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Alphonse E. Sirica, PhD, MS

Alphonse E. Sirica, PhD, MSProfessor, Departments of Pathology and Internal Medicine
Chairman, Division of Cellular and Molecular Pathogenesis
Virginia Commonwealth University
Medical College of Virginia Campus, Room 4-019 Sanger Hall
PO Box 980297, Richmond, VA 23298-0297
Office: 804-828-9549; Fax: 804-828-4077
asirica@mcvh-vcu.edu

 

Awards | VCU/MCV Appointments | VCU/MCV Service | Professional Organizations | Professional Service | Editorial Advisory Boards | Recent Grants | Recent Invited Presentations | Recent Peer Reviewed Publications | Books

Awards

Dr. and Mrs. Michael A. Gerber Lectureship, Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, April 11, 2012

Visiting Professor, Mayo Medical Center, Rochester, MN, June 5-6, 2011

Inducted as a Fellow of the American Gastroenterological Association(AGAF), January 1, 2009

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

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

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, 2000

Virginia Commonwealth University and Medical Center Appointments

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.

Virginia Commonwealth University and Medical Center Service

Member, VCU Department of Pathology's Executive Committee
Member, VCU Department of Pathology Grand Rounds Committee

Professional Organizations

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 

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Professional Service

Discussion Leader, 2012/10 ZCA1 RPRB-0 (O1) P-NCI Program Project Review Panel Meeting 1. National Cancer Institute, National Institutes of Health. Held June 14-15, 2012

Director, Board of Directors of CanLiv – The Hepatobiliary Cancers Foundation, May 2008-2011.

Reviewer, ZCA1 RPRB-O (M1) Cellular & Tissue Oncology P01 Special Emphasis Panel, National Cancer Institute Scientific Review Group, National Institutes of Health, March 1-3, 2010.

Reviewer, ZCA1 GRB-P (01) Special Emphasis Panel-Drug Discovery, Chemoprevention, and Targeted Therapy P01 Review Group.  National Cancer Institute, National Institutes of Health. Held May 25-27, 2010.

Reviewer, ZCA1 GRB-I (J1) P, SPORE in Sarcoma, Brain, Liver, Lung, and Prostate Cancers. National Cancer Institute, National Institutes of Health. Held September 29-30, 2010.

National Conferences Organized:

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, held at the Emory Conference CENTER, Atlanta, GA, June 6-8, 2008. (see AASLD webpage for details)

National Study Sections:

Ad Hoc Member, NIH Study Sections, 1995-present.

Editorial Advisory Boards

In Vitro Cellular and Developmental Biology - Animal
Experimental and Molecular Pathology
Member of Editorial Board of Annals of Clinical and Laboratory Science

Recent Grants

NIH-National Cancer Institute RO1 Grant 1 RO1 CA 83650-06-10: Altered Growth Factor Pathways in Biliary Cancer. Total project period: 02/01/05-3/31/18. Total amount of award: $1,689,614.

NIH-National Cancer Institute 2RO1 CA 39225-22A1-26: Hepatic Oval Cells in Culture and In Vivo. Total project period: 7/01/07-5/31/13 Total amount of award: $1,426,593.

Merck Research Grant Vioxx MSGP# 284C entitled "COX-2 in Human and Rat Cholangiocarcinogenesis." Total project period: 8/1/01-7/31/03. Total amount awarded: $50,000. Supplementary funding of $25,000 awarded for 8/1/01-7/31/04.

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Recent Invited Presentations

“Tumor microenvironment and hepatic biliary cancer progression: New opportunities for therapy”. John F. Sander and Nancy K. Dunkel Memorial Lectureship in Physiology. Presented to the Department of Physiology of Michigan State University, East Lansing, MI on November 29, 2012.

“Organotypic cell culture modeling of desmoplastic cholangiocarcinoma progression”.  Presented in the Poster Session entitled “Experimental Hepatocarcinogenesis” at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases in Boston, MA on November 11, 2012.

Co-moderator, Early Morning Workshop entitled “HCC: Cellular Mechanisms of Carcinogenesis” held at The Liver Meeting 2012 (63rd Annual Meeting of the American Association for the Study of Liver Diseases) on November 11, 2012 in Boston, MA.

Invited Speaker at the 2nd CanLiv Biliary Tract and Gallbladder Research Symposium held on June 22, 2012 at ASCO Headquarters Conference Center, Alexandria, VA. Title of presentation: “Fibroblasts, cell signaling pathways in cholangiocarcinoma.”

Presenter of The Dr. and Mrs. Michael A. Gerber Memorial Lecture given at the 23rd Annual Health Sciences Research Days and the Department of Pathology & Laboratory Medicine, Tulane University on April 11, 2012. Lecture Title: “Modeling cholangiocarcinoma progression: Do cancer-associated myofibroblasts matter?”

Invited talk entitled “Cancer-associated myofibroblastic cells and cholangiocarcinoma progression” presented at the McArdle Laboratory for Cancer Research Symposium honoring Dr. Henry C. Pitot, held at the University of Wisconsin-Madison on June 3, 2011. 

“Cancer-associated fibroblastic cells significantly promote cholangiocarcinoma cell ductal growth in a novel 3-D co-culture model”. Presented in the oral session entitled “Mechanisms of Hepatobiliary Neoplasia”, sponsored by the American Association for the Study of Liver Diseases held at Digestive Disease Week 2011 in Chicago, IL on May 10, 2011.        

Molecular targeting strategies for cholangiocarcinoma therapy: Preclinical assessment of potential targets. Presented at the Department of Biochemistry, George Washington University Medical Center, Washington, DC on October 19, 2010.

Invited Speaker at the 1st Annual Biliary Tract-Gallbladder Cancer Research Symposium sponsored by CanLiv-The Hepatobiliary Cancers Foundation and by the Cholangiocarcinoma Foundation, held in Alexandria, VA on May 7, 2010. Title of presentation” Intrahepatic cholangiocarcinoma: New insights from a preclinical animal model suggesting novel therapeutic targeting strategies”.

Invited Presenter at the 2009 NCI Translational Science Meeting, “NCI Translates” held in Vienna, VA, November 5-7, 2009. Presented in Poster Discussion Session titled “Targeting the EGFR Family” on November 5, 2009. Title of poster presention: “Preclinical assessment of dual ErbB1/ErbB2 targeting in intrahepatic cholangiocarcinoma”.

Intrahepatic Cholangiocarcinoma Progression: Molecular Insights from a Novel Rat Model Closely Mimicking the Human Cancer. Presented at the 5th Joint Meeting of the Japanese Society of Gastroenterology and the American Gastroenterological Association held in Sapporo, Hokkaido, Japan on May 8, 2009.

A Novel “Patient-Like” Rat Model of Cholangiocarcinoma Progression Highly Suitable for the Rapid In Vivo Testing of Target-Based Therapies. Presented in the American Association for Investigative Pathology sponsored session entitled “Liver Pathobiology Symposium: Interdisciplinary Approaches to Liver Disease” at Experimental Biology 2009, New Orleans, LA on April 19, 2009.

A Novel "Patient-Like" Rat Model of Intrahepatic Cholangiocarcinoma Progression as a Preclinical Platform for Rapid Testing of Molecular Target-based Therapies. Presented as an "Advances in Molecular and Cellular Pathology" seminar sponsored by the Graduate Program of the Departments of Pathology and Genomics and Pathobiology, University of Alabama at Birmingham on October 9, 2008.

ErbB Family Receptor Tyrosine Kinases as Potential Targets for Intrahepatic Cholangiocarcinoma Therapy. Presented at the Yale Digestive Diseases Section Research Conference, Yale University School of Medicine on September 23, 2008.

A Novel "Patient-like" Rat Model of Intrahepatic Cholangiocarcinoma Progression Mimicking Cellular, Molecular, and Clinical Features of the Human Disease.Presented at the University of North Carolina-Charlotte, April 30, 2008.

Preclinical assessment of dual ErbB1/ErbB2 targeting as a potential adjuvant molecular therapy for intrahepatic cholangiocarcinoma. Given as an oral presentation in Parallel Session XXVI: Hepatobiliary Cancer: Basic at the 59th Annual Meeting of the American Association for the Study of Liver Diseases held in San Francisco, CA, November 3, 2008.

Hepatobiliary cancer: current concepts, new models, and future strategies for target-based therapies and chemoprevention. Presented at the 2008 Annual Meeting of the Association of Pathology Chairs in Colorado Springs, CO, July 18, 2008.

Establishment of a novel "patient-like" rat model of cholangiocarcinoma progression for molecular therapeutic studies. Presented at the 2008 Henry M. & Lillian Stratton Basic Research Single Topic Conference - Pathobiology of Biliary Epithelia and Cholangiocarcinoma, sponsored by the American Association for the Study of Liver Diseases (AASLD) and held in Atlanta, GA, June 6-8, 2008.

A novel "patient-like" model of cholangiocarcinoma progression based on bile duct inoculation of transformed rat cholangiocytes overexpressing ErbB2. Given as a Poster Presentation at the 47th Annual Meeting of the Society of Toxicology & ToxExpo™ in Seattle, WA, March 17th, 2008

A novel preclinical model of intrahepatic cholangiocarcinoma progression based on orthotopic cell transplantation of spontaneous versus erbB-2/neu-transformed rat cholangiocytes. Presented to the Department of Pathology of the University of  Pittsburgh School of Medicine on May 30, 2007.

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.

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.

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.

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

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

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.

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.

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: 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.

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.

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Recent Publications

Peer Reviewed Publications

Sirica, A.E.: 2012. Notching up on the cellular origins of intrahepatic cholangiocarcinoma. Hepatology Elsewhere section.  Hepatology, in press.

Mertens, J.C., Fingas, C.D., Christensen, J.D., Smoot, R.L., Bronk, S.F., Werneburg, N.W.., Gustafson, M.P., Dietz, A.B., Roberts, L.R., Sirica, A.E., and Gores, G.J.: 2012. Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma. Cancer  Res., Published OnlineFirst December 5, 2012; doi:10.1158/00085472.CAN-12-2130. E-Pub ahead of print. Print version: 73: 897-907, 2013.

Campbell, D.J.W., Dumur, C.I., Lamour, N.F., DeWitt, J.L., and Sirica, A.E.: 2012. Novel organotypic culture model of cholangiocarcinoma progression. Hepatology Research, 42: 1119-1130.

Fingas, C.D., Mertens, J.C., Razumiliva, N., Bronk, S.F., Sirica, A.E., Gores, G.J.: 2012. Targeting PDGFR-β in cholangiocarcinoma. Liver International, 32: 400-409.

Noda, T., Shimoda, M., Ortiz, V, Sirica, A.E., and Wands, J.W.: 2012. Immunization with aspartate –β-hydroxylase loaded dendritic cells produce anti-tumor effects in a rat model of intrahepatic cholangiocarcinoma. Hepatology, 55: 86-97.

Sirica, A.E.: 2012. The role of cancer-associated myofibroblasts in intrahepatic cholangiocarcinoma. Nature Reviews Gastroenterology & Hepatology, 9: 44-54.

Fingas, C.D., Bronk, S.F., Werneburg, N.W., Mott, J.L., Guicciardi, M.E., Cazanave, S.C., Mertens, J.C., Sirica, A.E., and Gores G. J.: 2011. Myofibroblast-derived PDGF-BB promotes hedgehog survival signaling in cholangiocarcinoma cells. Hepatology, 54: 2076-2088.

Sirica, A.E., Campbell, D.J., and Dumur, C.I.: 2011. Cancer-associated fibroblasts in intrahepatic cholangiocarcinoma. Current Opinion in Gastroenterology, 27: 276-284.

Dumur, C.I., Campbell, D.J.W., DeWitt, J.L., Oyesanya, R.A., and Sirica, A.E.: 2010. Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas. Expt. Mol. Pathol., 89: 227-235.

Zhang, Z., Oyesanya, R.A.,Campbell, D.J.W., Almenara, J.A., DeWitt, J.L., and Sirica, A.E.:2010. Preclinical assessment of simultaneous targeting of epidermal growth factor receptor (ErbB1) and ErbB2 as a strategy for cholangiocarcinoma therapy. Hepatology, 52 : 975-986. (For commentary on this paper, see Nanda, S.: 2010. Nat Rev Gastroenterol Hepatol. 7: 591).

Fingas, C.D., Blechacz, B.R.A., Smoot, R.L., Guicciardi, M.E., Mott, J., Bronk, S.F., Werneburg, N.W., Sirica, A.E., Gores, G.J.: 2010. A smac mimetic reduces TNF related apoptosis inducing ligand (TRAIL)-induced invasion and metastasis of cholangiocarcinoma cells. Hepatology, 52: 550-561.

Blechacz, B.R.A., Smoot, R.L. Bronk, S.F., Werneburg, N.W., Sirica, A.E., AND Gores, G.J.:2009. Sorafenib inhibits signal transducer and activator of transcription-3 signaling in cholangiocarcinoma cells by activating phosphatase shatterproof 2. Hepatology, 50:1861-1870.

Sirica, A.E., Dumur, C.I., Campbell, D.J.W., Almenara, J.A., Ogunwobi, O.O., and DeWitt, J.L.:2009. Intrahepatic cholangiocarcinoma progression: Prognostic factors and basic mechanisms. Clin Gastroenterol Hepatol, 7: S68-S78.

Sirica, A.E.: 2008. The role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma. World J. Gastroenterology, 14:7033-7058 .

Sirica, A.E., Nathanson, M.H., Gores, G.J., LaRusso, N.F.: 2008. Pathobiology of biliary epithelia and cholangiocarcinoma: Proceedings of the Henry M. and Lillian Stratton Basic Research Single-Topic Conference. Hepatology (AASLD Single Topic Conference Report), 48:2040-2046.

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, 47:1178-1190. (Profiled on April 2008 journal cover).

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

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.

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.

Books:

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.

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

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, The Pathobiology of Neoplasia, 1989, pp. 1-583, Plenum Publishing Corp., New York, NY.

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