Christopher M. Waters, Ph.D.
Professor and Vice Chair
Voice: 1-901-448-5799
Fax: 1-901-448-7126
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Education

1985 B.S.E., University of Tennessee at Chattanooga
1987 M.S., University of Miami, Miami, FL
1991 Ph.D., Vanderbilt University, Nashville, TN
Research interest image

Research Interest

 My laboratory focuses on mechanotransduction and acute lung injury. Patients with acute respiratory distress syndrome (ARDS) are placed on mechanical ventilators to improve oxygenation, but the ventilator may cause additional injury to the lungs due to either overdistention or airway collapse and reopening.  Recent clinical trials have demonstrated a substantial reduction in mortality in ARDS patients when ventilation strategies are used that reduce overdistention (lower tidal volumes) and minimize airway collapse and reopening (positive end expiratory pressure).  The lung is a mechanically dynamic organ, and cells in the lung are subjected to shear stress due to fluid flow, tensile and compressive forces due to respiratory motion, and normal forces due to vascular or airway pressure.  High tidal volume mechanical ventilation induces mechanical stresses that increase injury to the lung epithelium, stimulate inflammatory responses, and decrease repair mechanisms.  We are focusing on the mechanisms by which mechanical forces inhibit wound healing of lung epithelial cells and stimulate inflammation.  We are examining cell migration and wound healing, Rho GTPase signaling, cytoskeletal remodeling, stimulation of reactive oxygen species, and regional variations in cellular tension.  In addition we are examining lung injury in vivo.  My research seeks to identify the levels of mechanical forces and the types of lung injury that cells experience in vivo, to develop in vitro models to evaluate cellular responses, and to identify mechanisms by which mechanical forces are transduced into biological signals.

Current Techniques utilized:

Research Support

Principal Investigator (40% effort):  ?Mechanotransduction in Acute Lung Injury,? National Institutes of Health (R01 HL094366-01); 04/01/09-01/31/13.

Principal Investigator, sub-contract (10% effort): ?Regulation of Airway Epithelial Repair,? National Institutes of Health (R01 HL080417), Steven R. White, P.I. (University of Chicago); 07/01/06-06/30/11.

Co-Investigator (10% effort): ?Stretch and Hyperoxia in Ventilator-Induced Lung Injury,? National Institutes of Health (R01 HL081297), Scott Sinclair, P.I.; 07/01/06-06/30/11.

Co-Investigator (0% effort):  ?CAREER:  Integrated Computational Optical Framework for Quantitative Space-Invariant Imaging in Live-Cell Fluorescence Microscopy,? National Science Foundation (NSF 0844682), Chrysanthe Preza, P.I.; 03/01/09-02/28/12.

Principal Investigator:  Administrative Supplement to ?Mechanotransduction in Acute Lung Injury,? Research experience for undergraduates, National Institutes of Health (R01 HL094366-01); 06/01/09-08/31/11.


Selected Publications

1.         Desai, L.P., S.E. Sinclair, K.E. Chapman, A. Hassid, and C.M. Waters.  High tidal volume mechanical ventilation with hyperoxia alters focal adhesions of alveolar type II cells, Am. J. Physiol. Lung Cell. Mol. Physiol. 293:  L769-L778, 2007. PMID: 17601798

 

2.         Sinclair, S.E., R.C. Molthen, S.A. Hayworth, C.A. Dawson, and C.M. Waters.  Airways strain during mechanical ventilation in an intact animal model, Am J. Resp. Crit. Care Med. 176:  786-794, 2007. PMID: 17626911

 

3.         Xi, Q., A. Adebiyi, G. Zhao, K.E. Chapman, C.M. Waters, A. Hassid, and J.H. Jaggar.  IP3 constricts cerebral arteries via IP3 receptor-mediated TRPC3 channel activation and independently of sarcoplasmic reticulum Ca2+ release, Circ. Res. 102:  1118-1126, 2008. PMID: 18388325

 

4.         Wagh, A.A., E. Roan, K.E. Chapman, L.P. Desai, D. Rendon, E.C. Eckstein, and C.M. Waters.  Localized elasticity measured in epithelial cells migrating at a wound edge using atomic force microscopy, Am. J. Physiol. Lung Cell. Mol. Physiol. 295:  L54-L60, 2008. PMID: 18487359

 

5.         Narang, V.S., C. Fraga, N. Kumar, J. Shen, S. Throm, C.F. Stewart, and C.M. Waters.  Dexamethasone increases expression and activity of multi-drug resistance transporters at the rat blood-brain barrier, Am. J. Physiol. Cell Physiol. 295:  C440-C450, 2008. PMID: 18524938

 

6.         Desai, L.P., K.E. Chapman, and C.M. Waters.  Mechanical stretch decreases migration of alveolar epithelial cells through mechanisms involving Rac1 and Tiam1, Am. J. Physiol. Lung Cell. Mol. Physiol. 295:  L958-L965, 2008. PMID: 18805958

 

7.         Shen, J. A.M. Carcaboso, E. Hubbard, H.G. Wynn, J.C. Panetta, C.M. Waters, M. Elmeliegy, C.F. Stewart.  Compartment-specific roles of P-glycoprotein and breast cancer resistance protein at the blood-brain and blood-CSF barriers define differential topotecan distribution in brain parenchyma and CSF, Cancer Res. 69:  5885-5892, 2009. PMID: 19567673

 

8.       Desai, L.P., S.R. White, and C.M. Waters.  Mechanical stretch decreases FAK phosphorylation and reduces cell migration through loss of JIP3-induced JNK phosphorylation, Am. J. Physiol. Lung Cell. Mol. Physiol. 297:  L520-529, 2009. PMID: 19574423

 

9.         Mugabe, B.E., F.A. Yaghini, C.Y. Song, C.K. Buharalioglu, C.M. Waters, and K.U. Malik.  Angiotensin II-induced migration of vascular smooth muscle cells is mediated by p38-MAPK activated c-Src through spleen tyrosine kinase and EGFR transactivation, J. Pharmacol. Exp. Ther. 332:  116-124, 2010. PMID: 19797620

 

10.       Desai, L.P., S.R. White, and C.M. Waters.  Cyclic mechanical stretch decreases cell migration by inhibiting phosphatidylinositol 3-kinase- and focal adhesion kinase-mediated JNK1 activation, J. Biol. Chem. 285:  4511-4519, 2010.  JBC paper of the week. PMID: 20018857

 

11.       Crosby, L.M., and C.M. Waters.  Epithelial repair mechanisms in the lung, Am. J. Physiol. Lung Cell. Mol. Physiol. 298:  L715-L731, 2010.  Reprint

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