Molly Kulesz-Martin

Ph.D., State University of New York, Buffalo, New York, 1979
Professor and Associate Chair of Dermatology
Director of Research, Dermatology
Professor, Cell and Developmental Biology

Genetic changes are being linked to carcinogenesis stages of initiation, benign tumorigenesis, malignant conversion and progression. A mouse epidermal cell clonal lineage has been used to detect deregulated expression of candidate oncogenes and suppressor genes at these discrete stages. Altered expression and activity of distinct forms of the tumor suppressor protein p53 occur at malignant conversion prior to coding region mutations. Cellular regulators of p53 activity are being identified based on presence in complexes with endogenous p53 and DNA. Squamous cell carcinogenesis and tumorigenesis stages are being analyzed using RNA differential display and genetic microarrays in order to define cooperating oncogene and tumor suppressor gene pathways that drive these processes. The expression of these genes, their tissue specificity and their functions are being characterized in mouse and human cells and tissues.

Potential significance and applications of these studies of molecular events in cancer development include improved early cancer detection and ability to define molecular profiles of individual tumors to assist in treatment plan and targeted therapy. Since cancer genes are fundamental regulators of normal cellular activities, these findings and approaches may have applications to other proliferative disorders.

Liu, Y., Asch, H., and Kulesz-Martin, M. (2001) Functional quantification of DNA-binding proteins p53 and estrogen receptor in cells and tumor tissues by DNA affinity immunoblotting. Cancer Res. 61: 5402-5406.

Kaku, S., Iwahashi, Y., Albor, A., Yamagishi, T., Nakaike, S., and Kulesz-Martin, M. (2001) Binding to the naturally occurring double p53 binding site of the Mdm2 promoter alleviates the requirement for p53 C-terminal activation. Nucleic Acids Res. 29: 1989-1993.

Liu, Y. and Kulesz-Martin, M. (2001) p53 protein at the hub of cellular DNA damage response pathways through sequence-specific and non-sequence-specific DNA binding. Carcinogenesis 22: 851-860, 2001.

Liu, Y., Black, J., Kisiel, N., and Kulesz-Martin, M. (2000) SPAF, a new AAA-protein specific to early spermatogenesis and malignant conversion. Oncogene 19:1579-1588.

Wu, Y., Huang, H., Miner, Z., and Kulesz-Martin, M. (1997) Activities and response to DNA damage of latent and active sequence-specific DNA binding forms of mouse p53. Proc. Natl. Acad. Sci. USA 94: 8982-8987.

To contact Dr. Kulesz-Martin directly: kuleszma@ohsu.edu