Faculty Profiles

Current Research:

My laboratory studies cellular and molecular mechanisms underlying chronic airways diseases such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis and bronchopulmonary dysplasia. At this time, we are focusing on three main projects. First, we are studying the mechanisms by which rhinovirus, a common cold virus, induces exacerbations of asthma and COPD. We hypothesize that, in airway epithelial cells, binding and internalization of rhinovirus is sufficient to increase the activity of pro-inflammatory biochemical signaling pathways which are co-stimulated by pro-asthmatic cytokines and bacteria, leading to additive or synergistic responses. Specifically, we are examining the roles of the phosphatidylinositol (PI) 3-kinase/Akt and mitogen-activated protein kinase pathways in this process.

 

Second, we are studying the biochemical signaling mechanisms by which airway smooth muscle cells increase their size and contractile protein expression, each of which would be expected to increase smooth muscle contraction and airway narrowing in asthma. We are examining the role of translational control pathways in this process, including those regulated by PI 3-kinase, mammalian target of rapamycin (mTOR), eukaryotic initiation factor (eIF)-4E, 4E-binding protein (4E-BP), p70 ribosomal S6 kinase and glycogen synthase kinase-beta.

 

Third, we are studying the role of lung mesenchymal stem cells in the pathogenesis of chronic lung disease in infants. We have isolated these cells from the airway secretions of premature infants with respiratory distress syndrome. We plan to determine how mesenchymal stem cells are recruited to airspaces, characterize potential mechanisms by which these cells participate in lung repair, and determine whether they are a biomarker for the development of chronic lung disease. Based on their potential role in lung development, we would like to extend this work to determine whether mesenchymal stem cells could be used to treat diseases like emphysema, bronchopulmonary dysplasia and congenital diaphragmatic hernia, diseases in which air sacs are broken down by chronic inflammation or do not form normally.

 

 

 

Recent Publications:

Zhou L, Goldsmith AM, Bentley JK, Jia Y, Abe M, Fingar D, Hershenson MB. 4E-BP phosphorylation and eIF4E release are required for airway smooth muscle hypertrophy. Am J Respir Cell Mol Biol 33:195-202,2005.

 

Newcomb DC, Sajjan U, Nanua S, Jia Y, Goldsmith A, Bentley JK, Hershenson MB. PI 3-kinase is required for rhinovirus-induced airway epithelial cell IL-8 expression. J Biol Chem 280:36952-61, 2005.

 

Goldsmith AM, Bentley JK, Zhou L, Jia Y, Bitar KN, Fingar DC, Hershenson MB. Transforming growth factor-beta induces airway smooth muscle hypertrophy. Am J Respir Cell Mol Biol 34: 247-254, 2006.

 

Nanua S, Zick SM, Andrade JE, Burgess JR, Lukacs NW, Hershenson MB. Quercetin blocks airway epithelial cell chemokine expression. Am J Respir Cell Mol Biol 35:602-10, 2006.

 

Sajjan U Jia Y, Newcomb DC, Bentley JK, LiPuma JJ, Hershenson MB. H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ICAM-1 and TLR3 expression. FASEB J 20:2121-3, 2006.

 

Bentley JK, Newcomb DC, Goldsmith AM, Jia Y, Sajjan US, Hershenson MB. Rhinovirus activates IL-8 expression via a Src/p110 beta PI 3-kinase/Akt pathway in human airway epithelial cells. J Virol 81:1186-1194.

 

Hennrick KT, Keeton AG, Nanua S, Sajjan US, Bentley JK, Lama VN, Moore BB, Thannickal VJ, Hershenson MB. Lung cells from neonates show a mesenchymal stem cell phenotype. Am J Respir Crit Care Med 75:1158-64, 2007.

 

Newcomb DC, Sajjan US, Nagarkar DR, Goldsmith AM, Bentley JK, Hershenson MB. Cooperative effects of rhinovirus and TNF-alpha on airway epithelial cell chemokine expression. Am J Physiol: Lung Cell Mol Physiol 293:L1021-8, 2007.

 

Deng H, Dokshin GA, Lei J, Goldsmith AM, Bitar KN, Fingar DC, Hershenson MB, Bentley JK. Inhibition of glycogen synthase kinase-3 beta is sufficient for airway smooth muscle hypertrophy. J Biol Chem. In press, 2008.

 

Newcomb DC, Sajjan US, Nagarkar DR, Wang Q, Nanua S, Zhou Y, McHenry CL, Hennrick KT, Tsai WC, Bentley JK, Lukacs NW, Johnston SL, Hershenson MB. Human rhinovirus 1B exposure induces PI 3-kinase-dependent airway inflammation in mice. Am J Respir Crit Care Med. In press, 2008

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