Gail Clinton, Ph.D. Professor of Biochemistry and Molecular Biology Oregon Health Sciences University School of Medicine Gail Clinton, Ph.D., a Professor in the Department of Biochemistry and Molecular Biology at Oregon Health & Sciences University (OHSU) School of Medicine in Oregon's largest city, Portland, grew up in a small logging town in a rural part of the state. Her career goal was elementary education, but this changed after her first year in college. She spent that summer in a research laboratory, and “after one week,” said Gail, she knew she wanted to do research. Although Gail is interested in studying basic science, she also wants to see her research have practical applications in terms of understanding and treating disease.

From left to right: Gail Clinton, Ph.D., professor of biochemistry and molecular biology, OHSU School of Medicine; Adam Evans, Ph.D., senior research sssociate (biochemistry and molecular biology), OHSU School of Medicine; Herstatin co-inventor John Adelman, Ph.D., senior scientist, OHSU Vollum Institute. (Photo by Anne Rybak.)

Gail runs a very active laboratory that is seeking answers that will benefit those afflicted with cancer and other diseases. As Gail points out, she, like many other people, is affected by cancer among family and friends. Most research scientists have moments when they feel discouraged with how the research is progressing, but Gail has been encouraged in her research by friends whose lives are touched by cancer, and says she found motivation from her friends during such times.

Gail’s areas of interest include the molecular and biochemical mechanisms by which the HER-2/neu (c-erbB-2) oncogene causes tumor development and malignant progression of human cancers. The HER-2/neu oncogene encodes a receptor tyrosine kinase that is overexpressed in several types of human cancer. In breast cancer, overexpression of HER-2 occurs in 30 percent of the cases where it leads to more aggressive tumor growth and poor outcome.

The structure and function of alternative HER-2/neu products may impact oncogenesis, and Gail’s lab is actively pursuing such products. Currently she is focusing on the role of introns. Human genes have many functional parts, two of which are called “introns” and “exons.” An exon is the region of the gene that contains information for producing the protein encoded by that gene. An intron is a generally non-coding sequence of DNA that is initially copied into RNA, but then cut out of the final RNA transcript. However, Gail and her team recently discovered an alternative HER-2/neu transcript that retains an intron and is expressed in developing human tissues. This alternative transcript encodes a secreted protein that contains part of the HER-2 receptor itself and a novel domain encoded by the retained intron. This unique ligand, which they named “Herstatin,” behaves as an HER-2 receptor inhibitor, in contrast to all the previously characterized ligands that activate mammalian receptor tyrosine kinases. Gail’s ultimate goal is to define how the Herstatin ligand impacts HER-2 mediated signal transduction pathways that culminate in growth or cell death and to evaluate its potential utility as a cancer therapeutic.

Many research projects culminate in scientific publications and further research. In Gail’s case, however, the research results literally are coming out of the lab and into the clinic, and will be applied to the development of a new class of therapeutics to treat cancer and other diseases. This is exactly the goal Gail hoped for when she embarked on her research career. The practical results of Gail’s work have already led to two patents, including U.S. Patent Nos. 6,414,130 and 6,541,214 for Herstatin-encoding nucleic acids, and a truncated HER-2 receptor, respectively, as well as multiple pending U.S. and foreign patent applications.

Receptor BioLogix Inc., a Portland- and San Francisco-based company, has been formed to develop this promising new class of therapeutics discovered in Gail’s lab at OHSU to treat cancer and other diseases. Receptor BioLogix’s lead clinical product will be Herstatin (TM), also referred to as Dimercept (TM), for use as a broad-spectrum anticancer agent. The Dimercept discovery led to the development of an intron fusion protein (IFP) discovery platform, a new strategy that will leverage the enormous recent progress in human genome DNA sequencing and bioinformatics. Dimercept is readily produced by standard gene expression methods and is likely to be non-immunogenic, which would facilitate its path through drug development and FDA approval.

The HER-2 gene is also the target of an existing drug, Herceptin (TM), which is approved strictly to treat breast cancer. Unlike Herceptin, Dimercept is naturally occurring and targets a broader spectrum of cancers. The potential of Dimercept is believed to be considerably greater than Herceptin because it may be useful against about half of all cancers, affecting some 500,000 patients a year.

Such accomplishments might cause some scientists to consider retirement or at least a reduced work schedule. However, when asked about her future research plans and goals, Gail indicated that she will continue to work in this area in order to learn more about the physiological role of Dimercept and more generally about the mechanism for protein diversity based on the use of introns. This is wonderful news to anyone touched by cancer in a loved one or a friend or colleague.

Although the field of elementary education would have benefited from Gail’s talents and drive, she still serves as an inspiration to young students who dream of a career that will benefit society, perhaps by finding new treatments for disease.

Finally, Gail credits several organizations for support of her work through the years: The OHSU School of Medicine's Department of Biochemistry and Molecular Biology, the American Cancer Society, the National Cancer Institute, and the Department of Defense Breast Cancer Program.

Davis Wright Tremaine congratulates Gail for her accomplishments and her dedication in pursuing a question over the long years of daily work that have led to an exciting new cancer treatment.

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