XIAOMING
LIU, D.V.M, Ph.D.
Postdoctoral Associate
xiaoming-liu@uiowa.edu
Training:
D.V.M., Department of Veterinary Medicine, Jiangxi Agriculture University,
Nanchang, Jiangxi, China, 1987
M.S., Changchun Veterinary College, Changchun, Jilin, China, 1990 (Bacteriology)
Ph.D., Changchun University of Agriculture and Animal Science, Changchun,
Jilin, China, 1995 (Molecular Microbiology)
Hot Off the Press in 2002
Click here to retrieve a PDF format of Dr. Liu's paper, "Partial
correction of endogenous delta F508 CFTR in human cystic fibrosis airway
apithelia by spliceosome-mediated RNA transplicing."
Click here to see the critique entitled, "Fooling Mother Nature" by Ronald Crystal.
Research Interests:
The key factors for successful gene therapy include effective gene transfer
strategies and regulation of expression of the therapeutic gene, and most
efforts have attempted to deliver a full-length cDNA copy of the mutant
gene. Over the past several years, a number of alternative gene therapy
strategies have emerged with the aim of repairing, rather than replacing
the mutant gene. Some of them, such as spliceosome mediated RNA trans-splicing,
target and repair the RNA transcripts with the objective to replace a
defective gene product with a functional counterpart in the appropriate
tissue.
Splicing of mRNA precursors (pre-mRNA) is an essential step in the mRNA
maturation in higher organisms. The factors involved in the process of
mRNA splicing assemble to form an enzymatic complex known as the spliceosome.
Cis-splicing is the process in which the introns in a single pre-mRNA
are excised, and the adjoining exons are ligated together to form mature
mRNA. Trans-splicing refers to the recombination of sequences from two
independently transcribed pre-mRNAs to form a composite mRNA. Splicesome
mediated RNA trans-splicing (SMaRT) is technology to take advantage of
the endogenous cellullar splicing machinary as a strategy for modifying
pre-mRNA and translating normal functional proteins. The SMaRT process
uses pre-therapeutic or pre-trans-splicing RNA molecules (PTMs) that are
designed to base pair with the intron of a targeted pre-mRNA to suppress
target cis-splicing (by masking important cis-elements used in splicing),
while promoting trans-splicing between the PTM and target. As a method
to repair a gene at the RNA level, SMaRT gene repair offers potential
advantages over conventional gene replacement therapy. PTMs that correct
mutant target pre-mRNAs need only the code for a portion of entire coding
sequence. This decreases the size of the therapeutic construct to be delivered,
while providing more room for the inclusion of other elements. Since SMaRT
is contingent on the presence of trans-splicing to the target, repaired
mRNA will only be generated in those cells that are expressing target
mRNA. Thus, gene therapy will be more specific and regulated, and over
expression and inappropriate expression can be avoided.
Experiments have demonstrated that SMaRT can be achieved in vitro, using
PTM-LacZ and PTM-CFTR (corrected coding region) cotransfected with mutant
LacZ and CFTR expression vectors. Normal functional LacZ and CFTR protein
were expressed in tissue culture. We hope to demonstrate that PTMs can
modify mutant targets in vivo bymeans of PTM Adenovirus, AAV infection
and/or a PTM transgenic animal model. Currently, we are testing this technology
in animal models, with the eventual goal of providing a new therapy for
CF.
Selected Publications:
1. Xiaoming Liu, Liu Zhi,Monoclonel Antibodies in Exotoxin of Bateria
(Minireview). J.Monoclonal Antibody,1991; 7(1):72
2. Xiaoming Liu, Liu Zhi, Examination of Heat-Stable Enterotoxin I of
ETEC.
Chinese J.Zoonoses,1992;8(1):56
3. Xiaoming Liu, Shuzhang Feng,Liu Zhi, et al. Preparing and Using of
STI gene Probe of ETEC. Chinese J. Animal and Poultry Infectious Disease,
1992;1(Tol issue 61):46
4. Xiaoming Liu, Liu Zhi, Li Runping, et al. Preparation and Identification
of McAbs Specific for Chicken IgM and IgG. J. Monoclonal antibody ,1992;8(1):42
5. Xiaoming Liu, Shuzhang Feng, Liu Zhi, et al. STI gene probe of ETEC
Prepared by PCR. Chinese J. Zoonoses, 1992;8(3):6
6. Xiaoming Liu, Liu Zhi, Ma Chonglin, et al. Using McAbs Analyse the
Surface Antigens of Ps.mallei and Ps,pseudomallei by Immunoblotting. Bulletin
of Veterinary College, 1992;12(3):213
7. Xiaoming Liu, Zhu Ping, Recombinant Protein A(RecA) of Bacteria and
Its Analogue of Eukaryotic Cell(minireview). Chinese J. Biology,1994;5(Tol
Issue 60):1
8. Xiaoming Liu, Chonglin Ma, Liu Zhi, et al. Preparation and Identification
of McAbs to RecA Protein of E. coli., J. Monoclonal Antibody,1995,12(4):30
9. Xiaoming Liu, Zhu Ping, Liu Zi, et al. The Purification of Exotoxin
A of P. aeruginosa. Chinese J. Veterinary Science, 1996,16(5):460
10. Xiaoming Liu,Feng Shouzhang, Ma Chonglin, et al. Study on Recombinant
Toxins of P. aeruginosa exotoxin A and Heat?stable enterotoxin of E.coli:
Recombination and expression of ST?PEA gene in E.coli,Amino Acids and
Biotic Resources, 1996, 18(Issue of Applied Biochemistry):5
11. Xiaoming Liu, Zhu Pin, Liu Zhi, et al. Construction and Expression
of PEA?recA Fussion Gene of P. aeruginosa. Chinese J. Veterinary Science,
1997,17(2):135
12.Guo Xuejun, Xiaoming Liu,Zhu Ping, et al. Cloning of PEA Receptor Binding
Subunit Gene and Its Expression in E.coli. Chinese J. Veterinary Science,
1997, 17(3):226
13. Xiaoming Liu, Guo Xuejun, Ma Conglin, et al. Purification of Recombinant
Protein Containning Receptor Binding Domain of Exotoxin A of P. aeruginosa
Expressed in E. coli. Chinese J. Veterinary Science, 1998.18(1):37
14. Xiaoming Liu,Ma Conglin, Guo Xuejun, et al. Preliminary Renaturation
and Detection of cytobiological Activity of Recombinant Receptor Binding
Protein of Exotoxin A of P. aeruginosa. Chinese J.Veterinary Science,
1998,18(5):361
.
15. Xiaoming Liu, Zhonghai Wan,Ma Conglin, et al. The animal protection
experiment of the immunization of Recombinant Receptor Binding Protein
of Exotoxin A of P. aeruginosa. Chinese J.Veterinary Science, 1999,19(6):452.
16. Ying Ying, Xiaomoing Liu, Marbol Amy, et al. Requirement of Bmp8b
for the Generation of Primordial Germ Cells in the Mouse. Molecular Endocrinology,
July, 2000, in press.
17. Xiao-Ming Liu, Ying Ying, and Guang-Quan Zhao, Bmp7 cooperates with
Bmp8a in spermatogenesis and epididymal function. Endrocrinology, 2000,
manuscript.