Emeritus Professor, Department of Biochemistry and Molecular Biology
Ph.D., Columbia University, 1967
Primary Research/Clinical Interests/Expertise:
Gene regulation in normal and cancer cells; Role of DNA methylation; Mechanism of action of DNA methyltransferases; Role of dietary methyl deficiency in carcinogenesis; Role of DNA methylation in regulating expression of hepatitis B virus genes; Role of estrogen and estrogen receptor-mediated processes in breast cancer development; Function of CD9 in normal hematopoietic and epithelial cells
The basic goals of research in Dr. Christman's laboratory are to understand what abnormalities in gene regulation lead to malignant transformation of cells and what mechanisms are involved in restoring tumor cells to a normal phenotype.
Ongoing projects in Dr. Christman's laboratory include a variety of studies on regulation of DNA methylation and the effects of DNA methylation on gene expression. These range from characterization of the mechanism of action of DNA methyltransferases using defined oligomer substrates and suicide inhibitors to studies of the role of changes in DNA methylation induced by dietary deficiencies in methyl donors in development of liver cancer in rats. Current focus is on development and mechanistic studies of inhibitors of de novo methyltransferase and high throughput analysis of CpG island methylation in inhibitor treated cancer cells (breast, prostate and lymphoma).
Other studies are aimed at understanding how exposure to estrogens impacts on progression of breast cancer using in vitro and animal models. These include studies on the effects of dietary restriction on growth and progression of preneoplastic human breast cells (MCF10AT).
Yang JL, Klinkebiel D, Boland MJ, Tang L, Christman JK. Promoter methylation and mRNA expression of APC gene in MCF10 breast cancer model. Zhonghua Bing Li Xue Za Zhi. 35:32-36, 2006. Abstract
Yang JL, Klinkebiel D, Boland MJ, Tang L, Christman JK. Promoter methylation and mRNA expression of WT1 gene in MCF10 breast cancer model. Zhonghua Bing Li Xue Za Zhi. 36:253-258, 2006. Abstract
Radhakrishnan P, Basma H, Klinkebiel D, Christman J, Cheng PW. Cell type-specific activation of the cytomegalovirus promoter by dimethyl sulfoxide and 5-aza-2'-deoxycytidine. Int J Biochem Cell Biol. 40(9):1944-55, 2008. Abstract
Boland MJ and Christman JK. Characterization of Dnmt3b: Thymine-DNA glycosylase interaction and stimulation of thymine glycosylase-mediated repair by DNA methyltransferase(s) and RNA. J Mol Biol. 379:492-504, 2008. Abstract
Chew YC, West JT, Kratzer SJ, Ilvarsonn AM, Eissenberg JC, Dave BJ, Klinkebiel D, Christman JK, Zempleni J. Biotinylation of histones represses transposable elements in human and mouse cells and cell lines and in drosophila melanogaster. J Nutr. 138(12):2316-2322, 2008. Abstract
van Bemmel DM, Brank AS, Eritja R, Marquez VE, Christman JK. DNA (cytosinie-C5) methyltransferase inhibition by oligodeoxyribonucleotides containing 2-(1H)-pyrimidinone (zebularine aglycon) at the enzymatic target site. Biochem Pharmacol. 2009 May 23. [Epub ahead of print] PMID:19467223. Abstract
Iqbal J, Kucuk C, Deleeuw RJ, Srivastava G, Tam W, Geng H, Klinkebiel D, Christman JK, Patel K, Cao K, Shen L, Dybkaer K, Tsui IF, Ali H, Shimizu N, Au WY, Lam WL, Chan WC. Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies. Leukemia 2009 Feb 5. [Epub ahead of print] PMID:19194464. Abstract
Current Grants and Contracts:
National Institutes of Health
Signaling in Androgen-Refractory Prostate Cancer
Principal Investigator: M.F. Lin
9/25/2006 - 7/31/2011