One area of funded investigation is arsenic and cadmium toxicity and the role of metallothionein in the development and progression of bladder cancer (R01CA/ES94997; D. Sens, P.I.). Metallothionein (MT) is a metal binding protein that sequesters the toxic metal cadmium. Initial studies demonstrated that all human bladder cancers express the third isoform of MT while MT is not expressed in normal urothelium. Biomarker studies include the determination if MT is a marker for the early development of bladder cancer and if reoccurrence of bladder cancer can be diagnostically determined by the presence of MT positive cells on urine cytology. Mechanistic aims focus on determining the transcriptional and translational mechanisms of expression.

The second funded project (R01 ES/CA11333; D. Sens, P.I.) is to determine the role of MT-3 in cadmium-induced nephrotoxicity. Biomarker studies include the analysis of MT-3 expression in biopsies of renal disease and in renal cell carcinoma. Mechanistic studies have discovered that MT-3 expression controls the switch between apoptosis and necrosis when the human renal proximal tubule cell is exposed to cadmium.

The role of cadmium and MT in the development and progression of breast cancer is the third active area of investigation (R01CA098832, MA Sens, PI). The laboratory had previously shown that MT-3 expression is associated with DCIS lesions destined to progress. Another research group has recently shown that cadmium functions as a estrogen mimic at extremely low concentrations. Current investigations center on the analysis of MT expression in breast cancer and the role that cadmium might play in such expression.

Educational and collaborative efforts are also prominent in the research activities of the Department of Pathology. North Dakota INBRE with a theme of "Health and the Environment" is based in the Department of Pathology, under the Principle Investigator, Dr. Donald Sens. The goal of North Dakota INBRE is to build biomedical research capacity by serving research universities, baccalaureate institutions, and tribal colleges within the state and is featured at the INBRE web site.