Broad Institute of MIT and Harvard

Carbapenem-resistant Enterobacterales (CRE) bacteria counter antibiotics using multiple molecular mechanisms, including carbapenemase (CP) production and porin deficiencies. CRE can also exhibit the "inoculum effect," where bacterial samples show variable resistance levels depending on their density when tested, and which can result in misdiagnosis and improper antibiotic selection. Alexis Jaramillo Cartagena, PhD, D(ABMM), Kyra Taylor, Leslie Lopez, Roby Bhattacharyya, and colleagues found that CP-producing, but not porin-deficient, CRE exhibited an inoculum effect, releasing enough CP into their environment to protect both their bacterial neighbors and themselves, especially when exposed to lethal doses of antibiotics. This study, published in mBio, provides insight into carbapenem resistance and has future implications for patient care. 🔗: https://lnkd.in/edpSh8Vz #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Cancer treatment, heavy alcohol use, and pregnancy complications can all cause secondary cardiomyopathies, but it's been unclear whether genetic risk factors for a primary cardiomyopathy like dilated cardiomyopathy (DCM) can contribute to these other conditions. Using data from nearly 1.3 million Mass General Brigham Biobank, UK Biobank, FinnGen, and Million Veteran Program participants, a team led by Dimitri Maamari, Kiran Biddinger, Sean Joseph Jurgens, and Krishna Aragam found that people with one of these secondary cardiomyopathies often also had high DCM polygenic scores or carried DCM-associated gene variants. The findings, published in JAMA Cardiology, suggest that secondary and dilated cardiomyopathies share similar genetic roots, influenced by different environmental factors. 🔗: http://ja.ma/4pMpEIE #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

We recently set the record for the fastest DNA sequencing technique and analysis — under 4 hours. Now see the research that made it possible. The pre-release publication details our optimized workflow—from rapid sample processing through clinical interpretation—that enabled same-day genomic diagnosis for critically ill Boston Children's Hospital NICU patients. These results demonstrate the potential of ultra-rapid whole genome sequencing to bring same-day genomic insights closer to frontline care. Read the pre-release publication: https://bit.ly/4nPbLIl #WorldRecord #RapidWGS #CriticalCare #GenomicInnovation #BroadClinicalLabs #RocheSBX

Cell state and function are shaped by how cells regulate gene expression. Current spatial transcriptomics methods generally capture snapshots of the RNA life cycle, not how RNAs emerge and behave over time. A team including Jingyi ("Rena") Ren, 曾虎, Jiahao Huang, and Xiao Wang have introduced a combined protocol for studying single cells' and tissues' transcriptomes that integrates their lab's STARmap PLUS, RIBOmap, and TEMPOmap transcription- and translation-mapping technologies. This new protocol will enable researchers to study single-cell spatial and temporal dynamics of thousands of RNAs in heterogeneous cells and tissues. Read more in Nature Protocols. 🔗: https://lnkd.in/ePa9vPm7 #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Antimalarial drug resistance in Plasmodium falciparum is a large and growing public health problem. Selina Bopp (Harvard School of Public Health), Lọla Fagbami (Harvard School of Public Health), Amanda Lukens, Ralph Mazitschek, Dyann F. Wirth, and colleagues in the Metabolomics Program have found a molecular basis for a known resistance mechanism, called the adaptive proline response (APR), to proline-competitive prolyl-tRNA synthetase inhibitors. They used several -omic approaches to show that loss-of-function mutations in the P. falciparum apicomplexan amino acid transporter 2 (PfApiAT2) are the primary driver of the APR. The team says this opens up new avenues for antimalarial drug development. 🔗: https://lnkd.in/ej-KW-ai #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Researchers with the Broad-Bayer oncology research alliance have developed a new drug candidate, sevabertinib, that could help some lung cancer patients who have few therapeutic options today. Led by Franziska Siegel at Bayer | Pharmaceuticals, Matthew Meyerson, and Heidi Greulich, the team developed sevabertinib, currently under FDA Priority Review, to target tumors carrying mutations in the ERBB2 gene, which encodes the HER2 protein. They showed that sevabertinib inhibits tumor cell growth in various lung cancer models with alterations in HER2, and they shared clinical trial data on two patients whose tumors shrank after treatment. The drug candidate is currently under FDA Priority Review and, if approved, it could be a new treatment option for a type of lung cancer that has been historically difficult to treat. It could also be the first FDA-approved cancer drug based on genetic discoveries from Broad scientists, and the first new medicine from the Broad-Bayer research alliance. 🔗: https://lnkd.in/eS2Gm5XH #BroadInstitute #LungCancer #LungCancerResearch #Science #ScienceNews #Research #ScientificResearch

Immune checkpoint inhibitors are only modestly effective in head and neck squamous cell carcinoma (HNSCC), a leading cause of cancer deaths worldwide. Cong Fu, Ph.D., Ravindra Uppaluri (Dana-Farber Cancer Institute, Brigham and Women's Hospital), Robert Manguso, and collaborators conducted an in vivo CRISPR screen in an HNSCC mouse model and found several regulators of immune checkpoint blockade response, including ubiquitin C-terminal hydrolase 5 (UCHL5). Loss of this gene increased CD8+ T cell infiltration and reduced extracellular matrix (ECM) production, especially collagens, which have been associated with reduced immunotherapy responses. The team suggests targeting Uchl5 and modulating ECM production as potential therapeutic strategies for this cancer type. 🔗: https://lnkd.in/eu4N7qfn #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

The primary way of diagnosing mitral valve prolapse (MVP) is through transthoracic echocardiography, which requires time and expertise. Mostafa Al-Alusi, Mahnaz Maddah, Patrick Ellinor, and others in Machine Learning for Health (ML4H) and the Cardiovascular Disease Initiative developed a deep learning model, DROID-MVP (Dimensional Reconstruction of Imaging Data-Mitral Valve Prolapse), that classifies the condition from digital echocardiogram videos. They trained and validated DROID-MVP using more than a million videos from nearly 17,000 cardiology patients, demonstrating its ability to identify MVP from echocardiogram videos and predict clinical endpoints. Read more in JACC Cardiovascular Imaging. 🔗: https://lnkd.in/ejXgVAD2 #BroadInstitute #Science #ScienceNews #Research #ScientificResearch

Innovation to power translation and human impact is alive and well in the field of genomics. Today we announced that we achieved the Guinness World Records title for Fastest DNA sequencing technique(3hrs 59m from DNA to variants) using the new Roche SBX technology. The record is just for fun, but it does point to a potentially transformative application of genome sequencing - same day results in the critical care setting like a neonatal intensive care unit. To that end we were fortunate to collaborate with Boston Children’s Hospital to run a small research study in which we received samples from the NICU in the morning and returned our geneticist-interpreted research reports (of potentially important variants) that afternoon. This study was published today in the New England Journal of Medicine. Huge thanks to everyone at Broad Clinical Labs, Roche Sequencing Solutions, and Boston Children’s Hospital that worked on this exciting and rewarding  project over the last few months. We are excited to see where this can go next. Broad Clinical Labs Guinness World Records https://lnkd.in/eBFDDr6A

Broad Clinical Labs (BCL), in collaboration with Roche Sequencing USA and Boston Children's Hospital, has received official recognition by Guinness World Records for fastest DNA sequencing technique to date! The teams completed sequencing and analysis of the whole human genome in less than 4 hours, surpassing the previous benchmark of 5 hours and 2 minutes. This shows it is possible to create a timeframe in which a lab can receive a sample and return actionable results within a single day — a significant difference from current timeframes of two to five days or more. Learn more: https://lnkd.in/ei2W8QQr #BroadClinicalLabs #BroadInstitute #Genomics