Paul D. Soloway
Professor

Paul D. Soloway

Phone

607-254-6444

Address

Division of Nutrition
108 Savage Hall
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Lab Web Site
Department Profile

Background

Post-doc 1994 - Whitehead Institute / MIT, Molecular Genetics - Advisor, R. Jaenisch

Ph.D. 1989 - Princeton University, Molecular Genetics - Advisor, T. Shenk

BA 1979 - Cornell University, Biochemistry

Research Description

Methylation of cytosines within CpG dinucleotides is critical for normal development in mammals and responds to environmental factors including nutrition. In cancer, proper regulation of DNA methylation goes awry often leading to silencing of tumor suppressors or activation of growth-stimulating genes. These events can strongly contribute to tumorigenesis. Many loci have been identified that acquire methylation or whose expression is methylation-sensitive in the normal and cancer genome, but virtually nothing is known about how methylation is regulated. Imprinted loci are useful for identifying cis-acting DNA sequences that regulate local methylation since these loci undergo predictable patterns of allele-specific methylation in normal tissue. RASGRF1 is a GTP exchange factor that activates RAS and has transforming activity. In mice, the Rasgrf1 locus is imprinted: There is paternal allele-specific methylation within a differentially methylated domain (DMD) 30 kbp 5' of the promoter and the locus is paternally-expressed. We have shown that a repeated sequence element found immediately 3' of the DMD regulates establishment and maintenance of methylation of the DMD.

Selected Publications

M. M. Lee, B. J. Yoon, K. Osiewicz, M. Preston, B. Bundy, A. M. van Heeckeren, Z. Werb and P. D. Soloway; Tissue inhibitor of metalloproteinase 1 regulates resistance to infection; Infect Immun 73; 661-5 (2005).

H. Zhao, M. M. Bernardo, P. Osenkowski, A. Sohail, D. Pei, H. Nagase, M. Kashiwagi, P. D. Soloway, Y. A. DeClerck and R. Fridman; Differential Inhibition of MT3-MMP and MT1-MMP by TIMP-2 and TIMP-3 regulates Pro-MMP-2 activation; J Biol Chem 279; 8592-8601 (2004).

F. Sabeh, I. Ota, K. Holmbeck, H. Birkedal-Hansen, P. Soloway, M. Balbin, C. Lopez-Otin, S. Shapiro, M. Inada, S. Krane, E. Allen, D. Chung and S. J. Weiss; Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP; J Cell Biol 167; 769-81 (2004).

F. Sabeh, I. Ota, K. Holmbeck, H. Birkedal-Hansen, P. Soloway, M. Balbin, C. Lopez-Otin, S. Shapiro, M. Inada, S. Krane, E. Allen, D. Chung and S. J. Weiss; Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP; J Cell Biol 167; 769-81 (2004).

Click here for Dr. Soloway's PubMed listings.