David Underhill, PhD Director, Graduate Program in Biomedical Sciences and Translational Medicine Research Scientist, Gastroenterology
Email: david.underhill@cshs.org Phone: (310) 423-7654 Fax: (310) 423-0224

Institute Affiliation

Academic Appointments

Awards and Activities

Research Focus

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.

Research Contributions

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.

Selected Publications

1. 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
2. Goodridge HS, Shimada T, Wolf AJ, Hsu YM, Becker CA, Lin X, Underhill DM: Differential use of CARD9 by Dectin-1 in macrophages and dendritic cells. J. Immunol., 182(2): 1146-54, 2009
3. Underhill DM: Collaboration between the innate immune receptors dectin-1, TLRs, and Nods. Immunol. Rev., 219: 75-87, 2007
4. Goodridge HS, Simmons RM, Underhill DM: Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J. Immunol., 178(5): 3107-15, 2007
5. Underhill DM, Rossnagle E, Lowell CA, Simmons RM: Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood, 106(7): 2543-50, 2005
6. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM: Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J. Exp. Med., 197(9): 1107-17, 2003