for better understanding of these interactions. My current research investigates the innate immune response of neurons and the impact of microglia in recovery from WNV neurotropic infection. Cognitive dysfunction is a well-documented correlate of viral encephalitis; however the underlying molecular mechanisms are unclear, in part due to lack of murine recovery models. To study the mechanisms of recovery from viral encephalitis, I use a murine model of intracranial infection with an attenuated strain of West Nile virus (WNV). My overarching hypothesis is that viral encephalitis incites inflammation that accelerates processes of CNS aging, contributing to the development of AD pathology and neurodegeneration.
Research in my laboratory uses the WNV encephalitis model to investigate I) how neuroinflammation alters genetic and synaptic programs, which affect and denote aging processes, II) how aging affects microglial response to inflammatory events, altering neuroinflammatory signatures, and III) how neuroinflammatory events affect pathological Tau accumulation, a well-studied correlate of neurodegeneration.
Education and Training
- 2014-2019 – Postdoctoral research associate with Robyn Klein M.D. Ph.D., Washington University School of Medicine, St Louis, Missouri, Department of Internal Medicine, Division of Infectious Diseases
- 2012-2014 – Postdoctoral research associate with Marc Diamond M.D., Washington University School of Medicine, St Louis, Missouri, Department of Neurology
- 2007-2012 – Ph.D. in Molecular, Cellular, and Developmental Biology with Jeff Kuret Ph.D., Ohio State University, Columbus, Ohio, Department of Molecular and Cellular Biochemistry
- 2004-2007 – B.A. in Zoology, Miami University, Oxford, Ohio
Current Research Support
R00 AG053412 PI: Funk 8/19/2019-8/18/2022, Neurotropic Viral Infection in CNS Aging and Alzheimer’s disease
- Klein RS, Garber CJ, Funk KE, Salimi H, Soung A, Kanmogne M, Manivasagam S, Agner S, Cain M. Neuroinflammation during RNA viral infections. Annu Rev of Immunol. 2019; 37.
- Funk KE and Klein RS. CSFR1 antagonism limits local restimulation of antiviral CD8+ T cells during viral encephalitis. J Neuroinflammation. 2019; 16:22
- Vasek MJ, Garber C, Dorsey D, Durrant DM, Bollman B, Soung A, Yu J, Perez-Torres C, Frouin A, Wilton DK, Funk K, DeMasters BK, Jiang X, Bowen JR, Mennerick S, Robinson JK, Garbow JR, Tyler KL, Suthar MS, Schmidt RE, Stevens B, Klein RS. A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature. 2016 Jun 23; 534 (7608): 538-43. PMID: 27337340.
- Funk KE, Mirbaha H, Jiang H, Holtzman DM, Diamond MI. Distinct therapeutic mechanisms of Tau antibodies: promoting microglial clearance vs. blocking neuronal uptake. J Biol Chem 2015; 290(35): 21652-62. PMID: 26126828
- Funk KE*, Thomas SN*, Schafer KN, Cooper GL, Liao Z, Clark DJ, Yang AJ, Kuret J. Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity. Biochem J 2014; 462(1): 77-88. PMID: 24869773 *These authors contributed equally to this work
- Thomas SN*, Funk KE*, Wan Y, Liao Z, Davies P, Kuret J, Yang AJ. Dual modification of Alzheimer’s disease PHF-tau protein by lysine methylation and ubiquitylation: a mass spectrometry approach. Acta Neuropathol 2012; 123(1):105-117. PMID: 22033876 *These authors contributed equally to this work