DAYTON, OHIO--Julian Gomez-Cambronero, Ph.D., just received a $1.4 million grant from the National Institutes of Health to examine the molecular and cellular biology of cell migration behind healthy tissue damage caused by our own immune system. The four-year project places Wright State University School of Medicine at the forefront of an exciting new biomedical research field.
Gomez-Cambronero, professor of physiology and biophysics at Wright State's School of Medicine, has studied white blood cell migration and the chemical agents that signal that movement. "The study of the molecular mechanisms is crucial," he says, "to our understanding of more than 15 human inflammatory diseases where healthy tissue is destroyed."
White blood cells of the innate immune system, according to Dr. Gomez-Cambronero, are natural born killers. Their rapid deployment and toxicity defend us against pathogens and infection on a daily basis. But, too often this defense system goes awry, attacking healthy tissue or lingering too long at the site of injury. The inflammation caused by the immune system's response is just beginning to be recognized as a possible cause for heart disease and cancer as well as for the well-known autoimmune diseases.
We do not know, he explains, exactly what calls the white blood cells into action and, equally as important, what tells them to stop. The chemical agents responsible for this signaling represent a potential for pharmaceutical interventions that would ensure that inflammation subsides when the need for it is gone. Internal inflammation, the same basic biological process that is obvious at the site of a splinter, can cause damage to arterial lining or to the heart itself.
Gomez-Cambronero's research team works with neutrophils, the main white blood cell that destroys foreign material, debris, and bacteria. This cell is on the front line of our defense system and produces active chemicals derived from oxygen, some of which are similar to peroxide and household bleach."It is interesting," says Gomez-Cambronero, "that we use similar compounds to get rid of microbes in our clothes and inside our bodies."
When we are injured, cells near the wound immediately send "emergency assistance" signals. These signals travel into the healthy cells near the wound and into nearby blood vessels, calling to the damage site three kinds of cells. First to appear is the "repair crew," infection-fighting white blood cells. Next to arrive are new skin cells and endothelial cells needed to form new blood vessels and to begin wound healing.
Gomez-Cambronero has discovered that one of these emergency chemical signals is GM-GSF, a natural hormone normally produced in bone marrow. He has also discovered that a fungal product, Rapamycin, has a profound inhibitory effect on cell migration and upon the molecular signaling mechanisms that take place inside those cells. These findings have great implication in a wide variety of inflammation-related tissue injury and disease as well as leukemia. In leukemia, the white blood cells born in the bone marrow become more numerous but never reach the status of mature infection-fighting cells and they do not respond to the chemical signaling in the same way as healthy neutrophils.
Gomez-Cambronero has authored or coauthored articles on this research theory in four scientific journals in the past year, and he now serves as an ad hoc grant panel reviewer for the National Institutes of Health.
Dr. Julian Gomez-Cambronero received his Ph.D. (cum laude) in Biochemistry and Immunology at the Complutense University in Madrid, Spain. He was a postdoctoral fellow at the University of Connecticut Health Center. He joined Wright State faculty in 1995 and has been continuously funded by the American Heart Association and the National Institutes of Health.