New Gene Database Could Expand Asthma Research
Scientific researchers can now benefit from a new National Institutes of Health (NIH) resource that provides information on the link between genes and asthma health. The Web‐based database gives researchers free access to information on 2,332 people with asthma and 805 families whose DNA was tested for 1 million genetic variations. As well as genetic information, the database—an expansion of the NIH's SNP Health Association Resource (SHARe) project—includes clinical data gathered during asthma trials, such as lung function, allergy status, and respiratory symptoms.
The new Web‐based dataset, called the SHARe‐Asthma Resource Project (SHARP), is funded by the National Heart, Lung, and Blood Institute (NHLBI) and is meant to enable researchers to link participants’ genetic variations to their clinical and laboratory test results. This research could pave the way for future discoveries that associate genes, asthma health, and other airway diseases, according to the NHLBI.
SHARe has been in existence since 2007, when it began to give researchers access to a Web‐based database that included a wealth of information from multiple large population‐based studies, starting with the Framingham Heart Study. The expansion of the SHARe program to include the new asthma information was made possible by the collaboration of 3 asthma clinical research networks that will provide data, including the Childhood Asthma Management Program, the Childhood Asthma Research and Education Network, and the Asthma Clinical Research Network. For more than 10 years, these networks have been major sources of information about best practices in asthma care and have helped develop new knowledge for both patients and physicians.
“The clinical asthma networks have been the backbone of our translational research program at NHLBI for many years,” says NHLBI Division of Lung Disease Director James P. Kiley, PhD. “Creating this new resource not only provides new opportunities for our own network investigators to use this unique data but opens it up to the broader scientific community as well.”
SHARP data can be accessed through the database of Genotypes and Phenotypes (dbGaP), a Web‐based resource for archiving and distributing data from genome‐wide association studies, at http://view.ncbi.nlm.nih.gov/dbgap.
HHMI Establishes
Collaborative Research Awards
The Howard Hughes Medical Institute (HHMI) has always had the motto “people, not projects.” That motto has translated into funding individual investigators with top talent in their fields, rather than those that presented attractive research proposals. Yet, in an era of funding cutbacks for scientific research, administrators at HHMI have also felt the need to fund groundbreaking projects that might not be able to obtain funding from traditional sources, despite their daring approach to biomedical research.
To support scientists who need to pool time, expertise, and resources to produce the most forward‐thinking biomedical research, HHMI established the Collaborative Innovation Awards. At a cost of $40 million over 4 years, HHMI will fund 8 teams of scientists who will pursue collaborative, potentially transformative research projects. The awards represent a departure from HHMI's usual approach of funding individual scientists and instead provide financial backing for special projects that depend on the collaboration of a diverse team of scientists.
HHMI will fund 8 teams of scientists who will pursue collaborative, potentially transformative research projects.
“Many of these projects are those that even our investigators couldn't raise the money to do, because they are so risky and cutting‐edge,” says Philip Perlman, PhD, senior scientific officer at HHMI. The scientific problems that the HHMI scientists are attacking also need the expertise of diverse experts in several scientific fields to bring them to fruition, he added.
HHMI received 62 applications from its investigators for the awards, and the process of winnowing down the field was “very competitive,” Dr. Perlman says. After 4 years of funding, however, HHMI hopes that the projects will be established enough to receive financial support from other sources.
Funded projects include one headed by HHMI investigator Xiaowei Zhuang, PhD, professor of chemistry and chemical biology and physics at Harvard University in Boston, that will investigate new ways of using light microscopes. The researchers hope to thoroughly map a mammalian brain with the techniques they develop. Another HHMI investigator, Simon John, PhD, a neurobiology researcher at the Jackson Laboratory in Bar Harbor, Maine, is working to revolutionize treatment for glaucoma. He will collaborate with engineers at Purdue University in West Lafayette, Indiana, to design and fabricate implantable integrated circuits and antennas for wireless sensor networks. His goal is to eventually create a wireless sensor so tiny it can be implanted into the eye of a mouse to provide constant monitoring of intraocular pressure.
Institute Brings Together medical researchers and industry leaders
Funded by an $8.1 million grant from the Ewing Marion Kauffman Foundation, the University of Kansas (KU) aims to establish a unique life science think tank, the Institute for Advancing Medical Innovation. The institute will bring together biomedical researchers and drug development and medical device leaders. The object of the collaboration is to smooth the way from early stage translational research to drug development and approval and to bring research advances to the clinic, according to Lesa Mitchell, vice president of Advancing Innovation for the Kauffman Foundation. “The goal is to look at the linear model for developing drugs and devices through a new lens,” Mitchell says. The ultimate objective of the new institute will be to accelerate the number and quality of new drugs, medical devices, and drug‐medical device combinations that make it from the bench to the bedside, she adds.
To support the new institute, the KU Endowment Association will match the Kauffman Foundation's grant. “We felt that the University of Kansas had some unique and significant knowledge—in medicinal chemistry as well as pharmacology—and could draw on the expertise of pharmaceutical industry experts who had returned to the university environment,” Mitchell says.
The Kauffman grant includes seed funds for up to 24 proof‐of‐concept projects per year. Three drug projects, headquartered at the KU Institute for Pediatric Innovation, have already been identified. “The need in the pediatric market is great,” Mitchell says. “Most drugs are developed for adults, and 70% of today's medications are given to children off label.”
The Kauffman Foundation and KU Endowment grants will also help educate the next class of drug and medical device development specialists through workshops and courses on the drug commercialization process. “The Institute represents an unparalleled training opportunity for KU graduate and postdoctoral students,” says Dale Seuferling, president of the KU Endowment. “It's gratifying for us to help the university advance the frontiers of knowledge.”
Gastrointestinal Cancer Meeting Features Translational Research
New gastrointestinal cancer research was featured at the American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium in San Francisco. Here are some highlights.
Biomarkers May Predict Barrett's Esophagus Progression
Using a methylation biomarker‐based panel to predict neoplastic progression in Barrett's esophagus has the potential to improve the efficiency of surveillance endoscopy as well as the early detection of neoplasia, according to a study presented by Stephen Meltzer, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland. The investigators performed a multicenter, double‐blind validation study of 8 methylation biomarkers implicated in Barrett's esophagus and esophageal adenocarcinoma. The biomarkers of 145 patients who progressed from no or low‐grade dysplasia at baseline to high‐grade dysplasia or esophageal adenocarcinoma were compared with those of 50 patients who did not progress beyond low‐grade dysplasia.
The researchers found that the combination of age plus the 8 genetic biomarkers was predictive of progression to higher‐grade dysplasia and carcinoma. Such biomarker panels offer a costeffective alternative to periodic surveillance by endoscopy for patients with Barrett's esophagus, Dr. Meltzer says. “Using such a panel of biomarkers could have a profound effect on the efficacy and efficiency of surveillance in Barrett's esophagus.”
New Insights on Anti‐VEGF
While inhibitors of angiogenesis are beginning to show promise in cancer treatment, their clinical utility is only realized in combination with more traditional chemotherapy agents. A better understanding of how angiogenesis inhibitors influence the VEGF pathway could lead to more efficacious treatments, according to a presentation by David Cheresh, PhD, of the University of California, San Diego.
Dr. Cheresh described research showing that VEGF is a potent inhibitor of neovascularization because it has the capacity to disrupt pericyte and vascular smooth muscle cell function. On the molecular level, VEGF activates the assembly of a previously undescribed receptor complex that consists of PDGF‐R‐beta and VEGF‐R2. The research has also revealed that mice with a deletion of myeloid cell VEGF develop tumors with a more mature vasculature than their wildtype counterparts. “To our surprise, these tumors lacking VEGF grow at a faster rate yet are more sensitive to the effects of standard chemotherapy,” Dr. Cheresh says. Research suggests that anti‐VEGF drugs increase blood flow to tumors, helping the cancers grow but also enhancing the effects of chemotherapy, he concluded.
Novel Hepatocellular Cancer Therapies
“There are tremendous needs for effective systemic therapy [for advanced stage hepatocellular carcinoma (HCC)],” says Andrew Zhu, MD, PhD, of the Massachusetts General Hospital Cancer Center in Boston. “What we need is to understand the molecular pathways that lead to this cancer and identify key molecular targets.” The first step in this effort has been the development of the anti‐angiogenesis agent sorafenib, which shows an improved survival benefit in HCC as well as a favorable toxicity profile. Other medications that could be useful include anti‐angiogenesis drugs and those that target epidermal growth factor receptor (EGFR). However, while antiangiogenesis drugs such as bevacizumab have shown early promise in treating HCC, EGFR inhibitors have been less successful. Only erlotinib shows modest activity against the disease, Dr. Zhu notes. “What may be most attractive is to combine agents that target diff erent pathways with traditional chemotherapeutic drugs,” he says. For instance, data on the combination of bevacizumab and erlotinib show a 25% response rate and a progression‐free survival of 62.5% at 16 weeks.