CHRISTOPHER M. WATERS, Ph.D., M.S., B.S.E.

Professor and Vice Chair
Physiology
 
Professor
Medicine-Pulmonary

Office: 201 Nash Research Building
894 Union Avenue
Memphis Tn 381630000
Tel: (901) 448-5799
cwaters2@uthsc.edu

Education

  • PostDoc, Vanderbilt University, Biomedical Engineering
  • Ph.D., Vanderbilt University, Nashville, TN, Biomedical Engineering
  • M.S., University of Miami (FL), Biomedical Engineering
  • B.S.E., University of Tennessee at Chattanooga, Chemical Engineering

Curriculum Vitae

Research Interests

Research Interests:

My laboratory focuses on mechanobiology 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.  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 in injured lungs 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 contribute to lung injury, 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, cytokine secretion, and regional variations in cellular tension.  In addition we are examining lung injury in vivo and the effects of exposure to high levels of oxygen (hyperoxia).  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.

Research interest/specialty

My laboratory focuses on two main areas: (1) acute lung injury, and (2) mechanobiology.

Research keywords

Acute lung injury; Mechanotransduction; Mechanobiology; Epithelial wound healing and cell migration; Acute respiratory distress syndrome; Cellular biomechanics and transport; Ventilator-induced lung injury; Asthma; Airway mechanics; Vascular endothelial and lung epithelial cell barrier function and the effects of mechanical stresses; Growth factors and receptors:  function and regulation; Mass transport in the pulmonary circulation; Drug transport and metabolism by vascular endothelium in the lungs and the brain; Mathematical modeling of cellular and physiological systems.

Research description

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.

Publications

  1. Roan, E, Waters, CM, Teng, B, Ghosh, M, Schwingshackl, A. The 2-pore domain potassium channel TREK-1 regulates stretch-induced detachment of alveolar epithelial cells. PLoS One, 9 (2), e89429, 2014.
  2. Samak, G, Gangwar, R, Crosby, LM, Desai, LP, Wilhelm, K, Waters, CM, Rao, R. Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism. Am J Physiol Gastrointest Liver Physiol, 306 (11), G947-58, 2014.
  3. Wilhelm, KR, Roan, E, Ghosh, MC, Parthasarathi, K, Waters, CM. Hyperoxia increases the elastic modulus of alveolar epithelial cells through Rho kinase. FEBS J, 281 (3), 957-69, 2014.
  4. Schwingshackl, A, Teng, B, Ghosh, M, Waters, CM. Regulation of Monocyte Chemotactic Protein-1 secretion by the Two-Pore-Domain Potassium (K2P) channel TREK-1 in human alveolar epithelial cells. Am J Transl Res, 5 (5), 530-42, 2013.
  5. Ghosh, MC, Gorantla, V, Makena, PS, Luellen, C, Sinclair, SE, Schwingshackl, A, Waters, CM. Insulin-like growth factor-I stimulates differentiation of ATII cells to ATI-like cells through activation of Wnt5a. Am J Physiol Lung Cell Mol Physiol, 305 (3), L222-8, 2013.
  6. Schwingshackl, A, Teng, B, Ghosh, M, Lim, KG, Tigyi, G, Narayanan, D, Jaggar, JH, Waters, CM. Regulation of interleukin-6 secretion by the two-pore-domain potassium channel Trek-1 in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol, 304 (4), L276-86, 2013.
  7. Ghosh, MC, Makena, PS, Gorantla, V, Sinclair, SE, Waters, CM. CXCR4 regulates migration of lung alveolar epithelial cells through activation of Rac1 and matrix metalloproteinase-2. Am J Physiol Lung Cell Mol Physiol, 302 (9), L846-56, 2012.
  8. Makena, PS, Gorantla, VK, Ghosh, MC, Bezawada, L, Kandasamy, K, Balazs, L, Luellen, CL, Thompson, KE, Parthasarathi, K, Ichijo, H, Waters, CM, Sinclair, SE. Deletion of apoptosis signal-regulating kinase-1 prevents ventilator-induced lung injury in mice. Am J Respir Cell Mol Biol, 46 (4), 461-9, 2012.
  9. Schwingshackl, A, Teng, B, Ghosh, M, West, AN, Makena, P, Gorantla, V, Sinclair, SE, Waters, CM. Regulation and function of the two-pore-domain (K2P) potassium channel Trek-1 in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol, 302 (1), L93-L102, 2012.
  10. Waters, CM, Roan, E, Navajas, D. Mechanobiology in lung epithelial cells: measurements, perturbations, and responses. Compr Physiol, 2 (1), 1-29, 2012.
  11. Roan, E, Waters, CM. What do we know about mechanical strain in lung alveoli. Am J Physiol Lung Cell Mol Physiol, 301 (5), L625-35, 2011.
  12. Makena, PS, Gorantla, VK, Ghosh, MC, Bezawada, L, Balazs, L, Luellen, C, Parthasarathi, K, Waters, CM, Sinclair, SE. Lung injury caused by high tidal volume mechanical ventilation and hyperoxia is dependent on oxidant-mediated c-Jun NH2-terminal kinase activation. J Appl Physiol (1985), 111 (5), 1467-76, 2011.
  13. Crosby, LM, Luellen, C, Zhang, Z, Tague, LL, Sinclair, SE, Waters, CM. Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing. Am J Physiol Lung Cell Mol Physiol, 301 (4), L536-46, 2011.
  14. Tagen, M, Zhuang, Y, Zhang, F, Harstead, KE, Shen, J, Schaiquevich, P, Fraga, CH, Panetta, JC, Waters, CM, Stewart, CF. P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett, 4 (4), 195-201, 2010.
  15. Makena, PS, Luellen, CL, Balazs, L, Ghosh, MC, Parthasarathi, K, Waters, CM, Sinclair, SE. Preexposure to hyperoxia causes increased lung injury and epithelial apoptosis in mice ventilated with high tidal volumes. Am J Physiol Lung Cell Mol Physiol, 299 (5), L711-9, 2010.
  16. Crosby, LM, Waters, CM. Epithelial repair mechanisms in the lung. Am J Physiol Lung Cell Mol Physiol, 298 (6), L715-31, 2010.
  17. Carcaboso, AM, Elmeliegy, MA, Shen, J, Juel, SJ, Zhang, ZM, Calabrese, C, Tracey, L, Waters, CM, Stewart, CF. Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas. Cancer Res, 70 (11), 4499-508, 2010.
  18. Desai, LP, White, SR, Waters, CM. Cyclic mechanical stretch decreases cell migration by inhibiting phosphatidylinositol 3-kinase- and focal adhesion kinase-mediated JNK1 activation. J Biol Chem, 285 (7), 4511-9, 2010.
  19. Mugabe, BE, Yaghini, FA, Song, CY, Buharalioglu, CK, Waters, CM, Malik, KU. Angiotensin II-induced migration of vascular smooth muscle cells is mediated by p38 mitogen-activated protein kinase-activated c-Src through spleen tyrosine kinase and epidermal growth factor receptor transactivation. J Pharmacol Exp Ther, 332 (1), 116-24, 2010.
  20. Desai, LP, White, SR, Waters, CM. Mechanical stretch decreases FAK phosphorylation and reduces cell migration through loss of JIP3-induced JNK phosphorylation in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol, 297 (3), L520-9, 2009.
  21. Desai, LP, Chapman, KE, Waters, CM. Mechanical stretch decreases migration of alveolar epithelial cells through mechanisms involving Rac1 and Tiam1. Am J Physiol Lung Cell Mol Physiol, 295 (5), L958-65, 2008.
  22. Narang, VS, Fraga, C, Kumar, N, Shen, J, Throm, S, Stewart, CF, Waters, CM. Dexamethasone increases expression and activity of multidrug resistance transporters at the rat blood-brain barrier. Am J Physiol Cell Physiol, 295 (2), C440-50, 2008.
  23. Wagh, AA, Roan, E, Chapman, KE, Desai, LP, Rendon, DA, Eckstein, EC, Waters, CM. Localized elasticity measured in epithelial cells migrating at a wound edge using atomic force microscopy. Am J Physiol Lung Cell Mol Physiol, 295 (1), L54-60, 2008.
  24. Xi, Q, Adebiyi, A, Zhao, G, Chapman, KE, Waters, CM, Hassid, A, Jaggar, JH. IP3 Constricts Cerebral Arteries via IP3 Receptor-Mediated TRPC3 Channel Activation and Independently of Sarcoplasmic Reticulum Ca2+ Release. Circ Res, 2008.
  25. Sinclair, SE, Molthen, RC, Haworth, ST, Dawson, CA, Waters, CM. Airway strain during mechanical ventilation in an intact animal model. Am J Respir Crit Care Med, 176 (8), 786-94, 2007.
  26. Kumar, N, Mishra, J, Narang, VS, Waters, CM. Janus kinase 3 regulates interleukin 2-induced mucosal wound repair through tyrosine phosphorylation of villin. J Biol Chem, 282 (42), 30341-5, 2007.
  27. Desai, LP, Sinclair, SE, Chapman, KE, Hassid, A, Waters, CM. High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion. Am J Physiol Lung Cell Mol Physiol, 293 (3), L769-78, 2007.
  28. Zhuang, Y, Fraga, CH, Hubbard, KE, Hagedorn, N, Panetta, JC, Waters, CM, Stewart, CF. Topotecan central nervous system penetration is altered by a tyrosine kinase inhibitor. Cancer Res, 66 (23), 11305-13, 2006.
  29. Motl, S, Zhuang, Y, Waters, CM, Stewart, CF. Pharmacokinetic considerations in the treatment of CNS tumours. Clin Pharmacokinet, 45 (9), 871-903, 2006.
  30. Ceacareanu, AC, Ceacareanu, B, Zhuang, D, Chang, Y, Ray, RM, Desai, L, Chapman, KE, Waters, CM, Hassid, A. Nitric oxide attenuates IGF-I-induced aortic smooth muscle cell motility by decreasing Rac1 activity: essential role of PTP-PEST and p130cas. Am J Physiol Cell Physiol, 290 (4), C1263-70, 2006.
  31. Chapman, K.E., S.E. Sinclair, A. Hassid, D. Zhuang, L.P. Desai, and C.M. Waters. Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. American Journal of Physiology: Lung Cellular Molecular Physiology, 289, 834-841, 2005.
  32. Geiger, R.C., Waters, C.M.. KGF prevents DNA damage in ARPE-19 cells. Investigative Opthamalogy & Visual Science, 46, 3435-3441, 2005.
  33. Desai, LP, Aryal, AM, Ceacareanu, B, Hassid, A, Waters, CM. RhoA and Rac1 are both required for efficient wound closure of airway epithelial cells. Am J Physiol Lung Cell Mol Physiol, 287 (6), L1134-44, 2004.
  34. Ahmed, A, Waters, CM, Leffler, CW, Jaggar, JH. Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries. Am J Physiol Heart Circ Physiol, 287 (5), H2061-9, 2004.
  35. Tomar, A, Wang, Y, Kumar, N, George, S, Ceacareanu, B, Hassid, A, Chapman, KE, Aryal, AM, Waters, CM, Khurana, S. Regulation of cell motility by tyrosine phosphorylated villin. Mol Biol Cell, 15 (11), 4807-17, 2004.
  36. Leggas, M, Zhuang, Y, Welden, J, Self, Z, Waters, CM, Stewart, CF. Microbore HPLC method with online microdialysis for measurement of topotecan lactone and carboxylate in murine CSF. J Pharm Sci, 93 (9), 2284-95, 2004.
  37. Zhuang, D, Ceacareanu, AC, Lin, Y, Ceacareanu, B, Dixit, M, Chapman, KE, Waters, CM, Rao, GN, Hassid, A. Nitric oxide attenuates insulin- or IGF-I-stimulated aortic smooth muscle cell motility by decreasing H2O2 levels: essential role of cGMP. Am J Physiol Heart Circ Physiol, 286 (6), H2103-12, 2004.
  38. Waters, C.M.. Reactive oxygen species in mechanotransduction, Editorial comment. American Journal of Physiology: Lung Cellular Molecular Physiology, 287, L484-L485, 2004.
  39. Boardman, K.C., W.M. Miller, and C.M. Waters. Actin redistribution in response to hydrogen peroxide in airway epithelial cells. Journal of Cellular Physiology, 199, 57-66, 2004.
  40. Savla, U., L.E. Olson, and C.M. Waters. Mathematical modeling of airway epithelial wound closure during cyclic mechanical strain. Journal of Applied Physiology, 96, 566-574, 2004.
  41. Leffler, CW, Balabanova, L, Fedinec, AL, Waters, CM, Parfenova, H. Mechanism of glutamate stimulation of CO production in cerebral microvessels. Am J Physiol Heart Circ Physiol, 285 (1), H74-80, 2003.
  42. Waters, CM, Sporn, PH, Liu, M, Fredberg, JJ. Cellular biomechanics in the lung. Am J Physiol Lung Cell Mol Physiol, 283 (3), L503-9, 2002.
  43. Chapman, K.E., C.M. Waters, and W.M. Miller. Continuous exposure of airway epithelial cells to hydrogen peroxide: protection by KGF. Journal of Cellular Physiology, 192, 71-80, 2002.
  44. Salva, U., H.J. Appel, P.H.S. Sporn, and C.M. Waters. Prostaglandin E2 regulates wound closure of airway epithelial cells. American Journal of Physiology: Lung Cellular Molecular Physiology, 280, L421-L431, 2001.
  45. Haber,R., J.B. Grotberg, M.R. Glucksberg, G. Miserocci, D. Venturoli, M. Del Fabbro and C.M. Waters. Steady_state pleural fluid flow and the effects of lung buoyancy. Journal of Biomechanic Engineering, 123, 485-492, 2001.
  46. Waters, C.M., M.R. Glucksberg, E.P. Lautenschlager, C.-W. Lee, R.M. VanMatre, R.J. Warp, U. Salva, K.E. Healy, B. Moran, D.G. Castner, and J.P. Bearinger. A system to impose prescribed homogeneous strains on cultured cells. Journal of Applied Physiology, 91, 1600-1610, 2001.
  47. Albuquerque, M.L., C.M. Waters, U. Salva, H.W. Schnaper, and A. Flozak. Shear stress enhances human endothelial cell wound closure. American Journal of Physiology: Heart Circulation Physiology, 279, H293-H302, 2000.
  48. Waters, C.M., T.C. Krejcie, and M.A. Avram. Facilitated uptake of fentanyl, but not alfentanil, by human pulmonary endothelial cells. Anesthesiology, 93, 825-831, 2000.
  49. Waters, C.M., and U. Salva. Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain. Journal of Cellular Physiology, 181, 424-432, 1999.
  50. Gillis, P., U. Salva, O.V. Volpert, B. Jimenez, C.M. Waters. Keratinocyte growth factor induces angiogenesis and protects endothelial barrier function. Journal of Cell Science, 112, 2049-2057, 1999.
  51. Waters, C.M., M.A. Avram, T.C. Krejcie, and T.K. Henthorn. Uptake of fentanyl in pulmonary endothelium. Journal of Pharmacology and Experimental Therapeutics, 288, 157-163, 1999.
  52. Waters, C.M., K. Ridge, G. Sunio, K. Venetsanou, and J.I. Sznajder. Mechanical stretching of alveolar epithelial cells increases Na,K-ATPase activity. Journal of Applied Physiology, 87, 715-721, 1999.
  53. Wagers, A.J., C.M. Waters, L.M. Stoolman, and G.S. Kansas. Interleukin 12 and interleukin 4 control T cell adhesion to endothelial selectins through opposite effects on a 1,3-fucosyltransferase VIi gene expression. Journal of Experimental Medicine, 188, 2225-2231, 1998.
  54. Salva, U. and C.M. Waters. Barrier function of airway epithelium: effects of radiation and protection by keratinocyte growth factor. Radiation Research, 150, 195-203, 1998.
  55. Salva, U and C.M. Waters. Mechanical strain inhibits repair of airway epithelium in vitro. American Journal of Physiology, 274, L883-L892, 1998.
  56. Waters, C.M., U. Salva, and R. Pancos. Keratinocyte growth factor prevents hydrogen peroxide-induced increases in airway epithelial cell permeability. American Journal of Physiology, 272, L681-L689, 1997.
  57. Salva, U., P.H.S. Sporn, and C.M. Waters. Cyclic stretch of airway epithelum inhibits prostanoid synthesis. American Journal of Physiology, 273, L1013-1019, 1997.
  58. Rezania, A., C.H. Thomas, A.B. Branger, C.M. Waters, and K.E. Healy. The detachment strength and morphology of bone cells contacting materials modified with a peptide derived form bone sialoprotein. Journal of Biomedical Materials Research, 37, 9-19, 1997.
  59. Waters, C.M., J. Chang, M.R. Glucksburg, N. DePaola, and J.B. Grotberg. Mechanical forces after growth factor release by pleural mesothelial cells. American Journal of Physiology, 272, L552-L557, 1997.
  60. Waters, C.M.. Flow-induced modulation of the permeability of endothelial cells cultured on microcarrier beads. Journal of Celluar Physiology, 168, 403-411, 1996.
  61. Waters, C.M., M.R. Glucksberg, N. DePaola, J. Chang, and J.B. Grotberg. Shear stress alters pleural mesothelial cell permeability in culture. Journal of Applied Physiology, 81, 448-458, 1996.
  62. Waters,C.M., J. Taylor, A. Molteni, and W.F. Ward. Dose-response effects of radiation on endothelial cell permeability in culture. Radiation Research, 146, 321-328, 1996.
  63. Sorkin, A., C.M. Waters, K.A. Overholser, and G. Carpenter. Multiple autophosphorylation site mutations of the epidermal growth factor receptor: analysis of kinase activity and endocytosis. J. Biology Chemistry, 266, 8355-8362, 1991.
  64. Waters, C.M., K.O.Oberg, G. Carpenter, and K.A. Overholser. Rate constants for binding, dissociation, and internalization of epidermal growth factor: effect of receptor occupancy and ligand concentration. Biochemistry, 29, 3563-3569, 1990.