Hepatobiliary Currents
News from the
LIVER CENTER
of the
University of California, San Francisco
Fall/Winter, 1998
Fall/Winter, 1998
Robert Ockner is stepping down as Center director, after leading the organization since 1983; he succeeded founding director Rudi Schmid. In accepting Ockner's resignation, Dean Haile Debas wrote "Your thoughtful and dedicated leadership of the Center over the past 15 years has assured its success." The Dean has appointed D. Montgomery Bissell as the new director. Dr. Ockner will continue to be actively involved in Center programs.
This combined event was held again at the Marconi Conference Center, overlooking Tomales Bay, in beautiful fall weather and was well-attended. All members of the Advisory Board were present except for Harry Greenberg, M.D., Stanford University, whose absence was necessitated by illness. Other members of the Board include James Boyer, M.D., Chairman, Yale University; Nelson Fausto, M.D., University of Washington; Robert Glickman, M.D., New York University; Bettie Sue Masters, Ph.D., University of Texas at San Antonio; David Perlmutter, M.D., Washington University; and John Vierling, M.D., UCLA (Cedars Sinai Medical Center).
A highlight of the Retreat was a special lecture by Nelson Fausto on the topic "Liver Regeneration", a field of investigation to which he and his colleagues have contributed enormously. A day and one-half were filled otherwise with a broad array of presentations by Center members reflecting the substantial growth in the use of molecular approaches to disease, not only in basic but also in clinical research. Subject areas included cell biology, biotransformation and heme proteins, viral hepatitis, intermediary metabolism and clinical cholestasis. The oral presentations by Dr. Fausto and by Center members generated lively discussion.
In response to the announcement of pilot/feasibility funding, the Center received six letters of intent, of which five were deemed eligible and submitted as formal applications. After review by the Center's Executive Committee and external Advisory Board, three were funded. These are:
G. Enns, M.D., Ch.B.: "Treatment of hepatic inborn errors of metabolism with adenoassociated viral vectors." The primary aim of this proposal is to study the potential applications of adeno-associated virus (AAV) vectors in the treatment of a relatively common (1:40,000-1:80,000) inborn error of metabolism affecting the urea cycle, ornithine transcarbamylase (OTC) deficiency. The specific objectives are to: 1) construct and characterize in cell cultures AAV vectors expressing mouse OTC; 2) test the ability of these vectors to correct the biochemical and clinical characteristics of naturally occurring mouse models (spf and spf-ash mice) of OTC deficiency; and 3) test the potential of these vectors for fetal gene therapy by direct in-utero liver injection.
J. Huerte-Perez, Ph.D.: "Mechanisms of protein sorting of lysosomal proteases." The PI hypothesizes that the mechanism of protein sorting in primitive eukaryotes is the evolutionary precursor to the mannose-6-phosphate-independent mechanism proposed for hepatocytes, and that this mechanism is dependent upon a prodomain/receptor interaction. This project is aimed at further elucidating this mechanism of protein sorting using a Trypanosoma cruzi transfection system. Specific aims are: 1) to determine whether the prodomain of the mammalian cathepsin L can correctly target GFP-chimeric proteins in more primitive eukaryotic cells; 2) to identify the specific amino acid motifs in the protease which are necessary for proper trafficking; and 3) to identify and isolate the putative membrane receptor.
N. Lomri, Ph.D.: "Analysis of a gene responsible for cholestatic diseases." The long-term objectives of the proposed studies are to understand the molecular mechanisms that govern the biology of bile formation, solute secretion and the pathophysiology of inherited and acquired liver disease. The general strategy is to focus predominantly on the Fic1 gene, that belongs to a newly described subfamily of P-type ATPases.
ALF Research Awards:
Liver Scholar Awards (3 year, $30,000/year)
Junior faculty, MD or PhD
Postdoctoral Research Fellow Awards(1 year, $10,000)
First or second year Fellow or Trainee, MD or PhD
Student Research Fellowship Awards (3 month stipend, $2,500)
Full time medical student
Deadline January 15, 1999
973-256-2550, ext. 230
Blowitz-Ridgeway Foundation
Two-Year Liver Scholar Award (2 years, $50,000/year)
Third or fourth year MD or PhD Fellow
Deadline January 15, 1999
973-256-2550, ext. 230
AGA Generation of Research Interest Awards
Sponsored Research Symposium Awards ($10,000, travel funding)
Senior faculty/established investigator
Deadline January 8, 1999
301-654-2635
Student Research Fellowship Awards (10 weeks, $1,500-2,500)
Medical student
Deadline March 3, 1999
301-654-2635
AASLD Research Training
Jan Albrecht Commitment to Clinical Research Award in Liver Disease (2 years, $25,000)
Junior faculty
Deadline January 8, 1999
301-654-2635
ASGE Research Training
Wilson-Cook Endoscopic Research Career Development Award (1 year, $36,000)
Junior faculty
Deadline January 8, 1999
301-654-2635
AGA Research Grants
Elsevier Research Initiative Award (1 year, $25,000)
Junior or senior faculty
Deadline January 8, 1999
301-654-2635
Miles & Shirley Fiterman Foundation Basic Research Award (1 year, $25,000)
Junior faculty
Deadline January 8, 1999
301-654-2635
AGA Travel Awards
International Travel Fellowship Awards ($1,500)
Junior faculty
Deadline January 8, 1999
301-654-2635
AGA Recognition of Research Achievement
Miles & Shirley Fiterman Foundation Clinical Research in GI or Hep/Nutrition Awards ($35,000)
Senior faculty
Deadline, January 8, 1999
301-654-2635
The external Advisory Board at its recent review also certified proposed changes in the Center's core facilities. This was the culmination of a process that was begun almost two years ago by the Center's Executive Committee. The Committee's initial step was to obtain an outside review of the number and function of the then-existing cores. Two nationally recognized investigators, Drs. Harry Greenberg (Stanford) and Nicholas LaRusso (Mayo) agreed to undertake this task and visited in August, 1996. After member input was obtained at the 1997 annual retreat, restructuring proceeded with a net reduction in the number of cores from nine (+ Administrative) to four (+ Administrative). In some cases, specific core functions that were considered valuable were retained but merged with those from another core. Cores were also renamed so as to better reflect their function and the major foci of Center member research. The new cores are as follows: