Mike Vitek Lab

Michael Vitek, Ph.D.

Associate Professor, Neurology

Duke University Medical Center

PO Box 2900

Durham, NC 27710

Phone: (919) 684-0055

Fax: (919) 684-6514

Email: vitek001@mc.duke.edu

Express Mail Deliveries:

Bryan Research Building 201D

Duke University Medical Center

Durham, NC 27710

Description of Research Interests in the Laboratory of Michael P. Vitek, Ph.D.

In collaboration with the Colton-lab, we have pursued and expanded our understanding of the role that apolipoprotein-E (apoE) plays in a number of chronic and acute neurodegenerative diseases. Unlike all other animals, humans possess multiple alleles of the APOE gene that encode multiple apoE protein isoforms. As first described by Vance and Roses, patients carrying the APOE epsilon 4 allele that encodes the apoE4 protein isoform suffer an earlier onset of Alzheimer's disease (AD); by 10 years if they carry one APOE4 allele and by almost 20 years if they carry two APOE4 alleles.

Emergent work from a number of labs around the world has confirmed the finding that APOE4 does not cause AD, but is a susceptibility gene for an earlier and/or more pronounced form of the disease. This linking of APOE4 to increased susceptibility and/or of a more severe disease has been extended to traumatic brain injury (TBI), hemorrhagic stroke, subarachnoid hemorrhage (SAH), dementia pugilistica, parkinson's disease (PD) and multiple sclerosis (MS). These genetic findings, association of APOE4 and earlier/worse disease severity, has guided our quest to understand how apoE protein isoforms confer a more severe disease state.

Working with the Colton lab, we have developed the hypothesis that apoE3 suppresses inflammation more than apoE4 protein isoforms. Inflammation in the brain is mainly due to cells of the innate immune system. These innate immune cells are microglia, the brains' equivalent of a macrophage, and astrocytes. Innate immune reactions present in acute brain infections include release of cytokines, release of reactive nitrogen and reactive oxygen free radicals, release of proteases and activation of phagocytic programs. Some or all of these aspects of inflammation are also present in chronic neurodegenerative diseases. In both acute and chronic conditions, it appears that the inflammatory response is more pronounced when apoE4 is present and is less severe when apoE3 protein isoforms are present.

Using this working hypothesis, we have tested transgenic animal models of Alzheimer's disease, Huntington's disease and models of oxidative and nitrosative stress. Together with immunological models of Multiple Sclerosis, pharmacological models of Parkinson's disease and whole body ionizing radiation, we continue to study the signaling pathways that are differentially influenced by apoE protein isoforms. We have recently found that certain disease conditions are associated with classical activation state of inflammation, while others are associated with an alternative activation state of inflammation. These states are very important to both acute and chronic insults to the brain, because they define both the extent of inflammatory damage that can be inflicted upon neurons, but also because they define the time course and quality of the resolution of the brain inflammation associated with disease. To extend these concepts, we are also extremely interested in the role played by innate immunity in the repair of brain cells damaged by inflammatory disease.

Recent publications from the Laboratory of Michael P. Vitek, Ph.D.:

Current Lab Members:

Nastaran Gharkholonarehe

Former Lab Members:

Feng Qiao Li, Ph.D.

Nobutaka Ohkubo, Ph.D.

Candice Brown, Ph.D.

Nolan Yeung

Current Positions Available:

None at present.