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AASLD-FDA-NIH-PhRMA Hepatotoxicity Steering Group Meeting, 2006 Presentations: Interplay between liver regeneration and hepatoprotection

Becky Taub, MD 
VP Metabolic Diseases Research,
Hoffmann-LaRoche
Interplay between liver regeneration and hepatoprotection [PDF]

The unusual regenerative properties of the liver are a logical adaptation by organisms, as the liver is the major detoxifying organ of the body and first in line to be injured by ingested toxins. The multiple cytokine and growth factor pathways that are involved in regulating liver regeneration are being successfully dissected using molecular and genetic approaches. Growth factors and cytokines such as HGF, IGFBP-1, IL-6/Stat3/gp130 and NF-kappaB promote hepatic survival by stimulating liver regeneration and providing hepatoprotection in a variety of liver injury models including Fas-mediated injury, toxic damage caused by hepatotoxins such as CCL4, and by ischemia. These growth factors provide protection against chronic liver injury that ultimately leads to fibrosis. The relationship between the pro-mitogenic and anti-injury effects of these factors has not been clearly defined, but at least part of this protection against injury is mediated by the induction of anti-apoptotic proteins that regulate the caspase cascade. These findings offer new insights into common mechanisms of hepatoprotection in both Fas- and toxin-mediated acute liver injury, and allow for predictions about potential therapeutic interventions that could prove beneficial for treating liver injury.

Biographical Sketch

Becky was educated at Yale in biochemistry (B.A., 1974) and medicine (M.D., 1978), and at the Yale-New Haven Hospital as an internal medicine resident (1978-81). She was then a post-doctoral fellow in genetics with Philip Leder at Harvard Medical School (1981-4). She was a Howard Hughes Medical Institute research associate at the Joslin Diabetes Center of Harvard (1984-6), before coming to the University of Pennsylvania as an assistant, associate, and full professor of Human Genetics and Medicine, and an associate investigator, Howard Hughes Medical Institute. In 2000 she was Executive Director of Biology at Dupont Pharmaceutical Company, in 2001-3 at Bristol-Myers Squibb, and since 2004 Vice President for Metabolic Diseases Research, Hoffmann-LaRoche, and tetains an appointment at the University of Pennsylvania as an Adjunct Professor of Surgery.

She was the Senior Scholar of the House at Yale in 1974, received the academic book award there in 1978, was awarded post-doctoral research fellowships from the Damon Runyon-Walter Winchell Cancer Foundation and the Cancer Research Institute 1981-4 and the Henry Christian Award for excellence in research 1991 and 1992. She served as member (1996-9) and chair (1999-2000) of the metabolic pathology study section of the National Cancer Institute.