Research: Tackling the hard questions


Emory researchers made important advances last year in tackling the hard questions, whether in neuroscience, cancer, or vaccines for flu and HIV. These scientists received more than $380 million in sponsored research, including awards received by medical faculty at Yerkes National Primate Research Center and the Atlanta VA Medical Center. Thanks to their work, the Association of University Technology Managers ranked Emory 16th among universities in revenue received from commercializing research discoveries.

 

In this section

Advances in neuroscience

Understanding the immune system

Inroads against cancer

Heart and vascular research

New resources for research

Advances in neuroscience 

Traumatic brain injury
If results from a phase III clinical trial of the hormone progesterone confirm the positive findings of a pilot study conducted at Emory, where the treatment was pioneered, clinicians will have the first effective medication ever identified for traumatic brain injury (TBI). It’s badly needed. TBI leads annually to 50,000 deaths and 80,000 new cases of long-term disability in the United States and has become the “signature wound” of U.S. soldiers serving in Iraq and Afghanistan. 

Neuroscientist Don Stein discovered the neuro-protective properties of progesterone more than 25 years ago and persevered with his research, even when many in his field thought he was off track. ER specialist David Wright partnered with Stein in a small NIH trial, conducted at Emory-affiliated Grady Memorial Hospital. The safety findings and stunning clinical results led the NIH to fund the large phase III clinical trial beginning this fall. Wright is lead investigator of the $14.5 million study, conducted at 17 medical centers in 15 states that will enroll 1,140 patients. If all milestones are met during the first three years, the trial can be extended for three more years with an additional$14 million.

Autism, one gene at a time—As the only Simons Foundation Autism Research Initiative program in the Southeast, a team from Emory and the Marcus Autism Center, a subsidiary of Children’s Healthcare of Atlanta, is responsible for recruiting 150 families with only one child with autism spectrum disorder (ASD). It’s part of a multi-center effort to collect clinical assessment and genotyping of up to 2,000 “simplex” families by the year 2010. The scientists also are involved with the “multiplex” database organized by the Autism Genetics Resource Exchange (AGRE), identifying families and performing cytogenetic and molecular studies that identify specific chromosomal etiology among AGRE families. Finding genes involved in ASD means enhanced understanding of underlying biological processes: the first step toward developing better diagnostic tests and potential new treatments.

Alzheimer’s—Yerkes/Emory researchers discovered a structural difference in the beta-amyloid protein produced by nonhuman primates, which never develop Alzheimer’s, and humans. When injected into the bloodstream, Pittsburgh compound B (PIB), traveled to the brain of both human and nonhuman primates, but it bound to beta-amyloid only in humans. The finding may help isolate what makes people susceptible to neurodegenerative diseases and suggest new drug targets. The researchers now are trying to create PIB binding sites in transgenic Alzheimer’s mouse models so they will more closely resemble Alzheimer’s as it occurs in humans. 

Understanding the immune system

Vaccine basics—Emory researchers recently received a $16 million NIH renewal grant to understand fundamental questions about how vaccines work. The new grant builds on previous work to analyze the entire human immune response to vaccines, ranging from innate response to development and maintenance of immune memory. 

Flu vaccines—Emory is conducting clinical trials of an H1N1 vaccine in its role as one of the NIH’s eight national vaccine and treatment evaluation units (VTEUs). Scientists at Emory’s NIH-sponsored Influenza Pathogenesis and Immunology Research Center are investigating ways to manufacture vaccines more efficiently, using virus-like particles (VLPsthat look like viruses but don’t replicate. Mice immunized with the particles were protected for months against an otherwise lethal H5N1 infection. In mice, the particles appear to deliver several times more potency than other types of vaccines, suggesting that they could offer more bang for the buck in a pandemic demand, especially one in which the poultry industry could be crippled, wiping out the ability to make vaccines in chicken eggs.

HIV/AIDS—A $13 million NIH grant led by Emory scientists focuses on the role of the “programmed death” (PD)-1 protein in HIV and other chronic viral infections. The grant comes as a result of a seed grant from Concerned Parents for AIDS Research that allowed Emory scientists and their collaborators to discover that PD-1 helps switch off the immune response in chronic infection, resulting in apparent “exhaustion” of the T-cell response. With the new NIH grant, the scientists plan to identify drugs to turn off PD-1, reactivate the immune response, and possibly clear HIV infection in humans, based on their previous work in primates. 

Inroads against cancer 

The Emory Winship Cancer Institute received long-awaited designation this year as an NCI cancer center, opening new doors for clinical trials and research funding and helping undergird research initiatives already under way.

Predicting effectiveness of chemo—Clinicians and engineers in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory have developed a method to measure leakiness of blood vessels to predict how well chemotherapy may work. After injecting a contrast agent into rats with six-day-old breast tumors and then measuring the uptake of the agent over three days of imaging, the scientists intravenously injected a standard chemo drug and demonstrated that the variability in uptake of the contrast agent by the tumors provided an accurate prognosis on how well the chemo worked to slow tumor growth. Researchers say this approach may help physicians personalize doses and predict effectiveness more accurately. 

Gene silencing—Colleagues at Emory and Georgia Tech also have developed a set of guidelines to predict which genes have an increased risk of silencing by DNA methylation. The researchers found that human breast and lung cancers have a common pattern of genes vulnerable to silencing, resulting in the inactivation of several tumor-suppressor genes that usually prevent cancer formation. Identifying which genes are at increased risk of DNA methylation silencing could provide good markers for diagnosis and risk assessment.

Better quantum dots—Clinical use of quantum dots, tiny luminescent particles made of semiconductors, has been limited by their size and possible cadmium toxicity. Scientists at Emory and Georgia Tech have exploited a property of semiconductors called lattice strain to create quantum dots made mostly of zinc and selenium. The new dots are smaller than previous ones (between 4 and 6 nm wide), making them more likely to be able to pass through the kidneys, meaning reduced toxicity.

Finding pancreatic cancer earlier—Emory researchers have created a diagnostic tool in which a molecule that binds specifically to pancreatic cells is joined to tiny nanoparticles of iron oxide. The iron makes the particles clearly visible under magnetic resonance imaging. The nanoparticles also discriminate tumor cells from regular cells irritated by chronic pancreatitis and could be used to detect tumor margins and metastases during surgery and monitor response to therapy. The researchers now are refining the technology for testing in patients. 

Heart and vascular research 

Increasing circulation after heart attack—In an Emory-led multi-center study, patients treated with their own bone marrow stem cells after heart attack had increased circulation within the heart. Investigators now are extending the study to determine if such treatment can reduce long-term complications after heart attack. The study was one of the first to use a preparation of bone marrow cells enriched for endothelial progenitor cells (EPCs), which are thought to replenish blood vessel lining. Patients receiving higher doses of cells had greater improvement in blood flow within the heart than patients treated with lower doses or receiving medication alone. Higher doses also appeared to provide some benefit in cardiac function.

Replenishing vessels in diabetes—Emory researchers also showed that EPCs could restore nerve function in mice with diabetic neuropathy. EPCs can divide into endothelial cells, forming a “patch” for damaged blood vessels. When the cells were injected near the sciatic nerves of the diabetic mice, the EPCs not only appeared to develop into endothelial cells but also restored signal speed and sensitivity to temperature in the nearby sciatic nerves. 

Pediatric research 

A consortium headed by Emory expanded its participation in the multi-center, multi-year National Children’s Study (NCS), designed to examine the impact of environmental and genetic factors on the health of children in the United States. A recent award of $28.5 million will allow Emory and its partners to also recruit study volunteers in rural Georgia and Tennessee. This follows a $25.5 million NCS grant the previous year to collect genetic, biological, and environmental samples from study volunteers in two metro Atlanta counties. 

New resources for research 

Genomics—The new Emory-Georgia Research Alliance Genomics Center is equipped with two “next generation” DNA sequencing instruments with the ability to read more than 1,000 megabases—almost a third of the entire human genome—in a single experiment. The center is one of 13 core facilities supported by Emory’s medical school to ensure availability of centralized expertise and resources in specialized areas. Scientists around the world have used DNA sequencing to characterize newly identified bacteria and viruses, track how HIV mutates in response to antiviral drugs, and find genetic differences between healthy tissue and tumor cells.

Bioinformatics—The health sciences-wide Center for Comprehensive Informatics was created a year ago, with recruitment of bioinformatics pioneer Joel Saltz as director and as chief medical information officer for Emory Healthcare. Saltz is leading initiatives to enhance Emory’s programs in neurosciences, predictive health, computational and life sciences, transplantation, global health, vaccines, inflammation, regenerative medicine, respiratory health, cardiovascular health, cancer, and clinical trials. He also leads development of Emory’s external partnerships in bioinformatics with Georgia Tech, Children’s Healthcare of Atlanta, Morehouse School of Medicine, the Atlanta VA Medical Center, the Georgia Research Alliance, and the Georgia Cancer Coalition. 

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