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Brouwer, C.

Publications and source records attributed to Brouwer, C..

2 recordsLinked to original sources

The Aliment to Bodily Condition knowledgebase (ABCkb): A database connecting plants and human health

ObjectiveOverconsumption of processed foods has led to an increase in chronic diet-related diseases such obesity and type 2 diabetes. Although diets high in fresh fruits and vegetables are linked with healthier outcomes, the specific mechanisms for these relationships are poorly understood. Experiments examining plant phytochemical production and breeding programs, or separately on the health effects of nutritional supplements have yielded results that are sparse, siloed, and difficult to integrate between the domains of human health and agriculture. To connect plant products to health outcomes through their molecular mechanism an integrated computational resource is necessary. ResultsWe created the Aliment to Bodily Condition Knowledgebase (ABCkb) to connect plants to human health by creating a stepwise path from plant [->] plant product [->] human gene [->] pathways [->] indication. ABCkb integrates 11 curated sources as well as relationships mined from Medline abstracts by loading into a graph database which is deployed via a Docker container. This new resource, provided in a queryable container with a user-friendly interface connects plant products with human health outcomes for generating nutritive hypotheses. All scripts used are available on github (https://github.com/atrautm1/ABCkb) along with basic directions for building the knowledgebase.

bioinformatics

Tumor -Associated MUC1 Regulates TGF-β Signaling and Function in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human cancers. Transforming Growth Factor Beta (TGF-{beta}) is a cytokine that switches from a tumor-suppressor to a tumor promoter throughout tumor development, by a yet unknown mechanism. Tumor associated MUC1 (tMUC1) is aberrantly glycosylated and overexpressed in >80% of PDAs and is associated with poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) interacts with other oncogenic proteins promoting tumor progression and metastasis. We hypothesize that tMUC1 levels regulate TGF-{beta} functions in PDA in vitro and in vivo. We report that high-tMUC1 expression positively correlates to TGF-{beta}RII and negatively to TGF-{beta}RI receptors. In response to TGF-{beta}1, high tMUC1 expressing PDA cells undergo c-Src phosphorylation, and activation of the Erk/MAPK pathway; while low tMUC1 expressing cells activate the Smad2/3 pathway, enhancing cell death. Correspondingly, mice bearing tMUC1-high tumors responded to TGF-{beta}1 neutralizing antibody in vivo showing significantly retarded tumor growth. Analysis of clinical data from TCGA revealed significant alterations in gene-gene correlations in the TGF-{beta} pathway in tMUC1 high versus tMUC1 low samples. This study deepens our understanding of tMUC1-regulated TGF-{beta}s paradoxical function in PDA and establishes tMUC1 as a potential biomarker to predict response to TGF-{beta}-targeted therapies.

cancer biology