Hiltbold-Schwartz Laboratory

Elizabeth Hiltbold

Assistant Professor
B.S., Auburn University
Ph.D., Emory University, 1996

e-mail: bhiltbol@wakehealth.edu
phone: (336) 716-8246


“I am the product of excellent mentoring and strive to pass along the skills and insights I have acquired from my training to my students. My lab environment enables me to interact with my students side-by-side and witness their growth and development as scientists. I try to create an environment in which my students can become comfortable with a broad repertoire of scientific techniques and develop their skills as independent researchers through a free exchange of ideas.”

Antigen Presenting Cell Activation in Response to Bacterial Infection
My lab is interested in how adaptive immune responses to intracellular bacterial pathogens are initiated and regulated. In order to clear intracellular bacterial infection, T cells must be activated to specifically kill infected cells. Naïve T cells require three signals for activation. The first signal is provided by presentation of the appropriate MHC-peptide complexes, the second signal is mediated by costimulatory molecules and the third is cytokines such as interleukin 12 and type I interferon. Dendritic cells (DC) are a population of antigen presenting cells that is uniquely qualified to provide all of these signals and activate naïve T cells. Upon exposure to pathogen-associated molecules, DC undergo a maturation process characterized by enhanced expression of MHC and co-stimulatory molecules. This process is coordinately regulated by pattern recognition receptors such as Toll-Like Receptors (TLR), cytoplasmic receptors, scavenger receptors, and cytokine receptors.

Listeria monocytogenes, an intracellular bacterial pathogen, is an excellent model organism to investigate the molecular mechanisms through which DC maturation is regulated the intersection of the innate and adaptive immune responses. Protective immunity to Listeria is primarily mediated by cytolytic T cells (CTL). Initiation of this adaptive immune response however, requires the active participation of the innate immune system. Interaction of Listeria monocytogenes with TLR on DC triggers a cascade of signaling events resulting in the up-regulation of costimulatory molecules and the production of a host of cytokines and bactericidal molecules. A second wave of activating signals is initiated when the bacteria escape from the phagosome into the cytoplasm. These combined events cause the DC to differentiate into very potent cells for T cell priming. Our goal is to delineate the molecules on the DC involved in the recognition of the bacteria and how the activation of these signaling pathways gives rise to the maturation phenotypes that impact T cell activation.

DC maturation is a highly complex, time-ordered process involving changes at many levels including gene expression, intracellular transport, cytoskeletal activity, and localization within the host. The gene expression network, the dynamic process of interaction among gene expression, regulatory sequences, and trans-acting factors, underlying this process is extremely important for controlling many of the observed changes. The long-term goal of our computational modeling project is to understand, at a systems level, the biology that underlies DC maturation following stimulation by infectious agents. We aim to identify novel, previously undefined components of the DC maturation network and to identify cause-and-effect relationships that explain how DC maturation is controlled upon exposure to various infectious agents. Because DC maturation is such a pivotal event for protective immune response development, and these cells are currently targeted in the design of many vaccine formulations, gaining a broader understanding of the gene expression program and the comprehensive transcriptional regulatory network underlying their maturation is key for the identification of new targets for the design and development of vaccines and therapies against infectious agents.