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Faculty Catherine H. Wu
Professor of Medicine
cwu@nso1.uchc.edu
Dr. Wu’s laboratory is involved in research in gene therapy of liver
diseases and creating novel animal models for studying liver diseases.
Dr. Wu’s laboratory has developed a protein base carrier molecule that
can deliver molecular reagents such as genes and antisense DNA and RNA
molecules specifically to liver cells (1). The original liver-specific
carrier molecule has been used to deliver human albumin gene and human
low density lipoprotein receptor in animals deficient in albumin or LDLR
expression resulting in partially reversal of metabolic liver diseases.
The novel carrier protein has also been show to be successful in
delivering molecular agents for treatment of acquired liver diseases
such as Hepatitis B and hepatic fibrosis (2).
Research in this area is now focused on modifying the liver specific
carrier protein to include elements that would enhance the efficiency of
delivery process so that molecular agents taken into liver cells by this
system can be rendered more biologically active and thus more
therapeutically effective (3).
The laboratory is in the process of characterizing a normal rat with
humanized liver. We have produced a rat with normal immune system
capable of hosting human liver cells in its liver. The animal has been
shown to be susceptible to human hepatitis B viral infection (4). We are
now studying the molecular regulation of human Hepatitis C virus and its
structure since not much is know about either of the two areas of HCV
viral genome (5). We will use rats with humanized liver to develop a
rodent model of HCV infection and to use this model to test novel HCV
therapeutics.
Selected Publications:
Wu CH, Walton CM, Wu GY. Targeted gene transfer to liver using
protein-DNA complexes. Methods Mol Med.;69:15-23 (2002).
Wu, C.H., Sapozhnikov, E., and Wu, G.Y.: Evaluation of multicomponent
non-viral vectors for liver directed gene delivery. J. Drug Target.
10(2): 105-111 (2002).
Smith RM, Walton CM, Wu CH, Wu GY. Secondary structure and
hybridization accessibility of hepatitis C virus 3'-terminal sequences.J
Virol.;76(19):9563-74 (2002).
Wu, C.H., Ouyang, E.C., Walton, C.M. and Wu, G.Y.: Human hepatocytes
transplanted into genetically immunocompetent rats are susceptible to
infection by hepatitis B virus in situ. J. Viral Hepatitis 8:111-119
(2001).
Wu, C.H., Walton, C.M., and Wu, G.Y.:Targted inhibition of type I
procollgen synthesis by antisense DNA oligonucleotides. Gene Ther and
Reg 1:193-205 (2000). |
