Faculty Research Awards 2004

Distinguished Professor D. James Morré

Medicinal Chemistry and Molecular Pharmacology

The Sigma Xi Faculty Research award for 2004 is presented to Professor James Morré for his long record of innovative ideas and approaches starting with his development of the membrane flow hypothesis to his remarkable practical work in the isolation of Golgi, and plasma membrane. The most significant of his discovery is the isolation of unique family of cell surface time-keeping and growthrelated proteins (cell surface NADH oxidase or ECTO-NOX proteins) that drive cell enlargement.

Dr. Morré earned his Bachelors of Science degree from the University of Missouri, Columbia, his MS from Purdue, and his Ph.D. in Biochemistry from the California Institute of Technology in Pasadena. Dr. Morré started his career in Purdue in 1962 and became a distinguished professor in 1986. He served as the director of Purdue Cancer Center for 10 years. Dr. Morré received many accolades, to list a few. He is the recipient of a senior investigator award of the American Heart Association, a senior scientist award of the German Cancer Research Center, and an Alexander von Humboldt Foundation Senior US scientist Award given by Germany. He was awarded a 2 years Tage Erlander Professorship by the Swedish Natural Research Council. He has two honorary doctorates, one from the University of Geneva, Switzerland, and the other from the Université Victor Segalan, Bordeaux, France. Dr. Morré has published 625 papers and 9 patents.

Professor Morré and his colleagues work on the NADH oxidases of the cell surface led to findings that are of singular importance to an understanding of both growth control and of the biological clock. This breakthrough research on oscillating oxidoreductases opened a tremendous application in the field of cancer. Dr. Morré and his colleagues have discovered a 34 kD hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity located at the external plasma membrane surface (ECTO-NOX). The constitutive activity (CNOX) normally is sensitive to transplasma membrane signaling. In cancer cells, a second activity (tNOX) is found that is constitutively activated and no longer hormone- or growth factorresponsive. Certain anticancer drugs, characterized as a class by a propensity to occupy quinone-binding sites, inhibited, the cancer cells fail to enlarge following cell division and undergo programmed cell death (apoptosis) typified by characteristic nuclear and cell membrane changes.

Dr. Morré and his colleagues have purified, cloned and expressed the 34 kD drug-responsive tNOX protein in bacteria. It is released from the cell surface and accumulates in the blood where it serves as a marker of cancer presence. The protein occurs in sera of cancer patients and characterizes most, if not all, forms of human cancer. While anchored at the external cell surface, the tNOX protein is exposed to the environment. Thus drugs targeted to tNOX need not enter cells to be effective. Anthracyclines, antitumor sulfonylureas or vanilloids immobilized on impermeant supports are more effective antitumor agents than free drug in animal models and less toxic. A 10- to 100-fold increase in the therapeutic index results from conjugation. Its surface location and universal association with human cancer make the drug-responsive tNOX an excellent potential anticancer vaccine and drug target. The function of both the growth factorregulated and drug-inhibited NOX proteins of the mammalian plasma membrane is in concert with other membrane proteins to result in cell enlargement following cell division. Following division, cells must reach some minimal size in order to divide again. The unregulated cell enlargement provided by tNOX appears advantageous to growth of cancer cells and when inhibited, the cancer cells fail to enlargement provided by tNOX appears advantageous to growth of cancer cells and when inhibited, the cancer cells fail to enlarge normally, division ceases and apoptosis is initiated.

The Purdue Chapter of Sigma Xi is pleased to recognize Professor James Morré with its 2004 Faculty Research Award, an award designed to honor a person of this caliber.