The Stimulus Hits Home

An extraordinary effort by medical school faculty results in $98 million in new funding under the American Recovery and Reinvestment Act and exciting new directions in research at Yale.

The federal government’s stimulus program—the American Recovery and Reinvestment Act (ARRA), signed into law last February—has had a major impact on American universities and medical schools, including ours. Our faculty and staff did a tremendous job in submitting more than 775 applications under ARRA during the spring and early summer, and as a result, the School of Medicine has been awarded close to $98 million in new funding for research during the next two fiscal years. In addition to the 200 awards already approved, another 41 proposals totaling $60 million for construction projects and high-end instrumentation are still under review.

The act signed by President Obama on February 17 included $10.4 billion to be administered by the National Institutes of Health. This was an inspired choice by Congress; not only will it create and preserve jobs but it will also improve science and medical care very significantly in the future. The infusion of so many research dollars during this two-year period will, without a doubt, dramatically accelerate critical projects in many fields.

At Yale, this is perhaps most apparent in genomics, especially neurogenomics, which under ARRA is receiving several of the largest grants made to the university. The timing could not have been better, since the university had already made the decision to invest significantly in the technology necessary to conduct large-scale studies built around DNA sequencing. Thanks to a generous allocation from the Provost, the new Yale Center for Genome Analysis will be established on the West Campus by the end of this month, under the direction of Richard Lifton and Shrikant Mane. Its 12 Illumina sequencing machines vastly increase our capacity to do high-throughput analysis of DNA samples. This capability is available to researchers throughout the university, across many departments and disciplines. Of the six Grand Opportunity grants received by Yale under ARRA, five are dependent on the resources of this core, which in effect made it possible for Yale to receive these major awards totaling $21 million.

For example, David Hafler will lead a new study of genetic risk factors for multiple sclerosis (MS) using the largest available collection of samples from MS patients. To date, genome-wide association studies of MS have focused on relatively common genetic variants that confer risk for the disease, but leveraging the additional high-throughput power of the Illumina platform, Dr. Hafler will probe the role of rare variants in the disease. Murat Günel will sequence the complete protein-coding regions in 250 families to discover recessive genes underlying structural brain disorders, which have been implicated in autism, epilepsy, and mental retardation.

In a third neurogenomic study, Nenad Sestan, with additional support from the Allen Institute for Brain Science, will compile an unprecedented, comprehensive atlas of gene regulation and expression in a number of human brain regions as the brain develops, from its embryonic stages to adolescence and adulthood. Matthew State is taking a close look at two molecules—CNTNAP2 and piccolo—to find rare variants that may help explain these genes’ role in autism spectrum disorders. Finally, Joel Gelernter will use both Affymetrix and Illumina microarrays in a genome-wide association study of cocaine dependence, to be followed by an analysis of genetic copy-number variations on a subset of cocaine-dependent subjects and controls.

Cindy Crusto will lead a sixth Grand Opportunity grant examining the multiple social determinants of the health of young children.

In addition to the Grand Opportunity grants, which are intended to support high-impact, large-scale projects that accelerate critical breakthroughs, the medical school received two large training grants and 13 Challenge grants. These awards address a number of the 15 “challenge areas” identified by the NIH that include stem cells, translational science, clinical research, regenerative medicine, biomarkers, and information technology, among others. These projects focus on specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds to quickly advance the area in significant ways. Specific disease areas with research benefiting from these funds include cardiovascular medicine; cancer; diabetes; infectious disease; mental illness and brain disorders; substance abuse; digestive, kidney, and urological diseases; asthma and emphysema; pediatrics; ophthalmology; and obstetrics and gynecology.

The sharp increase in funding under ARRA presents a few challenges. The ideal scenario for researchers is one that provides steady, predictable increases in the NIH budget that keep pace with inflation and allow scientists to seize on new opportunities as they arise. In the case of ARRA, we are required to spend these funds over a 20-month timeframe. Although it is possible that this period will be extended, the ARRA program will not be renewed. Funded grants will have to receive new support from sources after the ARRA funds are expended, or else those projects will end. We must anticipate this moment and be prepared to redouble our efforts. That will mean aggressively submitting grants and encouraging Congress to support predictable funding in future years.

For now it is important to recognize the phenomenal success by our faculty in the current environment. The medical school’s impressive 25 percent success rate in ARRA applications is a testament to the very high caliber of science conducted at Yale and the phenomenal energy of our investigators and their research and administrative teams.

Photos by Harold Shapiro (top) and Terry Dagradi (bottom)