Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School and a biomedical research facility located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United States and the oldest and largest hospital in New England with 950 beds. Massachusetts General Hospital conducts the largest hospital-based research program in the world, with an annual research budget of more than $750 million. It is currently ranked as the #2 hospital in the United States by U.S. News & World Report. Wikipedia.
President And Fellows Of Harvard College, The Broad Institute Inc. and Massachusetts General Hospital | Date: 2015-04-17
The present invention generally relates to microfluidic devices, including systems and methods for tagging droplets within such devices. In some aspects, microfluidic droplets are manipulated by exposing the droplets (or other discrete entities) to a variety of different conditions. By incorporating into the droplets a plurality of nucleic acid tags, and optionally ligating then nucleic acids together, the conditions that a droplet was exposed to may be encoded by the nucleic acid tags. Thus, even if droplets exposed to different conditions are mixed together, the conditions that each droplet encountered may still be determined, for example, by sequencing the nucleic acids.
Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center and Massachusetts General Hospital | Date: 2015-12-11
Provided herein are methods for treating cancer that is resistant to treatment with an anti-ErbB therapeutic agent and which is associated with an activating MET gene mutation or a MET gene amplification. The methods involve administering to a subject a combination of an anti-ErbB therapeutic and an anti-MET therapeutic. Also provided are methods for reducing ErbB mediated signaling or PI3 kinase mediated signaling in a cancer cell.
The Broad Institute Inc., Massachusetts General Hospital and NanoString Technologies | Date: 2016-10-14
The present disclosure relates to method of distinguishing between two or more species of one or more organisms in a sample, by contacting a biological sample comprising ribosomal ribonucleic acid (rRNA) with a set of antisense probes, wherein the set of probes contains at least one detectable probe that is specific for a target rRNA sequence of each species to be tested, and wherein the individual probes specific for each species comprises less than about 85% sequence identity; and, detecting hybridization between one or more of the probes and the rRNA, thereby distinguishing between two or more species in a sample.
Massachusetts General Hospital | Date: 2017-03-22
Embodiments of the invention provide knee prostheses (100) which more faithfully and closely replicate the function, anatomy and physiology of the normal human knee yielding a number of advantages. Among other things, such prostheses can provide an increased range of motion and function more normally particularly in extension, deep flexion and during normal gait. Knee prostheses according to various aspects of the invention recognize that during movement of the knee, particularly during flexion, the kinematics of the bones of the knee are a result of achieving equilibrium of the forces that cause motion of the knee. In addition, the shape of the articular surfaces acting in combination with forces imposed by various muscles, ligaments and tendons, determines the direction of the large contact forces.
Siemens AG and Massachusetts General Hospital | Date: 2017-01-18
A magnetic resonance (MR) method and system are provided for generating real-time prospective motion-corrected images using fast navigators. The real-time motion correction is achieved by using a 2D EPI navigator that is obtained using a simultaneous multi-slice blipped-CAIPI technique. The navigator parameters such as field of view, voxel size, and matrix size can be selected to facilitate fast acquisition while providing information sufficient to detect rotational motions on the order of several degrees or more and translational motions on the order of several millimeters or more. The total time interval for obtaining and reconstructing navigator data, registering the navigator image, and providing feedback to correct for detected motion, can be on the order of about 100 ms or less. This prospective motion correction can be used with a wide range of MR imaging techniques where the pulse sequences do not have significant intervals of dead time.
Scadden D.T.,Massachusetts General Hospital |
Scadden D.T.,Harvard Stem Cell Institute
Cell | Year: 2014
No metazoan cell survives on its own, absent the signals and support of its milieu. For multicellular life with specialized tissues to persist, organization is everything and so defining the association of position with cell state is critical to understanding how tissues function, maintain, and repair. This review focuses specifically on place for progenitor and stem cells. Especially emphasized are hematopoietic cells that balance free movement and stable position and where concepts of regulatory interrelationships have been shown with some precision. It reviews classical and emerging concepts of the niche, particularly considering how niche functions may participate in neoplastic disease. © 2014 Elsevier Inc.
Smoller J.W.,Massachusetts General Hospital
The Lancet | Year: 2013
Background Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specifi c variants underlying genetic eff ects shared between the fi ve disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention defi cit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. Methods We analysed genome-wide single-nucleotide polymorphism (SNP) data for the fi ve disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic eff ects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fi tting model of relations between genotype and phenotype. We examined cross-disorder eff ects of genome-wide signifi cant loci previously identifi ed for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such eff ects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the fi ve disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. Findings SNPs at four loci surpassed the cutoff for genome-wide signifi cance (p< 5×10-8) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported eff ects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specifi city. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all fi ve disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. Interpretation Our fi ndings show that specifi c SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic eff ects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.
Joung J.K.,Massachusetts General Hospital |
Sander J.D.,Massachusetts General Hospital
Nature Reviews Molecular Cell Biology | Year: 2013
Engineered nucleases enable the targeted alteration of nearly any gene in a wide range of cell types and organisms. The newly-developed transcription activator-like effector nucleases (TALENs) comprise a nonspecific DNA-cleaving nuclease fused to a DNA-binding domain that can be easily engineered so that TALENs can target essentially any sequence. The capability to quickly and efficiently alter genes using TALENs promises to have profound impacts on biological research and to yield potential therapeutic strategies for genetic diseases. © 2012 Macmillan Publishers Limited. All rights reserved.
Chen J.X.,Massachusetts General Hospital
Circulation research | Year: 2012
Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown. To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). We induced GMT overexpression in murine tail tip fibroblasts (TTFs) and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying different cardiomyocyte lineage reporters. We found that the induction of GMT overexpression in TTFs and CFs is inefficient at inducing molecular and electrophysiological phenotypes of mature cardiomyocytes. In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes. Significant challenges remain in our ability to convert fibroblasts into cardiomyocyte-like cells and a greater understanding of cardiovascular epigenetics is needed to increase the translational potential of this strategy.
Pober B.R.,Massachusetts General Hospital
New England Journal of Medicine | Year: 2010
Williams-Beuren syndrome (also known as Williams' syndrome; Online Mendelian Inheritance in Man [OMIM] number, 194050), a multi-system disorder, is caused by deletion of the Williams-Beuren syndrome chromosome region, spanning 1.5 million to 1.8 million base pairs and containing 26 to 28 genes. Exactly how gene loss leads to the characteristic phenotype of Williams-Beuren syndrome is unknown, but hypoexpression of gene products is likely to be involved. Estimated to occur in approximately 1 in 10,000 persons,1 Williams-Beuren syndrome is a microdeletion disorder, or contiguousgenedeletion disorder, that can serve as a model for the study of genotype-phenotype correlations and potentially reveal genes contributing to diabetes, hypertension, and anxiety. The first cases of Williams-Beuren syndrome were described as two seemingly unrelated disorders. One presentation was characterized by hypercalcemia plus persistent growth failure, characteristic facial appearance, "mental retardation," heart murmur, and hypertension,2,3 while the other was characterized by supravalvular aortic stenosis (narrowing of the ascending aorta above the aortic valve, involving the sinotubular junction) plus a distinctive facial appearance, "mental retardation," "friendly" personality, and growth retardation.4,5 Subsequent description of a patient with features common to both phenotypes indicated that these were variations of the same disorder,6 now referred to as Williams-Beuren syndrome. Copyright © 2010 Massachusetts Medical Society.