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. A competing renewal application for this NIH grant is currently pending review.
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 test in 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.
Hepatobiliary Cancers: Pathobiology and Translational Advances was first held on December 7-10, 2017 at the Virginia Commons Hotel and Conference Center in Glen Allen, VA. This conference, which was organized and chaired by Dr. Al Sirica, represented the first of its kind three day single topic conference on this important and timely subject matter held in the USA. The conference was co-sponsored and partially funded by the American Association for the Study of Liver Diseases and The Cholangiocarcinoma Foundation, as well as Virginia Commonwealth University’s Department of Pathology and Massey Cancer Center. In addition, the conference also was supported in part by funding from NIH Grant R13CA216895. Complete details of this conference, including objectives, invited speakers list, scientific program, accepted abstracts, and Progress Report for R13CA216895 can be found at www.livercancerconference.vcu.edu. As detailed in this Progress Report, this conference was highly rated and 100% of the attendees indicated by a show of hands at the event, and/or in their written evaluations that they would like to see this scientific meeting continued. Based on this overwhelming unanimous response, efforts are now underway to repeat the conference at an expanded national/international level in 2020/21. The following leaders in the hepatobiliary cancers field have agreed to serve as conference organizers with Dr. Sirica: Anna Mae Diehl, M.D., Duke University, Gregory J. Gores, M.D., Mayo Clinic-Rochester, George K. Michalopoulos, M.D., Ph.D., University of Pittsburgh, and Lopa Mishra, M.D., George Washington University. Their individual titles and academic positions can be found under the Speakers link on the conference website.