Karpf, Adam, PhD

Department of Pharmacology and Therapeutics
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo NY USA 14263
Tel: 716 - 845 - 8305
E-mail: adam.karpf@roswellpark.org
Website: www.roswellpark.org/Karpf_Lab

Education
PhD, University of Texas at Austin
Postdoctoral, Huntsman Cancer Institute/University of Utah

Overview

Our laboratory investigates the role of epigenetic alterations in oncogenesis. We have broad interests ranging from deciphering the molecular mechanisms of epigenetic gene regulation, using animal models to examine the functional contribution of epigenetic change to oncogenesis, and conducting translational and clinical research using DNA methyltransferase inhibitors to treat human cancer. Our research is currently focused in two areas:

Project 1: Epigenetic regulation of cancer/germline (CG) antigen gene expression

CG antigens are a class of genes expressed specifically in germ cells of the testis and ovary, trophoblast, and human cancer. While the function of these proteins is obscure, members of this gene class include both the first described human tumor antigens and medically important cancer vaccine targets. In this project, we use molecular biology and pharmacological methods to examine the role of specific DNA methyltransferase and histone methyltransferase enzymes in regulating the expression of CG antigens, including MAGE-A1 and NY-ESO-1. Ovarian cancer is one malignancy in which NY-ESO-1 vaccines are being actively tested in clinical trials. In an important facet of this project, we collaborate with Dr. Kunle Odunsi of the Immunology Department to examine the role of epigenetic mechanisms in regulating NY-ESO-1 expression in ovarian tumors and normal ovary tissues. Furthermore, we are currently examining whether DNA methyltransferase inhibitors augment immunological and clinical responses to NY-ESO-1 directed vaccines against recurrent ovarian cancer.

Key Publications

Karpf, A. R., A. W. Lasek, T. O. Ririe, A. N. Hanks, D. Grossman, and D. A. Jones. (2004). Limited gene activation in tumor and normal epithelial cells treated with the DNA methyltransferase inhibitor 5-aza-2¢-deoxycytidine. Molecular Pharmacology 65, 18-27.

Samlowski, W. E., S. A. Leachman, M. Wade, P. Cassidy, P. Porter-Gill, L. Busby, R. Wheeler, K. Boucher, F. Fitzpatrick, D. A. Jones, and A. R. Karpf. (2005). Evaluation of a 7-day continuous intravenous infusion of decitabine: Inhibition of promoter-specific and global genomic DNA methylation. Journal of Clinical Oncology 23, 3897-3905.

James, S. R., P. A. Link, and A. R. Karpf. (2006). Epigenetic regulation of X-linked cancer/germ-line antigen genes by DNMT1 and DNMT3b. Oncogene 25, 6975-6985.

Karpf, A. R. (2006). A potential role for epigenetic modulatory drugs in the enhancement of cancer/germ-line antigen vaccine efficacy. Epigenetics 1, 116-120.

Woloszynska-Read, A, James, S. R., Link, P. A., Yu, J., Odunsi, K., and A. R. Karpf. (2007). DNA methylation-dependent regulation of BORIS/CTCFL expression in ovarian cancer. Cancer Immunity, 7:21.

Woloszynska-Read, A, Mhawech-Fauceglia, P., Yu, J., Odunsi, K., and A. R. Karpf. (2008). DNA methylation regulates NY-ESO-1 expression heterogeneity in ovarian cancer. Clinical Cancer Research 14, 3283-90.

Project 2: Assessing the role of altered DNA methylation in murine prostate cancer

While a tremendous amount of correlative evidence exists showing alterations in DNA methylation in human cancer specimens, there is a relative dearth of evidence that these changes functionally contribute to cancer formation or progression. For this reason, we are performing studies using the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) murine model to investigate the contribution of epigenetic change to prostate cancer. Our previous studies have shown that both DNA hyper- and hypo- methylation may play a key role in prostate oncogenesis. We utilize TRAMP, in concert with genetic and pharmacological manipulations of the DNA methylation pathway, to examine the role of aberrant DNA methylation in prostate cancer.

Key Publications

Karpf, A. R. and S-I. Matsui. (2005). Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Research 65, 8635-8639.

Morey, S. R., Smiraglia, D. J., James,S. R., Yu, J., Moser, M. T., Foster, B. A., and A. R. Karpf. (2006). DNA methylation pathway alterations in an autochthonous murine model of prostate cancer. Cancer Research 66, 11659-67.

Morey Kinney, S. R., Smiraglia, D. J., James, S. R., Moser, M. T., Foster, B. A., and Karpf, A. R. (2008). Stage-specific alterations of Dnmt expression, DNA hypermethylation, and DNA hypomethylation during prostate cancer progression in the TRAMP model. Molecular Cancer Research 6, 1365-74.

Camoriano M, Kinney SR, Moser MT, Foster BA, Mohler JL, Trump DL, Karpf AR, Smiraglia DJ.Phenotype-specific CpG island methylation events in a murine model of prostate cancer. Cancer Research 68, 4173-82.

Please click here for a complete list of PubMed publications for Dr. Karpf.