Douglas Hixson, PhD
COBRE CCRD Director and Principal Investigator

Douglas Hixson, PhD, is a professor of medicine and pathology at Brown University and Rhode Island Hospital. He received his research training at Purdue University and the University of Texas at Austin. He is internationally known for his research on hepatic stem cells and CEACAM1, an immunoglobulin-like tumor suppressor. The author of more than 80 research articles and book chapters, he is currently the principal investigator (PI) of three NIH RO1 cancer research grants. Hixson has served on multiple National Institutes of Health (NIH) review panels and was past chair of the NIH chemical pathology study section. He is on the editorial board of hepatology.

Research Focus
Research in our laboratory is focused on two major questions: What are the progenitors of hepatocellular carcinoma and what role do altered adhesive interactions play in the control of cell growth in normal and malignant cells?

These questions are being addressed using both rat and human models for liver and prostate cancer. Current studies on progenitor cells are directed towards defining stage specific cell-surface phenotypes in developing rat and human liver and the recapitulation of these phenotypes in primary and transplantable carcinoma using a unique panel of monoclonal antibodies (MAbs) developed in our laboratory. The differentiation capacity of subpopulations of fetal liver hepatoblasts and ductal cells isolated with MAbs by fluorescent-activated-cell sorting or magnetic bead protocols are being analyzed to determine their capacity for differentiation into hepatocytes or bile duct epithelial cells following transplantation into the adult rat liver and to identify differences in their gene expression profiles.

We have currently defined three different populations of fetal liver cells that show large variations in their ability to colonize the adult liver and in the size and morphology of their colonies. We are also devoting a major effort towards identifying MAb-defined-cell surface markers by mass spectrometry of purified proteins. To date we have determined the identity of two Mabs-defined proteins that preliminary studies indicate play a role in growth/morphogenesis and in the initiation/progression to malignancy of hepatic stem cells of ductal origin.

Selected Publications
Hixson DC, Animals Models for Assessing the Contribution of Stem Cells to Liver Development, In Stem Cell Handbook, Stewart Sell, Editor, Humana Press, 2002.

Comegys MM, Carreiro MP, Brown JF, Mazzacua A, Flanagan DL, Makarovsky A, Lin S-H and Hixson DC. C-CAM1 expression: Differential effects on morphology, differentiation state and suppression of human PC-3 prostate carcinoma cells, Oncogene (1999) 18:3261-3276.

Hixson DC, Brown J, McBride AC and Affigne S. Differentiation status of rat ductal cells and ethionine-induced hepatic carcinomas defined with surface-reactive monoclonal antibodies. Molecular Cellular Pathology, (2000) 68:152-169.

Gordon GJ, Coleman WB, Hixson DC, Grisham JW. "Liver regeneration in rats with retrorsine-induced hepatocellular injury reveals the existence of a novel liver progenitor cell population," American Journal of Pathology, 156:607-619, 2000.

Britt, D.E., Yang, D.F., Yang, D.Q., Flanagan, D., Callanah, H., Lim, Y.P., Lin, S.H., and Hixson, D.C. Identification of a novel protein, LYRIC, localized to tight junctions of polarized epithelial cells. Experimental Cell Research, 300: 134-148, 2004.

Laurie, N.A., Comegys, M.M., Carreiro, M.P., Brown, J.F., Flanagan, D.L., Brilliant, K.E., and Hixon, D.C. Carcinoembryonic antigen-related cell adhesion molecule 1a-4L suppression of rat heatocellular carcinomas. Cancer Research, 65: 11010-11017, 2005.

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