Dr. Yuriko Mori

Assistant Professor of Medicine
Division of Gastroenterology
Department of Medicine
The Johns Hopkins University School of Medicine

1503 E. Jefferson St, Rm 108
Tel :(410) 502-6057
Fax: (410) 502-1329
Email: ymori3@jhmi.edu

1986~1992 M.D.  Tohoku University School of Medicine; Miyagi, Japan
1995~1999 Ph.D. Tohoku University Graduate School; Miyagi, Japan                                  

Internal Medicine (Molecular Pathology)
Mentor: Akira Horii, M.D., Ph.D.
Thesis Project: “Analyses of chromosomal, genetic, and epigenetic changes of a candidate tumor suppressor gene CDH13 in human cancers”

Research Interest:

Identification and characterization of novel tumor suppressor genes in gastrointestinal cancers utilizing systematic genome wide genetic and epigenetic screening methods. Subspecialties: Inflammatory bowel disease associated carcinogenesis and mismatch repair
deficiency associated carcinogenesis.

Frequently used methodologies:
Microarray analysis (mRNA/methylation/microRNA), real time quantitative PCR, bioinformatics.
 

Figure: Outline of search for colon cancer specific methylation target genes
 

This Figure outlines one of our genome wide searches for tumor suppressor gene candidates that are epigenetically downregulated in colon cancer (Mori Y. et. al., Gastroenterology 131(3): 797 808,
2006).

This search strategy consisted of two parts: the gene filtering for candidate methylation targets and the epigenetic validation .

The gene filtering part consisted of two sets of expression microarray experiments and a two step in silico genetic search. The first set of expression microarray experiments was performed to identify genes that
were downregulated in primary colon cancers relative to normal colonic mucosae. The second set of expression microarray experiments was to identify genes that were upregulated in colon cancer cell lines after the treatment with a global genomic DNA demethylating agent, 5 aza dC(PostAzaC), relative to cells before the treatment (PreAzaC).

Genes that were identified in both sets of expression microarray experiments were subjected to the subsequent selection using in silico search.The in silico search consisted of screenings for genes possessing: a) the DNA sequence susceptible to methylation, CpG island, overlapping the 5’untranscribed region or the first exon and b) putative tumor
suppressive function. Candidate methylation targets meeting both of these selection criteria were then validated for the presence of
promoter methylation in colon cancer cell lines and primary colon cancers using real time quantitative methylation specific PCR. Numbers
in this Figure represent the actual number of genes that fell into each of the corresponding categories. This study successfully identified
seven novel epigenetic silencing target genes in colon cancer.
 

Selected Publication:

1. Mori Y., Shiwaku H., Fukushige S., Wakatsuki S., Sato M., Nukiwa T., Horii A. Alternative splicing of hMSH2 in normal human tissues.        Human Genetics, 99: 590 595 (1997)
 

2. Mori Y., Matsunaga M., Abe T., Fukushige S., Miura K., Sunamura M., Shiiba K., Nukiwa T., Horii A. Chromosome band 16q24 is frequently
deleted in human gastric cancer. British Journal of Cancer, 80: 556 562 (1999)
 

3. Mori Y., Yin J., Rashid A., Leggett B. A., Young J., Simms L. A., Kuehl P. M., Langenberg P., Meltzer S. J., Stine O. C. Instabilotyping:
comprehensive identification of frameshift mutations caused by coding region microsatellite instability. Cancer Research, 61: 6046 6049
(2001)

4. Mori Y., Sato F., Selaru F. M., Olaru A., Perry K., Kimos M. C., Tamura G., Matsubara N., Wang S., Xu Y., Yin J., Zou T. T., Leggett B., Young J., Nukiwa T., Stine O. C., Abraham J. M., Shibata D., Meltzer S. J. Instabilotyping reveals novel unique mutational spectra in microsatellite unstable gastric cancers. Cancer Research, 62: 3641 3645, (2002)

5. Wang S., Mori Y., Sato F., Yin J., Xu Y., Zou T. T., Olaru A., Kimos M. C., Perry K., Selaru F. M., Deacu E., Sun M., Shi Y. C., Shibata D., Abraham J. M., Meltzer S. J. An LOH and mutational investigation of the  ST7 gene locus in human esophageal carcinoma. Oncogene, 22(3): 467 470 (2003)

6. Nakamura A., Mori Y., Hagiwara K., Suzuki T., Sakakibara T., Kikuchi T., Igarashi T., Ebina M., Abe T., Miyazaki J., Takai T., Nukiwa T.
Increased susceptibility to LPS induced endotoxin shock in secretory leukoprotease inhibitor (SLPI) deficient mice. Journal of Experimental Medicine. 197(5): 669 74 (2003)
 

7. Mori Y. Selaru F. M., Sato F., Yin J., Simms L. S., Xu Y., Olaru A., Deacu E., Wang S., Taylor J. M., Young J., Leggett B., Jass J. R., Abraham J. M., Shibata D., Meltzer S. J. The impact of microsatellite instability on the molecular phenotype of colorectal tumors. Cancer
Research, 63(15): 4577 4582 (2003)

8. Olaru A., Mori Y., Yin J., Wang S., Kimos M. C., Perry K., Xu Y., Sato F., Selaru F. M., Deacu E., Sterian A., Shibata D., Abraham J. M.,
Meltzer S. J. An LOH and Mutation Analysis of the ACTRII Gene Locus in Human Clorectal Tumors. Laboratory Investigation. 83(12):1867 71 (2003)

9. Mori Y., Yin J., Sato F., Sterian A., Simms L. A., Selaru F. M., Schlumann K., Xu Y., Olaru A., Wang S., Deacu E., Abraham J.M., Young
J., Leggett B. A., and Meltzer S. J. Identification of Genes Uniquely Involved in MSI H Colon Carcinogenesis by Expression Profiling Combined with Epigenetic Scanning. Cancer Research: 64: 2434 2438 (2004)
 

10. Deacu E*., Mori Y.*, Sato F., Yin J., Olaru A., Sterian A., Xu Y., Wang S., Schulmann K., Bryant L., Kan T., Abraham J. M., Meltzer S. J. Activin Type II Receptor Restoration in ACVR2 Deficient Colon Cancer Cells Induces TGF Response Pathway Genes. Cancer Res., 64 7690 7696 (2004). Deacu E. and Mori Y. equally contributed to this work.

                                             Last modified 05/12/2009