The long-range goal of Dr. Apicella's research is to understand the factors involved in the pathogenesis of human infections with a focus on nontypeable Haemophilus influenzae, a bacteria most commonly detected in lower airway of patients in the early stages of many diseases including CF, COPD, primary ciliary dyskinesia, and diffuse panbronchiolitis. Dr. Apicella hopes to ultimately develop pharmacologic and/or vaccination methods to inhibit the infectious process. To this end, his laboratory is combining state-of-the-art methodologies in molecular biology, cell biology, bioinformatics and macromolecular chemistry. Studies on nontypeable Haemophilus influenzae (NTHi) have shown that NTHi invades host cells by binding the platelet-activating factor (PAF) receptor via lipooligosaccharide glycoforms containing phosphorylcholine (ChoP). The binding of the PAF receptor by NTHi initiates receptor coupling to a pertussis toxin-sensitive heterotrimeric G protein complex, resulting in a multifactorial host-cell signal cascade and bacterial invasion. This signaling initiates a process that results in the movement of intracellular Ca2+ from the mitrochrondria to the cytosol, with the consequence that actin polymerizes and NTHi is internalized. Since Dr. Apicella joined the center, his research has expanded significantly to include mechanisms of NTHi infection in the airway epithelium. His research has benefited greatly from the use of in vitro polarized airway epithelia and in vivo human bronchial xenograft models through both the Cells and Tissue Core and the Animal Models Core. Future studies on NTHi will focus on mechanisms that this organism utilizes to survive within human airway epithelial cells, and the molecular mechanisms that are responsible for the transition of this usually commensal organism to the pathogenic state.
Selected Publications:
Greiner, L.L., Watanabe, H., Phillips, N.J., Shao, J., Morgan, A., Zaleski, A., Gibson, B.W., and Apicella, M.A. 2004. Nontypeable Haemophilus influenzae Strain 2019 Produces a Biofilm Containing N-Acetylneuraminic Acid That May Mimic Sialylated O-Linked Glycans. Infect Immun 72:4249-4260.
Allen, S., Zaleski, A., Johnston, J.W., Gibson, B.W., and Apicella, M.A. 2005. Novel sialic acid transporter of Haemophilus influenzae. Infect Immun 73:5291-5300.
Starner, T.D., Zhang, N., Kim, G., Apicella, M.A., and McCray, P.B., Jr. 2006. Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am J Respir Crit Care Med 174:213-220.
Johnston J.W., Coussens, N.P., Allen, S., Houtman, J.C.D., Turner, K.H., Zaleski, A., Ramaswamy, S., Gibson, B.W., and Apicella, M.A. Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (Siap) of nontypeable Haemophilus influenzae strain 2019. J Biol Chem, 283:855-865, 2008.
