Arthur Polans, PhD
Madison, WI 53792-0001
Biomolecular Chemistry, UW Comprehensive Cancer Center.
B.A. 1976, U.C. Berkeley
Postdoctoral Fellowship, 1980-83, U.C. Berkeley
Cancer is a multistage process impacting on a large number of genes and their related cellular pathways. Recent advances in both biochemical and molecular methods make it possible to study the pathways which endow tumor cells with properties related to their malignant and metastatic capabilities. Such studies can provide significant information about the course of the disease and about effective treatments.
My research focuses on uveal melanoma, the primary malignancy originating in the eye. One study concerns the initial genetic events that may predispose individuals towards the development of a tumor. These events may involve structural mutations in chromosome 1p that we are characterizing with innovative cytogenetic methods. In a second project using DNA chip arrays, subtractive hybridization and mass spectrometry, we have identified several gene products with altered levels of expression that may contribute to the malignant and metastatic phenotype of the tumor, in some instances as potential angiogenic factors governing the tumor?s blood supply. We are unraveling the biochemical pathways in which these gene products participate as well as their functional significance using stably transformed melanoma cell lines. Finally, the structure of some the identified proteins and their interactions with other effector proteins are being studied in the laboratory. In particular we are interested in the role of certain calcium-binding proteins. Calcium-binding proteins mediate a variety of physiological responses in which calcium acts as a second messenger. Aside from interest in their normal function, mutations in genes encoding calcium-binding proteins have been associated with the development and progression of certain neoplasms. ALG-2, for example, is a calcium-binding protein involved in programmed cell death that is down-regulated in uveal melanoma, thus providing further selection advantage for these tumor cells. In addition to structural studies of these calcium-binding proteins we are continuing to investigate their cellular distribution, as well as to identify effector molecules and develop functional assays. Several of these proteins also may be useful tumor markers and sites for intervention either by drug treatment or through gene therapy.