Utilizing modern molecular biologic techniques such as the polymerase chain reaction, gene cloning and gene transfer, Dr. Wayne Grody's laboratory is involved in the elucidation, diagnosis and ultimately the treatment of single-gene defects at the molecular level.
Using human arginase deficiency, a defect in the urea cycle, as a model system, Grody and his colleagues are exploring, in close collaboration with the laboratory of Dr. Stephen Cederbaum, the molecular structure and tissue-specific regulation of the arginase genes in health and disease. The researchers have determined the mutation sites in a large cohort of arginase-deficient patients worldwide; identified important regulatory sequences governing tissue-specific expression and extinction by transferring the cloned genes and promotor sequences into various recipient cells types; and recently constructed an arginase-deficient knockout mouse. Alternatives for gene replacement therapy have been explored by re-directing the transfected genes to different subcellular compartments. Both the ontogeny and the regulated expression of the arginase isozymes are being studied in a variety of developmental and adult systems and in certain malignant tumors in which their expression is induced.
As director of the UCLA Medical Center's Diagnostic Molecular Pathology Laboratory, Grody can offer his trainees exposure to the latest clinical applications of molecular biology in the diagnosis of a wide range of genetic, neoplastic and infectious diseases as well as DNA fingerprinting. A major effort in this area has been a pilot project, funded by the Human Genome Initiative, to study the effectiveness of large-scale population screening for cystic fibrosis mutations by DNA analysis. This experience has served as a paradigm for the more recent development of other important DNA-based screening tests in Grody's laboratory, such as those for multiple endocrine neoplasia and heritable breast and colon cancer.
Selected Cancer-Related Publications:
Mumenthaler SM, Rozengurt N, Livesay JC, Sabaghian A, Cederbaum SD, Grody WW. Disruption of arginase II alters prostate tumor formation in TRAMP mice. Prostate. 2008 Oct 1;68(14):1561-9.
Mumenthaler SM, Yu H, Tze S, Cederbaum SD, Pegg AE, Seligson DB, Grody WW. Expression of arginase II in prostate cancer. Int J Oncol. 2008 Feb;32(2):357-65.
Elshimali, Y. and W.W. Grody. 2006. Clinical significance of circulating tumor cells in the peripheral blood. Diagn Molec Pathol. 15:187-194.