Ph.D. (State University at Stony Brook, 1970)
1430 Tulane Ave., Box SL-31
New Orleans LA 70112
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Ph.D. (State University at Stony Brook, 1970) |
| Phone: (504) 584-2449 | |
| FAX: (504) 584-2739 | |
| Address: 1430 Tulane Ave., Box SL-31 New Orleans LA 70112 |
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| Email: ehrlich@tulane.edu | |
My research projects on naturally programmed DNA methylation have spanned studies of microbial methylation of cytosine at the 5 and N4 positions to analysis of human DNA methylation leading to the first discovery of a protein that binds preferentially to methylated DNA and the first report of aberrant methylation in human cancers. This interest led to my founding the international DNA Methylation Society four years ago, an e-mail-based society.
Recently, my lab has shown that inhibitors of DNA methylation, but not other genotoxins, can target at extraordinarily high frequencies the formation of rearrangements of chromosome 1, and to a lesser extent, chromosome 16, in cultured human cells of normal origin. The spectrum of resulting chromosomes, visualized at metaphase, includes whole-arm deletions (Fig. 1, C), isochromosomes with two long arms and no short arms joined at the centromere (Fig. 1, D), and strange multibranched chromosomes with 3 - 7 arms joined in the centromeric region (Fig. 1, E-J and L). We are pursuing this line of research using cultured cells and autopsy material from patients with a rare human disease which is diagnosed by exactly the same spectrum of chromosomal abnormalities. In this research, we hope to gain insight into the functions of DNA methylation in normal development and in carcinogenesis. This disease is called ICF (immunodeficiency, centromeric region instability, and facial anomalies) and is often fatal in childhood. It is the only known disease with aberrations in DNA methylation transmitted by Mendelian inheritance. Patients with this disease have abnormal hypomethylation of the chromosomal regions that are prone to rearrangements, namely, the heterochromatin around the centromeres of chromosomes 1 and 16. We have shown that these chromosomal regions are also undermethylated in breast cancer, Wilms tumors, and ovarian cancers, three types of cancer in which rearrangements in the vicinity of the centromeres of chromosomes 1 and 16 have been implicated in carcinogenesis. Our research in this area will include characterization of which genes are hypomethylated in cells from ICF patients and why ICF cells are prone to these chromosomal characteristic rearrangements.
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