Transplant Program
Directing Human Embryonic Stem Cells (ESC) Along a Hepatocyte Lineage/ Other Projects in Liver Pathophysiology
Mentor: Mark A. Zern, M.D.

Description: Treatment of liver disease with orthotopic liver transplantation (OLT) carries considerable morbidity and mortality. Moreover, due to organ shortages, tens of thousands of people die each year without getting transplanted. Therefore, safer and more convenient alternative therapies will benefit many people requiring liver transplantation. An approach that might address this problem is the development of a human liver cell (hepatocyte) line that expresses liver-specific genes which could beemployed for cell transplantation or for a bioartificial liver. Unfortunately, a key for these two therapeutic modalities is that the lack of donor livers makes it difficult to obtain enough viable human hepatocytes for the further advancement of these therapies. Thus, it would be highly advantageous if functional human hepatocytes could be generated from other sources. Our lab is trying to address this issue by differentiating human ESC to become liver cells

Duration: A long-term commitment from a student is encouraged. Less desirable is a short-term commitment.

References:
Wege, H, Le, HT, Chui, MS, Liu, L, Wu, J, Giri, R, Malhi, H, Sappal, BS, Kumaran, V, Gupta, S, and MA Zern. Telomerase reconstitution immortalizes human fetal hepatocytes without disrupting their differentiation potential. Gastroenterology 124:432-444. 2003.

Shirahashi, H, Wu, J, Yamamoto, N, Catana, A, Wege, H, Wager, B, Okita, K and MA Zern. Differentiation of human and mouse embryonic stem cells along a hepatocyte lineage. Cell Transplantation. 13: 197-211, 2004

Wu J, Liu J, Yen YD, Catana C, Michael H. Nantz, Zern MA. Liposome-mediated extracellular superoxide dismutasegene delivery protects against acute liver injury in mice. Hepatology; 40: 195-204, 2004

Dear Student:

We have been doing basic/translational liver research for more than 25 years. We have a series of studies ongoing in our very active laboratory at this time, including the molecular bases of liver injury and cirrhosis, targeting of therapeutics to the liver by the use of liposomes, the use of siRNA or gene therapy for the treatment of liver fibrosis, and the differentiation of human and primate ESC towards hepatocytes. We would be pleased to encourage a student to consider a career in basic/translationalresearch by helping in his/her training. Our preference is for a long-term commitment so that the training would be meaningful and truly beneficial to the student. Please contact us for further information

Sincerely yours,

Mark A. Zern, M.D.
Professor of Medicine
The Fred and Pat Anderson Professor of Transplant Research
Director, Transplant Research Program
UC Davis Medical Center
4635 2nd Ave., Rm. 1001
Sacramento, CA 95817
Phone: 916-734-8063
Fax: 916-734-8097