Christoph Plass, PhD
Associate Professor
Department of Medical Microbiology and Immunology
Division of Human Cancer Genetics
484A Tzagournis Medical Research Facility
420 W 12th Ave
Columbus , OH 43210
Phone: (614) 292-6505
Fax: (614) 688-4761
christoph.plass@osumc.edu
Research Interests
Dr. Plass' research is aimed towards a better understanding of changes in DNA methylation patterns in normal developmental processes, as well as in human cancers. His research has been based on various applications of the Restriction Landmark Genomic Scanning (RLGS) method, a two-dimensional DNA gel electrophoresis technique. This method allows researchers to compare DNA patterns from different strains of mice to identify (polymorphic) markers that differ between them, these markers can then be cloned. RLGS has been useful in genome mapping projects in mouse interspecific backcrosses and in facilitating positional cloning efforts in the mouse. However, when RLGS is combined with methylation sensitive restriction enzymes it has the unique ability to scan the vertebrate genome for differences in methylation patterns at cytosine residues in CpG dinucleotides. Analysis of DNA methylation status is key to identifying imprinted genes, which are expressed in a parent-of-origin specific manner. Imprinted genes are known to be associated with sites which show allele-specific patterns of DNA methylation. Therefore, Dr. Plass' laboratory is working on identifying imprinted genes and determining the molecular mechanism underlying this phenomenon.
Changes in DNA methylation have also been associated with tumorigenesis. Therefore, a second research area is the use of RLGS to detect genetic alterations in human tumors. The methylation changes can lead to alterations in gene regulatory pathways, such as increased expression of tumor growth promoting genes or the inactivation of tumor growth suppressing genes. In order to obtain a more detailed picture of the genes and pathways involved in tumor formation and progression, the Plass lab is using RLGS to compare tumor DNA to normal tissue DNA to identify genetic sequence alterations; RLGS can also be used to scan the entire genome for changes in DNA methylation patterns.
Education & Training
Freie Universität Berlin 1987 General/Molecular Biology/Zoology
Medizinische Universität zu Lübeck, Germany 1993 Ph.D. Molecular Genetics/Evolution
Roswell Park Cancer Institute, Buffalo NY - Post-doc1996 Molecular Genetics
Select Publications
Yu L, Liu C, Vandeusen J, Becknell B, Dai Z, Wu Y, Raval A, Liu T, Ding W, Mao C, Liu S, Smith LT, Lee S, Rassenti L, Marcucci G, Byrd J, Caligiuri MA and Plass C. Global assessment of promoter methylation in a murine model of cancer identifies ID4 as a putative novel tumor suppressor gene in human leukemia. Nature Genetics 2005; 37:265-274.
Rush LJ, Heinonen K, Mrozek K, Wolf BJ, Abdel-Rahman M, Szymanska J, Peltomaki P, Kapadia F, Bloomfield CD, Caligiuri MA, C Plass. Comprehensive Cytogenetic and Molecular Genetic Characterization of the TI-1 Acute Myeloid Leukemia Cell Line Reveals Cross-Contamination with K-562 cell line. Blood, 99:1874-1876, 2002.
Smiraglia DJ, Rush LJ, Frühwald MC, Zunyan D, Held WA, Costello JF, Lang JC, Eng C, Li B, Wright FA, Caligiuri MA, Plass C. Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies. Hum Mol Genet 15:1413-1419, 2001.
Costello JF, Frühwald MC, Smiraglia DJ, Rush L, Robertson GP, Gao X, Wright F, Feramisco JD, Peltomäki P, Lang JC, Schuller DE, Yu L, Bloomfield C, Caligiuri M, Yates A, Nishikawa R, Su Huang H-J, Petrelli NJ, Zhang X, O'Dorisio MS, Held WA, Cavenee WK, Plass C. Aberrant CpG island methylation has non-random and tumor type specific patterns. Nature Genetics: 25:132-138, 2000.
Plass, C., Shibata, H., Kalcheva, I., Mullins, L., Kotelevtseva, N., Mullins, J., Sasaki, H., Kato R., Hirotsune, S., Okazaki, Y., Held, W., A., Hayashizaki, Y., and Chapman, V, M. Identification of the mouse Grf1 on chromosome 9 as an imprinted gene by RLGS-M. Nature Genetics 14:106-109, 1996
Costello J., Plass, C., Arap W., Chapman V., Held W., Berger M., Huang H-J., and Cavenee W. 1997. Cyclin -dependent kinase 6 (CDK6) amplification in human glioblastomas identified using two-dimensional separation of genomic DNA. Cancer Res. 57: 1250-1254
Shibata H. and Plass, C. 1997. Application of RLGS to screening endogenously imprinted genes. In Restriction Landmark Genomic Scanning (RLGS). Springer Lab Manual. Eds. Hayashizaki Y. and Watanabe S. pages 95-114
Plass, C., Yu, F., Yu, L., El-Rafai, W., Strout, M., Knuutila, S., Held, W., Bloomfield, C., and Caligiuri, M.: Restriction Landmark genome scanning for aberrant methylation in acute leukemia; Involvement of the WIT-1 gene. Oncogene 20:3159-3165, 1999
Smiraglia DJ, Frühwald MC, Costello JF, McCormick SP, Dai Z, Peltomaki P, O'Dorisio MS, Cavenee WK, Plass C. A new tool for the rapid cloning of amplified and hypermethylated human DNA sequences from restriction landmark genome scanning gels. Genomics. 58:254-262, 1999