Eric Boerwinkle receives $26 million federal stimulus grant to identify genetic factors influencing common diseases

Project seeks to identify genetic factors influencing common diseases

Eric Boerwinkle, Ph.D., a professor at The University of Texas Health Science Center at Houston, has received a $26 million federal stimulus grant to lead an effort to pinpoint genetic factors affecting the risk of heart, lung and blood diseases. Boerwinkle leads Human Genetics Centers at both The University of Texas School of Public Health and the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), which are part of the UT Health Science Center at Houston.

"This project, conducted by one of the most renowned teams in the world, will provide the most in-depth information to date on mapping the human genome. Gene findings for major chronic diseases such as heart disease and stroke have already revolutionized our approach to management and this will accelerate that discovery process," said Roberta B. Ness, M.D., M.P.H. , dean and M. David Low Chair in Public Health at the UT School of Public Health.

Boerwinkle and his Health Science Center colleagues have been awarded 47 federal stimulus grants totaling about $49 million. Forty-four of the grants are from the National Institutes of Health (NIH), two are from National Science Foundation and one is from the Health Resources and Services Administration. Some grants are for one year and others are for two.

The American Recovery and Reinvestment Act of 2009 (ARRA) provided $8.2 billion to the NIH to help stimulate the U.S. economy through the support and advancement of scientific research.

Peter Davies, M.D., Ph.D., executive vice president for research at the Health Science Center, said a recent survey of the economic impact of research grants from the NIH has shown that, in Texas, every dollar of NIH funding generates $2.49 of economic activity in the community that receives the award. "By this measure the recent NIH economic stimulus grants received by Health Science Center investigators will generate in excess of $100 million of economic activity in our community," he said.

Boerwinkle received a NIH Grand Opportunities (GO) Grant, as did Health Science Center faculty members Mauro Ferrari, Ph.D., and James Hixson, Ph.D. These grants address large, specific biomedical and biobehavioral research endeavors.

Health Science Center faculty members receiving another type of ARRA-supported award known as a NIH Challenge Grant are Elmer Bernstam, M.D., Kim Dunn, M.D., Ph.D., and Lenard Lichtenberger, Ph.D. John Spudich, Ph.D., and Oleg Sineshchekov, Ph.D., are co-principal investigators on a Challenge Grant. These grants are designed to spur new areas of research.

Boerwinkle and his partners in the study for the National Heart, Lung and Blood Institute will be comparing the genetic makeup of about 40,000 individuals in order to identify genetic variants affecting disease risk. This information could aid in disease detection and treatment selection.

Boerwinkle's team, which includes Baylor College of Medicine's Human Genome Sequencing Center, will be using a new research technique called resequencing to find differences in the DNA of healthy and ill individuals. Participants are members of five long-term population studies.

"The project will not only enhance our understanding of the genetic architecture of multiple conditions of public health importance, but it will also benefit the broad scientific community by making these sequence and clinical data available," Boerwinkle said. 'This study is the first example of using state-of-the-art laboratory and computational methods to analyze the complete DNA sequence of a large population-based sample of well-characterized individuals."

Ferrari's $3 million NIH GO Grant is for nanoparticle research. Ferrari is a co-principal investigator for the collaborative project. Ferrari is professor and chairman of the Department of NanoMedicine and Biomedical Engineering at The University of Texas Medical School at Houston.

"On the science side, the award recognizes the importance of understanding how cells process nanoparticles, which is an infant science at this time. Many important practical advances will come from the basic science discoveries our team will make, with applications ranging from better therapies for cancer to environmental sciences and policies," Ferrari said.

"The award is also the reaffirmation of the global leadership Houston has in the field of nanomedicine. The team that was recognized with this unique grant comprises investigators from the Health Science Center, The University of Texas M. D. Anderson Cancer Center, Rice University and Baylor College of Medicine," he added.

Hixson's $2.9 million NIH GO Grant is to study genes that cause susceptibility to gout. He is a professor in the Human Genetics Center in the Division of Epidemiology and Disease Control at the UT School of Public Health.

Hixson's project involves new technologies for medical resequencing to identify genetic variants that influence uric acid levels (major gout risk factor) and gout, a painful and potentially debilitating disease that is one of the most common forms of arthritis. In collaboration with investigators at the IMM and Johns Hopkins University, targeted genes will be resequenced in more than 1,000 subjects from the Atherosclerosis Risk in Communities Study cohort to pinpoint novel DNA variants that occur in gout patients. The identification of such variants will provide an improved understanding of molecular mechanisms that regulate uric acid levels, and eventually lead to novel drug targets to improve treatment of gout.

The NIH Challenge Grant selection process was highly competitive with NIH officials receiving about 20,000 applications and awarding about 750 projects, an NIH representative said.

Lichtenberger received a $990,000 NIH Challenge Grant to study non-steroidal anti-inflammatory drugs (NSAIDs) and their side effects. He is a professor in the Department of Integrative Biology and Pharmacology at the UT Medical School.

Lichtenberger has found that chemically associating a substance called phosphatidylcholine with NSAIDs like aspirin and ibuprofen may reduce gastrointestinal bleeding and ulcers associated with NSAID use.

Dunn received a $960,000 NIH Challenge Grant for a study titled "A Medical Home Pilot Evaluation: A Model for Comparative Effectiveness Research." Dunn is an assistant professor of health informatics at The University of Texas School of Health Information Sciences at Houston.

Bernstam received a $950,000 NIH Challenge Grant to make clinical data more accessible to medical researchers. He is an associate professor at both the UT School of Health Information Sciences at Houston and UT Medical School at Houston.

"Healthcare data, unlike clinical trial data, are not collected with a research question in mind. Thus, they may be poorly structured and contain protected health information or identifying phrases such as 'senator with lymphoma.' Our unifying hypothesis is that concept level approaches can be applied to Clinical Data Warehouses to bring meaning to vast amounts of healthcare data while protecting subject privacy," Bernstam said.

Spudich and Sineshchekov received a $900,000 NIH Challenge Grant to develop new tools for photocontrol of neural activity. Spudich is the Robert A. Welch Distinguished Chair in Chemistry and director of the Center for Membrane Biology in the Department of Biochemistry & Molecular Biology in the UT Medical School. Sineshchekov is a research associate professor in Spudich's laboratory.

The researchers' proposal follows from their discovery of visual pigment-like photosensor proteins mediating phototaxis (movement toward or away from light) in green algae in 2002. The algal light-sensors, called channelrhodopsins, are membrane-embedded light-gated ion channels that depolarize the algal membrane when photoactivated, controlling the motility of the cells.

"Channelrhodopsins are extremely useful in neuroscience research because when expressed in mammalian cells they can be used for non-invasive l light-activation of neurons, providing an incisive new approach to stimulate targeted neural pathways and map brain circuitry," Spudich said.