1993 McCoy Award Recipient
Philip S. Low
Professor of Chemistry

Structure and functions of cell membranes

The recipient of the Herbert Newby McCoy Award for 1993 is Philip S. Low, Professor of Chemistry. Professor Low grew up in West Lafayette and is the son of Philip F. Low, Professor Emeritus of Agronomy and 1980 recipient of the McCoy Award. The younger Low received his B.S. from Brigham Young University in 1971 and his Ph.D. from the University of California, San Diego, in 1975. After one year as a postdoctoral research associate at the University of Massachusetts, he joined the Purdue chemistry faculty in 1976. His research on the structure and functions of cell membranes is described in more than 120 publications from his laboratory. He is a past fellow of the International Union Against Cancer, a recipient of the Purdue Cancer Research Award, and a member of an NIH Study Section. In addition to biochemistry, his interests include sports, backpacking, and music.

Research
The cell membrane serves as a barrier to prevent loss of needed cellular components and to protect against entry of unwanted foreign substances. While exclusion of toxins, pathogens, genes, antibodies, exogenous enzymes, and drugs, etc., is normally essential for cell survival, the same beneAcial barrier also can prohibit administration of desired exogenous molecules that repair diseased cells or exterminate cancer cells. To circumvent this barrier, Philip S. Low and colleagues have conjugated otherwise impermeable molecules to vitamins that enter cells by receptor-mediated endocytosis. In this process, the vitamin is chemically attached to the desired therapeutic agent at a site on the vitamin that doesn't interfere with its capture by a cell surface vitamin receptor. After the vitamin-drug conjugate diffuses to the cell, it docks with the above receptor, invaginates with the receptor and surrounding membrane to form an endosome inside the cell, traffics to the Golgi apparatus and endoplasmic reticulum, and then escapes into the cytoplasm by a process not yet fully understood. By this method, molecules of diverse chemical composition, different electrostatic charge, and varied size, with no natural ability to penetrate cell membranes, all have been success- fully delivered into vitamin receptor-bearing cells. Because specific vitamin receptors are highly enriched on certain cells, the vitamin conjugation technology also has been exploited to target attached drugs to speci6c cells in live animals and other heterogeneous cell systems. The most striking example of this selectivity involves folic acid whose receptor is found almost exclusively on cancer cells. By linking impermeable toxins to this vitamin, it has been possible to exterminate cancer cells without harming or modifying adjacent normal cells. Aside from the application to cancer therapy, uses in other areas of human medicine also have been explored or envisioned. These include:

• gene therapy for inherited disorders
• antisense DNA treatment to inhibit expression of unwanted genes
• oral or pulmonary delivery of hormones, drugs, and vaccines
• targeting of radio pharmaceuticals for imaging purposes
• delivery of therapeutic enzymes and other proteins into malfunctioning cells.