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NEWS & EVENTS

  • September 25, 2015. The Reilly Lab from the Pennsylvania Center suggests that knowledge of IRF2BP2 expression and signaling in human macrophages could provide opportunities for the development of novel anti-inflammatory therapeutics. Macrophages mediate tissue innate immune response and lipid metabolism, acting as a key player at the crossroads of innate immunity and lipid homeostasis in atherosclerosis. Restoring IRF2BP2 expression and signaling in macrophages could become a promising strategy to limit inflammatory response in cardio-metabolic diseases. Circ Res. 2015 Sep 25;117(8):656-8.
  • August 2015. The Rzhetsky Lab from the Coordination Center published a Nature Biotechnology paper on a novel health research opportunity index (ROI) to identify diseases where investment in research would yield the most benefits. If a disease is not seen as scientifically interesting, or is perceived as unlikely to yield a marketable therapy, it may remain under-researched and under-funded, even if it poses a substantial health burden. ROI is used for identifying diseases where investment in research would yield the most benefits. By considering the human benefits that could be gained from cure, society can improve its allocation of resources. Nat Biotechnol. 2015 Aug;33(8):807-11.
  • August 4, 2015. The Loscalzo Lab from the Harvard Center identifies L-2-hydroxyglutarate (L2HG), a metabolite of unknown function, as a universal adaptive determinant of the hypoxia response. L2HG inhibits electron transport and glycolysis, offsetting the adverse consequences of mitochondrial reductive stress caused by hypoxia. Cell Metab. 2015 Aug 4;22(2):291-303.
  • August 3, 2015. Studies of the Elias and Lee groups from the the Brown/Yale Center indicate that circulating chitinase-3-like-1 (CHI3L1) protein levels are higher in Hermansky-Pudlak syndrome (HPS) patients with pulmonary fibrosis compared with those who remain fibrosis free, and associate with disease severity. This suggests that levels of circulating CHI3L1 might be a clinically useful biomarker for predicting development of lung disease in HPS patients.J Clin Invest. 2015 Aug 3;125(8):3178-92
  • June 19, 2015. The Reilly Lab from the Pennsylvania Center develops an efficient protocol for generation of human induced pluripotent stem cell-derived macrophages (IPSDM), a significant step forward for the utilization of induced pluripotent stem cell-derived macrophages in defining subtle macrophage phenotypes in Mendelian disorders. This lays the groundwork for IPSDM’s use with genome editing technologies to model genetic effects of rare Mendelian mutations. Circ Res. 2015 Jun 19;117(1):17-28.
  • April 1, 2015. The Elias and Lee groups from the the Brown/Yale Center find that Chitinase-3-like-1 (CHI3L1) is induced by a high fat diet and Th2 inflammation, and simultaneously contributes to the genesis of obesity and asthma. Studies strongly suggest Chitinase-3-like-1 plays a role in the biology underlying asthma, obesity, and other disorders, yet there has been little insight in the mechanisms underlying this association. This research indicates that visceral adiposity and asthma share chitinase-3-like-1 dependent pathways, allowing for the hypothesis that a high-fat western diet increases visceral adiposity and asthma, at least in part, via chitinase-3-like-1 stimulation. This points towards novel therapeutic and preventative strategies for obesity-related asthma. Am J Respir Crit Care Med. 2015 Apr 1;191(7):746-57.
  • March 31, 2015. The Reilly Lab from the Pennsylvania Center performs the first in vivo experimental validation of the association of Adamts7 with atherogenesis, and indicates Adamts7 may promote progression and complications of human coronary atherosclerotic diseases. This research finds that Adamts7 has promises as a potentially safe drug target for the treatment of these diseases. Circulation. 2015 Mar 31;131(13):1202-13.
  • March 9, 2015. The 5th MAPGen Consortium meeting was held in Washingtong D.C.
  • February 20, 2015. The Barabási and Loscalzo groups from the Harvard Center published a Science paper that designs a novel approach to predict similarities between diseases by using the location of disease modules in the incomplete human interactome, even when they don’t share primary disease genes. The human interactome, the map of biologically relevant molecular interactions, is far from complete. They derive mathematical conditions to identify disease modules in this incomplete map. The framework can be extended to address numerous questions at the forefront of network medicine, from interpreting GWAS data to drug target identification and repurposing. Science. 2015 Feb 20;347(6224):1257601.
  • July 2014. The Coordination Center is pleased to announce that the DiseaseConnect database server (http://www.disease-connect.org/) is now public. This is a web server for analysis and visualization of a comprehensive knowledge on mechanism-based disease connectivity. DiseaseConnect, the first public web server, integrates comprehensive omics and literature data, including a large amount of gene expression data, Genome-Wide Association Studies catalog, and text-mined knowledge, to discover disease-disease connectivity via common molecular mechanisms. Moreover, the clinical comorbidity data and a comprehensive compilation of known drug-disease relationships are additionally utilized for advancing the understanding of the disease landscape and for facilitating the mechanism-based development of new drug treatments. Nucleic Acids Res. 2014 Jul;42(Web Server issue):W137-46.
  • June 11, 2014. Studies of the Elias and Herzog groups from the Brown/Yale Center suggest that Chitinase 3-like 1 (CHI3L1), a prototypic chitinase-like protein, exerts complex and seemingly opposed effects in pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis exhibit elevated CHI3L1 levels. This protein exerts complex and opposed effects in pulmonary fibrosis - inhibiting injury and decreasing fibrosis on one hand and increasing fibroproliferative repair and tissue scarring on the other. Sci Transl Med. 2014 Jun 11;6(240):240ra76.
  • April 25, 2014. The 4th MAPGen Consortium meeting was held in Washingtong D.C.
  • October 2, 2013. The Kaminski Lab from the Yale/Iowa/Pittsburgh Center identifies biomarkers capable of identifying idiopathic pulmonary fibrosis (IPF) patients destined for poor outcomes - something of considerable value in clinical evaluations and patient management. Microarray analyses identified 52 genes associated with transplant-free survival in IPF. Four genes were identified as potential outcome biomarkers in IPF and can be used for further studies involving patient prioritization in lung transplantation and stratification in drug studies. Sci Transl Med. 2013 Oct 2;5(205):205ra136.
  • September 26, 2013. The Rzhetsky Lab from the Coordination Center develops a new approach that links complex disorders to unique collections of Mendelian loci. While Mendelian disorders have a precise genetic cause, the etiologies of complex diseases are largely unknown. By mining the medical records of over 110 million patients, it is found that common variants in complex diseases were often enriched for Mendelian loci - illustrating a new approach for mapping complex disease loci and providing unique predictions about the causes of specific diseases. The results were published in Cell. 2013 Sep 26;155(1):70-80.
  • September 24, 2013. The Bar-Joseph Lab from the Harvard Center and the Kaminski Lab from the Yale/Iowa/Pittsburgh Center develop "MIRna Dynamic Regulatory Events Miner (mirDREM)", a novel modeling method to explain the regulation of gene expression by transcription factors and miRNAs. In idiopathic pulmonary fibrosis patients, mirDREM indicates some disease progression pathways may represent partial reversal of lung differentiation. Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15686-91.
  • August 2013. The Barabási Lab from the Harvard Center develops a novel method to prune erroneous connections in biological networks derived from experimental data. Biological networks are often based on correlations between experimental measurements, like gene expression. However, these correlations may be confounded by indirect paths - limiting our ability to truly identify pairwise interactions. Therefore, this method can take observed correlation matrices and enhance those correlations associated with direct, causal links. Nat Biotechnol. 2013 Aug;31(8):720-5. This research was highlighted in the Nature News and View.
  • July 2013. The Barabási Lab from the Harvard Center defines a small number of universal characteristics to predict the behavior of complex systems. Most of the advances in predicting the behavior of a complex system have been specific to the system at hand, requiring unique analytical and numerical tools for each system. Here, Barzle and Barabasi predict that a complex system reacts to perturbations according to a small number of universal characteristics. Nat Physics. 2013 July;9:673-81.
  • April 24, 2013. The 3rd MAPGen Consortium meeting was held in Washingtong D.C.
  • September 21, 2012. The 2nd MAPGen Consortium meeting was held in Washingtong D.C.
  • July 19, 2012. The Elias and Lee groups from the the Brown/Yale Center study the antimicrobial responses of wild type and chitinase-3-like-1 (CHI3L1) knockout mice infected with Streptococcus pneumoniae. Null mutations of CHI3L1 resulted in increased injury, inflammation, and diminished survival. They determine that CHI3L1 plays a central role in promoting bacterial clearance and mediating host tolerance, and these roles likely contributed to its retention over species and evolutionary time. Cell Host Microbe. 2012 Jul 19;12(1):34-46.
  • February 14, 2012. The 1st MAPGen Consortium meeting was held in Washingtong D.C.
  • October 5, 2011. The Loscalzo Lab from the Harvard Center develops genetically encoded fluorescent sensors for reduced NADH, which manifest a large change in fluorescence upon NADH binding. These sensors are able to monitor dynamic changes in NADH levels in subcellular organelles. With superior sensitivity and specificity to existing techniques, these sensors provide a very good alternative for the selective monitoring of total cellular and compartmental responses of this essential cofactor. Cell Metab. 2011 Oct 5;14(4):555-66.
  • August 2011. The MAPGen Consortium got funded from NIH/NHLBI.