Dwight Look, M.D. (Full Member)
Associate Professor of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA

http://www.int-med.uiowa.edu/Divisions/Pulmonary/Directory/DwightLook.html

Research Interest    

Epithelial cells play a critical role in regulating responses to injury or invasion in the airway, and are among the first lines of defense against inhaled infectious agents. Accordingly, Dr. Look's research interests focus on the regulation of genes that are critical in mediating immune and inflammatory responses to microbes by airway epithelial cells. His laboratory uses transformed and primary cultures of human tracheobronchial epithelial cells and airway infection of mice as model systems to examine the effects of viral (e.g., adenovirus, respiratory syncytial virus) and bacterial (e.g., Haemophilus influenzae, Pseudomonas aeruginosa) infection on airway epithelial cells. Studies of these infectious agents are directly relevant to our understanding of both the mucosal immunity elicited by gene therapy vectors and the pathogenesis of lung infections in cystic fibrosis (CF). Studies in Dr. Look's laboratory have suggested that interactions between adenovirus and a number of proteins in the IFN-gamma-dependent signal transduction pathway enable adenovirus to more fully subvert the immune response. They also suggest that it may be the inability of E1A-deficient recombinant adenovirus to perform this action that promotes the inflammatory response during gene therapy with adenoviral vectors. Damage to the respiratory system in CF is believed to result primarily from the overwhelming burden of bacterial infection and inflammation on the respiratory epithelial surface. A more in-depth understanding of mechanisms that regulate bacteria-induced airway inflammation may offer hints toward the development of selective regulators of inflammatory response gene expression, that may in turn modulate airway inflammation in patients with CF.

Selected Publications:

Look, D.C., Chin, C.L., Manzel, L.J., Lehman, E.E., Humlicek, A.L., Shi, L., Starner, T.D., Denning, G.M., Murphy, T.F., and Sethi, S. Modulation of airway inflammation by Haemophilus influenzae isolates associated with chronic obstructive pulmonary disease exacerbation. Proc Am Thorac Soc 3:482-483, 2006.

Groskreutz DJ, Monick MM, Powers LS, Yarovinksy TO, Look DC, Hunninghake GW. Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. J. Immunol. 176:1733-1740, 2006.

Humlicek AL, Manzel LJ, Chin CL, Shi L, Excoffon KJDA, Winter MC, Shasby DM, Look DC. Paracellular permeability restricts airway epithelial responses to selectively allow activation by mediators at the basolateral surface. J. Immunol. 178:6395-6403, 2007.

Shi L, Ramaswamy M, Manzel LJ, Look DC. Inhibition of Jak1-Dependent Signal Transduction in Airway Epithelial Cells Infected with Adenovirus. Am. J. Respir. Cell Mol. Biol. 37:720-728, 2007.

Publications from Gene Therapy Center

Publications from PubMed