John D MacMicking, PhD

Associate Professor of Microbial Pathogenesis and of Immunobiology; Investigator, Howard Hughes Medical Institute; Member, Yale Systems Biology Institute

Research Interests

Bacterial Infections and Mycoses; Cell Biology; Immunity, Innate; Interferons; Parasitic Diseases; Virus Diseases; Computational Biology; Inflammasomes

Research Organizations

Microbial Pathogenesis


Faculty Research

Office of Cooperative Research

Research Summary

Our laboratory focuses on the biological question of how all nucleated cells - irrespective of tissue origin - protect themselves against infection. This broad-based system of non-classical host defense is called cell-autonomous immunity and has recently been studied in plants but remains poorly understood in higher vertebrates. We are interested in characterizing the antimicrobial genes and circuitry which constitute the cell-autonomous defense network in mammals. Many of these genes including a new superfamily of immune GTPases are transcriptionally elicited via activating stimuli such as interferon (IFN) signalling. The overall goal is to understand how individual cells protect themselves against major human pathogens in vitro and in vivo. Some of the questions we are interested in are the following: What are the protein machineries and signaling hubs involved in restricting intracellular pathogens? Do such pathways operate in the cytosol or on specialized organelles, and is this response tailored to the subcellular lifestyle of the invading pathogen? Are common sets of host effectors shared across all diploid cells, or are there cell type-specific systems deployed in diverse histogenetic lineages and tissues? Lastly, can we reconstruct a virtual cell that assembles these host effector proteins and pathways in a computationally coherent way? Answering these questions should help define the basic principles underlying this unique form of host resistance in complex, multicellular organisms.

Specialized Terms: Cell-autonomous immunity; Constitutive and inducible host defense programs; Inflammasomes; Interferons (IFNs); Intracellular pathogens; Single cell analyses; Vertebrate and pathogen genetics

Selected Publications

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Contact Info

John D MacMicking, PhD
Mailing Address
Microbial PathogenesisHHMI, Yale Systems Biology Institute
850 West Campus Drive, ISTC 341

West Haven, CT 06516-7389