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NIH stimulus awards to Medical School top $47 million

The National Institutes of Health have granted 182 stimulus-package awards totaling nearly $47.5 million to researchers at the Medical School as of Nov. 1.

The grants will enable U-M scientists and physicians to continue or begin projects that explore innovative approaches to such important health issues as cancer treatment and prevention, the impact of endocrine disruptor chemicals on fetal development, kidney disease genetics, stress as a factor in childhood obesity and dozens of other areas on the frontiers of medical research.

The NIH awards, given through a competitive process, are part of the $787 billion federal economic stimulus package known as the American Recovery and Reinvestment Act or ARRA, approved in February.

"Our success in obtaining these awards is a measure of the broad array of talents and ideas our researchers have been able to present to NIH, and ARRA funds have provided NIH a much-needed opportunity to more adequately fund significant medical research," says Dr. James Woolliscroft, dean of the Medical School. "We are pleased to be able to bring significant funding to Michigan to help build the foundation for long-term economic growth."

Within the overall total, UMHS has received just over $26 million in new and renewal awards and nearly $21.5 million in supplementary grants. Many of the new and renewal awards are for worthy projects that NIH had previously reviewed but was unable to fund until ARRA funds became available. Others are awards from two new NIH grant categories that tap ARRA funds: Grand Opportunity and Challenge grants.

Grand Opportunity Grant

A Medical School team led by Dr. Fernando Martinez, has been awarded a Grand Opportunity Grant of just over $4.2 million for the first year and an additional nearly $3.7 million for the second year to study the molecular basis of the lung condition called rapidly progressive idiopathic pulmonary fibrosis. Martinez, professor of internal medicine, is associate chief for clinical research of the Division of Pulmonary and Critical Care Medicine, medical director of pulmonary diagnostics and co-medical director of lung transplantation. Dr. Kevin Flaherty, assistant professor of internal medicine, and Dr. Galen Toews, professor of internal medicine, also are principal investigators.

Idiopathic pulmonary fibrosis — a progressive, fatal disease that affects 100,000 Americans — is very difficult for physicians to accurately diagnose and treat using the limited available therapies, which include lung transplantation. Prognosis also is a significant challenge: although the disease usually causes fatal decline in lung function, its progression varies in individual patients.

Martinez and his team are setting up a new network of 10 clinical centers nationwide to procure biologic samples from 135 patients with suspected IPF and follow 100 patients for at least 45 weeks. The scientists will correlate and integrate biologically plausible molecular markers of disease activity from the same patient with measures of how their disease progresses over time.

"We need to get a much better understanding of the biology and progressive nature of this horrible disease," Martinez says. "Early diagnosis and accurate prognostication of idiopathic pulmonary fibrosis are key to providing the appropriate treatment. The multiple specimens collected from the patients will be invaluable to determine early indicators of progressive disease and to identify new targets for future therapy. We suspect that these data will provide a realistic approach to a personalized approach to patients with IPF."

According to Martinez, each of the centers involved will have the opportunity to retain and hire a group of employees for the study.

NIH Challenge Grants

Also among the Medical School's new stimulus awards are 15 NIH Challenge Grants totaling more than $7 million. NIH received more than 20,000 applications for Challenge Grants nationwide.

Among those receiving challenge grants is a team led by Dr. John LiPuma, professor and associate chair for research in pediatrics.

With a $1 million, two-year award from the National Heart, Lung and Blood Institute, the team will study the role of lung microbiota in cystic fibrosis. Sharing in the principal investigator role are Dr. Vincent Young, assistant professor of internal medicine and microbiology and immunology; Jun Li, assistant professor of human genetics; and co-investigator Jim Cavalcoli, director of the CCDU bioinformatics core at the Center for Computational Medicine and Biology.

"We will characterize the microbial community in the lungs of persons with cystic fibrosis and determine how changes in this community correlate with periods of relative health and illness," LiPuma says.

"This work will be critical to developing new strategies to better treat infections of the airways, which is the leading cause of premature death for persons with cystic fibrosis."

The scientists will benefit from a large existing repository of sputum samples LiPuma has obtained from several hundred cystic fibrosis patients during the past decade. The award made it possible to move this key interdisciplinary project forward, LiPuma says, providing funds to hire two postdoctoral fellows and retain a technician.

Dr. Sophie Paczesny, assistant professor in pediatric hematology-oncology, will lead a project to discover biomarkers that will help make informed decisions possible about transplants of bone marrow and other hematopoietic cells and the associated risk of developing graft vs. host disease. Her $1 million, two-year Challenge Grant award is from the National Heart, Lung and Blood Institute. Co-investigators are Dr. James Ferrara, blood and marrow transplantation program director; statistician Tom Braun; and Samir Hanash, biomarker director at the Fred Hutchinson Cancer Research Center.

Graft vs. host disease is a major complication for many patients who receive allogeneic hematopoietic cell transplants (HCT), often commonly called bone marrow transplants — an important therapy for leukemias, lymphomas and multiple myeloma. About 20,000 people receive such transplants yearly.

"Currently no laboratory tests exist to predict the risk of developing graft vs. host disease, responsiveness to treatment or patient survival," Paczesny says.

She and her team hope to identify biomarkers that correlate with clinical outcomes following allogeneic HCT, including the prediction of patient risk of GVHD development, prediction of responsiveness to therapy and prediction of the risk of transplant-related mortality and long term survival.

"If a biomarker panel that can predict responsiveness to therapy is validated, it could ultimately guide the intensity and duration of GVHD treatment and help minimize the toxicities of chronic steroid administration," Paczesny says.

Paczesny's Challenge Grant will result in two new full-time jobs at the Medical School.

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