Five New Members Selected to Serve on the NIH Advisory Committee on Research on Women's Health
The National Institutes of Health (NIH) recently announced the appointment of five new members to the Advisory Committee on Research on Women's Health, which advises the director of the Office of Research on Women's Health on research avenues to be pursued by national research institutes in areas pertaining to women's health. The members of the committee number up to 18 and are appointed by the NIH director. The new members are Constance Howes, JD, Nancy J. Norton, Eugene P. Orringer, MD, Susan P. Sloan, MD, and Barbara W.K. Yee, PhD. Constance Howes, JD, currently serves as president and chief executive officer of Women and Infants' Hospital in Rhode Island. She has served as general counsel of care for the New England Hospital system, as well as general counsel to businesses, with a focus on general business and corporate law, administrative law, and hospital law. Nancy J. Norton is the founder and president of the International Foundation for Functional Gastrointestinal Disorders and chairperson of the Digestive Disease National Coalition. Eugene P. Orringer, MD, is a physician who specializes in hematology and oncology and executive associate dean for faculty affairs and faculty development in the School of Medicine at the University of North Carolina at Chapel Hill. Dr. Orringer is a highly respected clinical researcher and has served as a principal investigator in the Building Interdisciplinary Research Careers in Women's Health program. Susan P. Sloan, MD, is associate professor of medicine and associate residency program director of internal medicine at the James H. Quillen College of Medicine at East Tennessee State University. She has also served as secretary of the Association of American Indian Physicians and as president and committee member of the Association of Native American Medical Students. Barbara W.K. Yee, PhD, is professor and chair of family and consumer sciences at the University of Hawaii at Manoa. She is a member of the PHS Expert Panel of Minority Women's Health and a fellow of the American Psychological Association and Gerontological Society of America.
National Center for Research Resources to Provide $24 Million to University of California, Irvine
The National Center for Research Resources (NCRR) has announced that it will provide $24.29 million over 5 years to the University of California, Irvine (UCI) in support of the Biomedical Informatics Research Network (BIRN). The BIRN is a consortium that includes 28 universities and 37 research groups. It is designed to develop and share tools, software applications, techniques, data, and expertise. Although it is anticipated that this NCCR-sponsored initiative will eventually be applicable to many other disciplines, the BIRN is initially focusing on research involving neuroimaging. Function BIRN, the part of the BIRN project that UCI will lead, involves the collaboration of researchers at 14 institutions, with the goal of developing and testing interdisciplinary techniques for integrating efforts in functional magnetic resonance imaging (fMRI) across multiple sites. The recent NCCR award will allow the Function BIRN team to better calibrate imaging equipment between sites, formulate protocols for cognitive assessment, and create techniques for analysis of subsequent data. A trial endeavor will interpret fMRI results from more than 200 subjects scanned at sites across the nation. Assistant Director of NCRR's Division of Clinical Research Elaine Collier, MD, says that the initiative offers a new method for collaboration of researchers at different locations. Dr. Collier added that Function BIRN will allow for more rapid scientific discoveries owing to the scientists' ability to take on complex questions that they were previously unable to address. In the initial stage of Function BIRN, the researchers focused on the development of a shared database and agreed on imaging methods for the numerous locations. Five research participants were scanned at nine sites around the country using a standard protocol. Tools and methods were devised to reduce variability between sites and to correct distortions of acquired image. Additional methods were devised to permit the manipulation of data for large and diverse neuroimaging research projects. The resulting open-source data and tools are available at <www.nbirn.net/Resources/Downloads/>. Professor of Psychiatry, Robert R. Sprague Director of Brain Imaging at UCI, and Director of Function BIRN Steven G. Potkin, MD, says that one of the most important accomplishments of Function BIRN is the creation of an environment of data sharing among researchers, which has considerably accelerated their progress. Collaborative studies are already under way with many other National Institutes of Health-supported organizations, including the NCRR-funded General Clinical Research Centers located throughout the nation. The overall BIRN study includes three components in addition to Function BIRN. The BIRN Coordinating Center is the principal software development and computational center; Morphometry BIRN is charged with investigating correlations between structural differences in the brain and symptoms of neuropsychiatric illnesses; and Mouse BIRN is focused on the study of animal models of diseases, including schizophrenia, brain tumors, and Parkinson's disease. The NCRR anticipates the expansion of the BIRN to support other types of major, collaborative investigations. Detailed information about the BIRN can be found at: <www.ncrr.nih.gov/biotech/btbirn.asp>.
NIH Scientists Discover Gene that Affects Antidepressant Response
Scientists at the National Institutes of Health (NIH) have discovered that the response of depressed patients to the effects of antidepressants is dependent, at least in part, by alterations in the serotonin 2A receptor. The presence of two copies of a specific version of the serotonin 2A receptor gene increased the likelihood of a favorable response to an antidepressant by as much as 18% compared with individuals possessing two copies of the other, more common serotonin 2A receptor genotype. The researchers suggested that these new findings may contribute to the discrepancy between the success of antidepressants in black patients and white patients because the less common version was over six times more prevalent in white patients. Also, these findings provide further evidence that this serotonin receptor plays a crucial role in the mechanism of antidepressant action. National Institute of Mental Health (NIMH) researchers Francis J. McMahon, MD, Silvia Buervenich, PhD, and Husseini Manji, MD, authored the study, which will appear in the May 2006 issue of the American Journal of Human Genetics. NIH Director Elias A. Zerhouni, MD, says that this study represents advancements toward the day when it will be possible to offer personalized treatments that are “optimally effective for individual patients.” In the first stage of the NIMH-funded trial, called the Sequence Treatment Alternatives for Depression (STAR*D), about 47% of the 2,876 participants showed some improvement with the serotonin selective reuptake inhibitor citalopram (Celexa). The scientists then sought to examine genetic factors that could explain the difference in the effectiveness of the drug among the patients. They examined deoxyribonucleic acid (DNA) from 1,953 of the STAR*D patients, specifically seeking correlations between treatment responses and 768 known sites of variability in 68 candidate genes. The researchers identified the strongest correlation with responsiveness and sequence variants in the gene that codes for the serotonin 2A receptor. Serotonin 2A receptor is located on cells in the cortex and regulates circuits that have been associated with depression. Studies in animals have demonstrated that the number of serotonin 2A receptors in the cerebral cortex is decreased after a few weeks of treatment with antidepressants. This temporal similarity in the length of time needed for such drugs to work in humans suggests that the serotonin 2A receptors are key in the mechanism of action of these drugs. Each individual has two copies of the serotonin 2A receptor gene, one from each parent, but owing to an anomaly in the gene's chemical sequence, some people have an adenine (A) at the same point at which others have a guanine (G). The researchers found that 14% of the participants had AA, 43% had AG, and 43% had GG. Based on scores on a depression rating scale, approximately 80% of the patients with AA responded to the antidepressant, whereas about 62% of those with GG responded. This observed association between gene type and treatment response held true only for white patients, whereas black patients tended to fare less well in the trial overall. Dr. McMahon says that although the study does make a strong case for the crucial role of the serotonin 2A receptor in the mechanism of antidepressant action, it also illustrates the need to examine “psychosocial issues” and genetic factors in the assessment of the effectiveness of antidepressants in black patients. Other participants in the study were A. John Rush and Madhukar Trivedi, University of Texas Southwestern Medical Center; Gonzalo Laje, NIMH; Dennis Charney, Mount Sinai Hospital; Robert Lipsky, National Institute on Alcohol Abuse and Alcoholism; Alexander Wilson, Alexa Sorant, and George Papanicolaou, National Human Genome Research Institute; Maurizio Fava, Massachusetts General Hospital; and Stephen Wisniewski, University of Pittsburgh.
National Human Genome Research Institute Reveals Latest Round of Sequencing Targets
The National Human Genome Research Institute (NHGRI) has announced its newest sequencing targets, focusing on increasing knowledge that will help define how human genes function and how genomic differences between individuals influence the risk of disease. NHGRI Director Francis S. Collins, MD, says that these new sequencing targets represent another step toward expanding knowledge of the human genome “to build the most powerful toolbox possible for advancing human health.” Three plans to specify the targets were approved by the National Advisory Council for Human Genome Research, which advises the NHGRI on program priorities and goals. The highest priority plan is an initiative to identify structural variations in the human genome, which focuses on the characterization of the most prevalent kinds of structural variation in human deoxyribonucleic acid (DNA). This effort will build on findings resulting from the recently completed International HapMap Project, which compiled an extensive catalog of human genetic variation, or haplotypes. Using 48 human DNA samples donated from the HapMap Project, the NHGRI structural variation initiative will attempt to identify circumstances in which larger sections of DNA have been deleted, duplicated, or rearranged. New data suggest that these large-scale variations are much more frequent than previously believed, with any two humans thought to vary by several hundred insertions, deletions, and inversions. The second plan offered by the National Advisory Council for Human Genome Research will seek to increase knowledge of the evolution of the human genome through more extensive sequencing, high-density genome sequencing, of already sequenced genomes. This effort will provide additional detail to the existing draft sequences of several primate species and increase the density of sequence information in areas believed to represent regions of high biologic interest within those genomes. The primates selected for this effort are rhesus macacque (Macaca mulatta), marmoset (Callithrix jacchus), and orangutan (Pongo pygmaeus), although it is likely that the NHGRI will add other organisms to this list. The third plan involves the initial low-density, draft sequence coverage of eight new mammalian genomes. These eight new mammals will be selected from the following 10 species: dolphin (Tursiops truncates), elephant shrew (Elephantulus species), flying lemur (Dermoptera species), mouse lemur (Microcebus murinus), horse (Equus caballus), llama (Llama species), mole (Cryptomys species), pika (Ochotona species), a cousin of the rabbit, the kangaroo rat (Dipodomys species), and tarsier (Tarsier species). When completed, the newly sequenced genomes will bring the total of mammalian genomes sequenced at twofold coverage to 24. The NHGRI-supported Large-Scale Sequencing Research Network will perform the sequencing for the initiative. The Network is made up of five centers: Agencourt Bioscience Corp., Beverly, Massachusetts; Baylor College of Medicine, Houston, Texas; the Broad Institute of MIT and Harvard, Cambridge, Massachusetts; the J. Craig Venter Institute, Rockville, Maryland; and Washington University School of Medicine, St. Louis, Missouri. The NHGRI relies on input from the research community to make proposals on which genomes to sequence. In each instance, the proposals are designed to contribute to advances in one or more of three scientific focus areas: selection of areas in genetic research in which the application of high-throughput sequencing resources is likely to lead to insights permitting key medical advances, increased understanding of the human genome, and insight into the evolutionary biology of genomes. The proposals of the working groups are reviewed and refined by a coordinating committee, and the suggestions of the coordinating committee are then evaluated and approved by the National Advisory Council for Human Genome Research. The recommendations of the Advisory Council are then passed on to the NHGRI ship. A thorough list of organisms and the status of their sequencing can be found at <www.genome.gov/10002154>.
Howard Hughes Medical Institute Awards $10 Million to Support Translational Research
The Howard Hughes Medical Institute (HHMI) has awarded $10 million to Baylor College of Medicine and 12 other institutions in support of translational research. Baylor College of Medicine will receive $850,000 over 4 years to fund its interdisciplinary graduate program in translational biology and molecular medicine, which was started in 2005. The program is designed to provide graduate students with increased exposure to human health and disease, in addition to the basic biomedical sciences. These goals are to be effected through the use of dual clinician-PhD mentorship of students, the institution of new medically related courses, the creation and development of medical conferences, and participation in clinical rounds. HHMI President Thomas R. Cech says that the awards are part of an attempt by the HHMI to increase cooperation between medicine and science and to transform graduate education to increase the number of scientists who are conducting medically oriented research. Other institutions that received awards include Yale University, Rice University, Harvard University, Case Western Reserve University, the Massachusetts Institute of Technology, the University of Washington, the University of Pennsylvania, and Stanford University.
Florida Board of Governors Votes to Create Two New Medical Schools
The Florida Board of Governors recently voted to create two new medical schools at the University of Central Florida and Florida International University, with the two new schools requiring $400 to $500 million of taxpayer expenditure over the next 10 years. The Board also requested that lawmakers take additional actions to increase the number of physicians by funding additional medical residency programs in Florida and by expanding existing medical schools in Florida, such as Florida State University College of Medicine. Of the 2006 graduating class at Florida State University's College of Medicine, only 54% are remaining in Florida to complete their residencies, a good indicator as to where these graduates will practice. The measure to establish the new medical schools passed by a 15 to 1 vote, with the one dissenting vote coming from former Florida State University president Stanley Marshall. Marshall advocates the funding of additional residency programs as a favorable alternative to the creation of new medical schools to increase the number of physicians in Florida, saying that the alternative is cheaper and faster. A significant concern of the Board is that the Legislature not harm the state's existing medical schools, such as the University of Florida, University of South Florida, Florida State University, or the private University of Miami, which is partnering with Florida Atlantic University. The University of Central Florida and Florida International University have each collected tens of millions of dollars in private and local government contributions to provide for some of the initial costs of the schools.
New Center of Cancer Nanotechnology Excellence to Be Located at Stanford University School of Medicine
The National Cancer Institute (NCI) has announced that it will provide roughly $20 million over 5 years in support of a new Center of Cancer Nanotechnology Excellence at Stanford University School of Medicine. Professor of Radiology and Bioengineering and Director of the Molecular Imaging Program at Stanford Sanjiv Sam Gambhir, MD, will lead the Center and will work closely with Shan Wang, PhD, associate professor of materials science and electrical engineering. The goal of the NCI's Centers of Cancer Nanotechnology Excellence program is to integrate nanotechnology into cancer research, via the collaboration of cancer centers, medical institutions, schools of engineering and physical sciences, nonprofit organizations, and private corporations. Faculty from Stanford's schools of Humanities and Sciences, Engineering, and Medicine will team with groups from the University of California-Los Angeles, Cedars-Sinai Medical Center, Fred Hutchinson Cancer Research Center, University of Texas-Austin, General Electric Global Research, and Intel Corp. These groups will collaborate to formulate new methods to use nanotechnology to detect cancer and evaluate therapies. Dr. Gambhir remarked at the novelty of this approach to research, with a research team composed of groups representing disciplines including chemistry, materials science, cancer biology, immunology, clinical oncology, radiology, and molecular imaging. Dr. Gambhir, who has trained in physics, applied mathematics, cell and molecular biology, medicine, nuclear medicine, and molecular imaging, believes that the main obstacle in the first year of the program will be to get all of the diverse groups working together. The Stanford group will focus its efforts on either imaging disease (in vivo) or identifying what is going on within patients via the analysis of blood or tissue samples outside the body (ex vivo). Dr. Gambhir believes that the grant has much potential, owing to the fact that the program seeks to work on both the in vivo and ex vivo subdisciplines. Until now, Gambhir's work has concentrated on the in vivo side, developing novel methods of molecular imaging in small animals and patients. Dr. Gambhir's laboratory has already begun to investigate potential applications of technologies derived from nanotechnology research. They have made the most progress with quantum dots, or “qdots,” which are tiny crystals with pieces of proteins attached to their surfaces that enable them to latch on to cancer cells and produce multicolored signals. Such methodologies could play a role in the assessment of a patient's response to therapy for improving cancer diagnosis. The Center of Cancer Nanotechnology Excellence at Stanford is scheduled to receive $3.83 million in its first year. NCI will determine annually the amounts to be received in the remaining 4 years of the grant. Other researchers from Stanford who are involved in the project include Hongji Dai of the Department of Chemistry; Rob Tibshirani of the departments of Health Research and Policy and Statistics; Michael Kelly, Bob Sinclair, and Robert Wilson of the Department of Materials Science and Engineering; Dean Felsher and P. J. Utz of the Department of Medicine; Garry Nolan of the departments of Microbiology and Immunology and Molecular Pharmacology; Xiaoyuan Chen, Samira Guccione, David Paik, Sylvia Plevritis, Jianghong Rao, and Meike Schipper of the Department of Radiology; and Ed Myers, Yoshio Nishi, and Mary Tang of the Stanford Nanofabrication Facility.