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CBCB faculty Eytan Ruppin’s group publish a review paper in Molecular Systems Biology on genome-scale modeling of cancer metabolism describing current accomplishments and future challenges
Cancer cells have fundamentally altered cellular metabolism that is associated with their tumorigenicity and malignancy. In addition to the widely studied Warburg effect, several new key metabolic alterations in cancer have been established over the last decade, leading to the recognition that altered tumor metabolism is one of the hallmarks of cancer. Deciphering the full scope and functional implications of the dysregulated metabolism in cancer requires both the advancement of a variety of omics measurements and the advancement of computational approaches for the analysis and contextualization of the accumulated data. Encouragingly, while the metabolic network is highly interconnected and complex, it is at the same time probably the best characterized cellular network. Following, these researchers discuss the challenges that genome‐scale modeling of cancer metabolism has been facing. They survey several recent studies demonstrating the first strides that have been done, testifying to the value of this approach in portraying a network‐level view of the cancer metabolism and in identifying novel drug targets and biomarkers. Finally, they outline a few new steps that may further advance this field.
“Modeling cancer metabolism on a genome scale” article: http://msb.embopress.org/content/11/6/817
CBCB faculty Zia Khan is part of multi-institutional team awarded $1M Human Frontier Science Grant
CBCB faculty Eytan Ruppin’s group publish a paper in Molecular Systems Biology on effectiveness of drugs that reverse disease transcriptomic signatures in a mouse model of dyslipidemia
High-throughputomics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the physiological manifestations of the disease, especially in response to treatment, has not been investigated in a systematic manner. To this end, these researchers studied a mouse model of dietinduced dyslipidemia and atherosclerosis that was subject to various drug treatments relevant to the disease in question. Both physiological data and gene expression data (from the liver and white adipose) were analyzed and compared. They found that treatments that restore gene expression patterns to their norm are associated with the successful restoration of physiological markers to their baselines. This holds in a tissue-specific manner—treatments that reverse the transcriptomic signatures of the disease in a particular tissue are associated with positive physiological effects in that tissue. Further, treatments that introduce large non-restorative gene expression alterations are associated with unfavorable physiological outcomes. These results provide a sound basis to in silico methods that rely on omic metrics for drug repurposing and drug discovery by searching for compounds that reverse a disease’s omic signatures. Moreover, they highlight the need to develop drugs that restore the global cellular state to its healthy norm rather than rectify particular disease phenotypes.
“Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia“ article: http://msb.embopress.org/content/11/3/791
CBCB alumni win prestigious Sloan Fellowship
CBCB faculty Zia Khan publishes a paper in Science on the impact of regulatory variation from RNA to protein
CBCB faculty Eytan Ruppin’s group publish a paper in eLife on phenotype-based cell-specific metabolic modeling
Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies. To this end, they present an approach termed PRIME for generating cell-specific genome-scale metabolic models (GSMMs) based on molecular and phenotypic data. They built >280 models of normal and cancer cell-lines that successfully predict metabolic phenotypes in an individual manner. They utilize this set of cell-specific models to predict drug targets that selectively inhibit cancerous but not normal cell proliferation. The top predicted target, MLYCD, was experimentally validated and the metabolic effects of MLYCD depletion were investigated. Furthermore, they tested cell-specific predicted responses to the inhibition of metabolic enzymes, and successfully inferred the prognosis of cancer patients based on their PRIME-derived individual GSMMs. These results lay a computational basis and a counterpart experimental proof of concept for future personalized metabolic modeling applications, enhancing the search for novel selective anticancer therapies.
“Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer” article: http://www.cs.tau.ac.il/~ruppin/prime.pdfCBCB researchers Keith Hughitt, Lee Mendelowitz, and Joseph Paulson create an interactive tool that compares country data on women’s empowerment and stunting
CBCB faculty Eytan Ruppin’s group publish a paper in Molecular Systems Biology on computational study of Warburg effect
CBCB faculty Eytan Ruppin's group has published a paper, led by Keren Yizhak, titled “A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration” on July 30, 2014 in the journal Molecular Systems Biology. This article presents a computational analysis of the Warburg effect, which is a key alteration characterizing the metabolism of many cancers. They show that gene knockouts reverting the Warburg effect can inhibit cancer migration and hence the likelihood of spreading metastasis. Their predictions were further tested and corroborated by their experimental collaborators from Leiden (van de Water) and Cambridge (Frezza).
“A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration” article: http://onlinelibrary.wiley.com/doi/10.15252/msb.20134993/pdf
CBCB scientists Héctor Corrada Bravo and Florin Chelaru publish a paper on Epiviz, a web-based tool for interactive visual analytics of genomics data, in Nature Methods
Next-generation sequencing has revolutionized functional genomics. These techniques are key to understanding the molecular mechanisms underlying cell function in healthy and diseased individuals and the development of diseases like cancer. Data from multiple experiments need to be integrated, but the growing number of data sets causes a thorough comparison and analysis of results to be challenging. In Corrada Bravo and Chelaru’s paper, Epiviz is shown to be capable of visualizing and analyzing DNA methylation and gene expression data in colon cancer.
“Epiviz: interactive visual analytics for functional genomics data” article: http://www.nature.com/nmeth/journal/v11/n9/full/nmeth.3038.html
For Florin Chelaru’s discussion on Epiviz and his research in bioinformatics and genomic research, please see: http://www.cs.umd.edu/article/2014/08/florin-chelaru-epiviz-research-and...
For more information, please see: http://cmns.umd.edu/news-events/features/2376
CBCB faculty Eytan Ruppin’s group publish a paper in Cell on predicting cancer-specific vulnerability
“Predicting Cancer-Specific Vulnerability via Data-Driven Detection of Synthetic Lethality” article: http://ac.els-cdn.com/S0092867414009775/1-s2.0-S0092867414009775-main.pd...