Curriculum Vitae (Abbreviated)

Current Position

Professor, Departments of Pathology and Internal Medicine
Chairman, Division of Cellular and Molecular Pathogenesis, Department of Pathology
Virginia Commonwealth University/Medical College of Virginia Campus,
Richmond, VA

Research Interests

Liver carcinogenesis and pathobiology; molecular mechanisms regulating biliary epithelial cell differentiation, proliferation and neoplastic transformation; bile ductular cell isolation and culture; liver stem cells, experimental therapeutics and chemoprevention of hepatobiliary cancer.

Current Editorial Boards

• In Vitro Cellular and Developmental Biology - Animal
• Experimental and Molecular Pathology
• World Journal of Gastroenterology

Membership - Scientific Societies

• The American Society for Cell Biology
• The American Association for Cancer Research
• American Society for Investigative Pathology
• Society for In Vitro Biology
• American Association for the Advancement of Science
• The New York Academy of Sciences
• Association of Clinical Scientists
• American Association for the Study of Liver Diseases
• Society for Experimental Biology and Medicine
• Hans Popper Hepatopathology Society
• Society of Toxicology
• American Gastroenterological Association 

Regular Membership - National Study Sections

Regular Member, American Cancer Society Study Section (National Office). Scientific Advisory Committee on Biochemistry and Chemical Carcinogenesis, 1/01/89-6/30/92. Committee reorganized in May/June 1989. Appointed to Scientific Advisory Committee on Carcinogenesis and Nutrition 6/21/89-6/30/92.

Regular Member, Metabolic Pathology Study Section, NCI, NIH, July 1, 1991 to June 30, 1995.

Academic Honors and Awards

2000 Burroughs Wellcome Fund's Visiting Professorship in the Basic Medical Sciences (Pathology) at Pennsylvania State University College of Medicine, 10/10/00-10/13/00; sponsored by the Burroughs Wellcome Fund and the Federation of American Societies for Experimental Biology

2002 Recipient of Virginia Commonwealth University School of Medicine Research Recognition Award

2007 Recipient of Virginia Commonwealth University School of Medicine Recognition Award for Research and Scholarship

Recent Grants

NIH-National Cancer Institute RO1 Grant 1 RO1 CA 83650-06-10: Altered Growth Factor Pathways in Biliary Cancer. Total project period: 02/01/05-12/31/09. Total amount of award: $1,536,705.

NIH-National Cancer Institute 2RO1 CA 39225-22A1-25A1: Hepatic Oval Cells in Culture and In Vivo. Total project period: 7/01/07-5/31/12 Total amount of award: $1,435,262.

Recent Publications

Ren, P., Silberg, D.G., and Sirica, A.E.: 2000. Expression of an intestine-specific transcription factor (CDX1) in intestinal metaplasia and in subsequently developed intestinal-type of cholangiocarcinoma in rat liver. American Journal of Pathology, 156: 621-627.

Lai, G.-H., Radaeva, S., Nakamura, T., and Sirica, A.E.: 2000. Unique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" biliary cancer chemically induced in rat liver. Hepatology, 31: 1257-1265.

Sirica, A.E., Lai, G.-H, and Zhang, Z.: 2001. Biliary cancer growth factor pathways, cyclo-oxygenase-2 and potential therapeutic strategies. J. Gastroenterology and Hepatology, 16: 363-372.

Sirica, A.E.: 2002. Bile duct epithelial cell culture. In: Methods in Molecular Biology, Vol. 188: Epithelial Cell Culture Protocols. (Wise, C., ed.). Chapter 5, pp. 37-52, Humana Press, Inc., Totowa, NJ. (Invited Chapter).

Endo K., Yoon, B., Pairojkul, C., Demetris, A.J., and Sirica, A.E.: 2002. ERBB-2 over-expression and cyclooxygenase-2 up-regulation in human cholangiocarcinoma and risk conditions. Hepatology, 36:439-450.

Sirica, A.E., Lai, G.-H., Endo K., Zhang, Z. and Yoon, B.: 2002. Cyclooxygenase-2 and ERBB-2 in cholangiocarcinoma: Potential therapeutic targets. Seminars in Liver Disease, 22:303-313.

Sirica, A.E.: 2002. Bile duct cancer, ERBB-2 and COX-2. Science & Medicine (Invited Paper), 8:268-277.

Lai, G.-H., Zhang, Z., Sirica, A.E.: 2003. Celecoxib acts in a cyclooxyenase-2 independent manner and in synergy with emodin to suppress rat cholangiocarcinoma growth in vitro through a mechanism involving enhanced Akt inactivation and increased activation of capases-9 and -3. Molecular Cancer Therapeutics, 2:265-271.

Zhang, Z., Lai, G.-H., Sirica, A.E.: 2004. Celecoxib-induced apoptosis in rat cholangiocarcinoma cells mediated by Akt inactivation and Bax translocation. Hepatology 39: 1028-1037.

Sirica, A.E.: 2005. Cholangiocarcinoma: Molecular targeting strategies for chemoprevention and therapy. Hepatology 41: 5-15.

Lai, G.-H., Zhang, Z., Shen, X.-N., Ward, D.J., DeWitt, J.L., Holt, S.E.., Rozich, R.A., Hixson, D.C., Sirica, A.E.: 2005.erbB-2/neu Transformated rat cholangiocytes recapitulate key cellular and molecular features of human bile duct cancer. Gastroenterology 129:2047-2057.

Sirica, A.E., Zhang, Z., Lai, G.-L., Asano, T., Shen, X.-N., Ward, D.J., Mahatme, A., and DeWitt, J.L. : 2008. A novel “patient-like” model of cholangiocarcinoma progression based on bile duct inoculation of tumorigenic rat cholangiocyte cell lines. Hepatology, in press. (Profiled on April 2008 journal cover).

Recent Abstracts

Lai, G.-H., and Sirica, A.E.: 2001. Up-regulation of cyclooxygenase-2 (COX-2) in C611B rat cholangiocarcinoma cells over-expressing NEU and in neu-transformed WB-F344 rat liver epithelial stem-like cells. The FASEB J., 15: A1085.

Sirica, A.E., Endo, K., Lai, G.-H., Zhang, Z., Demetris, A.J., Pairojkul, C., and Terada, T.: 2001, Cyclooxygenase-2 (COX-2) up-regulation: A common alteration in human and rat biliary cancers. Proc. Amer. Assoc. Cancer Res., 42: 696.

Lai, G.-H., and Sirica, A.E.: 2001. Up-regulation of cyclooxygenase-2 (COX-2) in C611B rat cholangiocarcinoma cells over-expressing NEU and in neu-transformed WB-F344 rat liver epithelial stem-like cells. The FASEB J., 15: A1085.

Zhang, Z., and Sirica, A.E.: 2001. The cyclooxygenase-2 (COX-2) inhibitor NS-398 selectively suppresses in vitro cell growth and induces apoptosis in C611B rat cholangiocarcinoma cells over-expressing COX-2. The FASEB J., 15: A1181.

Lai, G.-H., and Sirica, A.E.: 2001. Celecoxib and emodin act in combination to suppress growth of rat cholangiocarcinoma cells over-expressing cyclooxyenase-2 and NEU receptor tyrosine kinases. Abstract Booklet for FASEB Summer Research Conference on Growth Factor Receptor Tyrosine Kinases in Mitogenesis, Morphogenesis, and Tumorigenesis.

Sirica, A.E., Endo, K., Lai, G.-H., Zhang, Z., Demetris, A.J., Pairojkul, C., and Terada, T.: 2001. COX-2 and ERBB-2/NEU in human and rat cholangiocarcinomas: Potential therapeutic targets.  Hepatology, 34: 191A.

Sirica, A.E., Lai, G.-H., Zhang, Z.: 2002. Targeting ERBB-2 and COX-2 in a novel cholangiocarcinoma cell line. AACR Frontiers in Cancer Prevention Research Conference Proceedings, p.138.

Lai, G.-H., and Sirica, A.E.: 2003. Effect of GW572016 on ErbB-2 signaling, cell growth and apoptosis in rat biliary cancer cells. The FASEB J 17:A257.

Zhang, Z., and Sirica, A.E.: 2003. Molecular mechanisms of celecoxib-induced apoptosis in rat biliary cancer cells. The FASEB J 17:A677-A678.

Lai, G.-H., Rozich R.A., Hixson, DC., and Sirica, A.E.: 2004. Oncogenic neu transformation of rat cholangiocytes: A novel in vitro model of cholangiocarcinogenesis. Proc. Amer. Assoc. Cancer Res., 45: 1272.

Sirica, A.E., Lai, G.-H., Zhang, Z., Holt, S.E., and Shen, X.-N.: 2005. Oncogenic erbB-2/neu transformation of rat cholangiocytes in vitro accompanied by increased telomerase activity and COX-2 up-regulation., The FASEB J. 19: A478.

Sirica, A.E., Shen, X.-N., Zhang, Z., Ward, D.J., Asano, T., Lai, G.-H. and Mahatme, A.: 2006. A novel preclinical rat model of rapid mass-forming cholangiocarcinoma growth in liver with prominent extrahepatic metastases recapitulating the advanced human disease. Hepatology, 44:526A.

Sirica, A.E., Zhang, Z., Asano, T., Shen, X.-N., Ward, D.J., and Mahatme, A.: 2007. Bile duct obstruction is a potent promoter of intrahepatic cholangiocarcinoma growth and progression. The FASEB J., 21: A71 (selected by the American Society for Investigative Pathology for press release).

Zhang, Z., and Sirica, A.E.: 2007. Simultaneous inhibition of ErbB1 and ErbB2 signaling significantly enhances the growth suppression of rat and human cholangiocarcinoma cell lines. The FASEB J., 21: A71-72.

Sirica, A.E., Zhang, Z., and Mahatme, A. :2007. Significant COX-2 up-regulation and Akt activation positively correlate with in vitro spontaneous neoplastic transformation of a rat cholangiocyte cell line. Gastroenterology, 132: A-730.

Sirica, A.E., Asano, T., Zhang, Z., Mahatme, A., and Ward, D.: 2007. In vitro spontaneous transformation of rat BDE1 cholangiocytes compared with oncogenic erbB-2/neu transformants. In Vitro Cellul. Develop. Biol.-Animal 43:S34.

Books

Sirica, A.E., Editor/Author, The Pathobiology of Neoplasia, 1989, pp. 1-583, Plenum Publishing Corp., New York, NY.

Sirica, A.E., Editor/Author, The Role of Cell Types In Hepatocarcinogenesis, 1992, pp. 1-358, CRC Press, Boca Raton, Fl.

Sirica, A.E., Editor/Author, Cellular and Molecular Pathogenesis, 1996, pp. 1-557, Lippincott-Raven Publ., Philadelphia, PA.

Sirica, A.E., and Longnecker, D.S., Editors, Biliary and Pancreatic Ductal Epithelia: Pathobiology and Pathophysiology, 1997, pp. 1-575, Marcel Dekker, Inc., New York, NY. (peer-reviewed). Published as Volume 3 in Marcel Dekker's "Gastroenterology and Hepatology" series.

National Conferences Organized

Organizer and Director, Symposium and Workshop on the Pathobiology of Neoplasia. Held in Richmond, VA, April 24-28, 1989.

Vice Chairman, FASEB Summer Research Conference on Hepatic Regeneration and Carcinogenesis, held in Copper Mt. CO, July 29- August 3, 1990.

Organizer and Director, 2 ND Symposium and Workshop on the Pathobiology of Neoplasia (sponsored by the American Society for Investigative Pathology) held in Richmond, VA, April 19-23,1993.

Program Committee Chair, American Society for Investigative Pathology, July 1, 1994- June 30, 1996.

Organizer and Chair, FASEB Summer Research Conference on Growth Factor, Receptor Tyrosine Kinases in Mitogenesis, Morphogenesis, and Tumorigenesis (Vice-Chair, Dr. George Vande Woude). Held in Snowmass Village, CO, July 31- August 5, 1999.

Organizer and Chair, second FASEB Summer Research Conference on Growth Factor, Receptor Tyrosine Kinases in Mitogenesis, Morphogenesis, and Tumorigenesis (Vice-Chair, Dr. George Vande Woude). Held in Snowmass Village, CO, August 4-9, 2001.

Organizer and Chair (together with Dr. Nicholas LaRusso of the Mayo Clinic) of the Henry M. and Lillian Stratton Basic Research Single Topic Conference-Pathobiology of Biliary Epithelia and Cholangiocarcinoma, sponsored by the American Association for the Study of Liver Diseases, to be held at the Emory Conference CENTER, Atlanta, GA, June 6-8, 2008. (see AASLD webpage for details)

Select Invited Presentations

Cyclooxygenase-2 (COX-2) Up-regulation: A Common Alteration in Human and Rat Biliary Cancers. Presented in minisymposium entitled Clinical Research 16-Gastrointestinal Malignancies: Biology and Treatment at the 92nd Annual Meeting of the American Association for Cancer Research on March 27, 2001 in New Orleans, LA.

Up-regulation of Cyclooxygenase-2 (COX-2) in C611B Rat Cholangiocarcinoma Cells Over-Expressing NEU and in NEU-Transformed WB-F344 Rat Liver Epithelial Stem-Like Cells. Presented in minisymposium entitled Hepatic Stem Cells and Cellular Signaling at Experimental Biology 2001 on April 3, 2001 in Orlando, FL.

The Cyclooxygenase-2 (COX-2) Inhibitor NS-398 Selectively Suppresses In Vitro Cell Growth and Induces Apoptosis in C611B Rat Cholangiocarcinoma Cells Over-Expressing COX-2. Presented in Poster Discussion Session entitled Gene Expression, Silencing and Repair in Neoplasia held at Experimental Biology 2001 on April 4, 2001 in Orlando, FL.

Chair of American Society for Investigative Pathology Poster Discussion Session entitled Gene Expression, Silencing and Repair in Neoplasia held at Experimental Biology 2001 on April 4, 2001 in Orlando, FL.

Session Chair at the American Association for the Study of Liver Diseases Basic Research Single Topic Conference - The Pathobiology of Biliary Epithelia. Session: Malignant Transformation of Cholangiocytes. Title of Presentation: Therapeutic Targeting of Cyclooxygenase-2 and of ERBB-2 in Cholangiocarcinoma. Held on June 7-10, 2001 at the Airlie Conference Center, Warrington, VA.

Altered Growth Factor Pathways and COX-2 Up-regulation Common to Rat and Human Biliary Cancers: Relevance to Pathogenesis and New Therapeutic Strategies. Presented at the FASEB Summer Research Conference on Growth Factor Receptor Tyrosine Kinases in Mitogenesis, Morphogenesis, and Tumorigenesis held in Snowmass Village, CO,  August 4-9, 2001.

Session Chair: Young Investigator Minisymposium on Growth Factor Receptor Tyrosine Kinases at the FASEB Summer Research Conference on Growth Factor Receptor Tyrosine Kinases in Mitogenesis, Morphogenesis, and Tumorigenesis held in Snowmass Village, CO,  August 4-9, 2001.

COX-2 and ERBB-2/NEU in Human and Rat Biliary Cholangiocarcinomas: Potential Therapeutic Targets. Presented in the Poster Session entitled Liver Transplantation 1 at the 52nd Annual Meeting of the American Association for the Study of Liver Diseases held in Dallas, TX, November 10, 2001.

Co-Moderator of American Associate for the Study of Liver Diseases early morning workshop on Cholangiocyte Cell Biology, held on November 12, 2001 at the 52nd annual meeting of the AASLD in Dallas, TX.

Invited Speaker to FASEB Summer Research Conference on Mechanisms of Liver Growth, Differentiation and Molecular Pathogenesis of Hepatic Diseases held in Snowmass Village, CO, July 27-August 1, 2002. Title of Presentation: Molecular Mechanisms of Cholangiocarcinogenesis: Potential New Therapeutic Strategies.

Targeting ERBB-2 and COX-2 in a Novel Rat Cholangiocarcinoma Cell Line. Presented in a Poster Session entitled, Organ Site-Specific Investigations: Colon and Gastrointestinal Cancers, at the AACR Frontiers in Cancer Prevention Research Conference held October 14-18, 2002 in Boston, MA. Selected for presentation in Poster Discussion Session entitled, Gastrointestinal Cancer.

Lecturer at the Science Museum of Virginia Mini-Medical School Program entitled, Pathology: Linking Technology with Good Health. Title of Lecture: Molecular Targets in Cancer Treatment. Presented in Richmond, VA on October 30, 2002.

Co-moderator at the American Association for the Study of Liver Diseases (AASLD) Early Morning Workshop entitled Cholangiocyte Cell Biology held on November 4, 2002 at the 53rd Annul Meeting in Boston, MA.

Effect of GW572016 on ErbB-2 Signaling, Cell Growth and Apoptosis in Rat Biliary Cancer Cells. Presented in a poster session entitled Liver Cancer on April 12, 2002 in San Diego, CA.

Molecular Mechanisms of Celecoxib-Induced Apoptosis in Rat Biliary Cancer Cells. Presented in a Poster Session entitled Apoptosis at the Experimental Biology 2003 on April 13, 2002 in San Diego, CA.

Invited Speaker: Session entitled Liver Pathobiology: Molecular and Cellular Basis of Liver Cancer at the American Society for Investigative Pathology Annual Meeting at Experimental Biology 2003, held April 15, 2003 in San Diego, CA. Title of Presentation: Targeting HER-2/neu and COX-2 in Cholangiocarcinoma.

Invited Speaker: Lifespan COBRE Center for Cancer Research Development Research Symposium held in Providence RI, July 31, 2003. Title of Presentation: Signature Immunoreactivity Marker Profiles of Cholangiocarcinoma: Potential for Molecular Therapeutic Targeting in Biliary Cancer.

Chair of Session entitled Growth Factor Receptor Tyrosine Kinase in Tumorigenesis Invasion and Metastasis-II at the FASEB Summer Research Conference: Growth Factor Receptor Tyrosine Kinases in Mitogenesis, Morphogenesis, and Tumorigenesis held in Tucson, AZ,  August 2-7, 2003. Title of Presentation: ERBB-2 as a Therapeutic Target in Biliary Cancer.

Invited Speaker: 2004 FASEB Summer Research Conference entitled "Mechanisms of Liver Growth, Development and Disease" held in Snowmass Village, CO, August 7-12, 2004. Title of presentation: Altered growth factor receptor signaling and molecular therapeutic targeting in cholangiocarcinoma.

Invited Speaker: 2005 Hans Popper Hepatopathology Society Seminar on PRIMARY liver Tumors held in SAN Antonio, TX on February 27, 2005. Title of Presentation: Cholangiocarcinoma.

Growth Factor Pathways and Cyclooxygenase-2 in Biliary Carcinogenesis. Presented on January 30, 2001 to the Department of Pathology of the University of Pittsburgh.

Biliary Cancer: Cyclooxygenase-2, Altered Growth Factor Pathways and New Therapeutic Strategies. Presented at the Department of Pathology Grand Rounds, Virginia Commonwealth University/MCV Campus on May 11, 2001.

Therapeutic Targeting of p185 neu Receptor Tyrosine Kinase and of COX-2 in Cholangiocarcinoma. Presented at the University of Texas, M.D. Anderson Cancer Center-Science Park Research Division, Smithville, TX on November 13, 2001.

Molecular Targeting Strategies for Biliary Cancer. Presented to the Department of Pathology, University of Pittsburgh on June 24, 2002.

Molecular Mechanisms of Cholangiocarcinoma: Potential Therapeutic Targets. Presented to the Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University/MCV Campus on October 3, 2002.

Molecular Pathogenesis and Novel Therapeutic Strategies for Hepatobiliary Cancer. Presented to the MBG Seminar Program and to the Cancer Cell Biology Program at Virginia Commonwealth University on November 27, 2002.

Molecular Drug Targeting in Biliary Cancer. Presented to the Department of Pharmacology, Virginia Commonwealth University/MCV Campus on April 29, 2003.

Biliary Cancer: Immunochemical Profiling, Novel Models, and Potential Therapeutic Targets. Presented to the Department of Pathology and Microbiology of the University of South Carolina School of Medicine on July 19, 2004.

Cholangiocarcinoma: Immunochemical Profiling and Novel Models. Presented to the Department of Pathology of the University of Pittsburgh School of Medicine on November 10, 2004.

Cholangiocarcinoma: Molecular Pathogenesis and Potential Therapeutic Targets. Presented to the Department of Medical Physiology of Texas A & M University System Health Science Center on November 18, 2004.

Cholangiocarcinoma: Novel Models and Molecular Targeting Strategies. Presented to the Liver-Pancreatic-Biliary Center of the University of Connecticut Health Center on June 21, 2005.

A novel preclinical rat model of rapid mass-forming cholangiocarcinoma growth in liver with prominent extrahepatic metastases recapitulating the advanced human disease. Given as a Poster Presentation at the 57th Annual Meeting of the American Association for the Study of Liver Diseases on October 30, 2006.

A new and unique “patient-like” rat model of intrahepatic cholangiocarcinoma progression mimicking the human disease. Presented to the Department of Pathology of Emory University School of Medicine on February 27, 2007.

Co-Chair of American Association for the Study of Liver Diseases Session titled Hepatobiliary Neoplasia: Clinical and Experimental held at Digestive Disease Week 2007 in Washington, DC, May 20, 2007.