Systems Biology Commons^™

Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane

Biostatistics Faculty Publications

Introduction—We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.

Methods—We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions.

Results—We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ …

Transcriptional Pathways Associated With Skeletal Muscle Changes After Spinal Cord Injury And Treadmill Locomotor Training., Celine Baligand, Yi-Wen Chen, Fan Ye, Sachchida Nand Pandey, San-Huei Lai, Min Liu, Krista Vandenborne

Genomics and Precision Medicine Faculty Publications

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and …

Non-Invasive Mri And Spectroscopy Of Mdx Mice Reveal Temporal Changes In Dystrophic Muscle Imaging And In Energy Deficits., Christopher R. Heier, Alfredo D. Guerron, Alexandru Korotcov, Stephen Lin, Heather Gordish-Dressman, Stanley Fricke, Raymond W. Sze, Eric P. Hoffman, Paul Wang, Kanneboyina Nagaraju

Genomics and Precision Medicine Faculty Publications

In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein expression results in repeated muscle injury and chronic inflammation. Magnetic resonance imaging shows promise as a surrogate outcome measure in both DMD and rehabilitation medicine that is capable of predicting clinical benefit years in advance of functional outcome measures. The mdx mouse reproduces the dystrophin deficiency that causes DMD and is routinely used for preclinical drug testing. There is a need to develop sensitive, non-invasive outcome measures in the mdx model that can be readily translatable to human clinical trials. Here we report the use of magnetic resonance imaging …

Drawing Lines In The Sand: Even Skipped Et Al. And Parasegment Boundaries., James B. Jaynes, Miki Fujioka

Department of Biochemistry and Molecular Biology Faculty Papers

The pair-rule segmentation gene even skipped (eve) is required to activate engrailed stripes and to organize odd-numbered parasegments (PSs). The protein product Eve has been shown to be an active repressor of transcription, and recent models for Eve function suggest that activation of engrailed is indirect, but these models have not been fully tested. Here we identify the forkhead domain transcription factor Sloppy-paired as the key intermediate in the initial activation of engrailed by Eve in odd-numbered parasegments. We also analyze the roles of the transcription factors Runt and Odd-skipped in this process. Detailed analysis of engrailed and pair-rule gene …