BRI Briefs
BWH Medical Staff News brings you BRI Briefs to share some of the latest research news coming out of the Biomedical Research Institute (BRI).
Coat Proteins in Endocytic Recycling
Victor W. Hsu, MD, of the Department of Medicine and Department of Rheumatology, Immunology and Allergy, and colleagues have advanced a molecular understanding of how a glucose transporter undergoes endocytic recycling by identifying a novel clathrin coat complex that acts at its early mechanistic steps. This process that occurs in fat and muscle cells is critical for glucose homeostasis, and a defect in this process contributes to diabetes mellitus type 2.
Their findings advance a basic understanding of endocytic recycling, because in contrast to all other intracellular transport pathways currently known, coat proteins have not been predicted to play a significant role. These findings appear in the July 30 Journal of Cell Biology.
Breast Density, Sex Hormone Levels Increase Breast Cancer Risk
Rulla Tamimi, ScD, and colleagues at Channing Laboratory found that breast density and estrogen and testosterone levels are strongly and independently associated with breast cancer risk in postmenopausal women. Additionally, the researchers were surprised to find that women with high breast density and high levels of sex hormones are at the greatest risk for developing breast cancer. These findings appear in the July 24 Journal of the National Cancer Institute.
Kesari Receives Brain Cancer Research Award
Neurologist Santosh Kesari, MD, PhD, received the 2006 Distinguished Scientist Award by the Sontag Foundation. Kesari is one of two award recipients who will receive $500,000 in funding over a three-year period. Currently, his research seeks to clarify the role of transcription factor OLIG2 in human glioblastoma stem cells with the aim of discovering a new target, or targets, for the treatment of this lethal brain cancer, which is notoriously resistant to standard treatments.
Depression and Anxiety in Chronic Sinusitis
Research has shown that nearly 30 percent of people who suffer from chronic disease experience major depression or generalized anxiety disorder, both of which often modify or amplify a patient’s reported symptoms and disease sufferings. Chronic sinusitis affects 20 million to 30 million people in the U.S. Neil Bhattacharyya, MD, and colleagues from the Pain Management Center found that high levels of anxiety and depression are common among patients who undergo evaluation for chronic sinusitis and this comorbidity is associated with increased symptoms, health-care utilization and occupational impairment. These findings appear in the July Annals of Otology, Rhinology & Laryngology.
Major Vault Protein and Immunity to Lung Infection
According to researchers, there is no other infection so closely associated with a genetic disorder than Pseudomonas aeruginosa is with cystic fibrosis (CF). Gerald B. Pier, PhD, and colleagues at BWH and HMS report in the July 6 Science that one biological explanation for why over 80 percent of CF patients develop this chronic lung infection.
Pier and colleagues observed a biological function for major vault protein (MVP), which, until this study, had no clear role aside from forming a defined structure known as vaults in the cytoplasm in epithelial cells. The researchers found MVP made a substantial contribution to the resistance of cells to P. aeruginosa infection by promoting ingestion and clearance of the bacteria from the lung. This response is not seen in CF patients as the absence of functional CF transmembrane conductance regulator prevents the rapid innate immune response to infection, resulting in the failure to clear P. aeruginosa.
International Team Focuses on Copy Number Variants in the Human Genome
Canadian, British and American scientists will use state-of-the-art, high-density microarrays and new computer algorithms to improve the detection of variants in the human genome that are implicated in various diseases. The new systems are the foundation of Phase 2 of the Genome Structural Variation Consortium, which was set up in 2004 to identify structurally variable regions in the human genome.
Charles Lee, PhD, from BWH and Harvard Medical School, leads the international consortium along with researchers from the Wellcome Trust Sanger Institute. Lee anticipates they will be able to obtain fine-scale information on the anatomy of individual CNVs. And ultimately, the data generated from the Phase 2 studies will be important for disease association studies, cancer biomarker studies and accurate interpretation of many genetic diagnostic tests.