Among First Researchers to Discover Such Genes in Mammals

Dec 18, 2001

Dr. Zhong Sheng Sun, an Assistant Professor of Biochemistry in Pediatrics at Weill Cornell Medical College, has won a prestigious Mallinckrodt Foundation research award for his groundbreaking work in how biological clock genes affect the body's circadian rhythms and how such genes function in the blood, in the immune system, and in metabolism. Recently, his research was cited by the journal Science to be among the top 10 scientific breakthroughs of the year.

"Circadian" rhythms are the cycles of changes that an organism undergoes during the course of each day. Most people are familiar with them simply by feeling lively when it is morning and bright, and sleepy when it is late and at night. But Dr. Sun has broken new ground by showing such rhythms are genetically controlled and that they are part of even such unconscious systems as the immune system and metabolism.

The award will support Dr. Sun's research at Weill Cornell for the next several years (2001-2004). He thus becomes the 38th Mallinckrodt Scholar.

Dr. Sun, who earned degrees from Peking University and Texas A&M University, has been on the Weill Cornell faculty since 1999. He says that circadian rhythms are displayed "in most, if not all, living organisms, from bacteria to human beings." Dr. Sun has studied how certain genes, especially those called per1 and per2, govern circadian rhythms, even in the blood, the immune system, and metabolism.

The first circadian clock gene was identified in the fruit fly in 1985. Dr. Sun was among the first to find the mouse and human homologue for this gene in 1997. As he notes matter-of-factly, "my discovery of this initial murine clock gene was ranked by Science to be in the top ten scientific breakthroughs for 1997."

Dr. Sun has worked with both mice and humans. Since coming to Weill Cornell, he has extended his research in humans, experimenting with young volunteers in a sleep-deprived procedure, to learn more about the body's response to such factors as fatigue and jet lag.

"Recently," he says, "I have established a microarray facility at Weill Cornell. Through our genome-wide screening, ten genes have been shown to display a circadian expression pattern. In addition, we have found that 5-aminolevulinate synthase, an enzyme in blood biosynthesis, is regulated by per1 and per2 [circadian clock] genes, implying that mammalian metabolism functions in circadian fashion."

"We have also," he says, "initiated a project of screening small candidate molecules and hormones, which can reset the circadian clock gene's expression, thus regulating circadian rhythms. Our preliminary data have indicated that certain cytokines and some cell-specific growth factors have differential roles in resetting the biological clock in different tissues and cell lines. This opens the possibility of developing new drugs for the diagnosis and treatment of disorders associated with circadian abnormality, such as insomnia and jet lag."

Dr. Sun says that the long-term objective of his research is to elucidate the role of circadian clock genes in regulating circadian physiology and behavior. The "immediate focus" of his research is "to understand how the immune system's and the metabolism's clock function, and how circadian rhythms in the immune system and the metabolism are controlled by circadian clock genes." Toward these ends, he has an array of novel research projects underway.