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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. Pan-Chyr Yang. Joint appointment, NTUH. Cancer Research Group. Cancer Research Group. A pipeline integration of

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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

Pan-Chyr Yang

Joint appointment, NTUH

Cancer Research Group


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


Genomic and proteomic research tool developments

High throughput transcript-specific expression profiling system

(Konan Peck)

Aptamer arrays for protein-specific expression profiling

(Konan Peck)

Model cell lines & multi-well assay for cancer cell invasion studies

(Pan-Chyr Yang & Cheng-Wen Wu)

Bioinformatics tools and database

for hepatocarcinoma oncogenomics

(Yuh-Shan Jou)

Surface expressed proteins for therapy and imaging

(Steve Roffler)

Directed molecular evolution to

create new therapeutic proteins

(Steve Roffler)

enzyme

cytokine

antibody


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.


p53

J. Biol. Chem. 280: 7748-7757, 2005

Mol. Biol. Cell 16:1684-1695, 2005

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

  • DNA methylation may be involved in the regulation of the HCMV major IE promoter

  • TE2, a novel protein acetyltransferase that interacts with HCMV IE2, increases the activity of the DNA methyltransferase 1


100

P = 0.019

90

80

Probability of disease free

KLK8 high

70

N=22

60

50

KLK8 low

40

N=33

30

0

10

20

30

40

50

60

70

Time in months

CRMP-1

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

Cell biology studies

Histology studies

Mouse model studies

Clinical studies


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


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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)

Glucuronide prodrugs for cancer therapy

(Steve Roffler)

Anti-tumor Ribonucleases from Bullfrogs

(You-Di Liao)


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.


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

.

.

.


Achievements in the past 5 years

Multi-national intellectual property rights

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.

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

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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