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Research Highlights (more...)

  • 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.

  • Pd

    What does a catalytic converter have to do with drugs?

    A lot, it turns out. Catalytic converters in our cars convert toxic gas emissions into into acceptable ones. A key element is the metal palladium, which catalyses the oxidation of pollutants like carbon monoxide to carbon dioxide. In a recent article in Nature Communications, researchers at CSB have developed a medical version of nano-palladium to enable chemistry to take place inside cells in our body. The discovery allows the administration of harmless prodrugs, which then get specifically activated at sites of cancer.

  • Imrt

    A new trick for macrophages

    Macrophages, immune cells in our body, have a long to-do list. They defend us from bacteria, are essential in wound healing, keep the heart beating and perform other vital tasks. In a new twist, these cells are now shown to dramatically accumulate on the outside of cancer microvessels following radiation therapy. There, they elicit dynamic and focally localized bursts of capillary leaks. This in turn enhances drug delivery, especially of nanomaterials. These new insights have implications for the design of next-generation tumor targeted nanomaterials and clinical trials for adjuvant strategies.

  • Singature_achievement

    A signature achievement

    Pancreatic ductal adenocarcinoma is one of the deadliest types of tumors, in part because it is usually detected at a late stage. To facilitate the diagnosis of this tumor, researchers at CSB have developed a multiplexed nanoplasmonic assay to analyze extracellular vesicles in blood of patients. While some blood biomarkers have previously been proposed, none of them have proven sufficiently accurate in clinical practice. We have now identified a new five-marker signature that yielded the most accurate diagnosis in a large cohort of patient samples.

  • Checking_out_checkpoints

    Spotlight (literally) on immunotherapy

    Immunotherapy and especially immune checkpoint blockers (ICBs) are revolutionizing how we treat many cancers. Designed to activate the immune system, these drugs can be extraordinarily effective in some patients. But progress has been slowed by our limited understanding of why ICBs work well in some cancers and patients but not in others. Now, Mikael Pittet and colleagues have used molecular imaging to track ICBs in real time and at high resolution within tumors. Their study, published in Science Translational Medicine, uncovers a previously undiscovered mechanism of treatment resistance, which can be overcome with additional chemical modifications.

  • Macrophages

    Cardiac macrophages charging ahead

    While we knew for a while that the healthy heart contains tissue resident macrophages, these cells’ organ specific functions were unknown. Triggered by a serendipitous finding of ECG abnormalities during a cardiac MRI scan of a mouse after macrophage ablation, a CSB team of investigators now describes previously unknown electrical properties of macrophages. When coupled to myocytes via gap junctions, macrophages depolarize in sync with conducting cells. In a sink-source relationship, electric current flows back and forth between macrophages and cardiomyocytes. Macrophages influence conduction through the atrioventricular node, the electrical connection between the heart’s chambers. When macrophages are manipulated, the flow of electricity slows down, and may even cease altogether. Such a condition requires pacemaker treatment in humans. These surprising findings, published in Cell, jolt the field of electrophysiology and may lead to new therapeutic opportunities for patients with cardiac arrhythmias. The collaborative effort was spearheaded by teams at MGH but also involved investigators at the BWH and in Freiburg, Germany.

  • Tiny_nanoparticles_hunt_for_macrophages

    Tiny nanoparticles hunt for macrophages

    Macrophages are white blood cells that can turn against us in atherosclerosis. Instead of cleaning up tissue as usual, they attack the arterial wall and destroy its architecture. The resulting stoppage of blood flow causes myocardial infarction and stroke. An entire field of research focuses on understanding these cells, and how to stop them from becoming turn coats. Until now, it was not even possible to detect them reliably in patients. In a recent Nature Communications report, a modified polyglucose nanoparticle (18F-Macroflor) was developed for imaging macrophages by PET. Macroflor enriches in cardiac and plaque macrophages, thereby increasing PET signal in murine infarcts and both mouse and rabbit atherosclerotic plaques. This work marks an important step towards a clinical tool to non-invasively monitor macrophage biology in patients. Such an imaging tool can then be used to spot danger spots in several diseases, and test new macrophage-targeted therapeutics while directly watching the cells.

  • Iron_highlight_sm

    Ingest, Digest, Recycle: Where red blood cells and the iron they contain are recycled.

    Iron gives blood its red color. The metal is essential to life, but it can be toxic because of its oxidative properties. Remarkably, we receive relatively little of our daily iron needs through diet. By far the majority of the iron we need is recycled. According to current thinking, as red blood cells age, large phagocytes residing in the spleen capture them, digest the cell structures, and recycle iron. A new paper from CSB published in Nature Medicine shows that most red blood cell disposal actually occurs in the liver, especially when demands for disposal increase (as they do in many physiologic and pathophysiologic situations). Moreover, specialized white blood cells consume old red blood cells in the circulation before migrating to the liver to shuttle iron for storage and new red blood cell production. The process buffers against dangerous fluctuations in iron availability, keeping the body in balance.

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...)

Engblom C*, Pfirschke C*, Zilionis R, Da Silva Martins J, Bos SA, Courties G, Rickelt S, Severe N, Baryawno N, Faget J, Savova V, Zemmour D, Kline J, Siwicki M, Garris C, Pucci F, Liao HW, Lin YJ, Newton A, Yaghi OK, Iwamoto Y, Tricot B, Wojtkiewicz GR, Nahrendorf M, Cortez-Retamozo V, Meylan E, Hynes RO, Demay M, Klein A, Bredella MA, Scadden DT, Weissleder R, Pittet MJ
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils
Science. 2017;358:eaal5081 - PMID: 29191879 - DOI: 10.1126/science.aal5081
Puram SV, Tirosh I, Parikh AS, Patel AP, Yizhak K, Gillespie S, Rodman C, Luo CL, Mroz EA, Emerick KS, Deschler DG, Varvares MA, Mylvaganam R, Rozenblatt-Rosen O, Rocco JW, Faquin WC, Lin DT, Regev A, Bernstein BE
Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.
Cell. 2017;:ePub - PMID: 29198524 - DOI: 10.1016/j.cell.2017.10.044
Miller MA
It’s what’s inside that counts for nanoparticle vaccines
Sci Transl Med. 2017;9(417):eaar2438 - DOI: 10.1126/scitranslmed.aar2438
Miller MA, Kim E, Cuccarese MF, Plotkin AL, Prytyskach M, Kohler RH, Pittet MJ, Weissleder R
Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease
Chem Commun. 2017;:ePub - PMID: 29185561 - DOI: 10.1039/c7cc07581b

Recent News (more...)

2017-12-06: Two CSB PIs - Ralph Weissleder and Bradley E. Bernstein - are included in the Clarivate Analytics 2017 Highly Cited Researchers list (formerly the Thompson Reuters list).
2017-12-04: Preprints are changing the culture of communicating results: To publish or not? Science's preprint guide.
2017-12-01: "Tumors talk to bones, and bones answer back" - Study by Engblom, Pfirschke et al. from the Pittet Lab is featured in Science and Nature. See also interview with the authors.
2017-11-07: "Food Allergy Detection Device Could Remove Danger Of Dining Out" - CBS News report on the iEat device developed at CSB
2017-10-10: Dennis Brown, PhD has been elected as a member of Academia Europaea (The Academy of Europe). Academia Europaea is the only Europe-wide academy with individual membership from Council of Europe states and other nations across the world.