Kevan L. Hartshorn, MD
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PI: Kevan L. Hartshorn, MD
Title: Professor of Medicine, Fellowship Program Director |
Research Summary:
Our research principally deals with innate immunity, which refers to immune responses that are hard-wired into the genome and provide a first line of protection against infection or transformed cells. Innate immune responses are sometimes also responsible for damaging inflammation. Defects or variants in innate immunity account for increased propensity for infections or harmful inflammation. As an example, people lacking one of the collectins found in blood are at greater risk for infection during neutropenia and have a greater risk for certain cancers. There is surprising complexity and specificity to innate immunity despite the fact that it provides protection even when a person has not been exposed to a specific infection. The main aspects of innate immunity we study include neutrophils and monocyte/macrophages, toll like receptors, and soluble immune defense proteins called collectins and defensins. We study how neutrophils and monocytes become activated in response to infectious organisms (viruses and bacteria), including studies of cell signaling, phagocytosis and oxidant production. We study how defensins and collectins kill bacteria or viruses and promote their uptake by neutrophils and monocytes. We have created or collaborate to create and test a variety of new recombinant versions of collectins and defensins, some of which have strongly increased antiviral or antibacterial activity. We also collaborate with members of the department of Biophysics in crystallographic studies of collectin structure in order to predict protein changes that might confer greater antimicrobial activity. We also collaborate in use of mouse models (e.g., mice in which collectin genes are deleted) to study the role of specific innate immune mediators in infection. A particular area of interest for us is the innate immune response to respiratory infection, especially influenza virus infection. Influenza virus and HIV (which we also study to some extent) are important examples of infections for which innate immunity is important since these viruses undergo continuous mutation thus evading adaptive immune responses (i.e., specific T and B cell responses). Below are listed some of our recent publications.
Lab Personnel:
Mitch White, MPH
Lab Manager
Shweta Tripathi, PhD
Post-Doctoral Fellowr
Tanya Cafarella
Research Techinian
Publications:
1. Tecle T, White MR, Crouch EC, and Hartshorn KL. 2007. Human neutrophil defensins increase neutrophil uptake of influenza A virus and bacteria and modify virus induced respiratory burst responses. Journal of Immunology. 178: 8046-8052.
2. White MR, Tecle T, Crouch EC, and Hartshorn KL. 2007. Impact of neutrophils on antiviral activity of human bronchoalveolar lavage fluid. American Journal of Physiology Lung Cell Molec Physiol. 293: L1293-9.
3. Tecle T, White MR, Sorensen GL, Gantz D, Kacak N, Holmskov U, Smith K, Crouch EC, Hartshorn KL. 2008. Critical role for crosslinking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus. Biochemical Journal. 412:323-9
4. Mitchell R. White, Eva J. Helmerhorst, Antoon Ligtenberg, Marshall Karpel, Tesfaldet Tecle, Walter L. Siqueira, Frank G. Oppenheim, Kevan L. Hartshorn. 2008. Multiple components contribute to the ability of saliva to inhibit influenza viruses. Oral Microbiology and Immunology. 24:18-24.
5. Hartshorn KL, Webby T, White MR, Tecle T, Pan C, Boucher S, Moreland RJ, Crouch EC, and Scheule RK. 2008. Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D. Respiratory Research. Sept. 9:1
6. White MR, Kingma P, Tecle T, Kacak N, Linders B, Heuser J, Crouch EC, and Hartshorn KL. 2008. Multimerization of surfactant protein D, but not its collagen domain, is required for antiviral and opsonic acitivities related to influenza virus. Journal of Immunology. 181: 7936-7943.
