Cancer Biology, Developmental Biology
The University of Texas Southwestern Medical Center
Dr. Morrison is also Mary McDermott Cook Chair in Pediatric Genetics and the director of the Children's Research Institute at the University of Texas Southwestern Medical Center.
Mechanisms That Regulate Stem Cell Self-Renewal
Adult stem cells are the body's ultimate repair system. These immature cells maintain a low profile within tissues and organs until activated by disease or injury. Stem cells then can rive rise to specialized cells within their tissue of origin, and they also have the remarkable ability to replenish themselves through a process called self-renewal. Sean Morrison is unraveling the mechanisms that regulate stem cell function in the blood and nervous systems, particularly those involved in stem cell self-renewal and aging. The Morrison laboratory also compares the mechanisms that regulate stem cell self-renewal and cancer cell proliferation. Ultimately, Morrison hopes to identify new treatments for diseases caused by stem cell defects, including cancer, degenerative disease, and birth defects.
Morrison began his pioneering stem cell work only after a brief stint as a biotech entrepreneur. For his high school science fair project, the Canadian native developed a hydroponically grown fungal fertilizer that dramatically increased the nutrient uptake in plants. The fertilizer attracted the interest and support of the Canadian government and Dalhousie University in Halifax, where he attended college. But when the project failed to garner enough venture capital at a critical point, Morrison shifted gears, opting instead for a career in medical research. He was fascinated by the process of discovery and the elegance he found in well-conceived research. "The best scientists are like artists in the sense that they are constantly motivated by the challenge of doing more and more beautiful work," Morrison explains. "They push themselves to generate the most beautiful data and to perform the most elegant experiments. The best scientists find beauty and satisfaction in the process."
As a graduate student, Morrison identified key markers that distinguish hematopoietic stem cells, which give rise to blood and immune system cells, from other immature hematopoietic cells. He determined that stem cells are fundamentally different from other immature cells, and his results also suggested that certain factors are involved in regulating stem cell self-renewal. Later, as a postdoctoral fellow in the Caltech laboratory of David Anderson, a fellow HHMI investigator, Morrison became the first to isolate uncultured neural crest stem cells, which give rise to the peripheral nervous system. This led to his discovery that stem cells persist throughout adult life in the peripheral nervous system, where they were not previously believed to exist.
Today, Morrison's research focuses on neural stem cells and hematopoietic stem cells. By studying both, he hopes to understand the extent to which mechanisms that control self-renewal and other critical functions are conserved among stem cells in different tissues. Morrison has discovered that there are mechanistic differences between the self-renewal of normal stem cells and the proliferation of cancer cells that can be exploited to kill the cancer cells without harming the normal stem cells. He also has traced a potentially fatal birth defect that causes Hirschsprung disease to defects in the generation and migration of neural crest stem cells in the developing intestines. And, using techniques he developed as a graduate student, Morrison identified a family of cell surface receptors that scientists can use to separate hematopoietic stem cells from other, less primitive, hematopoietic progenitors. Each of these studies has the potential to change the way in which patients are treated.
Morrison strongly believes in the potential of medical research. "The greatest opportunities to change medicine arise from fundamental scientific discoveries, and I believe those opportunities exist in stem cell biology," he says. "Stem cell biology is so central to a variety of important scientific and medical questions that it commands a lot of attention from researchers in diverse fields. That attracted me, because if I invest years of my life answering a question, I really want people to care what the answer is."