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Research Highlights (more...)

  • 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.

  • 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.

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...)

Frodermann V, Nahrendorf M
Macrophages and Cardiovascular Health.
Physiol Rev. 2018;98(4):2523-2569 - PMID: 30156496 - DOI: 10.1152/physrev.00068.2017
Duivenvoorden R, Senders ML, van Leent MMT, Pérez-Medina C, Nahrendorf M, Fayad ZA, Mulder WJM
Nanoimmunotherapy to treat ischaemic heart disease.
Nat Rev Cardiol. 2018;:ePub - PMID: 30209355 - DOI: 10.1038/s41569-018-0073-1
McBrayer SK, Mayers JR, DiNatale GJ, Shi DD, Khanal J, Chakraborty AA, Sarosiek KA, Briggs KJ, Robbins AK, Sewastianik T, Shareef SJ, Olenchock BA, Parker SJ, Tateishi K, Spinelli JB, Islam M, Haigis MC, Looper RE, Ligon KL, Bernstein BE, Carrasco RD, Cahill DP, Asara JM, Metallo CM, Yennawar NH, Vander Heiden MG, Kaelin WG
Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma.
Cell. 2018;:ePub - PMID: 30220459 - DOI: 10.1016/j.cell.2018.08.038
Hedgire S, Kilcoyne A, Tonyushkin A, Mao Y, Uyeda JW, Gervais DA, Harisinghani MG
Effect of androgen deprivation and radiation therapy on MRI fiber tractography in prostate cancer: Can we assess treatment response on imaging?
Br J Radiol. 2018;:20170170 - PMID: 30209952 - DOI: 10.1259/bjr.20170170

Recent News (more...)

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!
2018-08-27: "AI-powered cancer diagnoses for resource limited settings" - CSB work is featured on the Nature Bioengineering blog.
2018-08-23: Hsing-Ying Lin (Lee Lab) has been selected to receive a MGH ECOR Fund for Medical Discovery (FMD) Postdoctoral Fellowship Award. Congratulations!
2018-07-17: Matthias Nahrendorf joins the Advisory Board for Nature Reviews Cardiology.
2018-07-16: Kamila Naxerova has been awarded the AACR NextGen Grants for Transformative Cancer Research. This award represents the AACR’s flagship funding initiative to stimulate highly innovative research from young investigators. Congratulations, Kamila!