We are broadly interested in understanding how the physiology and evolution of multicellular organisms is shaped by their interaction with microbes. Our experimental system is focused on Caenorhabditis elegans, which we were motivated to use in our studies because of the powerful molecular genetic tools that have been developed over forty years to study biology in this simple animal host organism. We started with a forward genetic approach to identify genes required for host survival during microbial infection, identifying a role for evolutionarily conserved innate immune signaling pathways in C. elegans defense against pathogenic bacteria (Kim et al., 2002). The genetic analysis of host defense of C. elegans, using both standard laboratory strains as well as strains of C. elegans isolated from the wild, has led to the identification and characterization of multiple modes of host defense, including innate immunity (Troemel et al., 2006; Shivers et al., 2010; Youngman et al., 2011), host tolerance to the stress induced by infection (Richardson et al., 2010; Richardson et al., 2011), and behavioral avoidance (Reddy et al., 2009, Shivers et al., 2009; Reddy et al., 2011; Chang et al., 2011).
Our studies in these areas have broadened our perspectives and developed into three principal areas of current interest: 1) Genetic analysis of chemosensory signaling mechanisms and neuroendocrine signals involved in microbial recognition (Meisel et al., 2014), 2) Cell-autonomous and cell-non-autonomous mechanisms of stress signaling and homeostasis in development, immunity, and aging (Kulalert et al., 2013), and 3) The identification and characterization of small molecules, derived from both host and microbe, that mediate communication between host and microbe and may serve as the basis for the development of novel antimicrobial agents (in collaboration with F. Schroeder at Cornell U.).
Pagano D.J., Kingston E.R., and Kim D.H. (2015) Tissue Expression Pattern of PMK-2 p38 MAPK Is Established by the miR-58 Family in C. elegans. PLoS Genetics 10(2): e1004997.
Meisel, J.D., Panda, O., Mahanti, P., Schroeder, F.C., Kim, D.H. (2014) Chemosensation of Bacterial Secondary Metabolites Modulates Neuroendocrine Signaling and Behavior of C. elegans. Cell 159, 267-280.
Meisel, J.D., Kim, D.H. (2014) Behavioral avoidance of pathogenic bacteria by Caenorhabditis elegans. Trends in Immunology 35, 465-470.
Kulalert, W., Kim, D.H. (2013) The Unfolded Protein Response Promotes C. elegans Entry into Dauer Diapause. Current Biology 23, 2540-2545.
Kim, D.H. (2013) Bacteria and the Aging and Longevity of Caenorhabditis elegans. Annual Reviews of Genetics 47, 233-246.
Chang, H.C., Paek, J., Kim, D.H. (2011) Natural Polymorphisms in C. elegans HECW-1 E3 Ligase Affect Pathogen Avoidance Behaviour. Nature 480, 525-529.
Richardson, C.E., Kinkel, S., Kim, D.H. (2011) Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Development and Immunity. PLoS Genetics 7(11), e1002391.
Youngman, M.J., Rogers, Z.N., Kim, D.H. (2011) A Decline in p38 MAPK Signaling Underlies Immunosenescence in Caenorhabditis elegans. PLoS Genetics 7(5), e1002082.
Reddy, K.C., Hunter, R.C., Bhatla, N., Newman, D.K., Kim, D.H. (2011) Caenorhabditis elegans NPR-1-Mediated Behaviors Are Suppressed by Mucoid Bacteria. Proc. Natl. Acad. Sci. USA 108, 12887-12892.
Richardson, C.E., Kooistra, T., Kim, D.H. (2010) An Essential Role for XBP-1 in Host Protection against Immune Activation in C. elegans. Nature 463, 1092-1095.
Shivers, R.P.*, Pagano, D.J.*, Kooistra, T., Richardson C.E., Reddy, K.C., Whitney, J.K., Kamanzi, O., Matsumoto, K., Hisamoto, N., Kim, D.H. (2010) Phosphorylation of the Conserved Transcription Factor ATF-7 by PMK-1 p38 MAPK Regulates Innate Immunity in Caenorhabditis elegans. PLoS Genetics 6(4):e1000892.
Shivers, R.P.*, Kooistra, T.*, Chu, S.W., Pagano, D.A., Kim, D.H. (2009) Tissue-Specific Activities of an Immune Signaling Module Regulate Physiological Responses to Pathogenic and Nutritional Bacteria in C. elegans. Cell Host Microbe 6, 321-330.
Reddy, K.C., Andersen, E.C., Kruglyak, L., Kim, D.H. (2009) A Polymorphism in npr-1 Is a Behavioral Determinant of Pathogen Susceptibility in C. elegans. Science 323, 382-384.