Jeffrey B. Matthews, M.D.

Primary:

Dallas B. Phemister Professor and Chair, Department of Surgery

Secondary:

Committee on Cellular and Molecular Physiology 

Education:
Degree Year Institution Area
BA
1981
Harvard College, cum laude

MD
1985
  
Harvard Medical School, cum laude



Phone: (773) 702-0881
E-Mail: jmatthews@surgery.bsd.uchicago.edu
Address: AMB O-220 (MC 5029)
Web page:
 http://surgery.uchicago.edu/Department_of_Surgery/Educational_Programs/index.php

Research Summary

Vectorial transport and barrier function are two fundamental and defining properties of epithelial cells that line the gastrointestinal tract, airway, kidney, and other organs. Dysregulation of these properties accounts in part for the clinical manifestations of a variety of inflammatory, infectious, and ischemic disorders. Our laboratory investigates the cell biology of electrogenic chloride secretion and intercellular junctional complex regulation using cultured epithelial cell lines as well as native intestine from rodent and human. Specific projects include the short- and long-term regulation of basolateral membrane transport pathways including NKCC1 (Na-K-Cl cotransporter) and K+ channels. NKCC1 mediates basolateral membrane Cl- uptake and may represent a rate limiting step in transepithelial secretion. NKCC1 appears to be regulated by cell Cl-, protein phosphorylation, acute changes in cell surface expression, and long-term changes in gene expression. In addition, previously unsuspected pathways of functional modulation by the actin cytoskeleton and by endogenous factors including luminal short chain fatty acids and ammonia have been identified. Recently, the role of specific isoforms of protein kinase C (PKC) in the acute regulation of plasma membrane dynamics, ion transporter surface expression, and of tight junction integrity has been explored. Ischemic stress has been found to activate PKC and to engage downstream mitogen-activated kinases, which may represent an adaptive response to cell injury. Stimulation or inhibition of specific PKC isoforms may represent a novel strategy to prevent mucosal injury or enhance reparative processes.

Statement of Research Interest Related to the Cardiovascular System

The Matthews laboratory has a central interest in the cell biological response to ischemic stress, with specific interest in the mesenteric vasculature and epithelial cell layers of the mucosa.  The role of specific protein kinase C isozymes in the cellular response to ischemia and reperfusion is studies using reductionist cell culture models.

Selected Publications

Saldinger, P.F., Reilly, M., Reynolds, K., Raptopoulos, V., Chuttani, R., Steer, M.L. and Matthews, J.B. Is CT-angiography sufficient for prediction of resectability of pancreatico-duodenal neoplasms? J. Gastrointest. Surg., 4:233-239, 2000.

Riegler, M., Castagliuolo, I., Wang, C., Wlk, M., Sogukoglu, T., Wenzl, E., Matthews, J.B. and Pothoulakis, C. Neurotensin stimulates Cl- secretion in human colonic mucosa in vitro: role of adenosine. Gastroenterology, 119:348-357, 2000.

Song, J.C., Hanson, C.M., Tsai, V., Farokhzad, O.C., Lotz, M. and Matthews, J.B. Regulation of epithelial transport and barrier function by distinct protein kinase C isoforms. Am. J. Physiol. (Cell), 281:C649-C661, 2001.

Yoo, J., Nichols, A., Song, J.C., Mun, E.C. and Matthews, J.B. PKCe dampens the secretory response of model intestinal epithelia during ischemia. Surgery, 2001:130:310-318.

Song, J.C., Ranagachari, P.K. and Matthews, J.B. Opposing effets of PKCα and PKCε on basolateral membrane dynamics in intestinal epithelia. Am. J Physiol. (Cell), 283:C1548-56, 2002.

Yoo, J., Nichols, A., Song, J.C., Mammen, J., Calvo, I., Worrell, R.T., Cuppoletti, J., Matlin, K. and Matthews, J.B. Bryostatin-1 attenuates TNF-induced epithelial barrier dysfunction: role of novel PKC isozymes. Am. J. Physiol. (Gastrointestinal and Liver), 284:G703-712, 2003.

Lotz, M., Wang, H.H., Chance, W., Matthews, J.B. and Pories, S. Epidermal growth factor stimulation can substitute for c-Src overexpression in promoting breast carcinoma invasion. J. Surg. Res., 109:123-129, 2003.

Yoo, J., Nichols, A., Mammen, J., Calvo, I., Song, J., Worrell, R., Matlin, K. and Matthews, J.B. Bryostatin-1 enhances barrier function in T84 epithelia through PKC-dependent regulation of tight junction proteins. Am. J. Physiol. (Cell), 285:C300-309, 2003.

Rodriguez Rilo, H.L., Ahmad, S.A., D'Alessio, D., Iwanaga, Y., Kim, J., Choe, K.A., Moulton, J.S., Martin, J., Pennington, L.J., Soldano, D.A., Biliter, J., Martin, S.P., Ulrich, C.D., Somogyi, L., Welge, J., Matthews, J.B. and Lowy, A.M. Total pancreatectomy and autologous islet cell transplantation as a means to treat severe chronic pancreatitis.  J. Gastrointest. Surg., 7:978-989, 2003.

Kim, J., Ahmad, S.A., Lowy, A.M., Buell, J.F., Pennington, L.J., Soldano, D.A., James, L.E., Matthews, J.B. and Hanto, D.W.  Increased biliary fistulas following liver resection with the harmonic scalpel. Am. Surgeon, 69:815-819, 2003.

Mayol, J.M., Alarma-Estrany, P., O'Brien, T.C., Song, J.C., Prasad, M., Adame Navarrete, Y., Fernandez-Repressa, J.A., Mun, E.C. and Matthews, J.B. Electrogenic ion transport in mammalian colon involves an ammonia-sensitive apical membrane K+ conductance. Dig. Dis. Sci., 48:3116-25, 2003.

Kim, J., Ahmad, S.A., Lowy, A.M., Buell, J.F., Pennington, L.J., Moulton, J.S., Matthews, J.B. and Hanto DW. An algorithm for the accurate identification of benign liver lesions.  Am. J. Surg., 187:274-279, 2004.

Worrell, R.T., Oghene, J. and Matthews, J.B.  Ammonium effects on colonic Cl- secretion: Anomalous mole fraction behavior.  Am. J. Physiol. (Gastrointestinal and Liver), 286:G14-G22, 2004.

Prahalad, P., Calvo, I., Waechter, H, Matthews, J.B., Zuk, A. and Matlin, K.S. Regulation of MDCK cell-substratum adhesion by RhoA and myosin light chain kinase after ATP depletion. Am. J. Physiol. (Cell), 286:C693-C707, 2004.

Updated 10/12/07.