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Joe Costello, PhD

Joe Costello, PhD
Professor, Neurological Surgery
Karen Osney Brownstein Endowed Chair
Research Summary:
Integrated genomic and epigenomic mechanisms contributing to cancer

Gene silencing by deletion and by aberrant methylation are two predominant mechanisms of tumorigenesis, yet their interaction is largely unknown. Our research brings together these genomic and epigenomic perspectives of human tumorigenesis, primarily in human brain and breast tumors. As a complementary approach to the tumor studies, we investigate the role of normal methylation patterns in human cells and tissues using a genome scanning method along with custom bioinformatic tools. To facilitate these studies we are also developing an array method for genome-wide methylation analysis.

Selected Publications

Zardo G; Tiirikainen M, Hong C; Misra A; Feuerstein BG; Volik S; Collins CC; Lamborn KR; Bollen A; Pinkel D; Albertson, DG; Costello JF. Integrated Genomic and Epigenomic Analyses Pinpoint Biallelic Gene Inactivation in Tumors. Nature Genetics, 2002, 32(3):453-458.

Costello JF. DNA methylation in brain development and gliomagenesis. Frontiers in Biosciences, 2003, 8: S175-S184.

Smiraglia DJ; Rush LJ; Frühwald M; Dai Z; 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, Human Molecular Genetics, 2001, 10: 1413-1419.

Costello JF; Frühwald MC; Smiraglia DJ; Rush L; Robertson GP; Gao X; Wright FA; Feramisco JD; Peltomäki P; Lang JC; Schuller DE; Yu L; Bloomfield CD; Caligiuri MA; Yates A; Nishikawa R; Huang HJS; 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, 2000, 25:132-138.

Ching TT, Maunakea AK, Jun P, Hong C, Zardo G, Pinkel D, Albertson DG, Fridlyand J, Mao JH, Shchors K, Weiss WA, Costello JF. Epigenome analysis using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3. Nat Genet. 2005 Jun;37(6):645-51.
 
Hong C, Maunakea A, Jun P, Bollen AW, Hodgson JG, Goldenberg DD, Weiss WA, Costello JF. Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8. Cancer Res. 2005 May 1;65(9):3617-23.