Fall 2000 Newsletter: Edwin L. Ferguson, Jr., Ph.D.

Associate Professor
Department of Molecular Genetics and Cellular Biology
University of Chicago

Cancer Research Foundation Fletcher Scholar 1999 Dr. Ferguson’s research focuses on stem cells and
their use in cancer therapy.

We are not accustomed to thinking that the human body has the potential for massive tissue regeneration
and repair. However, in every individual, many differentiated cell types, such as red blood cells or skin cells, have a short lifetime and must be replaced at regular intervals. Normally when a cell differentiates it stops dividing, becomes specialized to perform a particular function, and ultimately dies. How then can differentiated cells be continually renewed? The answer lies in the action of a remarkable class of cells, called stem cells. A stem cell is a non-differentiated cell that has a unique property. When a stem cell divides it produces two types of cells: a cell like itself, and a cell that differentiates. The capacity of various types of stem cells for self renewal thus assures the continual replacement of many differentiated tissues throughout our lives.
The isolation, culture, and characterization of different types of stem cells could be the first step toward the ultimate goal of tissue restoration through stem cell transplantation. Such therapy could be vital to combat diseases that cause tissue degeneration, ranging from cardiovascular disease to Alzheimer's and Parkinson's diseases, to certain types of diabetes. The use of stem cells in cancer treatment could also be widespread. Certain cancers respond to chemotherapy. However, while the underlying purpose of chemotherapy is to kill the rapidly dividing cancer cells, it has the unavoidable side effect of killing all rapidly dividing normal cells in the body, including the cells of the hematopoietic (circulatory) system. It therefore becomes necessary to repopulate the cells of the circulatory system after successful chemotherapy. The ideal solution would be isolation of the patient's own hematopoietic stem cells before the onset of therapy, the culture of these cells during therapy, and their reimplantation after the completion of therapy.
However, much basic knowledge about stem cells must be gained before they can be used to combat disease. First and foremost, we must understand at a molecular level why one daughter of a stem cell remains as a stem cell while the other daughter differentiates. In work very generously supported by the Fletcher Scholar Award from the Cancer Research Foundation, my lab is attempting to address this question for a particular type of stem cell, one that is present in the fruit fly Drosophila melanogaster. While the fruit fly may seem far removed from humans, work over the past fifteen years has demonstrated multiple times that similar molecular mechanisms are used to control cell behavior and function in both fruit flies and mammals. Moreover, the fruit fly is an unparalleled system in which to perform genetic experiments.
We have initiated a series of experiments that should allow us to perturb the pattern of division of this particular stem cell. While stem cells normally divide to produce two distinct cell types, we will use the tools of genetics to cause this particular type of stem cell to divide to produce two cells of the same type, either two stem cells or two differentiated progeny, depending on the experimental conditions we use. By manipulating the patterns of cell division in one particular type of stem cell, we expect to obtain insights into the molecular programs responsible for the maintenance and differentiation of stem cells in all organisms, thus furthering their ultimate use to alleviate disease in humans.