John E. Coligan, Ph.D.

Chief, Receptor Cell Biology Section

Dr. Coligan received his Ph.D. from Indiana University and did postdoctoral research at the City of Hope Research Institute. After 2 years as an assistant professor at Rockefeller University, he was a founding member of the Laboratory of Immunogenetics, NIAID, NIH. He has served as head of the Biological Resources Branch and Laboratory of Molecular Structure. In 1998, he joined the Laboratory of Allergic Diseases and became chief of the Receptor Cell Biology Section. In 2007, this section moved to the Laboratory of Immunogenetics.

Description of Research Program

The primary focus of our research is the receptors that dictate natural killer (NK) cell function. NK cells are an integral component of the innate immune response against infectious diseases and malignant transformation. In addition to their ability to lyse infected and transformed cells, they serve as a potent source of cytokines for potentiating both the innate and adaptive immune responses.

NK cells express a large variety of "activation" receptors for recognizing potential target cells; many of these receptors recognize ligands on normal cells. "Inhibitory receptors" that also recognize ligands expressed on normal cells, but are down-regulated on aberrant cells, modulate the potentially self-destructive activation signals.

Our interests encompass all facets of factors that regulate NK-cell receptor expression, ligand recognition, signal transduction, and intracellular trafficking, with particular emphasis on the NKG2 family of receptors, which contains both activating (CD94/NKG2C,NKG2D, CD94/NKG2E,-H) and inhibitory members (CD94/NKG2A,-B). The activating receptors must associate with adaptor molecules, DAP-10 or DAP-12, to gain signaling capabilities and to facilitate cell surface expression. Because of NKG2D's importance in fighting tumorigenisis and its demonstrated involvement in autoimmune diseases, such as celiac disease and diabetes, we have an intense interest in factors that regulate the expression of NKG2D. Transcriptional regulation of DAP-10 expression appears to be of prime importance.

Recent observations indicating that NKG2 receptors play a role in T-cell function have led us to expand our interest to this cell type, particularly CD8+ T cells. In particular, we are examining the role that NKG2D plays in co-stimulating the TCR-induced response of human, naïve CD8+ T cells. Our studies indicate that NKG2D, through interaction with its ligands, MICA, MICB, and UBLP-1,-2, or -3, may provide an important pathway for inducing and channeling the human immune response. In conjunction with these studies, we are examining how the ITIM bearing inhibitory receptors, LAIR-1 and IRp60, serve to down regulate or prevent activation of human T cells, as well as other immune cells.

Finally, we have recently begun to study the relationship of receptor-ligand interaction and trafficking to signal transduction for the IgE receptor on mast cells, FcεRI. This mast cell receptor plays a primary role in inducing allergic reactions.

Major Areas of Research

• Transcriptional regulation of expression of DAP-10, CD94, and NKG2 genes
• Analysis of NK receptor/target ligand interaction, emphasizing confocal microscopic and other cell imaging techniques
• Cell biology of NK-receptor trafficking focusing on common and distinguishing features of activation and inhibitory receptors
• NK-receptor signal transduction emphasizing the interplay of activating and inhibitory signals
• Role of NKG2 receptors in regulating T-cell function
• Interplay of receptor trafficking and signaling in mast cells
• Function of the LAIR-1 and IRp60 inhibitory receptors on immune cells 

Memberships

• American Association of Immunologists
• Society for Natural Immunity
• American Society for Biochemistry and Molecular Biology

Research Group Members

Francisco Borrego, M.D., Ph.D.; Steven Burgess, Ph.D.; Gul’nar Fattakhova, Ph.D.; Xiaobin Tang, Ph.D.; Kerima Maasho, Ph.D.; Alina Marusina, Ph.D.; Madhan Masilamani, Ph.D.; Sriram Narayanan, Ph.D.; Yelina Alvarez; Martha Prieto; Robert Valas.

Editorial Boards

• Current Protocols in Immunology
• Current Protocols in Protein Science
• Journal of Biomedical Science
• Immunologic Research

Selected Recent Publications

To view a complete listing, visit PubMed.

Fattakhova G, Masilamani M, Borrego F, Gilfillan A, Metcalfe DD, Coligan JE. The high affinity IgE receptor (FceRI) is endocytosed by an AP-2/clathrin-independent, dynamin-dependent mechanism. Traffic. 7: in press 2006.

Burgess SJ, Marusina AI, Pathmanathan I, Borrego F, Coligan JE. IL-21 down-regulates NKG2D/DAP-10 expression on human NK and CD8+ T cells. J Immunol. 2006. 176: 1490-1497.

Marusina A, Kim D-K, Lieto LD, Borrego F, Coligan JE. GATA-3 is an important transcription factor for regulating human NKG2A gene expression. J Immunol. 2005. 174: 2152-2159.

Kim D-K, Kabat J, Borrego F, Sanni TB, You C-H, Coligan JE. Human NKG2F is expressed and can associate with DAP-12. Molecular Immunol. 2004. 41: 53-62.

Sanni T, Masilamani M, Kabat J, Coligan JE, Borrego F. Exclusion of lipid rafts and decreased mobility of CD94/NKG2A receptors at the inhibitory NK cell synapses. Mol Biol Cell. 2004. 15: 3210-3223.

Lieto LD, Borrego F, You C-H, Coligan JE. Human CD94 gene expression: dual promoters differing in responsiveness to IL-2 or IL-15. J Immunol. 2003. 171: 5277-5286.

Borrego F, Kabat J, Kim D-K, Lieto L, Maasho K, Pena J, Solana R, Coligan JE. Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Molecular Immunol. 2002. 38: 637-660.

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