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Research at Mass General
Here's a quick look at some recent publications, press releases and stories featuring researchers from Massachusetts General Hospital.
Here's a quick look at some of the recent publications, press releases and stories about the Mass General research community.
In this issue we highlight:
This is just a small snapshot of the incredible research that takes place at Mass General each day—there's lots more to find at massgeneral.org/research/news.
ALLERGENS AND THE NERVOUS SYSTEM RESPONSEActivation of mas-related G-protein receptors by the house dust mite cysteine protease der p1 provides a new mechanism linking allergy and inflammationReddy, VB, Lerner EA.Published in the Journal of Biological Chemistry on August 2, 2017 | Summary available
INFLAMMATORY RESPONSE TO TOXINSPseudomonas aeruginosa ExoU augments neutrophil transepithelial migrationPazos MA, Lanter BB, Yonger LM, Eaton AD, Pirzai W, Gronert K, Bonventre JV, Hurley BP.Published in PLOS on August 3, 2017 | Summary available
USING OPTICAL SENSORS FOR ANTICOAGULANT DOSINGOptical sensing of anticoagulation status: Toward point-of-care coagulation testingTshikudi DM, Tripathi, MM, Hajjarian Z, Van Cott, EM, Nadkarni SK.Published in PLOS on August 3, 2017 | Summary available
METABOLISM AND GENETICSDevelopment of a genetically encoded tool for manipulation of NADP+/NADPH in living cellsCracan V, Titov, DV, Shen H, Grabarek Z, Mootha VK.Published in Nature Chemical Biology on August 7, 2017 | Summary available
IDENTIFYING GENETIC IMBALANCESGenomic wide identification of autosomal genes with allelic imbalance of chromatin stateSavol AJ, Wang PI, Jeon Y, Colognori D, Yildirim E, Pinte SF, Payer B, Lee JT, Sadreyev RI.Published in PLOS on August 10, 2017 | Summary available
DETECTING STIFF TUMORSMolecular MR imaging of fibrosis in a mouse model of pancreatic cancerPolasek M, Yang Y, Schühle DT, Yaseen MA, Kim YR, Sung YS, Guimaraes AR, Caravan P.Published in Nature Scientific Reports on August 14, 2017 | Summary available
IMMUNOTHERAPY TREATMENT FOR GLIOBLASTOMAMacrophage polarization contributes to glioblastoma eradication by combination immunotherapy and immune checkpoint blockadeSaha D, Martuza RL, Rabkin SDPublished in Cancer Cell on August 14, 2017 | Summary available
LUNG INFLAMMATION AND AIRWAYSDevelopment of a primary human co-culture model of inflamed airway mucosaYonker, LM Mou H, Chu KK, Pazos MA, Leung H, Cui D, [et al] Hurley B.Published in Nature Scientific Reports on August 15, 2017 | Summary available
METHOD TO REDUCE COST FOR PET IMAGINGSynthesis-free PET imaging of brown adipose tissue and TSPO via combination of disulfarim and 64CuCI2Yang, Jing, Yang, Jian, Wang L, Moore A, Liang SH, Ran C.Published in Nature Scientific Reports on August 15, 2017 | Summary available
IMPACT OF BLOOD AND URINE FILTRATION IN LEAKY KIDNEY FILTERS Re-characterization of the glomerulopathy in CD2AP deficient mice by high-resolution helium ion scanning microscopyTsuji K, Păunescu TG, Suleiman H, Xie D, Mamuya FA, Miner JH, Lu HAJ.Published in Scientific Reports on August 16, 2017 | Summary available
NEW METHOD FOR PET IMAGINGPseudo-reference regions for glial imaging with 11C-PBR28: Investigation in two clinical cohortsAlbrecht DS, Normandin, MD, Shcherbinin S, Wooten, DW, Schwarz AJ, Zurcher NR, [et al] Loggia, ML.Published in the Journal of Nuclear Medicine on August 17, 2017 | Summary available
BRAIN ACTIVITY AND CONNECTIVITY BETWEEN REGIONSDynamic connectivity modulates local activity in the core regions of the default-mode networkTang W, Liu H, Douw L, Kramer MA, Eden, UT, Hamalainen MS, Stufflebeam SMPublished in PNAS on August 21, 2017 | Summary available
MEASURING BLOOD CLOTTINGClinical evaluation of whole blood prothrombin time (PT) and international normalized ratio (INR) using a laser speckle rheology sensorTripathi MM, Egawa S, Wirth AG, Tshikudi DM, Van Cott EM, Nadkarni SKPublished in Scientific Reports on August 23, 2017 | Summary available
TREATING LYMPHOMA WITH TUMOR-TARGETING IMMUNE CELLSAnti-CD19 CAR-T cells in CNS diffuse large B cell lymphomaAbramson JS, McGree BM, Noyes S, Plummer S, Wong C, Chen Y, Palmer E, Albertson T, Ferry JA, Arrillaga-Romany, IC.Published in the New England Journal of Medicine on August 24, 2017 | Summary available
OBSERVING THE DEVELOPMENT OF TYPE 1 DIABETESImaging the emergence and natural progression of spontaneous autoimmune diabetesMohan JF, Kohler RH, Weissleder R, Mathis D, Benoist C.Published in PNAS on August 24, 2017 | Summary available
NON-INVASIVE MEASUREMENT OF BRAIN ACTIVITY AND MEMORY ENCODINGfNIRS can robustly measure brain activity during memory encoding and retrieval in healthy subjectsJahani S, Fantana AL, Harper D, Ellison JM, Boas DA, Forester BP, Yucel MA.Published in Scientific Reports on August 25, 2017 | Summary available
HOW BACTERIA DETERMINE AMOUNT OF ENZYME TO PRODUCE Investment in secreted enzymes during nutrient-limited growth is utility dependentCezairliyan B, Ausubel FMPublished in PNAS on August 28, 2017 | Summary available
IMPACT OF CUTBACKS TO FOREIGN AID FOR HIV PROGRAMSDo less harm: Evaluating HIV programmatic alternatives in response to cutbacks in foreign aidWalensky RP, Borre ED, Bekker LG, Hyle EP, Gonsalves GS, Wood R, [et al.] Paltiel, ADPublished in Annals of Internal Medicine on August 29, 2017 | Summary available
MODIFICATIONS IN DIFFERENT CLASSES OF RNAGenome-wide maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAsZhou C, Molinie B, Daneshvar K, Pondick JV, Wang J, Van Wittenberghe N, [et al.] Mullen, ACPublished in Cell Reports on August 29, 2017 | Summary available
NEW METHODS FOR SEPARATING BLOODNon-equilibrium inertial separation array for high-throughput, large-volume blood fractionationMutlu BR, Smith KC, Edd JF, Nadar P, Dlamini M, Kapur R, Toner M.Published in Scientific Reports on August 30, 2017 | Summary available
OBSERVING GROWTH OF PANCREATIC TUMORS IN ANIMAL MODELS Tumor engraftment in patient-derived xenografts of pancreatic ductal adenocarcinoma is associated with adverse clinicopathological features and poor survivalPergolini I, Morales-Oyarvide V, Mino-Kenudson M, Honselmann KC, Rosenbaum MW, Nahar S, [et al.] Liss ASPublished in PLoS One on August 30, 2017 | Summary available
1. ALLERGENS AND THE NERVOUS SYSTEM RESPONSEActivation of Mas-Related G-Protein Receptors By the House Dust Mite Cysteine Protease Der p1 Provides a New Mechanism Linking Allergy and InflammationReddy, V. B., Lerner, E.A.Published in the Journal of Biological Chemistry on August 2, 2017
Allergens trigger eczema and asthma and thus insufferable itch and difficulty breathing. New work from our lab helps to explain these symptoms. While it has been known for decades that allergens turn on the immune system, our recent publication in the Journal of Biological Chemistry reveals that allergens also turn on the nervous system. This exciting finding makes sense, as the sensation of itch requires nerves, which has only recently been found for asthma. These observations suggest that targeting the nervous system could lead to new treatments for eczema and asthma.
(Summary submitted by Ethan Lerner, MD, PhD, of the Cutaneous Biology Research Center)
2. INFLAMMATORY RESPONSE TO TOXINSPseudomonas Aeruginosa ExoU Augments Neutrophil Transepithelial MigrationPazos, M.A., Lanter, B. B., Yonger, L.M., Eaton, A.D., Pirzai, W., Gronert, K., Bonventre, J.V., Hurley, B.P.Published in PLOS on August 3, 2017Pseudomonas aeruginosa is a bacterium adept at infecting those who are already fighting illness or resolving injury, making bad situations worse. This microbe exacerbates burns, wounds, and airway distress by colonizing damaged tissue and manipulating inflammation to its advantage. We discovered a novel function of a toxin produced by Pseudomonas aeruginosa, known as ExoU. ExoU is injected into inflammatory cells recruited to the infectious site. Once inside, ExoU amplifies a key signal calling more inflammatory cells and intensifying things in a harmful way, while helping the microbe thrive. Impeding ExoU might recalibrate the inflammatory response towards benefiting the health of the patient.
(Summary submitted by Bryan Hurley, PhD, of the Mucosal Immunology & Biology Research Center)
3. USING OPTICAL SENSORS FOR ANTICOAGULANT DOSINGOptical Sensing of Anticoagulation Status: Toward Point of Care Coagulation TestingTshikudi, D.M., Tripathi, M.M., Hajjarian Z., Van Cott, E.M., Nadkarni, S. K.Published in PLOS on August 3, 2017
Millions of patients treated with Warfarin and other anticoagulant drugs (drugs that hinder blood clotting) have an increased risk of bleeding complications. Consequently, most patients require frequent laboratory testing to ensure safe anticoagulant dosing, imposing a staggering load on patients and primary care services. An optical sensor developed in the Nadkarni laboratory at the Wellman Center for Photomedicine facilitates comprehensive coagulation profiling in whole blood and opens new opportunities for rapid and inexpensive coagulation testing in the doctor’s office and for patient self-testing. In this study, we demonstrated that dose-dependent anticoagulation can be quantified with excellent accuracy and precision within minutes using a drop of blood. Our optical sensing approach is poised to improve anticoagulation management in patients while reducing the burdensome need for frequent laboratory testing.
(Summary submitted by Seemantini Nadkarni, PhD, of the Wellman Center for Photomedicine)
4. METABOLISM AND GENETICSDevelopment of a Genetically Encoded Tool for Manipulation of NADP+/NADPH in Living CellsCracan, V., Titov, D.V., Shen, H., Grabarek, Z., Mootha, V.K.Published in Nature Chemical Biology on August 7, 2017
At the very foundation of life is the ability of each cell in the human body to perform sophisticated chemical reactions, broadly referred to as metabolism. Investigating metabolism is challenging in part because we lack methods to manipulate it in a defined way. We used structure-based protein design to invent a new genetic tool with which it is possible to manipulate one of the most central chemical co-factors in human metabolism. We anticipate that with these new tools it will be possible to investigate in much greater detail how cells cope with metabolic challenges under various disease conditions.
(Summary submitted by Zenon Grabarek, PhD, of the Department of Molecular Biology)
5. IDENTIFYING GENETIC IMBALANCESGenomic Wide Identification of Autosomal Genes with Allelic Imbalance of Chromatin StateSavol, A.J., Wang, P.I., Jeon, Y., Colognori, D., Yildirim, E., Pinter, S.F., Payer, B., Lee, J.T, Sadreyev, R. I.Published in PLOS on August 10, 2017
Genes in mammals are expressed as sums of signals from two alleles. Previous efforts to deconstruct these sums into individual alleles identified a number of genes with unequal expression from the two alleles. To better understand regulatory mechanisms behind this imbalance, we performed genome-wide analysis of epigenetic chromatin states of genes at the allele level, with the focus on autosomal genes with unequal levels of chromatin marks between two alleles. We identified approximately 4% of these autosomal genes that show imbalance between chromatin states of two alleles, analyze major sources of this imbalance, and show that it is predictive of allele-specific gene expression. The results provide a better understanding of this specific type of allelic imbalance, which has important implications in cell biology and human disease.
(Summary submitted by Ruslan Sadreyev, PhD, Director of Bioinformatics in the Department of Molecular Biology)
6. DETECTING STIFF TUMORSMolecular MR Imaging of Fibrosis in a Mouse Model of Pancreatic CancerPolasek, M., Yang, Y., Schühle, D.T., Yaseen, M.A., Kim, Y. R., Sung, Y.S., Guimaraes, A.R., Caravan, P.Published in Nature Scientific Reports on August 14, 2017
In tumors, cancer cells are surrounded by a collection of proteins, enzymes, sugars, lipids, and minerals called the extracellular matrix (ECM). Many cancers have a fibrotic ECM, making the tumor stiff and preventing delivery of anti-cancer drugs. The presence of a fibrotic ECM is often associated with poor prognosis. We developed a new MRI method to detect tumor fibrosis non-invasively, and studied its effect in a mouse model of pancreatic cancer. The potential impact of this work is a new tool to stage the aggressiveness of tumors, guide treatment planning, and monitor the effectiveness of new tumor ECM altering treatments.
(Summary submitted by Peter Caravan, PhD, of the Martinos Center for Biomedical Imaging)
7. IMMUNOTHERAPY TREATMENT FOR GLIOBLASTOMAMacrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunotherapy and Immune Checkpoint BlockadeSaha, D., Martuza, R.L., Rabkin, S.D.Published in Cancer Cell on August 14, 2017
Glioblastoma is an invariably fatal brain cancer with no effective treatments. Immunotherapy has produced curative responses in a subset of cancers, but not glioblastoma. In this study, we show that curative therapy for glioblastoma requires multiple immunotherapeutic strategies (oncolytic viruses, immunomodulatory cytokine expression, and two distinct checkpoint inhibitors). This treatment strategy has highly interconnected effects on multiple immune cell types in the tumor microenvironment—namely an increase in T effector cells, a decrease in T regulator cells, and an infiltration of macrophages and their polarization to an anti-tumor phenotype. This reveals a new combination strategy to treat glioblastoma and other tumors that historically have been unresponsive to immunotherapy.
(Summary submitted by Samuel Rabkin, PhD, of the Molecular Neurosurgery Laboratory and the Brain Tumor Research Center)
8. LUNG INFLAMMATION AND AIRWAYSDevelopment of a Primary Human Co-Culture Model of Inflamed Airway MucosaYonker, L. M., Mou, H., Chu, K.K., Pazos, M.A., Leung, H., Cui, D., [et al] Hurley, B.Published in Nature Scientific Reports on August 15, 2017
Lung inflammation can be beneficial or harmful depending on degree and context. White blood cell neutrophils rapidly breach protective airway linings to confront microbes, but can be quite destructive. Our research team of immunologists, pediatricians, bioengineers, and stem cell biologists developed a new model of inflamed human airway mucosa. Airway stem cells from biopsy were cultured to develop beating cilia and secrete mucus. Neutrophils from blood donors were applied to infected airway cultures and live-imaged to reveal rapid mobilization and migration through airways in response to identified signals. This model has enormous potential for investigating inflammation and evaluating new therapies.
9. METHOD TO REDUCE COST FOR PET IMAGINGSynthesis-Free PET Imaging of Brown Adipose Tissue and TSPO via Combination of Disulfarim and 64CuCI2Yang, Jing, Yang, Jian, Wang, L., Moore, A., Liang, S.H., Ran, C.Published in Nature Scientific Reports on August 15, 2017
Positron emission tomography (PET) imaging, a very useful imaging method for disease diagnosis, treatment monitoring,and drug development, is particularly known for its high cost, which has been the key roadblock for its widespread routine use. The need to produce and prepare chemicals used in PET imaging on-site (called on-site synthesis) weightily contributes to the high cost. In this report, our team demonstrated that synthesis-free PET imaging is feasible, and has the potential to significantly reduce the cost of PET imaging. Specifically, step-wise injection of 64CuCl2 and disulfiram, a FDA-approved drug for alcoholism, could be used to avoid the on-site synthesis and be applied for imaging brown adipose tissue (BAT), which is very important for maintaining the energy balance of the whole body.
(Summary submitted by Chongzhao Ran, PhD, of the Martinos Center for Biomedical Imaging)
10. IMPACT OF BLOOD AND URINE FILTRATION IN LEAKY KIDNEY FILTERS Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning MicroscopyTsuji, K., Păunescu, T.G., Suleiman, H., Xie, D., Mamuya, F.A., Miner, J.H., Lu, H.A.J.Published in Scientific Reports on August 16, 2017
One major function of the kidney is filtering blood through an intricate “glomerular filter”. Disruption of any components of this highly sophisticated and dynamic filter’s structure leads to proteinuria (protein in the urine), a condition frequently seen in diabetic nephropathy and many other glomerular diseases. How blood filters though the glomerular filter and how proteinuria develops when the filter becomes leaky has not been well understood. This paper reports the application of a novel and powerful scanning microscopy technology, the Helium Ion microscopy (HIM) to identify previously unrecognized ultrastructural abnormalities of proteinuric glomerulopathy in animals. These newly discovered abnormalities provide important insight into the molecular and cellular mechanism underlying proteinuria kidney diseases.
(Summary submitted by Hua A. Jenny Lu, MD, PhD, of the Nephrology Division)
11. NEW METHOD FOR PET IMAGINGPseudo-Reference Regions for Glial Imaging with 11C-PBR28: Investigation in Two Clinical CohortsAlbrecht, D.S., Normandin, M.D., Shcherbinin, S., Wooten, D.W., Schwarz, A.J., Zurcher, N.R., [et al] Loggia, M. L.Published in the Journal of Nuclear Medicine on August 17, 2017
Positron emission tomography (PET) allows visualization of numerous biological processes. Many PET studies require arterial blood sampling, a complicated and invasive procedure. One such type of PET data (“TSPO PET”) is used to assess brain inflammation, but recent evidence suggests traditional arterial blood analysis methods are suboptimal for these data. Therefore, researchers investigated alternative methods to analyze TSPO PET data without arterial sampling. They found that a ratio technique identified inflammation in patients with chronic pain and Lou Gehrig’s Disease similarly to traditional methods. These results suggest that TSPO PET studies, if properly validated, may be conducted without arterial catheters, an attractive prospect for studies where traditional methods are impractical or unavailable.
(Summary submitted by Daniel Albrecht, PhD, of the Martinos Center for Biomedical Imaging)
12. BRAIN ACTIVITY AND CONNECTIVITY BETWEEN REGIONSDynamic Connectivity Modulates Local Activity in the Core Regions of the Default-Mode NetworkTang, W., Liu, H., Douw, L., Kramer, M.A., Eden, U.T., Hamalainen, M.S., Stufflebeam, S.M.Published in PNAS on August 21, 2017
When a person is at wakeful rest, his/her brain activity will not drift into random noise. Instead, there are robust dynamical interactions between brain regions. It remains unclear how the long-range interactions may relate to local brain activity. Recently, our research team combined fMRI and MEG to study the relationship between the anterior and the posterior cingulate cortex (ACC and PCC), two core regions of the default-mode network that is important for self-referential thoughts, and discovered that local activity of the ACC changes according to its interactions with the PCC. This covariation between long-rage connectivity and local activity provides important insights into the neural underpinnings of human cognition, which is driven by complex interactions between different brain regions.
(Summary submitted by Hesheng Liu, PhD, of the Martinos Center for Biomedical Imaging)
13. MEASURING BLOOD CLOTTINGClinical Evaluation of Whole Blood Prothrombin Time (PT) and International Normalized Ratio (INR) Using a Laser Speckle Rheology SensorTripathi, M.M., Egawa, S., Wirth, A.G., Tshikudi, D.M., Van Cott, E.M., Nadkarni, S.K.Published in Scientific Reports on August 23, 2017
Prothrombin time (PT) and the associated international normalized ratio (INR) are routinely tested to measure how long it takes blood to clot and to monitor response to anticoagulant therapy in patients. Our team in the Nadkarni laboratory report on a portable and battery-operated optical sensor that can rapidly quantify PT/INR within seconds by measuring alterations in the viscoelastic properties of a drop of whole blood. Their findings confirm the accuracy of the new optical sensing approach for rapid PT/INR testing and highlight the opportunity for use at the point-of-care or for patient self-testing.
(Summary submitted by Seemantini K. Nadkarni, PhD, of the Wellman Center for Photomedicine)
14. TREATING LYMPHOMA WITH TUMOR-TARGETING IMMUNE CELLSAnti-CD19 CAR-T Cells in CNS Diffuse Large B Cell LymphomaAbramson, J.S., McGree, B.M., Noyes, S., Plummer, S., Wong, C., Chen, Y., Palmer, E., Albertson, T., Ferry, J.A., Arrillaga-Romany, I.C.Published in the New England Journal of Medicine on August 24, 2017
A 68-year-old woman with chemotherapy-refractory diffuse large B-cell lymphoma (DLBCL) with a brain metastasis was treated with CAR T-cell therapy (tumor-targeting immune cells) as part of a clinical trial. OUr researchers observed that treatment induced complete remission of the brain and all other sites of disease—the first report of a response to CAR T-cells in a central nervous system (CNS) lymphoma. In addition, when a subcutaneous tumor began to recur two months after CAR T-cell therapy and a surgical biopsy was performed, the CAR T-cells spontaneously re-expanded and the tumor again went into remission, a phenomenon that had also not previously been reported. These observations have implications for multiple types of CNS lymphoma, for which treatment options are limited, and few patents are cured.
(Summary submitted by Jeremy Abramson, MD, of the Cancer Center)
15. OBSERVING THE DEVELOPMENT OF TYPE 1 DIABETESImaging the Emergence and Natural Progression of Spontaneous Autoimmune DiabetesMohan, J.F., Kohler, R.H., Weissleder, R., Mathis, D., Benoist, C.Published in PNAS on August 24, 2017
Type 1 diabetes (T1D) is an autoimmune disease where insulin-producing cells are destroyed. Inflammation in islets of human patients has been hard to evaluate, given the challenging access to material. Now, our research team has discovered how the different cellular players interact. We created new reporter mice and new imaging agents where cells of interest (lymphocytes, macrophages, dendritic cells, beta cells) are fluorescent and can be observed by imaging. We were able to observe the intricate “dance” of different immune cells interacting with each other as diabetes develops. Throughout the process, Tregs (a unique type of T-lymphocyte) control the activation of many cell types. The “dynamic geography” of events uncovered here provide important clues to immunoregulation that underlies diabetes development.
(Summary submitted by Ralph Weissleder, MD, PhD, Director of the Center for Systems Biology)
16. NON-INVASIVE MEASUREMENT OF BRAIN ACTIVITY AND MEMORY ENCODINGfNIRS can Robustly Measure Brain Activity During Memory Encoding and Retrieval in Healthy SubjectsJahani, S., Fantana, A.L., Harper, D., Ellison, J.M., Boas, D.A., Forester, B.P., Yucel, M.A.Published in Scientific Reports on August 25, 2017
Alzheimer’s disease (AD) is the most frequent cause of severe memory loss in the elderly. Early detection of AD is the key to preventing, slowing or stopping the disease. Near-infrared spectroscopy (NIRS) is a non-invasive neuroimaging technique capable of monitoring brain activation. Here, we investigated the utility of fNIRS in measuring the brain activity of healthy adults during memory encoding and retrieval under a face-name paired-associate learning task. Their study demonstrates that fNIRS can robustly measure memory encoding and retrieval-related brain activity. Future work will include similar measurements in populations with progressing memory deficits. Their approach, if successful, will introduce a non-invasive, inexpensive and easily accessible tool for identifying early stages of AD.
(Summary submitted by Meryem Yucel, PhD, of the Martinos Center for Biomedical Imaging)
17. HOW BACTERIA DETERMINE AMOUNT OF ENZYME TO PRODUCE Investment in Secreted Enzymes During Nutrient-Limited Growth is Utility DependentCezairliyan, B., Ausubel, F.M.Published in PNAS on August 28, 2017
Bacteria secrete enzymes into the environment to digest large molecules into smaller molecules that can be used as nutrients for growth. How do bacteria determine how much enzyme to produce? To find the answer, the authors compared rates of bacterial growth and enzyme production to develop a model for bacterial growth. They inferred that special signaling molecules called autoinducers convey information about the benefit of secreting a particular enzyme, allowing bacteria to adjust their investment in that enzyme depending on how useful it is. The model provides a framework that can be applied to bacterial growth in many environments from contaminated food to microbial communities within a host.
(Summary submitted by Brent Cezairliyan, PhD , Department of Molecular Biology)
18. IMPACT OF CUTBACKS TO FOREIGN AID FOR HIV PROGRAMSDo Less Harm: Evaluating HIV Programmatic Alternatives in Response to Cutbacks in Foreign AidWalensky, R.P., Borre, E.D., Bekker, L.G., Hyle, E.P., Gonsalves, G.S., Wood, R., [et al.] Paltiel, A.D.Published in Annals of Internal Medicine on August 29, 2017
We used a mathematical model in collaboration with colleagues from Yale, South Africa and Cote d’Ivoire to project the impact of US government proposals to cut HIV-related funding to resource limited settings. Over the next decade, we report that budgetary scale backs could mean up to 1.7 million more deaths and up to 650,000 new HIV transmissions in these two countries alone. They further highlight that budgetary cuts could save no more than $900 per year of life lost in these countries. We ask the readers to “draw their own conclusions about whether posing such tradeoffs on vulnerable populations accurately reflects how donor countries value life in recipient nations.”
(Summary submitted by Rochelle Walensky, MD, MPH, Chief of the Infectious Diseases Division)
19. MODIFICATIONS IN DIFFERENT CLASSES OF RNAGenome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAsZhou, C., Molinie, B., Daneshvar, K., Pondick, J.V., Wang, J., Van Wittenberghe, N., [et al.] Mullen, A.C.Published in Cell Reports on August 29, 2017
Genes encode messenger (m) RNAs, which provide the instructions used by cells to make proteins. Molecules can also be attached to mRNAs to regulate their activity by sharing their electrons (called covalent bonding). Our study demonstrates that these covalent modifications extend to another class of RNAs called circular (circ) RNAs, which primarily form from DNA sequences that also encode mRNAs. We find that circRNAs are modified by the same mechanism that modifies mRNAs, but the sites of modification differ between circRNAs and mRNAs in the same cell type and are unique between different cell types. These results uncover a previously unrecognized level RNA modification that is likely to regulate gene expression and could serve to distinguish normal from abnormal cells in disease.
(Summary submitted by Alan Mullen, MD, PhD, Gastrointestinal Unit)
20. NEW METHODS FOR SEPARATING BLOODNon-equilibrium Inertial Separation Array for High-throughput, Large-volume Blood FractionationMutlu, B.R., Smith, K.C., Edd, J.F., Nadar, P., Dlamini, M., Kapur, R., Toner, M.Published in Scientific Reports on August 30, 2017
Blood fractionation (i.e. separation of desired components from whole blood) is used in a range of applications from cancer therapeutics to infectious disease diagnostics. As these applications are being translated to clinical use, processing larger volumes of blood in shorter timescales with high-reliability and robustness is becoming a pressing need. In this work, we report a scaled, label-free cell separation mechanism called non-equilibrium inertial separation array (NISA). This device presents a feasible alternative to blood fractionation for use in transfusion, cellular therapy and blood-based diagnostics, and could significantly improve the sensitivity of rare cell isolation devices by increasing the processed whole blood volume.
(Summary submitted by Mehmet Toner, PhD, Director of the BioMEMS Resource Center at the Center for Engineering in Medicine)
21. OBSERVING GROWTH OF PANCREATIC TUMORS IN ANIMAL MODELS Tumor Engraftment in Patient-Derived Xenografts of Pancreatic Ductal Adenocarcinoma is Associated with Adverse Clinicopathological Features and Poor SurvivalPergolini, I., Morales-Oyarvide, V., Mino-Kenudson, M., Honselmann, K.C., Rosenbaum, M.W., Nahar, S., [et al.] Liss, A.S.Published in PLoS One on August 30, 2017
Patient tumors grown in mice (xenograft tumors) provide an experimental system to evaluate the biology of human cancers. In this study, we implanted 133 human pancreatic cancers into mice to generate patient-derived xenograft tumors. The 57 patients whose tumors successfully grew in mice had worse prognosis, showing the ability of these models to reflect the aggressiveness of the disease. Importantly, xenograft tumors retained the features and diversity of the patient tumors, and therefore provide powerful tools to study this heterogeneous disease. Examining the dynamic behind xenograft tumor formation may offer new perspectives in the knowledge and treatment of pancreatic cancer.
(Summary submitted by Andrew S. Liss, PhD, Director of the Pancreatic Biology Laboratory in the Andrew L. Warshaw, MD, Institute for Pancreatic Cancer Research)
Predicting the Behavior of TuberculosisFeaturing Maha Farhat, MD, CMNew research reveals that when it comes to predicting response to treatment and risk of dying, molecular tests that detect resistance to a class of TB drugs known as fluoroquinolones may be as good and even superior to traditional drug-sensitivity tests conducted in lab cultures.
Sense of Smell Deficits are Common, Linked to Malnutrition in Patients with Kidney DiseaseFeaturing Teodor Păunescu, PhD, and Sagar Nigwekar, MD
The study found that the majority of patients with chronic kidney disease, particularly those in the more advanced stages who require dialysis, exhibited some degree of loss of their sense of smell, which correlated with reduced nutritional status.
Study Finds Patients Need Fewer Opioid Tablets Than Typically Prescribed After Hernia SurgeryFeaturing Peter Masiakos, MD
A study by investigators from Massachusetts General Hospital (MGH) and Newton-Wellesley Hospital (NWH) found that patients prescribed opioid medications after inguinal (groin) hernia surgery used significantly fewer tablets than prescribed, even though they had received fewer than typically administered for such surgery.
Growing Body of Evidence Supports the Effectiveness of Mental Health Programs in SchoolsFeaturing J. Michael Murphy, EdD
School-based mental health programs can reach large numbers of children, with increasing evidence of effectiveness in improving mental health and related outcomes, according to a research review in the September/October issue of the Harvard Review of Psychiatry.
Out-of-pocket health costs can lead to financial problems for survivors of childhood cancerFeaturing Ryan Nipp, MD
Adult survivors of childhood cancer face an increased likelihood of financial difficulties related to out-of-pocket costs for their health care, compared with adults not affected by childhood cancer, according to new research published by investigators at the Mass General Cancer Center.
Study estimates number of births, population prevalence of Down syndrome in nine statesFeaturing Brian Stotko, MD, MPP
A new study estimates, for the first time, both the numbers of children born annually with Down syndrome in nine U.S. states and the prevalence of Down syndrome in each of those states’ populations.
Mass General team reports first response of central nervous system tumor to CAR T cellsFeaturing Jeremy Abramson, MD
In a letter to the New England Journal of Medicine, a Massachusetts General Hospital research team reports a remarkable treatment response in a patient participating in a clinical trial of a novel immune-system-based cancer therapy.
Medical treatment may prevent, alleviate mitral valve damage after a heart attackFeaturing Robert Levine, MD, and Jacob Dal-Bianco, MD
A research team led by investigators from Massachusetts General Hospital has shown, for the first time, that it may be possible to nonsurgically treat or even prevent the damage to a major heart valve that often occurs after a heart attack.
Brain Structural Changes Linked to Physical, Mental Health in Functional Neurological Disorder (Conversion Disorder)Featuring David Perez, MD, MMSc
An imaging study by Massachusetts General Hospital investigators has identified difference in key brain structures of individuals whose physical or mental health has been most seriously impaired by a common but poorly understood condition called functional neurological disorder.
Cutbacks in Foreign Aid for HIV Treatment Would Produce Great Harm, Generate Few SavingsFeaturing Rochelle Walensky, MD, MPH
Proposed reductions in U.S. foreign aid would have a devastating impact on HIV treatment and prevention programs in countries receiving such aid, reports an international team led by researchers at Massachusetts General Hospital.
More than Just a Pastime: How Video Games Change Your Brain Post by our summer communications intern Shika Lakshman, a student at Emerson College
"Video games. We all play them, whether it’s Candy Crush on the way to work, or hours-long sessions of Call of Duty. So when I recently read an article about a new research study detailing the positive and negative effects of playing video games, I decided to follow up."
Faherty Hopes to Stop Shigella From Wreaking Havoc in the Digestive SystemFeaturing Christina Faherty, PhD
A research team at Massachusetts General Hospital is hoping to create new treatments for shigellosis, a potentially fatal digestive disorder, by factoring in genetic changes that occur in Shigella bacteria during the journey through the human digestive system.
Snapshot of Science for July 2017: Zebrafish, Steroid Replacements, and Much MoreFeaturing Caroline Burns, PhD, Patrick Purdon, PhD, Rohit Sharma, PhD, John Stone, MD, MPH
In this post we feature author-provided summaries of recent Mass General research studies that have been published in high-impact, top tier journals.
New Study Shows Lymph Nodes Aren't Always to Blame for Cancer's ProgressionFeaturing Rakesh K. Jain, PhD, and Kamila Naxerova, PhD
In a case of mistaken identity, researchers at Massachusetts General Hospital have found that lymph nodes are not always responsible for cancer’s deadly spread to other organs. These results buck many preconceived notions about lymph nodes’ role in cancer development and suggest a new pattern for the progression of certain types of cancer.
Sniffing Out the Root Cause of Malnutrition in Patients with Kidney DiseaseFeaturing Teodor Paunescu, PhD, and Sagar Migwekar, MD
Have you noticed that your sense of taste can get thrown off when you’re sick with a stuffy nose? That’s because the majority of a food’s flavor comes from our ability to smell it. Could a similar connection between smell and taste explain why kidney disease patients often lose their interest in food, reporting that it has little flavor or an unpleasant taste?
Shining a Light of MS-Related FatigueFeaturing Farrah Mateen, MD, PhD
When the days are short and daylight is scant in the winter months, using special lamps that create artificial sunlight can help alleviate the symptoms of seasonal affective disorder — commonly referred to as the winter blues. But could light therapy serve a grander purpose and help treat the debilitating symptoms associated with neurological diseases?
Making Migraines Less of A Headache: Researchers Test New Way to Predict Migraine AttacksFeaturing Tim Houle, PhD
If you’ve ever felt the pulsating pain, nausea and blinding light sensitivity that comes with a migraine, you’re not alone. In the US, more than 37 million people get these severe headache attacks that can last for several hours at a time. While more work is needed before the model is ready for clinical use, a system that reliably predicts the onset of migraines could provide much needed relief for chronic migraine sufferers.
Research Awards and Honors for August 2017Featuring Guardia Banister, RN, PhD, NEA-BC, FAAN, Jennifer Gatchel, MD, PhD, Aaron Hata, MD, PhD, Steven H. Liang, PhD, Mikael Pittet, PhD, and Dorothy Sippo, MD, MPHMassachusetts General Hospital’s talented and dedicated researchers are working to push the boundaries of science and medicine every day. In this series we highlight a few individuals who have recently received awards or honors for their achievements.
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