Joseph Costello, Ph.D.
	Epigenome-genome interactions in human tumorigenesis
	Email: jcostello@cc.ucsf.edu Website:
Selected Publications | Complete Publications

Genetic and epigenetic mechanisms contribute to the development of human tumors, yet the typical analysis of tumors is focused on only one or the other mechanism. This approach has led to a biased, primarily genetic view of human tumorigenesis. Epigenetic alterations such as aberrant DNA methylation are sufficient to induce tumor formation, and can modify the incidence and tumor type in genetic models of cancer. These initial studies raise important questions which our research addresses: understanding the degree to which genetic and epigenetic pathways cooperate in human tumorigenesis, the identity of the specific cooperating genes and how they interact functionally to determine the differing biological and clinical course of tumors.

To better understand the relative contribution of genetic and epigenetic mechanisms in human tumorigenesis, our lab utilizes global DNA methylation screening methods along with gene specific analysis, integrated comparative genomics and comparative epigenomics, and primary tumor xenografts. In collaborative research, we are focused on understanding the epigenetic regulation of cancer stem cells, particularly those in malignant brain tumors.

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.

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 analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3. Nature Genetics 2005 June; 37, 645 - 651.

Feltus FA, Lee EK, Costello JF, Plass C, Vertino PM. DNA motifs associated with aberrant CpG island methylation. Genomics. 2006 May; 87(5):572-9.

Cadieux B, Ching TT, VandenBerg SR, Costello JF. Genome-wide hypomethylation in human glioblastomas associated with specific copy number alteration, MTHFR allele status and increased proliferation. Cancer Research. 2006 Sep 1;66(17):8469-76.

Information last updated April 2007