Simon A. Lewis, Ph.D.

  • Affiliations: Department of Neuroscience & Cell Biology
  • Route: 1069, 2.143C Medical Research Building (MRB)
  • Tel: (409) 772-3397
  • Fax: (409) 762-9382
  • Lewis CV

Simon A. Lewis, Ph.D.


Ph.D 1975: Department of Physiology, University of California, Los Angeles

Postdoctoral: Physiology UCLA; Physiology and Biophysics, UTMB

Faculty: Department of Physiology Yale Medical School

MacLean-Frazier Fellowship

William Evans Visiting Professor, University of Otago, New Zealand

Chair: Cell and Molecular Physiology Section, American Physiological Society

Member: Academy of Master Teachers

Research Interests

photoThe long term objective is to elucidate the mechanisms by which the mammalian urinary bladder epithelium (urothelium) maintains the urine composition near constant (urothelial barrier function) without having its or the underlying tissue viability compromised. Bladder inflammation (cystitis) initiated by bacteria, sensory nerve stimulation, radiation, injury or xenobiotics, results in edema, leukocyte infiltration, hemorrhage, urothelial desquamation and pelvic pain. Inflammatory processes are associated with increased release of inflammatory mediators such as select interleukins, kinin, histamine, neuropeptides, prostaglandins, tumor necrosis factor α, and reactive oxygen species. The current research in the laboratory proposes that select inflammatory mediators causes urothelial damage leading to a loss of barrier function and opening a pathway for the movement of urine constituents into the submucosa. These urine constituents (in conjunction with inflammatory mediators) cause a further loss of barrier function and exacerbate the inflammation. Inflammatory mediators and urine constituents are sensed by the urothelium and it communicates this information to sensory neurons. Recent studies have demonstrated that ROS (hydrogen peroxide) as well as urine constituents alter the barrier properties (at the cell and paracellular level) of the urothelium. In addition, ATP release by the urothelium is bidirectional and extracellular ATP concentration is altered by ectonucleotidases. Future research will: 1. Determine the site of action and mechanism by which oxidative stress alters the barrier properties of the urothelium. 2. Determine the site of action and mechanism by which urine constituents alter the barrier properties of the urothelium. 3. Demonstrate that the urothelium functions as a mechanical and chemical sensory system. A multidisciplinary approach utilizing in vitro electrophysiology, imaging and cell biology methods will be used. An understanding of the underlying mechanism(s) by which ROS and urinary constituents result in epithelial damage and the role of the urothelium in sensing the changes will lead to a better understanding of urothelial physiology and pathophysiology.


Lewis, S.A., Traub, P. Spilker, C. The N-terminal domain of vimentin alters urinary bladder permeability. J. Urology. 170:2091-2094. 2003.

Lewis, J.R., Lewis, S.A. Colistin interactions with the mammalian urothelium. Am. J. Physiol. 286:C913-922. 2004

Hameed, BV., Smith, D.M., Verrechio, J.J. Schmidt, J.D., Gillooley, L.E., Valenzano, M.C., Lewis, S.A., Mullin, J.M. Indocyanine green alters transepithelial elelctrical parameters of the distal colon. Digestive Diseases Sciences. In the press. 2004.

Lewis, S. A. and Lewis J.R. Kinetics of urothelial ATP release. American Journal of Physiology. Renal. 291: F332-F340. 2006.