Broad Institute

About: Broad Institute is a nonprofit organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 6584 authors who have published 11618 publications receiving 1522743 citations. The organization is also known as: Eli and Edythe L. Broad Institute of MIT and Harvard.

Dynamic profiling of the protein life cycle in response to pathogens

Abstract: Protein expression is regulated by the production and degradation of messenger RNAs (mRNAs) and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics so as to build a quantitative genomic model of the differential regulation of gene expression in lipopolysaccharide-stimulated mouse dendritic cells. Changes in mRNA abundance play a dominant role in determining most dynamic fold changes in protein levels. Conversely, the preexisting proteome of proteins performing basic cellular functions is remodeled primarily through changes in protein production or degradation, accounting for more than half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction for newly activated cellular functions and by protein life-cycle changes for remodeling of preexisting functions.

The genomic landscape of pediatric Ewing sarcoma

Abstract: Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions of EWS and ETS family transcription factors, representing a paradigm for studying cancers driven by transcription factor rearrangements. In this study, we describe the somatic landscape of pediatric Ewing sarcoma. These tumors are among the most genetically normal cancers characterized to date, with only EWS – ETS rearrangements identified in the majority of tumors. STAG2 loss, however, is present in more than 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely nongenetic mechanisms; and is associated with disease dissemination. Perhaps the most striking finding is the paucity of mutations in immediately targetable signal transduction pathways, highlighting the need for new therapeutic approaches to target EWS – ETS fusions in this disease. Significance: We performed next-generation sequencing of Ewing sarcoma, a pediatric cancer involving bone, characterized by expression of EWS – ETS fusions. We found remarkably few mutations. However, we discovered that loss of STAG2 expression occurs in 15% of tumors and is associated with metastatic disease, suggesting a potential genetic vulnerability in Ewing sarcoma. Cancer Discov; 4(11); 1326–41. ©2014 AACR . This article is highlighted in the In This Issue feature, [p. 1243][1] [1]: /lookup/volpage/4/1243?iss=11

Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection - United Kingdom and United States, March-August 2020.

Abstract: During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections, interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition.

The road to restoring neural circuits for the treatment of Alzheimer's disease

Abstract: Alzheimer's disease is a progressive loss of memory and cognition, for which there is no cure. Although genetic studies initially suggested a primary role for amyloid-in Alzheimer's disease, treatment strategies targeted at reducing amyloid-have failed to reverse cognitive symptoms. These clinical findings suggest that cognitive decline is the result of a complex pathophysiology and that targeting amyloid-alone may not be sufficient to treat Alzheimer's disease. Instead, a broad outlook on neural-circuit-damaging processes may yield insights into new therapeutic strategies for curing memory loss in the disease.