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Drs. Fridman (left) and Mobashery (right) published the cover article in the prestigious FASEB Journal. |
Rafi Fridman, PhD, associate professor of pathology, and Shahriar Mobashery, PhD, professor of chemistry, have a long-established collaboration to achieve an important goal: to develop new compounds that will help prevent the dissemination of cancer cells, a process known as metastasis. This is done by targeting a group of enzymes that degrade the extracellular matrix and are known to be key players in cancer metastasis. These enzymes, known as matrix metalloproteinases or MMPs, have been the focus of Dr. Fridman’s research for the last 15 years.
"MMPs are thought to help tumor cells break down tissue barriers during their metastatic spread. Therefore, inhibiting their action would stop cancer cells at the primary site where they can be better managed by surgery or conventional approaches. Preventing tumor metastasis would have an impact on patient survival," Dr. Fridman explained.
The collaboration of Drs. Fridman and Mobashery brings together an ideal combination of expertise and knowledge to tackle the control of MMP activity in tumor cells. It relates the biology of the metastatic processes and the knowledge of the chemical elements that regulate enzyme structure and function. It also brings together the biochemical and cellular tools and the methodology and reagents to approach the inhibition of MMPs in a comprehensive manner.
Their work together has resulted in several publications. The latest was the cover article in the September 1998 issue of FASEB Journal, published by the Federation of American Societies for Experimental Biology, the leading journal in the biomedical field. "We are very proud of this article because it provides the first comprehensive study using state-of-the art technologies to study the organization and structure of the evolution and structure of the MMP family (64 members in total).
"The studies highlighted in the article are the result of the hard work of Irina Massova, a graduate student, and Lakshmi Kotra, a postdoctoral fellow, in Dr. Mobashery’s lab," Dr. Fridman remarked. "It is a good example of how scientists from different fields can work together to produce useful and relevant information."
Dr. Fridman explains that beyond their role in metastasis, MMPs are important because they are involved in many physiological processes that require modifications of the extracellular matrix from development, tissue remodeling, wound healing and inflammation, conditions in which the enzymes are very well controlled. In disease conditions, the regulation of MMP goes awry and large amounts of these enzymes are produced, damaging tissues in arthritis or promoting tumor metastasis in cancer, for example.
"We believe that understanding the structure of MMPs and their mechanism of action is a necessary step toward developing new methods to control their damaging activity," said Dr. Fridman. "Based on studies like those published in the FASEB article, Dr. Mobashery developed a novel approach for the design of specific MMP inhibitors. Some of them are now being tested with our recombinant enzymes for inhibitory activity. We hope our combined efforts will result in new inhibitors that one day will reach the clinic."