Safeguarding memory and more
Dr. Ki-Young Lee's pioneering research has shed new light on an enzyme originally thought to exist only in the brain
Story by Sheelagh Matthews/Illustration by Warren Heise
"Without memory, there is no happiness," claims AHFMR Senior Scholar Dr. Ki-Young Lee. It is memory that harnesses the brain's ability to make new connections when we are learning. But it is also memory that allows us to relive the happy days of our youth, our first loves, our children's early lives, and our achievements at work. Neurodegenerative diseases such as Alzheimer's rob us of our memories.
Dr. Lee, originally from Korea, found himself Alberta-bound in 1993, attracted by an AHFMR award and the prospect of being able to concentrate on his major research interest. Feeling amply rewarded by his work—and his proximity to the Rockies—he decided to settle in Calgary.
For more than a decade Dr. Lee has specialized in researching an enzyme called cyclin-dependent kinase 5 (Cdk5), which regulates the division, differentiation, and death of cells. He is regarded as a pioneer and leader in this field. He has been studying abnormal activity of this enzyme in Alzheimer's disease. Recently, however, he has expanded his investigations to include its role in other devastating health problems, such as brain cancer, kidney disease, infertility, and birth defects.
Dr. Lee found that too much or too little Cdk5 activity could lead to disease. For example, in 1999 he and his team discovered that elevated activity of the enzyme is a feature of brains affected by Alzheimer's disease. Their recent studies suggest that Cdk5 is also involved in the spread of brain tumours.
The breakthrough came when Dr. Lee and his team discovered that Cdk5 activity exists outside of the brain. Although the enzyme is most abundant in the brain, a significant level is also found in the testes—the male reproductive organs that produce sperm and testosterone. Dr. Lee points out that there are several similarities between sperm cells in the testes and nerve cells in the brain. Both are non-dividing; both regulate their secretions; both migrate during development; and the growth of the flagella (sperm "tails") resembles the growth of the axons that project from nerve cells.Following up on this, Dr. Lee has begun investigations into the development of sperm flagella. The sperm flagellum is a specialized form of primary cilium—a microscopic hairlike extension of the cell membrane. The functions of primary cilia are believed to range from sensing and orientation to signalling and navigation. Dr. Lee has gathered evidence that Cdk5 plays an important role in regulating the development of primary cilia, and he expects the enzyme is probably also an important player in disorders related to that development.
Since primary cilia are found on nearly all cells of the human body, it's hardly surprising that faulty cilia are involved in a wide range of diseases and conditions. For example, a certain developmental defect can produce sperm flagella that are incapable of movement, one cause of infertility. Another type of ciliary defect can result in the complete left-right reversal of internal organs in a fetus. Other research implicates defective cilia in such diverse conditions as polycystic kidney disease, retinal degeneration, certain types of obesity, diabetes, neural tube defects, lung disease, and mental disorders.
Dr. Lee hopes that his Cdk5 research will lead him to understand the basic science that underlies these disorders, thereby helping to pave the way for the development of treatments.