Marc Hershenson, M.D. ~Frederick G.L. Huetwell Professor of Pediatrics ~Professor of Molecular and Integrative Physiology University of Illinois, 1981 L2219 Women's 0244 (734) 764-4123 mhershen@med.umich.edu

My lab 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 two 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, eukaryotic initiation factor (eIF)-4E, 4E-binding protein (4E-BP), p70 ribosomal S6 kinase and glycogen synthase kinase-beta

Recent Publications:

Funkhouser AW, Kang J-A, Tan A, Li J, Zhou L, Abe M, Solway J, Hershenson MB.  Rhinovirus 16 3C protease induces interleukin-8 and granulocyte macrophage-colony stimulating factor expression in human bronchial epithelial cells.  Pediatric Research 55:13-8, 2004.

Robin B, Kim Y, Huth J, Klocksieben J, Torres M, Tepper R, Castile M, Solway J, Hershenson MB, Goldstein A. Pulmonary function in infants with bronchopulmonary dysplasia.  Pediatric Pulmonology 37: 236-42, 2004.

Zhou L, Li J, Goldsmith A, Eves E, Rosner M, Solway, J, Hershenson MB.  Human bronchial smooth muscle cell lines show a hypertrophic phenotype typical of severe asthma.  American Journal of Respiratory and Critical Care Medicine  169: 703-711, 2004.

Zhou L, Hershenson MB. Yersinia YopJ attenuates bronchial epithelial cell chemokine expression. Respiratory Physiology and Neurobiology  140: 89-97, 2004.

Shimotake T, Izhar FM, Li J, Kim YJ, Rumilla K, Borg MJ, Page K, Brasier AR, Schreiber MD, Hershenson MB. Tracheal aspirates from mechanically-ventilated premature infants induce airway epithelial cell interleukin-8 expression via an NF-kB-dependent pathway.  Pediatric Research, 56:907-13, 2004.

Halayko AJ, Kartha S, McConville J, Tam J, Camoretti-Mercado B, Forsythe SM, Hershenson MB, Solway J.  PI 3-kinase/mTOR/p70S6K regulates contractile protein accumulation in airway myocyte differentiation. American Journal of Respiratory Cell and Molecular Biology 31:266-75, 2004.

Tsai WC, Rodriguez ML, Young KS, Deng JC, Thannickal VJ, Tateda K, Hershenson MB, Standiford TJ. Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection. American Journal of Respiratory and Critical Care Medicine 170:1331-9, 2004.

Page K, Hughes VS, Odoms KK, Dunsmore KE, Hershenson MB. German cockroach proteases regulate IL-8 expression via NF-IL6 in human bronchial epithelial cells.  Journal of Respiratory Cell and Molecular Biology  32:225-31, 2005.

Zhou L, Goldsmith AM, Bentley JK, Jia Y, Rodriguez ML, Abe MK, Fingar DC, Hershenson MB.  4E-BP phosphorylation and eIF4E release are required for airway smooth muscle hypertrophy.  American Journal of Respiratory Cell and Molecular Biology  33:195-202, 2005. 

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