The mammalian immune system can be divided into two arms that act together to provide both immediate and long-term immunity to pathogens, the innate and adaptive immune branches, respectively. The more primitive, innate branch of the immune system provides critical regulation of adaptive immunity, in part through numerous germline-encoded pattern recognition receptors (PRR). These receptors include Toll-like receptors (TLR), NOD-like receptors (NLR), RIG-I-like RNA helicases and C-type lectin receptors.

TLRs have been extensively studied in this innate-adaptive interface, however a new class of PRRs, the NOD-like receptors, has recently been found to also regulate adaptive immune responses. However, for a majority of the 22 known NLR human family members, their triggers and physiologic function remain unknown.

Research Focus

Our lab focuses specifically on the role of DCs in shaping adaptive immunity and the stimuli that guide their activation.

We recently identified an unexpected role for a molecule that regulates the actin cytoskeleton, Dock8, in dictating whether certain types of DCs can migrate to lymph nodes or within the spleen. By disturbing the movement of certain DCs during the course of an immune response we can block adaptive immunity to a given insult. Beyond DC migration from a tissue, we have further found that the spatial organization of different types of DCs after immunization specifies the type of T cell activated and the particular effector response induced. The lab is currently working on understanding the signals that dictate this unique cellular organization and how that informs T cell fate. Our ultimate goal is to modulate DC movement in order to promote wanted immune responses and conversely block those that are deleterious.

Current Projects

·        Identifying which DCs can induce a productive Tfh-driven antibody response and how

·        How is induction of IgE to aeroallergens regulated

·        How is the immune response to food antigens induced

·        Characterizing the molecular pathways that regulate DC migration

·        Identifying innate immune receptors that trigger red blood cellalloimmunization