Brief Biography:
Xin-yuan Liu, Molecular Biologist, was born on November 1927 in
Hunan Province，China. He graduated from
Department of Chemistry, Nankai University in 1952, then worked in Hebei
medical school from 1952-1957, completed his master thesis from 1960-1963 at
Shanghai Institute of Biochemistry (SIB), Chinese Academy of Sciences (CAS),
and was assigned to work in this institute till 2000.He went to USA and worked
as a visiting scientist in Roche Institute of Molecular Biology in
1983-1984. From 2000-date, he
worked in the Institute of Biochemistry and Cell Biology, CAS. He was promoted as associate professor
in 1979, as full professor in 1985 and as a supervisor for PhD student in the
same year. Now about 50 master and
PhD student have been graduated from his lab. He has published more than 280
papers and compiled 8 volumes of Xin-yuan Liu’s collected papers and got more
than 30 times different awards, among them, there are many first or second
class award, therefore, he was elected as an Academician of Chinese Academy of
Science in 1992, as a Foreign Academician of National Academy of Ukraine in
1992, as an Academician of The Third World Academy of Science in 2001. Now he
has been laureated three Academicians.
Many projects had been
carried out in his lab:
Structure-function of RNA: He firstly found
the rare bases in high molecular weight RNA (rRNA), a part work of the first
class Natural Science Prize of CAS;
Synthesis of RNA: In the total
synthesis of yeast Ala-tRNA, he developed an enzymatic method to synthesize
several oligoN with rare base which could not be succeeded by chemical methods,
giving very important contribution to this project;
Genetic engineering: Expression of g-interferon (IFN-g) reached high level up to
60%‒80% of total bacterial proteins, which was hardly occurred in literature
and was elected as one of the 10 top achievement of CAS in 1990, also got first
class award of scientific progress prize of CAS. After getting market license, a National second class award
of scientific progress prize was offered.
The studies of IL-2 from genetic engineering to clinical use got another
National second scientific progress prize;
Mechanism of IFN-Action: Discovered many
new functions of the interferon mediator 2’-5’ A and proved the existence of
its receptor, the firstly found receptor of an oligoN in the world;
Analgesic effect of
Interleukin-2: Discovered the analgesic effect of IL-2, its active center and
IL-2 gene therapy to prolong the half life time of the analgesic effect to 300
fold (using Lipofectamine as vector) and 1500 fold (using Adv. as vector). Further more they found that IL-2 could
bind to the opioid receptor, which was the first time in the world to provide
substantial data for the regulatory effect of an immune molecule on the
function of nerve system, and finally they found the suppression effect of IL-2
on morphine withdrawal syndrome;
Signal transudation: This had been
the ”95” key project of CAS. About twenty papers have been published in the
international famous Journals;
Gene Therapy of Parkinson’s
Disease: Good results have been already published in famous journals such as
“Human Gene Therapy’’, etc.;
Gene-virus therapy of
cancer: This is a new strategy for cancer treatment which has recently been
developed by Prof. Liu and outstanding results have been obtained.
From the above statement, it can be seen that Prof. Liu always made
good contribution and sometime outstanding contribution in his studies, such as
first discovery, first report, not be substitutional, hardly learned etc, a lot
of success have been obtained.
Therefore he was laureate different honor title such as Outstanding
scientist, Advanced worker, Superior innovator and superior mentor etc. In addition, he got the Academician
title of the Third World Academy of Science and a big award of HLHL prize in
2001 and was offered as a councilor of World High Technology Society in
2002. Since he resigned the
president position of Hua Xin High Biotechnology Inc. from 1999 and put his
total energy in science research, he got excellent results and papers. The IF value of his papers ranked the
first position in 2000 in Shanghai Institute of Biochemistry, a second prize in
the Institute of Biochemistry and Cell Biology in 2001, also very good score in
2002 and will be more better in 2003.
Recent researches:
The major researches of Prof. Liu are application and basis studies
on the targeting gene virus therapy of cancer. The gene-virus of cancer is a new strategy developed by him,
that is a combined efforts of both gene therapy and virus therapy. In the past, there is no big progress
of cancer gene therapy, while there are big breakthroughs by the combined use
of ONYX-015 virus therapy with chemotherapy. A total response of 63% was obtained, among them, one of the
tumor sizes in about 10cm diameter was completely eliminated. However, the therapeutic effect of
ONYX-015 (which can not insert antitumor gene) alone is 15-20%. In the lab of Prof. Liu, a vector
called pZD55, which can insert an antitumor killer gene, was constructed. In pZD55, the 55Kd gene in Adv. E1B
region was deleted which made this vector transudation only into tumor cells
and not normal cells. After
inserting antitumor gene into pZD55 to form pZD55-gene (called virus gene or gene
virus) it will target only to tumor cells and not to normal cells and was
called targeting gene-virus Therapy of Cancer. In the lab of Prof. Liu, a lot of important antitumor killer
genes were available such as Smac Trail (tTrail) and IL-12 etc. By the combined use of them, tumors in
animal model were completely eliminated.
In addition, they have many tumor specific promoters. By using them, very good results have
been also obtained. Especially
they have the third generation of adenovirus vector, the Gutless (GL) Vector,
which has no antigenicity and could not be eliminated by its induced
antibodies. It should be a best
vector. Furthermore, a regulable
targeting gene-virus system for cancer therapy was developed. In this system, two expression cassettes
have been inserted into the GL-vector, one is called Trans-Activator cassette
which will produce a trans-activator (TA), the other is called antitumor
cassette which will produce antitumor gene. In this system, TA is expressed by the control of telemerase
reverse transcriptase (TERT) which is consisted of more than 85% tumor cell,
and the antitumor gene is expressed by the control of RU486 to activated
TA. In normal cell, TA can not be
expressed since TA is controlled by cancer specific TERT, while without RU486,
the antitumor cassette can not be worked.
Therefore this is a regulable Targeting antitumor vector, which will
work only in TERT controlled tumor cell and in the presence of the regulatory
molecule RU486 which will never work in normal cells or without RU486
presence. It will be sure that
this system will give good contribution to fight with cancer. In addition to the antitumor studies,
they already have found the analgesic effect of IL-2 and the suppression effect
of IL-2 on morphine withdrawal syndrome.
A series of these findings in Prof. Liu’s lab made them in a leading
position worldwide in this field and will be further studied.
Major Publications: (With the IF value higher than 3.0)
1.
Liu, X.Y. et al (1981) “Mechanism of interferon action: Role of
pppA2′p5′A2′p5′ A in the Biology of the Interferon System (E. de Maeyer et al.
eds.)”. Elsevier/North Holland, p.115, cited in C. A. 96: 102223z
2.
Wang, T.P......and Liu, X.Y..... (1983) “Synthesis of 3′-half
molecular of yeast alanine tRNA”.
Scientia Sinica, (English edition), 26: 482-494
3.
Smith, J.H. ...... Liu, X.Y(1984) “Regulation of interferon
synthesis and action”. In “Interferon and Their Application” Handbook of
experimental Pharmacology, vol.71, Springer Verlage, p.101-105, see also
Scientia Sinica, 26: 809
4.
Li, B.L. and Liu, X.Y (1985) “Mechanism of Interferon Action VIII.
The Discovery of pppA2′p5A2′p5′ A Receptor”. Scientia Sinica, 28(7): 697-706
5.
Liu, X.Y., Li, B.L. and Li, S.W. (1986) “Measurement of a receptor
for (2′-5′) Oligoadenylate on macrophages”. In “Methods in Enzymology”,
Academic Press, Inc., 119: 351-356
6.
Liu, X.Y. et al. (1986) “Assay of effect of (2′-5′) -Oligoadenylate
on macrophages”. In ”Methods in Enzymology”, Academic Press, Inc., 119: 676-681
7.
Li, B.L......Liu, X.Y. (1990) “a-Interferon Structure and Natural
Killer Cell Stimulatory Activity”. Cancer Research, 50: 5328-5332
8.
Hu, Z.H. ......Liu, X.Y. (1993) “Nucleotide sequence of the Buzura
suppressaria single nucleocapsid nuclear polyhedrosis virus polyhedrin
gene”. J. General Virology, 74: 1617-1620
9.
Jiang, C.L. ......Liu, X.Y. (1995) “Multiple Actions of Cytokines
on the CNS”. Trends in Neurosciences, 18: 296
10.
Wang, Z.Y.......Liu,X.Y. (1995)
”Substitution at the Glu62 Residue of Human Interleukin-2 Differentially Action
Its Binding to the a Chain and the bg Complex of the Interleukin-2 Receptor”.
Eur J. Immunol, 25: 1212-1216
11.
Cao, L. ......Liu, X.Y. (1995)
“Gene Therapy of Parkinson Disease Model Rat by Direct Injection of Plasmid
DNA-Lipofectin Complex”. Human Gene Therapy, 6: 1497-1501178
12.
Wang, Y......Liu, X.Y. (1997) “The
analgesic domain of IL-2”. Biochem. Biophys. Res. Commun., 230 (3): 542-545
13.
Ge, K. ...... Liu, X.Y. (1997)
“Transduction of cytosine deaminase gene makes rat glioma cells highly
sensitive to 5-fluorocytosine”. Int. J. Cancer, 71: 675-679.
14.
Lu, L.R. ......Liu, X.Y.
(1998) “Jak-STAT pathway is
involved in the induction of TNF-b gene during stimulation by IL-2”. Eur. J.
Immunol., 28: 805-810
15.
Sabine Herblot......Liu, X.Y. et
al. (1999) “IL-2-Dependent Expression of Genes Involved in Cytoskeleton
Organization, Oncogene Regulation, and Transcriptional Control”. The Journal of
Immunology, 162: 3280-3288
16.
Cao, L. ….... Liu, X.Y. (2000)
“Long-term phenotypic correction of rodent hemiparkinsonism by gene therapy
using genetically modified myoblasts”. Gene Therapy, 7: 445-449
17.
Zhai, Q.W. …....Liu, X.Y. (2000)
“Copper Induces Apoptosis in BA/F3b Cells: Bax, Reactive Oxygen Species, and
NFkB are Involved”. J. Cellular Physiol, 184: 161-170
18.
Ji, H.B. ….... Liu, X.Y. (2000) “Novel
Protein MAJN Binds to Jak3 and Inhibits Apoptosis Induced by IL-2 Deprival”.
Biochem. Biophys. Res. Commun., 270: 267-271
19.
Yan, M.D. …....Liu, X.Y. (2000)
“Induction of Ref-1 Ensures AP-1 Activation in Intracellular Oxidative
Environment of IL-2- Stimulated BA/F3b Cells”. Biochem. Biophys. Res. Commun.,
278(2): 462-469
20.
Jayagopala Reddy. …....Liu, X.Y.
(2001) “IL-2-induced tumor necrosis factor (TNF-b) expression: Further analysis
in the IL-2 knockout model, and comparison with TNF-a, lymphotoxin-b, TNFR1 and
TNFR2 modulation”. Int. lmmunology, 13(2): 135-147
21.
Liu, X. Y. (2001) “A New Anticancer Strategy‒‒ Genetic and
Virological treatment of cancer.” Chinese J. Cancer Biother, 8 (1): 1
22.
Zou, W.G. …....Liu, X. Y. (2001) “Cobalt Chloride
Induces PC12 Cells Apoptosis through Reactive Oxygen Species and Accompanied by
AP-1 Activation”. J. Neuroscience Res., 64: 646-653
23.
Tang, W…....Liu, X.Y. (2001)
“Critical Sites for the Interaction between IL-2R g and JAK3 and the following
Signaling”. Biochem. Biophys. Res. Commun., 283(3): 598-605
24.
Qi-jun Qian …....Xin-yuan Liu (2001) “The Hot point of gene-virus Therapy of
Cancer”. Chinese J. Cancer Biotherapy. 8: p77
25.
Weijing Xu, Xin-yuan Liu (2001) The p38 MAPK pathway is involved in
the IL-2- induction of TNF-a gene via the EBS element. Biochem. Biophy. Res.
Comm., 289: 979-986
26.
Wei-guo Zou, Ming-fei Lang ….... Xinyuan Liu
(2002) Human Interleukin 10 Gene Therapy Decreases the Severity and Mortality
of Lethal Pancreatitis in Rats. J. Surgical Res., 103(1): 121-126
27.
Jin-hui Wang…....Xin-yuan Liu (2002)
“Blocking HSF1 by Dominant-Negative Mutant to Sensitizes Tumor Cells to
Hyperthermia”. Biochem. Biophys. Res. Commun.,
290(5): 1454-61
28.
Ming-zhong Yao…....Xin-yuan Liu
(2002) “Interleukin-2 Gene Therapy of Chronic Neuropathic Pain”. Neuroscience,
112(2): 409-416
29.
Weiguo Zou…....Xinyuan Liu (2002)
“Involvement of Caspase-3 and p38 Mitogen-Activated Protein Kinase in Cobalt
Chloride-Induced Apoptpsis in PC12 Cells”. J. Neuroscience Res., 67(6): 837-43
30.
Jing Liu…....Xin-yuan Liu (2002)
Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase
promoter. International Journal of Oncology, 2002, 21(3), 661-666
31.
Wen-xi Wu …....Xin-yuan Liu (2003)
Carcino-Embryonic Antigen Promotor Control the Specific Cytotoxicity of E.
coli Cytosine Deaminase Gene in Colorectal Carcinoma C ells in Vitro. China
J. Cancer Biother, 10(1): 5-8
32.
Chun-xia Luo…....Xin-yuan Liu (2003)
Recombinant Kringle 5 of Human Plasminogen for Mammary Cancer Gene Therapy
Mediated by Adenovirus. China J. Cancer Biother, 10(1): 9-12
33.
Ming-zhong Yao ….... Xin-yuan Liu
(2003) Adenovirus-mediated interleukin-2 gene therapy of nociception. Gene
Therapy, 10(16): 1392-6
34.
Hai-rong Huo…....Xin-yuan Liu (2003) Lipid
Rafts/Caveolae Are Essential for Insulin-like Growth Factor-1 Receptor
Signaling during 3T3-L1 Preadipocyte Differentiation Induction. The Journal of
Biological Chemistry, 278:1-9
35.
Jin-hui Wang…....Xin-yuan Liu(2003) Enhanced
suicide gene therapy by chimeric tumor-specific promoter based on HSF1
transcriptional regulation. FEBS Lett, Jul
10; 546(2-3): 315-20
36.
Zi-Lai Zhang…....Xin-Yuan Liu (2003) Current
Strategies and Future Directions of Antiangiogenic Tumor Therapy. Acta Biochim.
Biophys. Sinica, 35(10): 873-880
37. Zi-lai Zhang,
Wei-guo Zou …....Xin-yuan Liu (2003) An Armed Oncolytic
Adenovirus system, ZD55-gene, Demonstrating Potent Antitumoral Efficacy. Cell Research, 13(6): 481-89
38.
Wei-guo Zou…....Xin-yuan Liu (2004) A Novel
Oncolytic Adenovirus Targeting to Telomerase Activity in Tumor Cells with
Potent. Oncogene, 23(2): 457-464
39.
Weijing Xu ….... Xin-yuan Liu (2004)
Geldanamycin, a Heat Shock Protein 90-Binding Agent, Disrupts Stat5 Activation
in Il-2-Stimulated Cells. Journal of the Cellular Physiology, 198:188-196
40.
Song-bo Qiu….... Xin-yuan Liu (2004)
Combination Of Targeting Gene-ViroTherapy with 5-FU Enhances Antitumor Efficacy
in Malignant Colorectal Carcinoma. Journal of Interferon and Cytokine Research
(In press)
41.
Zi-fei Pei…....Xin-yuan Liu (2004) An
Oncolytic Adenovrial Vector of Smac Increases Antitumor Activity of TRAIL
Against HCC in Human Cells and in Mice. Hepatology, 39(5): 1371-1381
42.
Xin-yuan Liu (2004) Cytokine (more than 4000 words). Encyclopedia,
second edition (Published)
43.
Xin-yuan Liu (2004) Interferon (about 3000 words). Encyclopedia,
second edition (Published)
44. Xin-yuan Liu
(2004) Prospects of Antibody Therapy and Antibody Gene Therapy of Carcinoma. National Medical Journal of China, 84(14): 1145
45.
Xin-yuan Liu (2004) Interferon studies and its great progression. China Prescription Drugs, No.7, P.33
46.
Xin-yuan Liu (2004) The Important Progresses of Interferon
Research. A Bulletin of Chinese Medical Biotech. Association, No.8, P.47
47.
Yi-gang Wang…....Xin-yuan Liu (2004)
Antitumor Effect of A Novel Adeno-associated Virus Vector Targeting to
Telomerase Activity in Tumor Cells. Acta
Biochim. Biophys. Sinica, 36(7): 492-500
48.
Jin-hui Wang…....Xin-yuan Liu (2004) Tumor
Tolerance Abolishment by Blocking HSF1 Involves Activation of Caspase-3 and
c-Jun N-terminal Kinase Signaling Pathways. B.B.R.C., (Accepted)
49. Zhuo Ming….... Xin-yuan Liu (2004) Co-treatment with Ethanol Enhances the
Toxicity of 6-hydroxydopamine. Neuroscience
Lett. (In press)
50.
Qi Zhang…....Xin-yuan Liu (2004)
Effective gene-viral therapy for telomerase-positive cancers by selective
replicative -competent adenovirus combining with endostatin gene. Cancer Res., (Accepted)
51.
Xin-yuan Liu (2004) Targeting Dual Gene-ViroTherapy of Cancer.
Chinese Journal of Oncology (In press)
52.
Xin-yuan Liu, Song-bo Qiu …....Qian Cheng (2004)
Combined hTRAIL and Plasminogen k5 to Completely Eradicate Tumors via Targeting
Adenovirus—a Targeting Dual
Gene-ViroTherapy Strategy. Gene Therapy (Revised)
53.
Fu-rong Yu…....Xin-yuan Liu (2004)
Impairment of redox state and dopamine level induced by a-synuclein aggregation and
their prevention by Hsp70. Eur. J.
Neuroscience (Submitted)
54.
Jin-fa Gu (2004) Binding of interleukin-2 to opioid receptors and
its suppression of morphine withdrawal syndrome European Journal of
Neuroscience (Submitted)