BIOGRAPHICAL SKETCH Provide the following information
for the key personnel in the order listed for Form Page 2. Follow this format for
each person. DO NOT EXCEED FOUR PAGES. |
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| NAME
Alvin Y. Liu, Ph.D. aliu@u.washington.edu |
POSITION
TITLE
Research
Associate Professor
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| EDUCATION/TRAINING (Begin with baccalaureate or other initial professional
education, such as nursing, and include postdoctoral training.) |
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| INSTITUTION AND LOCATION |
DEGREE (if applicable) |
YEAR(s) |
FIELD OF STUDY |
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| University of California, Los Angeles |
B.A. |
1975 |
Biology |
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| University of California, Los Angeles |
Ph.D. |
1981 |
Biology |
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| University of Amsterdam & Netherlands Cancer Institute |
Post-doctorate |
1981-1983 |
Molecular Parasitology |
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A.
Positions and Honors. List in chronological order previous positions, concluding with your
present position. List any honors. Include present membership on any Federal
Government public advisory committee.
Positions and
Employment
1983-1988 Scientist,
INGENE, Inc., Santa Monica, CA
1988-1993 Scientist,
Cytometrics, Inc., San Diego, CA
1994-1996 Research
Scientist, VAMC-Puget Sound Health Care System and Department of Urology,
University of Washington, Seattle, WA
1996-2003 Research
Assistant Professor, University of Washington, Seattle, WA
2003- Research
Associate Professor, University of Washington, Seattle, WA
Honors
1975-1977 National
Cancer Institute Pre-doctoral Traineeship
1981-1983 Damon
Runyon-Walter Winchell Cancer Fund
1.
Browne J,
Paddock GV, Liu AY, Clarke P, Heindell HC, Salser W. Nucleotide sequences from the rabbit b-globin gene inserted into Escherichia coli
plasmids. Science 195
(1977) 389-391.
2.
Liu AY, Paddock GV, Heindell HC, Salser W. Nucleotide sequences from a rabbit a-globin gene inserted in a chimeric
plasmid. Science 196 (1977)
192-195.
3.
Heindell HC, Liu
AY, Paddock GV, Studnicka GM, Salser W. The primary sequence of rabbit a-globin mRNA. Cell 15 (1978) 43-54.
4.
Salser WA,
Cummings I, Liu A, Strommer J, Padayatty J, Clarke P. Analysis of chicken globin cDNA clones:
Discovery of a novel chicken a-globin gene induced by stress in young chickens. In: Cellular and Molecular Regulation
of Hemoglobin Switching (Stamatoyannopoulos G, Nienhuis AW, Eds.). Grune & Stratton, New York, pp.
621-645, 1979.
5.
Cummings IW, Liu
AY, Salser W. Identification
of a new chicken a-globin structural gene by complementary DNA
cloning. Nature 276 (1978)
418-420.
6.
Strathearn
MD, Strathearn GE, Akopiantz P, Liu AY, Paddock GV, Salser W. Characterization of an immunoglobulin
cDNA clone containing the variable and constant regions for the MOPC 21 k light chain. Nucl Acids Res 5 (1978) 3101-3115.
7.
Fong K, Liu
A, Salser W. Nucleotide sequence
of a mouse kappa light chain cDNA cloned in a bacterial plasmid. Biochem Biophys Res Comm 90
(1979) 832-841.
8.
Liu AY, Salser W. Complete nucleotide sequence of a chicken a-globin cDNA. Gene 13 (1981) 409-415.
9.
van der Ploeg LHT, Liu AY, Michels PAM, de Lange T, Borst P,
Majumder HK, Weber H, Veeneman GH, van Boom JH. RNA
splicing is required to make the messenger RNA for a variant surface antigen in
trypanosomes. Nucl Acids Res
10 (1982) 3591-3604.
10.
Borst P,
Bernards A, van der Ploeg LHT, Michels PAM, Liu AY, de Lange T. Gene rearrangements controlling the
expression of genes for variant surface antigens in trypanosomes. In: Proceedings for the ICN-UCLA
Symposium on Tumor Viruses and Differentiation (Scolnick EM, Levine AJ,
Eds.). AR Liss, New York, pp.
243-250, 1983.
11.
Borst P,
Bernards A, van der Ploeg LHT, Michels PAM, Liu AY, de Lange T, Sloof P,
Veeneman GH, Tromp MC, van Boom JH.
DNA rearrangements controlling the expression of genes for variant surface
antigens in trypanosomes. In:
Genetic Rearrangement, Proceedings of the Fifth John Innes Symposium on the
Biological Consequences of DNA Structure and Genome Arrangement (Chater KF,
Cullis CA, Hopwood DA, Johnston AWB, Woolhouse HW, Eds.). Croom Helm, London, pp. 207-233, 1983.
12.
Borst P, Bernards A, van der Ploeg LHT, Michels PAM, Liu AY, de
Lange T, Kooter JM. The control of variant surface antigen
synthesis in trypanosomes. Eur
J Biochem 137 (1983) 383-389.
13.
Borst P,
Bernards A, van der Ploeg LHT, Michels PAM, Liu AY, de Lange T, Sloof P,
Schwartz DC, Cantor CR. The role
of mini-chromosomes and gene translocation in the expression and evolution of
VSG genes. In: Gene Expression. UCLA Symposium on Molecular and
Cellular Biology, vol. 8 (Hamer D, Rosenberg M, Eds.). AR Liss, New York, pp. 413-435, 1983.
14.
Michels PAM, Liu
AY, Bernards A, Sloof P, van der Bijl MMW, Schinkel AH, Menke HH, Borst P,
Veeneman GH, van Boom JH.
Activation of the genes for variant surface glycoproteins 117 and 118 in
Trypanosoma brucei. J
Mol Biol 166 (1983) 537-556.
15.
Liu AY, van der Ploeg LHT, Rijsewijk FAM, Borst P. The
transcription unit of VSG gene 118 of Trypanosoma brucei: presence of
repeated elements at its borders and absence of promoter-associated
sequences. J Mol Biol 167
(1983) 57-75.
16.
de Lange T, Liu AY, van der Ploeg LHT, Borst P, Tromp MC, van Boom
JH. Tandem repetition of the 5’ mini-exon of variant
surface glycoproteins gene: a multiple promoter for VSG gene
transcription? Cell 34
(1983) 891-900.
17.
Bernards A, de Lange T, Michels PAM, Liu AY, Huisman MJ, Borst
P. Two modes of activation of a single surface antigen
gene of Trypanosoma brucei.
Cell 36 (1984) 163-170.
18.
van der Ploeg
LHT, Liu AY, Borst P.
Structure of the growing telomeres of trypanosomes. Cell 36 (1984) 459-468.
19.
Michels PAM, van der Ploeg LHT, Liu AY, Borst P. The activation and reactivation of an
expression-linked gene copy for a variant surface glycoprotein in Trypanosoma
brucei. EMBO J 3 (1984)
1345-1351.
20.
Liu AY, Michels PAM, Bernards A, Borst P. Trypanosome variant surface
glycoprotein genes expressed early in infection. J Mol Biol 182 (1985) 383-396.
21.
Liu AY, Mack PW, Champion CI, Robinson RR. Expression of mouse:human
immunoglobulin heavy-chain cDNA in lymphoid cells. Gene 54 (1987) 33-40.
22.
Liu AY, Robinson RR, Hellström KE, Murray ED,
Chang CP, Hellström I. Chimeric
mouse:human IgG1 antibody that can mediate lysis of cancer cells. Proc Natl Acad Sci 84 (1987)
3439-3443.
23.
Liu AY, Robinson RR, Murray ED, Ledbetter JA,
Hellström I, Hellström KE.
Production of a mouse:human chimeric monoclonal antibody to CD20 with
potent Fc-dependent biologic activity. J Immunol 139 (1987) 3521-3526.
24.
Liu AY, Abraham BA. Subtractive cloning of a hybrid human endogenous retrovirus
and calbindin gene in the prostate cell line PC3. Cancer Res 51 (1991) 4107-4110.
25.
Liu AY, Bradner RC. Elevated expression of the human mitochondrial hinge protein
gene in cancer. Cancer Res
53 (1993) 2460-2465.
26.
Liu AY, Bradner RC, Vessella RL. Decreased expression of prostatic
secretory protein PSP94 and other gene products in prostate
cancer. Cancer Lett 74
(1993) 91-99.
27.
Liu AY.
Expression of CD44 in prostate cancer cells. Cancer Lett 76 (1994) 63-69.
28.
Liu AY, Corey E, Bladou F, Lange PH, Vessella
RL. Prostatic cell lineage
markers: emergence of BCL2+ cells of human prostate cancer xenograft
LuCaP 23 following castration. Int
J Cancer 65 (1996) 85-89.
29.
Liu AY, Corey E, Vessella RL, Lange PH, True LD,
Huang GM, Nelson PS, Hood L.
Identification of differentially expressed genes: increased expression
of transcription factor ETS-2 in prostate cancer. Prostate 30 (1997) 145-153.
30.
Corey E,
Arfman EA, Liu AY, Vessella RL.
Improved protocol for reverse transcriptase-polymerase chain reaction
with exogenous internal competitive control detection of prostate cancer cells
in blood and bone marrow using prostate specific antigen mRNA. Clin Chem 43 (1997) 443-452.
31.
Liu AY, True LD, LaTray L, Nelson PS, Ellis WJ,
Vessella RL, Lange PH, Hood L, van den Engh G. Cell-cell interaction in prostate gene regulation and
cytodifferentiation. Proc Natl
Acad Sci 94 (1997) 10705-10710.
32.
Nelson PS, Ng
WL, Schummer M, Huang M, True L, Liu AY, Bumgarner R, Ferguson C, Dimak
A, Hood L. An
expressed-sequence-tag database of the human prostate: sequence analysis of
1,168 cDNA clones. Genomics
47 (1998) 12-25.
33.
Nelson PS,
Plymate SR, Wang K, Tennant M, True L, Liu AY, Ware J, Hood L. Hevin, an anti-adhesive extracellular
matrix protein, is down-regulated in metastatic prostate adenocarcinoma. Cancer Res 58 (1998) 232-236.
34.
Liu AY, True LD, LaTray L, Ellis WJ, Vessella RL,
Lange PH, Higano CS, Hood L, van den Engh G. Analysis and sorting of prostate cancer cell types by flow
cytometry. Prostate 40
(1999) 192-199.
35.
Liu AY, LaTray L, van den Engh G. Changes in cell surface molecules
associated with in vitro culture of prostatic stromal cells. Prostate 45 (2000) 303-312.
36.
Liu AY.
Differential expression of cell surface molecules in prostate cancer
cells. Cancer Res 60 (2000)
3429-3434.
37.
Liu AY, Peehl DM. Characterization of cultured human prostatic epithelial
cells by cluster designation antigen expression. Cell Tissue Res 305 (2001) 389-397.
38.
Liu AY, True LD. Characterization of prostate cell types by CD cell surface
molecules. Am J Pathol 160
(2002) 37-43.
39.
Liu AY, Nelson PS, van den Engh G, Hood L. Human prostate epithelial cell-type
cDNA libraries and prostate expression patterns. Prostate 50 (2002) 92-103.
40. True LD, Buhler K, Quinn J, Williams E, Nelson PS, Clegg N, Macoska JA, Norwood T, Liu A, Ellis W, Lange P, Vessella R. A neuroendocrine/small cell prostate carcinoma xenograft – LuCaP 49. Am J Pathol 161 (2002) 705-715.
41. Freedland SJ, Seligson DB, Liu AY, Pantuck AJ, Paik SH, Horvath S, Wieder JA, Zisman A, Nguyen D, Tso C, Palotie AV, Belldegrun AS. Loss of CD10 (neutral endopeptidase) is a frequent and early event in human prostate cancer. Prostate 55 (2003) 71-80.
42. True LD, Liu AY. A challenge for the diagnostic
immunohistopathologist. Adding the
CD phenotypes to our diagnostic toolbox.
Am J Clin Pathol 120 (2003) 13-15.
43. Liu AY, Brubaker
KD, Goo YA, Quinn JE, Kral S, Sorensen CM, Vessella RL, Belldegrun AS, Hood
LE. Lineage relationship between
LNCaP and LNCaP-derived prostate cancer cell lines. Prostate 60 (2004) 98-108.
44. Liu AY, Roudier MP,
True LD. Heterogeneity in primary
and metastatic prostate cancer as defined by cell surface CD profile. Am J Pathol, in press.
45. Liu AY, Zhang H, Sorensen CM, Diamond DL. Analysis of prostate
cancer by proteomics using tissue specimens. J Urol, in press.
C.
Research Support. List selected ongoing or completed (during the last
three years) research projects (federal and non-federal support). Begin with
the projects that are most relevant to the research proposed in this
application. Briefly indicate the overall goals of the projects and
responsibilities of principal investigator identified above.
1 P01 CA85859-01A2 Lange (PI) 5/1/02
– 4/30/07
NIH/NIDDK
Mechanisms
and Markers of Prostate Cancer Metastases. This proposed program is focused on
studies of the mechanisms of progression and metastasis in carcinoma of the
prostate (CaP). The program is comprised of four projects and three cores. The major goals of this program project
are: 1) To discover the expression
patterns of new and known genes during CaP progression using modern genomic
approaches (cDNA libraries, sequencing, micro-assays) in populations of cells
from a variety of CaP tissues and xenografts, 2) To learn about the mechanisms
of CaP-bone interactions, 3) To learn more about our two recently discovered
prostate specific serine proteases—Protease and TPMRSS2 and to discover and
characterize more of these proteases using modern genomic techniques., 4) To
discover how known or new growth factors, especially those associated with the
IGF system, influence the activation of the androgen receptor or
androgen-regulated signaling pathways when CaP progresses to androgen
independence. Dr. Liu is
Co-Director of Project I, Molecular Markers of Progressive Disease.
5 U01
DK63630-03
Liu (PI) 9/30/02
– 7/31/05
NIH/NIDDK
Urologic
Epithelial Stem Cells – Prostate Morphogenesis and Cytodifferentiation. This proposal
is designed to characterize epithelial stem cells in the human prostate and
bladder and the functional development of glandular epithelium under the
influence of stromal mesenchyme cells and their secreted factors, and to
determine the transcriptome of such stem cells isolated from prostate tissue
specimens. A stem cell
web-accessible database of genes and gene expression changes in differentiation
will be constructed.
5 R21
CA098699-02 Liu (PI) 5/1/03
– 4/30/05
NIH/NCI
CD Expression
in Prostate Cancer. The major
goal of this study is to improve prostate cancer diagnosis and prognosis using
an in vitro three-dimensional cell culture system to study the effect of absent
expression of cell surface peptidases in prostate epithelial cell
differentiation.
1 U01
CA11124-01
Liu (PI) 9/22/04
– 8/31/09
NIH/NCI
Biomarkers for
Prostate and Bladder Cancer.
This project uses quantitative proteomics to identify secreted proteins
that could be used as biomarkers for cancer. These are first identified by comparative analyses of cancer
vs. non-cancer tissues.
Candidate proteins are then screened for in voided urine from cancer
patients. Cancer specimens are
characterized by CD phenotyping for tumor composition of cancer cell types.
COMPLETED
CaP CURE Foundation Liu (PI)) 01/01/00
– 12/31/00
Use of ProteinChipTM to Discover Secreted Protein
Markers for Prostate Cancer Diagnosis.
The
major goal of this study is to find protein markers in the diagnosis of
prostate cancer.
CaP CURE Foundation Hood & Liu (PI) 1/1/01
– 12/31/02
Identification
of Prostate Cancer Genes by Analysis of Epithelial Cell-Type Transcriptome. To identify prostate cancer associated
genes by comparative transcriptome analyses of cDNA libraries made from four
epithelial cell types: CD57+
luminal cells, CD44+ basal cells, CD57+ cancer cells sorted
from primary tumors, CD44+ cancer cells sorted from metastases.
1 P50
CA97186-01
Lange (PI) (Hood Subcontract, Project 4) 7/1/02
– 6/30/04
NIH/NCI
Pacific
Northwest Prostate Cancer SPORE. The major
goals of this project are to 1) Determine the gene expression profiles of
prostate carcinoma that correlate with clinical phenotypes of progression or
non-progression as determined by PSA-free survival at 5 years post-therapy, 2)
Determine the molecular indicators of response to chemotherapeutic intervention
for high-risk prostate cancers, and 3) Determine the differences in
transcriptomes and proteomes between the androgen-dependent LNCaP cell line and
its derivative androgen-independent CL1 cell line. In Project 4, Dr. Liu, as Co-Investigator for Project 4,
will focus on the downstream analysis of individual genes of interest and will
be responsible for their functional characterization using in vitro and in
vivo model systems.