Sirica Lab Research


The study of cellular and molecular mechanisms of disease

Dr. Sirica is a Professor of Pathology and Internal Medicine. His research program in hepatobiliary pathobiology and the cellular and molecular pathogenesis and experimental therapeutics of cholangiocarcinoma has been supported by continuous NIH R01 grant funding from 1981 to the present. In April 2013, Dr. Sirica was awarded a 5 year competing continuation of his NIH grant 2R01CA083650- Altered Growth Factor Pathways in Biliary Cancer.

Cholangiocarcinomas are a class of highly malignant and most often lethal adenocarcinomas of the biliary tract that are frequently characterized by a prominent desmoplastic stoma. However, the biological significance of the desmoplastic stroma in cholangiocarcinoma is only just beginning to be addressed at the cellular and molecular levels. In an effort to provide new cellular and mechanistic insights into how desmoplastic reaction may be contributing to cholangiocarcinoma progression, Dr. Sirica’s current research is focused on utilizing unique orthotopic tumor and complementary organotypic culture models of rat cholangiocarcinoma developed in his laboratory to identify interactive cellular and molecular pathways that may act to modulate the desmoplastic microenvironment and enhance cholangiocarcinoma aggressiveness.

Another key component of Dr. Sirica’s current research is to identify and preclinically testin vitro and in vivo novel molecular strategies for intrahepatic cholangiocarcinoma therapy based on combinational targeting of tumor stromal and cancer cell signaling pathways linked to cholangiocarcinoma progression and chemotherapeutic resistance. Particular attention is now being placed on testing targeted agents for their ability to selectively deplete cancer-associated myofibroblasts from the cholangiocarcinoma microenvironment as a potential means of enhancing the therapeutic efficacy of select clinically relevant agents targeting dysregulated growth factor pathways associated with cholangiocarcinoma cell invasive growth and apoptosis resistance.  

Current & Past Postdoctoral Trainees/Fellows


Contact Us

Alphonse E. Sirica, PhD, MS, AGAF, FAASLD, FACSc
Office: (804) 828-9549
Fax: (804) 828-4077
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