Claire M. Doerschuk, professor of pediatrics with the CWRU School of Medicine and Rainbow Babies and Children's Hospital, has received the Method to Extend Research in Time (MERIT) Award from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH).

Claire Doerschuk

The NIH chooses MERIT Award recipients, who do not apply for the grant, based on their consistent achievement in previous NIH-funded projects and the promise that they will continue to be exceptionally competent and productive researchers in the project for which the grant is awarded.

Doerschuk received the 10-year grant for her research about the regulation of white blood cell recruitment to the lungs during bacterial pneumonia and acute respiratory distress syndrome (ARDS), a lung injury that occurs as part of a systemic response to major infections or trauma. Her work examines the recruitment of neutrophils, the first white blood cell to respond to a bacterial infection or injury. She also studies how pneumonia causes neutrophils to be released from the bone marrow where they are produced.

"Ultimately, the goal is to modulate the acute inflammatory response," Doerschuk said. "We want to make it more efficient when the response is helpful to the patient and to dampen it when it's detrimental, as in ARDS."

One clinical application of Doerschuk's goal is treatment of patients with life-threatening diseases such as cancer whose immune systems have been weakened by chemotherapy. Her research may also have implications for the treatment of infections induced by antibiotic-resistant organisms.

To this end, Doerschuk's research examines how mediators induced by bacteria cause restructuring of the neutrophil cytoskeleton and how this restructuring alters the mechanical properties of neutrophils. Changes in these properties are critical for these cells to recognize the infection. When neutrophils become stiff, they cannot deform and flow through the narrow lung capillaries, so they stop and accumulate at the infected site.

Once the neutrophils have recognized and stopped at the site of infection, Doerschuk's studies examine the adhesion molecules that they use to adhere to the capillary wall and crawl into the tissue. Her work examines the signaling pathways that are induced in both neutrophils and endothelial cells that line the capillaries of the lungs and how these signaling pathways result in migration of neutrophils into the tissue toward the infection or injury. These studies also identify novel molecules that regulate the inflammatory process and determine how they work using functional genomic and proteomic approaches.

Doerschuk is working with Roger Marchant, professor of biomedical engineering in the CWRU School of Engineering, to study the changes in the mechanical properties of neutrophils as well as endothelial cells. Neutrophils cause endothelial cells to undergo structural changes that alter their mechanical properties and facilitate neutrophil migration toward bacteria. Studies in collaboration with Qin Wang, assistant professor of pediatrics, examine the molecular mechanisms of these changes.

"Our goal is to identify steps in these signaling pathways that are opportunities for targeted therapeutic modulation of the inflammatory response," Doerschuk said. Doerschuk's collaboration with Marchant's lab is something she particularly enjoys.

"The greatest things about being a scientist are the excitement that comes from being at the forefront of knowledge about an interesting question, the wonderful interactions with colleagues like Roger, Qin and others here and at many other institutions and the opportunity to work with students and to see them develop as independent thinkers," she said. "The Department of Pediatrics provides a terrific environment for translational research."