Faculty Profile: Weibiao Cao, MD and M. Sc.

Weibiao Cao
Weibiao Cao, MD and M. Sc.
Surgical and Gastrointestinal Pathologist, Associate Professor of Pathology and Laboratory Medicine (Research), Associate Professor of Medicine (Research)
Department of Pathology and Medicine
Work: +1 401-444-8578
Associate Professor of Pathology and Medicine Weibiao Cao studies the role of a particular enzyme NOX5-S in the progression from Barrett esophagus, a condition where cells in the esophagus have been altered by acid reflux, to esophageal adenocarcinoma. His research examines how acid reflux increases the expression of this enzyme, production of hydrogen peroxide (which is known to cause DNA damage), and cell growth in Barrett cells. He hopes to find the potential therapeutic targets to prevent this progression.

Institutions

Rih

Research Description

Weibiao Cao studies the signal transduction pathways mediating contraction in normal esophageal smooth muscle and the inflammation-associated changes in signaling that occur in experimental esophagitis. His findings show that a low molecular weight phospholipase A2 (type I) mediates cat and human in vitro lower esophageal sphincter tone by producing arachidonic acid, which is metabolized to prostaglandin F2alpha and thromboxane A2. These arachidonic acid metabolites act on receptors linked to Gi3 and Gq proteins to activate phospholipases, producing second messengers, and maintaining LES tone.

He also investigates inflammation-induced changes in contractile signal transduction pathways of human sigmoid colon and study the effect of inflammatory mediators on colonic motor function in ulcerative colitis. His findings demonstrate that hydrogen peroxide and IL-1beta may play an important role in motor dysfunction in ulcerative colitis.

Currently he is studying the mechanisms of the progression from Barrett esophagus to esophageal adenocarcinoma, focusing on the role of NADPH oxidases-derived reactive oxygen species. His research on NADPH oxidase NOX5-S shows that NADPH oxidase NOX5-S is overexpressed in esophageal adenocarcinoma cells and mediates acid-induced hydrogen peroxide production. Acid-induced NOX5-S expression depends on an increase in intracellular calcium and activation of a transcription factor CREB. NOX5-S contributes to increased cell proliferation and decreased apoptosis in esophageal adenocarcinoma cells.

Grants and Awards

• Young Investigator Award Finalist (Basic Science Category), Lifespan – Rhode Island Hospital 9th Annual Hospital Research Celebration, 2001

• Young Investigator Award, 10th Biennial Meeting of the American Motility Society, Philadelphia, PA, 1998

• Second prize, National Scientific and Technological Advancement Award of China, 1998

• First Prize, Scientific Advancement Award, Ministry of Public Health, China, 1997

• First Prize, Academic Thesis, Peking Union Medical College Hospital (PUMC) Hospital, Beijing, P.R. China, 1994

• Third Prize, Excellent Thesis, First National Endocrinological Conference by the Middle Aged and Youth of Chinese Medical Association (Thesis: Nitric oxide inhibits the production of endothelin-1 in vivo and in cultured endothelial cells), 1994

• First Prize, Clinical Achievements, PUMC Hospital, Beijing, P.R. China, 1994

• Second Prize, Clinical Achievements, PUMC Hospital, Beijing, P.R. China, 1993

Affiliations

American Physiological Society 1997 – present
American Gastroenterological Association 1997 – present
College of American Pathologists 2009-present
American Society for Clinical Pathology 2010-present
United States & Canadian Academy of Pathology 2009-present

Funded Research

1. Principal Investigator, The Scientific Grant of Chinese Academy of Medical Sciences for young investigators in China, entitled "Endothelin in hypoxic pulmonary hypertension", Direct cost $10,000 (RMB), 1992.

2. Principal Investigator, The Scientific Grant of the Ministry of Public Health for young investigator in China, entitled "Nitric oxide and hypoxic pulmonary hypertension". Direct cost $10,000 (RMB),1993.

3. Principal Investigator, The Scientific Grant of Chinese Academy of Medical Sciences for young investigators in China, "Treatment of hypoxic pulmonary hypertension with inhalation of nitric oxide". Direct cost $10,000 (RMB), 1994.

4. Principal Investigator, Lifespan Research Funds, Providence, RI. Entitled "Interleukin 1 and contractile signal transduction in ulcerative colitis". Direct cost $29,960, April 2002 – Dec. 31, 2002.

5. Coinvestigator, NIH RO1-DK57030-02, entitled "Inflammation And Signal Transduction In Esophagitis", Direct cost $175,097, 12/1/99 – 2/28/03.

6. Principal Investigator, NIH R21 grant DK062775-01 entitled "Contractile signal transduction in ulcerative colitis". Direct cost $100,000 per year, Jan. 10, 2003-11. 30, 2004 (no cost extension to 12/31/2005).

7. Principal Investigator, subproject of NIH COBRE grant 1P20RR17695-01, "Signal Transduction in Acid induced Progression of Barrett's Esophagus (BE) from Metaplasia to Dysplasia." Direct cost $76,493 per year (Oct. 1, 2002 – Jan. 31 2006) and $130,000 (Feb. 1, 2006 - Jun. 30, 2007).

8. Coinvestigator, NIH RO1-DK28614, entitled "Biophysical Principles of Peristaltic Phenomena". Direct cost $242,000 per year, 8/1/03 – 6/30/07.

9. Coinvestigator, NIH RO1-DK57030, entitled "Inflammation And Signal Transduction In Esophagitis", Direct cost $200,000, 2/1/07 – 11/30/2007

10. Principal Investigator, NIH 1 R21 DK073327-01, entitled "NADPH oxidases-associated transition from Barrett's esophagus to adenocarcinoma". Direct cost $125,000 at the first year and $150,000 at the second year, 5/1/2006 – 4/30/2008 (no cost extension to 4/30/2009).

11. Principal Investigator, NIH R01 DK080703-01A1, entitled "NADPH oxidases-associated transition from Barrett's esophagus to adenocarcinoma". Direct cost $175,000 per year, 5/1/2009-4/30/2014.

Selected Publications

  • Jie Hong, Jose Behar, Jack Wands, Murray Resnick, Li Juan Wang, Ronald A. DeLellis, David Lambeth, Rhonda F. Souza, Stuart J. Spechler, Weibiao Cao*. Role of a novel bile acid receptor TGR5 in the development of esophageal adenocarcinoma. Gut. 2010;59(2):170-80. Epub 2009 Nov 18. (2010)
  • Jie Hong, Jose Behar, Jack Wands, Murray Resnick, Li Juan Wang, Ronald A. DeLellis, David Lambeth, Weibiao Cao*. Bile Acid Reflux Contributes To Development of Esophageal Adenocarcinoma via Activation of Phosphatidylinositol-Specific Phospholipase Cgamma2 And NADPH Oxidase NOX5-S. Cancer Res. 2010 Feb 1;70(3):1247-55. Epub 2010 Jan 19. (2010)
  • Jie Ma, Karen M. Harnett, Jose Behar, Piero Biancani, Weibiao Cao*. Signaling in TRPV1 induced platelet activating factor (PAF) in human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2010 Feb;298(2):G233-40. Epub 2009 Dec 3. (2010)
  • Hong J, Resnick M, Behar J, Wang LJ, Wands J, DeLellis RA, Souza RF, Spechler SJ, Cao W*. Acid-induced p16 hypermethylation contributes to development of esophageal adenocarcinoma via activation of NADPH oxidase NOX5-S. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G697-706. Epub 2010 Jun 24. (2010)
  • Cheng L, de la Monte S, Ma J, Hong J, Tong M, Cao W, Behar J, Biancani P, Harnett KM. HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa. Am J Physiol Gastrointest Liver Physiol. 2009 Jul;297(1):G135-43. Epub 2009 Apr 23. (2009)
  • Si J, Behar J, Wands J, Beer DG, Lambeth D, Chin YE, Cao W*. STAT5 Mediates Platelet-Activating Factor (PAF)-Induced NADPH Oxidase NOX5-S Expression In Barrett's Esophageal Adenocarcinoma Cells. Am J Physiol Gastrointest Liver Physiol. 2008 Jan; 294(1):G174-83. Epub 2007 Oct 18. (2008)
  • Si J, Fu X, Behar J, Wands J, Beer DG, Souza RF, Spechler SJ, Lambeth D, Cao W*. NADPH oxidase NOX5-S mediates acid-induced cyclooxygenase-2 expression via activation of NF-kappa B in Barrett's esophageal adenocarcinoma cells. J Biol Chem. 2007; 282(22):16244-55. (2007)
  • Weibiao Cao, Ling Cheng, Jose Behar, Piero Biancani, Karen M. Harnett. IL-1signaling in Cat Lower esophageal sphincter (LES) circular muscle. Am J Physiol Gastrointest Liver Physiol. 2006 Apr 27; [Epub ahead of print]. (2006)
  • Weibiao Cao*, Karen M. Harnett, Victor E. Pricolo. NK2 Receptors Mediated Spontaneous Phasic Contractions In Human Sigmoid Colon: Ulcerative Colitis-Induced Changes. JPET 2006; 317(3):1349-55. Epub 2006 Mar 22. (2006)
  • Xiao ZL, Cao W, Biancani P, Behar J. Non-Genomic Effects of Progesterone on the Contraction of Muscle Cells from Guinea Pig Colon. Am J Physiol Gastrointest Liver Physiol. 2006; 290(5):G1008-15. Epub 2006 Jan 6. (2006)
  • Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, Harnett KM. HCl-Induced Inflammatory Mediators in Cat Esophageal Mucosa and Inflammatory Mediators in Esophageal Circular Muscle in an In Vitro Model of Esophagitis. Am J Physiol Gastrointest Liver Physiol. 2006; 290(6):G1307-17. (2006)
  • Xiaoying Fu, David Beer, David Lambeth, Jack Wands, Jose Behar, Weibiao Cao*. cAMP reponse element binding protein (CREB) is responsible for acid-induced NOX5 expression in Barrett's esophageal adenocarcinoma cells. Journal of Biological Chemistry 2006; 281(29): 20368-82. (2006)
  • Cheng L, Cao W, Behar J, Fiocchi C, Biancani P, Harnett KM. Acid Induced Release Of Paf By Human Esophageal Mucosa Induces Inflammatory Mediators In Circular Smooth Muscle. J Pharmacol Exp Ther. 2006 Jun 28; [Epub ahead of print] (2006)
  • Cheng L, Harnett KM, Cao W, Liu F, Behar J, Fiocchi F, and P Biancani. Hydrogen Peroxide Reduces Lower Esophageal Sphincter Tone in Human Esophagitis. Gastroenterology 2005; 129(5): 1675-85. (2005)
  • Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, Harnett KM. IN VITRO MODEL OF ACUTE ESOPHAGITIS IN THE CAT. Am J Physiol Gastrointest Liver Physiol. 2005; 289(5): G860-9. Jul 21; [Epub ahead of print]. (2005)
  • Harnett KM, Cao W, and P. Biancani. Signal-transduction pathways that regulate smooth muscle function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles. Am J Physiol Gastrointest Liver Physiol. 2005; 288(3): G407-16. (2005)
  • Cheng L, Cao W, Behar J, Biancani P, and KM Harnett. Inflammation induced changes in arachidonic acid metabolism in cat les circular muscle. Am J Physiol Gastrointest Liver Physiol. 2005; 288(4):G787-97. (2005)
  • Cao W, Harnett KM, Cheng L, Kirber M, Behar J, and P. Biancani. H2O2, a mediator of esophagitis-induced damage to calcium-release mechanisms in cat lower esophageal sphincter (LES). Am J Physiol Gastrointest Liver Physiol. 2005; 288(6):G1170-8. (2005)
  • Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, Harnett KM. Platelet-activating factor and prostaglandin E2 impair esophageal ACh release in experimental esophagitis. Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G418-28. (2005)
  • Cao W*, Fiocchi C, Pricolo VE. Production of Interleukin-1{beta}, Hydrogen Peroxide, and Nitric Oxide by Colonic Mucosa Decreases Sigmoid Smooth Muscle Contractility in Ulcerative Colitis. Am J Physiol Cell Physiol. 2005; 289(6):C1408-16. Jul 20; [Epub ahead of print]. (2005)
  • Cao W, Cheng L, Behar J, Fiocchi C, Biancani P, and KM Harnett. Proinflammatory cytokines alter/reduce esophageal circular muscle contraction in experimental cat esophagitis. Am J Physiol Gastrointest Liver Physiol. 2004 Dec;287(6):G1131-9. (2004)
  • Cao W, Vrees MD, Potenti FM, Harnett KM, Fiocchi C, and VE Pricolo. Interleukin 1beta-induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis. J Pharmacol Exp Ther. 2004;311(1):60-70. (2004)
  • Weibiao Cao*, Matthew D. Vrees, Michael T. Kirber, Claudio Fiocchi, Victor E. Pricolo. Hydrogen peroxide contributes to motor dysfunction in ulcerative colitis. Am J Physiol Gastrointest Liver Physiol 2004;286(5):G833-43. (2004)
  • Kim N, Cao W, Song IS, Kim CY, Harnett KM, Cheng L, Walsh MP, and P Biancani. Distinct kinases are involved in contraction of cat esophageal and lower esophageal sphincter smooth muscles. Am J Physiol Cell Physiol. 2004;287(2):C384-94. (2004)
  • W.B. Cao, U.D. Sohn, J. Behar, P. Biancani, K.M. Harnett. Mitogen activated protein kinase mediates protein kinase C-dependent contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. Am J Physiol Gastrointest Liver Physiol 2003;285: G86–G95. (2003)
  • Cao W., Harnett K.M., Behar, J. and P. Biancani. PGF2a- induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2002; 283:G282-G291. (2002)
  • Vrees M. D., Pricolo V. E., Potenti, F. M., and W. Cao*. Abnormal Motility in Ulcerative Colitis: Role of Inflammatory Cytokines. Archives of Surgery. 2002; 137:439-446. (2002)
  • U.D. Sohn, Weibiao Cao, Da-chun Tang, J. T. Stull, J. R. Haeberle, C-L. A. Wang, K.M. Harnett, J. Behar and P. Biancani. Myosin light chain kinase dependent and PKC dependent contraction of LES and esophageal smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2001 Aug;281(2):G467-78 (2001)
  • W. Cao, Chen Q., Sohn, U.D., Kim, N., Kirber, M.T., Harnet, K.M., Behar, J. and P. Biancani. Ca++ induced contraction of cat esophageal circular smooth muscle cells. Am J Physiol Cell Physiol 2001; 280: C980–C992. (2001)
  • Weibiao Cao, Victor Pricolo, Liping Zhang, Jose Behar, Piero Biancani, Michael T. Kirber. Gq-linked NK2 receptors mediate neurally induced contraction of human sigmoid circular smooth muscle. Gastroenterology 2000;119:51-61. (2000)
  • Weibiao Cao, Karen M. Harnett, Jose Behar, Piero Biancani. Group I Secreted PLA2 in the Maintenance of Human Lower Esophageal Sphincter Tone. Gastroenterology 2000;119: 1243-1252. (2000)
  • W. Cao, K.M. Harnett, Q. Chen, M.K. Jain, J. Behar, and P. Biancani. Group I secreted PLA2 (sPLA2) and arachidonic acid metabolites in the maintenance of cat LES tone. Am J Physiology 1999; 277(3 Pt 1):G585-98. (1999)
  • Karen M. Harnett, Weibiao Cao, Nayoung Kim, Uy Dong Sohn, Harlan Rich, Jose Behar and Piero Biancani. Signal transduction in esophageal and LES circular muscle contraction. Yale J. Biology and Medicine 1999; 72:153-168. (1999)
  • N. Kim, W. CAO, I.S. Song, C.Y. Kim, U. D. Sohn, and P. Biancani. Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. Gastroenterology. 1998 Oct;115(4):919-28. (1998)
  • W. Cao, Zheng-pei Zeng, M. Naruse, Yuan-Jue Zhu, Weici Luo, H. Demura, Yifan Shi. Effects of tetramethylpyrazine, a Chinese medicine, on plasma endothelin-1 levels during acute pulmonary hypoxia in anesthetized dogs. J Cardiovasc Pharmacol. 1998;31 Suppl 1:S456-9. (1998)
  • Weibiao Cao, Weici Luo. Pulmonary Alveolar Proteinosis. In Current Pulmonology. Ed. Weici Luo. Renmin Junyi Press, Beijing. P767-771, 1997. (1997)
  • W.B. Cao, Z.P. Zeng, Y.J. Zhu, W.C. Luo. Effects of calcium blockers and calmodulin inhibitors on the secretion of endothelin-1 in cultured endothelial cells. Acta Academinae Medicinae Sinicae 1997;19(6):465-469. (1997)
  • Sohn, U.D., Harnet, K.M., Cao, W., Rich, H., Kim, N., Behar, J. and P. Biancani. Acute experimental esophagitis activates a second signal transduction pathway in cat smooth muscle from the lower esophageal sphincter. J Pharmacol Exp Ther. 1997 Dec;283(3):1293-304. (1997)
  • Junzhi Liao, Tianyin Sun, Weibiao Cao. Wegener's granulomatosis. In Current Pulmonology. Ed. Weici Luo. Renmin Junyi Press, Beijing. P762-766, 1997. (1997)
  • W.B. Cao, Z.P. Zeng, Y.J. Zhu, W.C. Luo, Z.F. Wang. Effect of L-arginine on acute hypoxic pulmonary hypertension and plasma endothelin-1 levels in anesthetized dogs. Acta Academinae Medicinae Sinicae 1996; 18(3):214:218. (1996)
  • W.B. Cao, Y.J Zhu, W.C. Luo, Z.F. Wang, B. Yao. Reversal of acute hypoxic pulmonary hypertension with inhalation of nitric oxide. Chinese Journal of Medicine 1995;34(1):9-12. (1995)
  • W.B. Cao, Z.P. Zeng, Y.J. Zhu, W.C. Luo, B.Q. Cai. Effect of NG-nitro-L-arginine methyl ester on the secretion of endothelin-1 in vivo and in cultured endothelial cells. National Medical Journal of China 1995; 75(3):164-166. (1995)
  • L.Y. Li, Y.J. Zhu, L. Yu, W.B. Cao, Y. Ma, S.Q. Jia, Y.H. Wang, X. Li. The Effect of recombinant granulocyte colony-stimulating factor in treatment of neuropenia caused by chemotherapy. Chinese Journal of New Drugs 1994;3(1):29-32. (1994)
  • W.B. Cao, Y.J. Zhu. A report of one case with acute hypersensitivity pneumonitis induced by ofloxacin. Chinese Journal of Tuberculosis and Respiratory Diseases 1994,17(5):300. (1994)
  • W.B. Cao, Y.J. Zhu, Y.L. Gao, W.C. Luo. A report of two cases with amyloidosis and pleural effusion. Acta Academinae Medicinae Sinicae 1994;16(5):401-402. (1994)
  • W.B. Cao, W.C. Luo, Z.J. Guo, Y.J. Zhu. Effects of ligustrazine and nitroglycerine on acute hypoxic pulmonary hypertension in mongrel dogs. Acta Academinae Medicinae Sinicae 1994;16(2):79-83. (1994)
  • W.B. Cao, Z.P. Zeng, W.C. Luo, Y.J. Zhu, S.Y. Xu. The effect of acute pulmonary alveolar hypoxia on canine plasma endothelin-1 levels. Acta Academinae Medicinae Sinicae 1994;16(5): 356-360. (1994)
  • W.B. Cao, Y.J. Zhu, W.C. Luo, B.Q. Cai, S.Y. Xu. Effect of endogenous nitric oxide on acute hypoxic pulmonary vasoconstriction in anesthetized dogs. Chinese Journal of Tuberculosis and Respiratory Diseases 1994,17(3):148-151. (1994)
  • W.B. Cao, Z.P. Zeng, Y.J. Zhu, W.C. Luo, B.Q. Cai. Inhibition of nitric oxide synthesis increases the secretion of endothelin-1 in vivo and in cultured endothelial cells. Chinese Medical Journal 1994; 107(11):822-826. (1994)
  • W.B. Cao, Y.J. Zhu, K.F. Xu, J. Wang, W.C. Luo. Pulmonary Nocardia infection. Chinese Journal of Medicine 1994; 33(10): 663-665. (1994)
  • R.Y. Sheng, A.X. Wang, W.B. Cao, Y.J. Zhu, Y. Yuan. Observation on efficacy of rulid in treatment of respiratory tract infections. Chinese Journal of New Drugs 1994;3(6):42-44. (1994)
  • W.B. Cao, W.C. Luo, Z.J. Guo, Y.J. Zhu. Methylene blue inhibits the decrease of the hypoxic pulmonary artery pressure produced by ligustrazine. Chinese Journal of Tuberculosis and Respiratory Diseases 1993,16(2):105. (1993)
  • W.B. Cao, W.C. Luo, Z.J. Guo, Y.J. Zhu, X.L. Liu. Changes of plasma lipoperoxide during acute hypoxia. Basic Medical Sciences & Clinics 1992;12(2):60. (1992)
  • W.B. Cao, W.C. Luo, Z.J. Guo, Y.J. Zhu. Effects of methylene blue on acute hypoxic pulmonary hypertension in anesthetized dogs. National Medical Journal of China 1992;72(3):165-166. (1992)
  • W.B. Cao, W.C. Luo. Vascular peptides and pulmonary circulation. GuoWai YiXue Huxi XiTong FenCe 1992;12(4):175-178. (1992)
  • W.B. Cao, W.C. Luo. Implications of angiotensin converting enzyme in serum and bronchial alveolar lavage fluid. Chinese Journal of Internal Medicine 1992;31(1):55-57. (1992)
  • W.X Lu, W.B. Cao. Pleural effusion and pulmonary shadows Chinese Journal of Tuberculosis and Respiratory Diseases 1991;14(2):114-115. (1991)
  • W.B. Cao, L.Y. Li, Y.J. Zhu, W.C. Luo, Z.G. He. Fever, cough and pulmonary shadows. Chinese Journal of Tuberculosis and Respiratory Diseases 1990;13(5):309-310. (1990)
  • F.C. Chang, W.B. Cao. Fever, rash and diarrhea. Chinese Journal of Pathology 1987;16(2):153-157. (1987)
  • Note: * corresponding author ()