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David Underhill, PhD
Director, Graduate Program in Biomedical Sciences and Translational Medicine
Research Scientist, Gastroenterology
Associate Director, Division of Immunology Research, Biomedical Sciences
|Professor, Biomedical Sciences|
Awards and Activities
|Janis & William Wetsman Family Chair in Inflammatory Bowel Disease||2009|
|Established Investigator of the American Heart Association||2006|
|Irvington Institute Postdoctoral Fellowship||1996 - 1999|
Although inflammation is essential for the body to protect itself against infection, when the process becomes overly aggressive it contributes to a host of inflammatory conditions including inflammatory bowel diseases, heart disease, autoimmune disorders, and sepsis. The laboratory studies the molecular mechanisms by which blood phagocytes such as macrophages and dendritic cells recognize microbial pathogens and initiate inflammatory responses. Further, a central question in immunology is to understand how inflammatory responses become tailored to specific microbial infections, and we hypothesize that phagocytosis, the process by which these cells eat foreign microbes, is a key part of this. The laboratory has used coordinated recognition of fungal pathogens by the C-type lectin receptor Dectin-1, and the Toll-like receptor TLR2 as a model for defining how different innate immune receptors can work together to orchestrate very specific inflammatory responses. Hopefully, understanding in exquisite detail how macrophages and dendritic cells translate recognition of microbes into inflammatory responses will lead to the design of targeted interventions to clinically manipulate these processes.
Key contributions to our understanding of how innate immunity initiates host defense. Have specifically championed the role of phagocytes in immunity and the role of phagocytosis in signal transduction.
Current investigations include:
Defining signal transduction mechanisms activated by innate immune receptors in macrophages and dendritic cells. Learning about how these signals can be modified to shape inflammatory responses - both for improved host defense and for tempering the inflammatory tissue damage that is often associated with active immunity.
- Underhill DM, Goodridge HS: Information processing during phagocytosis. Nat. Rev. Immunol., 12(7): 492-502, 2012
- Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, Brown J, Becker CA, Fleshner PR, Dubinsky M, Rotter JI, Wang HL, McGovern DP, Brown GD, Underhill DM: Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science, 336(6086): 1314-7, 2012
- Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, Ramanujan VK, Wolf AJ, Vergnes L, Ojcius DM, Rentsendorj A, Vargas M, Guerrero C, Wang Y, Fitzgerald KA, Underhill DM, Town T, Arditi M: Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity, 36(3): 401-14, 2012
- Wolf AJ, Arruda A, Reyes CN, Kaplan AT, Shimada T, Shimada K, Arditi M, Liu G, Underhill DM: Phagosomal degradation increases TLR access to bacterial ligands and enhances macrophage sensitivity to bacteria. J. Immunol., 187(11): 6002-10, 2011
- Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, Bose N, Chan AS, Magee AS, Danielson ME, Weiss A, Vasilakos JP, Underhill DM: Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. Nature, 472(7344): 471-5, 2011
- Shimada T, Park BG, Wolf AJ, Brikos C, Goodridge HS, Becker CA, Reyes CN, Miao EA, Aderem A, Götz F, Liu GY, Underhill DM: Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion. Cell host & microbe, 7(1): 38-49, 2010