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  • Sleep_emoji

    Study helps solve mystery of how sleep protects against heart disease

    Researchers say they are closer to solving the mystery of how a good night’s sleep protects against heart disease. In studies using mice, they discovered a previously unknown mechanism between the brain, bone marrow, and blood vessels that appears to protect against the development of atherosclerosis, or hardening of the arteries—but only when sleep is healthy and sound. The discovery of this pathway underscores the importance of getting sufficient, quality sleep to maintain cardiovascular health and could provide new targets for fighting heart disease, the leading cause of death among women and men in the United States. In a study published in Nature, the Swirski Lab at the MGH Center of Systems Biology identified a mechanism by which a brain hormone controls production of inflammatory cells in the bone marrow in a way that helps protect the blood vessels from damage. This anti-inflammatory mechanism is regulated by sleep, and it breaks down when you frequently disrupt sleep or experience poor sleep quality.

  • Iel

    A metabolic checkpoint that contributes to cardiovascular disease

    The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways, how our bodies handle nutrients depends on strategically-positioned metabolic sensors that link a meal’s intrinsic nutritional value with intermediary metabolism. In a study published in Nature, the Swirski Lab at the MGH Center of Systems Biology identifies a subset of immune cells in the gut that modulates metabolism. The team shows that gut intraepithelial T leukocytes (IELs) modulate systemic metabolism. Mice lacking natural IELs are metabolically hyperactive and, when fed a high fat and sugar diet, resist obesity, hypercholesterolemia, hypertension, diabetes, and atherosclerosis. The phenomenon depends on the incretin GLP-1, which IELs normally control via IEL GLP-1 receptor expression. While its function may prove advantageous when food is scarce, overabundance of diets high in fat and sugar render this metabolic checkpoint inimical to health.

  • Anti_pd_1

    A Small Population of Immune Cells Is Key For Cancer Immunotherapy

    The anti-PD-1 immune checkpoint blocker can induce sustained clinical responses in some patients. This drug is used to release the “brakes” on T cells but how it functions in vivo remains incompletely understood. In a study published in Immunity, the Pittet lab at the MGH Center for Systems Biology uncovers that effective antitumor responses to anti-PD-1 therapy requires a subset of tumor-infiltrating dendritic cells, which produce interleukin 12 (IL-12) and apply “gas” to fuel the antitumor reaction. The findings may lead to new treatment strategies that benefit more patients. [Image: KA-POW! A dendritic cell (yellow) interacts with antitumor T cells (blue) to get rid of cancer.]

  • Scant

    Antibody-DNA conjugates bring patient biopsies to light

    Modern oncology relies on molecular assessments of tumor tissue to develop new therapeutic combinations and select optimal treatments for individual patients. Conventional approaches to cellular fluorescence imaging allow for visualization of just 3-4 proteins at a time, limiting the amount of information we can gain from precious patient biopsy samples. In a new study published in Nature Communications, researchers at CSB developed an approach that uses antibody-DNA conjugates to efficiently “cycle” through the detection and quantification of multiple proteins of interest, dramatically increasing the number of pathways/targets that can be imaged from a single biopsy. This technique allows scientists/physicians to directly visualize complex protein signatures in the biopsied cells and has important implications for understanding how drug therapies affect patients' individual tumors.

  • Shortcut

    Shortcut to the brain

    White blood cells are our key defenders against infection, however if oversupplied, they may turn against us. Neutrophils are made in the bone marrow where they arise from hematopoietic stem cells. The bone marrow is distributed over many bones in our bodies, and the current thinking implies that the supply of leukocytes distributes evenly throughout the body. In work published in Nature Neuroscience, we describe that the skull marrow assumes a special role in inflammatory diseases of the CNS. Its proximity to the brain leads to a preferential supply of neutrophils. We detected a previously unknown shortcut that neutrophils use on their way from skull marrow cavities towards the central nervous system. Rather than traveling through the general blood circulation, leukocytes produced in skull bone marrow migrate through channels that directly connect the skull marrow with the meninges the brain is wrapped in. The channels exist in mice and humans.

  • Intellisense_1

    Artificial Intelli-sense

    Automating cellular diagnostics could have far reaching impact in healthcare. Cells - often obtained by aspirations, biopsies, swabs or through body fluids - typically require sophisticated instrumentation and time consuming experts analysis to provide diagnoses. The CSB engineering team has now developed a highly sensitive platform powered by digital imaging and artificial intelligence to automate such painstaking analyses. Moreover this platform is affordable and portable, thus uniquely suited for point-of-care diagnostics in low and middle income countries (LMIC). A recent study published in Nature Biomedical Engineering highlights the first clinical trial for lymphoma diagnostics.

  • Reeducating_tumors_1

    Re-educating Tumors

    Tumor-associated macrophages (TAM) are abundant in many cancers and often display an immune-suppressive phenotype that promotes tumor growth and resistance to treatment. Researchers at CSB have now developed a TAM targeted nanoparticle loaded with a toll-like receptor agonist which re-programs TAMs to support the immune-system’s fight against cancer. As a monotherapy, administration of the drug-loaded nanoparticle led to efficient drug delivery to TAMs, re-programming of TAMs to an immune-supportive phenotype, and controlled tumor growth. Importantly, the strategy worked synergistically in combination with checkpoint therapy (anti-PD1), dramatically improving response rates even in tumors resistant to treatment by anti-PD1 alone. These findings demonstrate the ability of rationally engineered drug–nanoparticle combinations to efficiently modulate TAMs to better sensitize the tumor microenvironment to standard checkpoint therapies.

  • Bone

    Bones and Neutrophils Control Lung Cancer

    Tumors are often infiltrated by diverse immune cell types, some of which remain largely unexplored. In a study published in Science, the Pittet lab at the MGH Center for Systems Biology uncovers a new type of neutrophil that promotes lung cancer. The production of these neutrophils involves an unexpected remote crosstalk between tumors and bones: lung tumors remotely activate osteoblasts; in turn, those bone cells shape immunity by supplying tumors with cancer-promoting neutrophils. The findings open new avenues for cancer immunotherapy. (Image from Wikipedia)

  • Irf3mi_sm

    Immune cells attend a heart attack masquerade

    Hearts attacks, result from occlusion of coronary arteries, which starves heart muscle cells of oxygen-rich blood and causes them to die. Immune cells respond by entering the dead tissue, clearing cell debris, and stabilizing the heart wall via fibrosis and repair. In their Nature Medicine report, CSB investigators describe the surprising finding that dying cell DNA mimics a virus, which causes immune cells to turn on antiviral programs after a heart attack even though there is no viral infection.

  • Ieat

    Keychain detector catches food allergens before it’s too late

    More than 50 million Americans display food reactions. Each year there are an estimated over 20,000 food allergy-related emergency department visits in the United States, including 90,000 cases of anaphylaxis. The best way to manage food allergy is to avoid products that contain allergen. But avoidance isn't always possible because food can be mislabeled or cross-contaminated.

    Meet iEAT (integrated Exogenous Antigen Testing) a $40 portable allergen-detection system that consists of a disposable kit to extract allergens from food and an electronic keychain analyzer for allergen detection. In less than 10 minutes, the iEAT completes food analyses and sends the results to a cloud server. The prototype was used to detect five model allergens from wheat, peanuts, hazelnuts, milk and egg white. Testing on food items from local restaurants revealed unexpected findings such as gluten in “gluten-free” dishes and egg protein in beer. The technology is being expanded to detect additional allergens, pesticides and environmental hormones.

The MGH Center for Systems Biology (CSB) was established as one of the five thematic interdisciplinary Centers at MGH. It is home to over 200 researchers in 12 PI groups. The mission of the Center is to analyze at a systems level how biological molecules, proteins and cells interact in both healthy and diseased states.

Through a multidisciplinary approach that combines clinical insight with powerful technologies, CSB faculty pursue systems-level research that is at once fundamental, and yet immediately linked to the diagnosis and treatment of human disease. While these approaches are generalizable to many diseases, the Center has particular strengths in complex human conditions such as cancer, cardiovascular disease, diabetes, autoimmune disease, and renal disease. This goal is enabled by particular faculty expertise in genomics, chemical biology, physiology, bioimaging, and nanotechnology.

The Center has close links with the HMS Department of Systems Biology, clinical departments at MGH, other MGH thematic centers, MIT, and the Broad Institute.

Recent Publications (more...)

Lee H, Castro CM
Thermophoretically enriched detection
Nat Biomed Eng. 2019;3:163-164 - DOI: 10.1038/s41551-019-0364-9
Choudhary A, Manna D, Maji B, Gangopadhyay SA, Cox KJ, Zhou Q, Law B, Mazitschek R
A singular system with precise dosing and spatiotemporal control of CRISPR-Cas9.
Angew Chem Int Ed Engl. 2019;:ePub - PMID: 30834641 - DOI: 10.1002/anie.201900788
van Galen P, Hovestadt V, Wadsworth Ii MH, Hughes TK, Griffin GK, Battaglia S, Verga JA, Stephansky J, Pastika TJ, Lombardi Story J, Pinkus GS, Pozdnyakova O, Galinsky I, Stone RM, Graubert TA, Shalek AK, Aster JC, Lane AA, Bernstein BE
Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity.
Cell. 2019;176(6):1265-1281.e24 - PMID: 30827681 - DOI: 10.1016/j.cell.2019.01.031
Tan X, Patil R, Bartosik P, Runnels JM, Lin CP, Niedre M
In Vivo Flow Cytometry of Extremely Rare Circulating Cells.
Sci Rep. 2019;9(1):3366 - PMID: 30833671 - PMCID: PMC6399281 - DOI: 10.1038/s41598-019-40143-2

Recent News (more...)

2019-01-30: Jouha Min and Jina Ko (Weissleder Lab) participated in the Mass General Research Institute Science Slam, which was co-hosted by Mass General's five thematic research centers. The event gave scientists the chance to speak about their science in front of a live audience without using slides or scientific jargon. Checkout video highlights!
2019-01-08: Weissleder Lab has earned a Blue Flame Award from Addgene. This accolade serves to congratulate researchers who have at least one plasmid that has been distributed to the research community more than 100 times.
2018-12-26: Five CSB PIs are on the list of Highly Cited Researchers of 2018. Congratulations to Brad Bernstein, Matthias Nahrendorf, Mikael Pittet, Fil Swirski, and Ralph Weissleder!
2018-10-30: Hyungsoon Im received Award of Excellence (1st place) at the 7th Annual MGH Radiology Research Celebration and Poster Session
2018-08-31: Sylvie Breton has been named the inaugural incumbent of the Richard Moerschner Endowed MGH Research Institute Chair in Men’s Health. Congratulations, Sylvie!