Cancer Research Group - PowerPoint PPT Presentation

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Cancer Research Group

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Cancer Research Group Konan Peck Tsann-Long Su Joanne Chen Cheng-Wen Wu Yuh-Shan Jou Steve R. Roffler Joint appointment, NHRI You-Di Liao Sheau-Yang Shieh – PowerPoint PPT presentation

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Title: Cancer Research Group


1
Cancer Research Group
2
Cancer Research Group
A pipeline integration of technology
development, basic, applied, and clinical studies
Genomic proteomic research tool developments
Bench
Molecular pathogenesis studies Carcinogenesis
metastasis
Identification of biomarkers for diagnosis,
prognosis and therapy
Therapeutic agents and clinical assays development
Clinical validation
Bedside
3
Genomic and proteomic research tool developments
Aptamer arrays for protein-specific expression
profiling (Konan Peck)
High throughput transcript-specific expression
profiling system (Konan Peck)
Model cell lines multi-well assay for cancer
cell invasion studies (Pan-Chyr Yang Cheng-Wen
Wu)
Surface expressed proteins for therapy and
imaging (Steve Roffler)
Bioinformatics tools and database for
hepatocarcinoma oncogenomics (Yuh-Shan Jou)
Directed molecular evolution to create new
therapeutic proteins (Steve Roffler)
enzyme
cytokine
antibody
4
Molecular pathogenesis studies (carcinogenesis)
Cancer genomics tumor biology of GI-track
cancer (Joanne Chen)
  • Genetic events associated with pathogenic
    development of GI-track cancers
  • Rho GTPases Wnt/b-catenin/TCF pathway

1. Overexpression of RTKN, a Rho GTPase
effector, contributes to GC pathogenesis,
and its overexpression is associated with GC
progression. 2. Abnormal expression of OPN and
its receptor CD44 contributes to cancer
progression.
Identify and study human hepatocellular carcinoma
genes by genomic approaches (Yuh-Shan Jou)
- HCC genes somatic mutation screening -
Homozygous deletion of chromosome 13q12.11 -
Integrated HCC database OncoDB.HCC for
bioinformatics analysis
Genome-wide minimal deleted regions, two major
tumorigenic pathways, and a homozygous deletion
of 13q12.11 in HCC have been identified.
5
Molecular pathogenesis studies (carcinogenesis)
p53 and cell cycle checkpoints (Sheau-Yann
Shieh) - The role of CHK1, CHK2-interacting
proteins in checkpoint control - The role of CHK1
and CHK2 in DNA double strand break repair
Pathogenesis of human cytomegalovirus (Cheng-Wen
Wu)
- The functions of the HCMV IE2 protein
  1. DNA methylation may be involved in the regulation
    of the HCMV major IE promoter
  2. TE2, a novel protein acetyltransferase that
    interacts with HCMV IE2, increases the activity
    of the DNA methyltransferase 1

6
Molecular pathogenesis studies (metastasis)
PPG to decipher the molecular mechanism of cancer
metastasis
- Genome-wide identification of metastasis
related genes (Pan-Chyr Yang Konan Peck)
- Identification of metastasis-related proteases
and protease inhibitors (Cheng-Wen Wu)
- Characterize novel and known invasion/metastasis
suppressors and enhancers CRMP-1, HLJ1,
LCRMP-1, Slug (Pan-Chyr Yang) TAL6 (Steve
Roffler) KLK8 (Konan Peck)
Empirical approaches for validation and
characterization
Clinical studies
Cell biology studies
Histology studies
Mouse model studies
7
Biomarkers identified in the research projects
In silico database search
Empirical genomic approaches
Candidate marker genes
Validation with cancer cell lines
Validation with mouse models
Validation with clinical specimens
Biomarkers
Metastasis and prognosis biomarkers CRMP-1,
LCRMP-1, HLJ1, Slug, KLK 8 TAL6, CD13,
CD44, RTKN, OPN Cancer therapy efficacy
assessment markers KRT19, UCHL1, FN1,
TRIM28 Drug target for metastasis inhibition
LCRMP-1, Slug
8
Therapeutic agent developments
Discovery and Development of Potential Anticancer
Agent (Tsann Long Su)
Gene alkylating agents (in preclinical studies)
Topoisomerase II Inhibitors (9-Anilinoacridine
Analogues)
Topoisomerase I Inhibitors (Camptothecin
Analogues)
Anti-tumor Ribonucleases from Bullfrogs (You-Di
Liao)
Glucuronide prodrugs for cancer therapy (Steve
Roffler)
9
Clinical assay developments
Microarray for prognosis of NSCLC
patients (Pan-Chyr Yang)
Microarray for subtyping of gastric
cancers (Joanne Chen)
Rapid assessment of therapy efficacy and relapse
detection method (Konan Peck Pan-Chyr Yang)
Using marker genes to detect the amount of
circulating tumor cells before and after the
treatment allows rapid efficacy assessment and
relapse detection.
10
Achievements in the past 5 years
Publications in academic journals
Technology transfer to biotech industry
Publications in basic research journals
American Journal of Respiratory Critical Care
Medicine American Journal of Pathology Cancer
Research Journal of Biological Chemistry Journal
of the National Cancer Institute Molecular
Biology of the Cell Oncogene The EMBO Journal
. . .
Publications in applied or clinical research
journals
Bioinformatics Clinical Cancer Research Journal
of Clinical Oncology New England Journal of
Medicine Nucleic Acids Research .
. .
11
Achievements in the past 5 years
Multi-national intellectual property rights
Granted patents K. Peck, et al. (2001) US Patent
6,218,114 K. Peck, et al. (2001) ROC patent
438889 K. Peck, et al. (2002) European Patent EP
0822261 K. Peck, et al. (2003) ROC patent 541340
S.R. Roffler, et al. (2003) US Patent
6,596,849 S.R. Roffler, et al. (2003) US Patent
6,617,118 S.R. Roffler, et al. (2003) European
Patent EP 0990661 S.R. Roffler, et al. (2004) US
Patent 6,699,972 S.R. Roffler, et al. (2004)
ROC Patent 205511 T.L. Su, et al. (2004) US
Patent 6,821,983 K. Peck, et al. (2005) US
Patent 6,867,050 K. Peck, et al. (2005) ROC
patent I232867
Pending patent applications P.C. Yang, et al.
(2003) European Patent 1271153 A2 P.C. Yang, et
al. (2003) US Patent 20030077624 A1. P.C. Yang,
et al. (2003) European Patent 1285970 A2 P.C.
Yang, et al. (2003) US Patent 20030054387
A1. S.R. Roffler, et al. (2004) US Patent
20040014156 A1. T.L. Su, et al. (2004) US Patent
20040198765 A1. P.C. Yang, et al. (2005) US
Patent 20050182016 A1. Y.D. Liao, et al. (2005)
US Patent 20050214899 A1.
Technology transfers to biotech industry
1. S.R. Roffler, et al. Monoclonal antibody
against polyethylene glycol to Bayer and
Hoffmann-LaRoche 2. K. Peck, et al. Method for
profiling gene expression pattern and isolation
of differentially expressed genes to Taiwan
Genome Sciences, Inc. and 4 other companies. 3.
K. Peck, et al. Method for constructing
high-density non-redundant gene arrays to
Taiwan Genome Sciences, Inc. and 2 other
companies. 4. K. Peck, et al. Methods for rapid
antimicrobial susceptibility testing to Cold
Spring Biotech, Inc. 5. P.C. Yang, et al.
Metastasis-associated genes to AdvPharma,
Inc. 6. P.C. Yang, et al. Collapsin response
mediator protein-1 as tumor metastasis marker to
AdvPharma, Inc.
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