How our cells deal with sugar — and there are many forms of it, for highly specific needs — is one of the most basic aspects of our biochemistry. Gerald Hart, Ph.D., should know; he is the DeLamar Professor and Director of Biological Chemistry at The Johns Hopkins University, and has been studying sugar regulation for decades. Now Hart, The Beth W. and A. Ross Myers Scholar, is working hard to fi nd out how the regulation of sugar within cells changes in prostate cancer — and whether understanding this could lead to new ways to fi ght this disease.
“In the early 1980s, we made the surprising discovery that many of the cell’s key regulatory proteins are dynamically modified by a sugar that serves to change how they work in response to nutrients and stress,” says Hart. Since then, Hart and others have learned that the activity of this particular sugar not only plays a fundamental role in most of the cell’s machinery; it also helps oversee nearly all of the cellular processes that go awry in cancer. For example: “This simple sugar modification of proteins regulates the cell’s signaling networks, the expression of genes, the structure of the nucleus, and processes controlling cell division.” Even though several studies have linked changes in this sugar modification with prognosis in certain cancers, “there have been almost no detailed studies of the roles of this sugar modification in cancer. The resources provided by the Patrick C. Walsh Prostate Cancer Research Fund are allowing us to systematically determine the roles of this important sugar modification of proteins in the properties of prostate cancer cells that contribute to their progression from benign to highly aggressive states.”
Hart’s first step in his pilot study is to identify which proteins are modified in prostate cancer cells — and more specifically, in all kinds of prostate cancer cells, from benign to the most hormone-resistant. Next, he plans to evaluate how changes in this sugar modification “affect the growth properties, the expression of steroid receptors, and the nuclear structure of prostate cancer cells.” This is an area of cell regulation that has been overlooked by cancer researchers. Hart hopes his findings will lead to the development of focused approaches that will create “completely unexpected avenues for diagnosis and treatment.”