Faculty

Dr. Howard R. Petty's goal is to understand the mechanisms that drive chemical signaling within the cell and how these mechanisms might be exploited to improve patient care. Utilizing some of the most innovative techniques and equipment, he has been able to observe and study the movement of signaling molecules, such as calcium waves and NADPH, within and among living cells and tissues.

Using high-speed optical microscopy with shutter speeds as fast as 50 nanoseconds and repetition rates shorter than one millisecond, Dr. Petty can track individual molecules illuminated by a fluorescent dye. This technique has helped to change the prevailing precept that signal transduction is merely the presence or absence of a chemical messenger. He has discovered that chemical signals travel as waves within immune cells, tumor cells, and retina. These signaling waves can be calcium concentrations, pH gradients or metabolites. They have dynamic initiation points, speeds, shapes and locations, and are thought not only to signal changes within a cell, but to propagate signals from one cell to another. Moreover, cell-cell contact seems to cause inflammatory cells to aggregate and behave as a single tissue, bringing about a cooperative and coordinated release of toxic metabolites.

The implications of Dr. Petty's findings are wide-ranging. Applying his techniques to retinal pigment epithelial cells which play a major role in the eyes' immune system, he is able to study how toxic oxidants are released and to monitor the effects of pharmacological treatments. Calcium waves participate in the phagocytosis and disruption of photoreceptor outer segments, an important activity of the retinal pigment epithelium. By studying changes in these calcium waves, Dr. Petty, in collaboration with Dr. Alan D. Schreiber of the University of Pennsylvania School of Medicine, has identified a gene mutation that disrupts both the calcium wave and target disruption. Drugs aimed at disrupting these waves may be useful in controlling inflammatory eye disease.

These images of fundamental mechanisms at work in immune reactions allow Dr. Petty and his collaborator, Dr. Roberto Romero at the National Institute of Child Health and Human Development, to understand how pregnancy can bring about immune suppression. Their studies are identifying agents with the potential to induce remission or immune suppression in patients with uveitis, multiple sclerosis, and other autoimmune and inflammatory disorders. Their work is paving the way for new and effective anti-inflammatory treatments.