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Beaker is Sanford-Burnham Medical Research Institute's science blog, updated frequently to highlight interesting research and news... especially relating to cancer, diabetes, neurodegenerative diseases, rare childhood diseases, stem cells and drug discovery.
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by Patrick Bartosch in Beaker
Sanford-Burnham researchers identified a potential drug target to prevent the hardening of arteries in patients with atherosclerosis. The gene Dkk1 encodes a protein that plays a key role in increasing the population of connective-tissue cells during wound repair, but prolonged Dkk1 signaling in cells lining blood vessels can lead to fibrosis and a stiffening of artery walls.... Read more »
Cheng, S., Shao, J., Behrmann, A., Krchma, K., & Towler, D. (2013) Dkk1 and Msx2-Wnt7b Signaling Reciprocally Regulate the Endothelial-Mesenchymal Transition in Aortic Endothelial Cells. Arteriosclerosis, Thrombosis, and Vascular Biology. DOI: 10.1161/ATVBAHA.113.300647
by Heather Buschman, Ph.D. in Beaker
Sanford-Burnham researchers discover that several children born with rare diseases called Congenital Disorders of Glycosylation (CDG) don’t contain the mutation in every cell type—raising new questions about inheritance, genomic sequencing, and diagnostics.... Read more »
Ng, B., Buckingham, K., Raymond, K., Kircher, M., Turner, E., He, M., Smith, J., Eroshkin, A., Szybowska, M., Losfeld, M.... (2013) Mosaicism of the UDP-Galactose Transporter SLC35A2 Causes a Congenital Disorder of Glycosylation. The American Journal of Human Genetics, 92(4), 632-636. DOI: 10.1016/j.ajhg.2013.03.012
by Heather Buschman, Ph.D. in Beaker
Sanford-Burnham researchers identify microRNAs as the missing link between the two defining features of muscle fitness—fuel-burning and fiber-type switching—providing a potential new target for interventions that boost fitness in people with chronic illness or injury.... Read more »
Gan, Z., Rumsey, J., Hazen, B., Lai, L., Leone, T., Vega, R., Xie, H., Conley, K., Auwerx, J., Smith, S.... (2013) Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism. Journal of Clinical Investigation. DOI: 10.1172/JCI67652
by Heather Buschman, Ph.D. in Beaker
Imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver in mice and humans—providing a new therapeutic target for these health conditions... Read more »
Mansuy-Aubert, V., Zhou, Q., Xie, X., Gong, Z., Huang, J., Khan, A., Aubert, G., Candelaria, K., Thomas, S., Shin, D.... (2013) Imbalance between Neutrophil Elastase and its Inhibitor α1-Antitrypsin in Obesity Alters Insulin Sensitivity, Inflammation, and Energy Expenditure. Cell Metabolism, 17(4), 534-548. DOI: 10.1016/j.cmet.2013.03.005
by Heather Buschman, Ph.D. in Beaker
Researchers discover that the extra chromosome inherited in Down syndrome impairs learning and memory because it leads to low levels of SNX27 protein in the brain.... Read more »
Wang, X., Zhao, Y., Zhang, X., Badie, H., Zhou, Y., Mu, Y., Loo, L., Cai, L., Thompson, R., Yang, B.... (2013) Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome. Nature Medicine. DOI: 10.1038/nm.3117
by Heather Buschman, Ph.D. in Beaker
Researchers discover that the protein BAF60C is necessary for generating "mini muscles" from stem cells.... Read more »
Albini S, Coutinho P, Malecova B, Giordani L, Savchenko A, Forcales SV, & Puri PL. (2013) Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres. Cell reports. PMID: 23478022
by Heather Buschman, Ph.D. in Beaker
Researchers discover that a protein called Siah2 helps prostate cancer cells resist hormone therapy—making it an attractive biomarker and therapeutic target.... Read more »
Qi, J., Tripathi, M., Mishra, R., Sahgal, N., Fazil, L., Ettinger, S., Placzek, W., Claps, G., Chung, L., Bowtell, D.... (2013) The E3 Ubiquitin Ligase Siah2 Contributes to Castration-Resistant Prostate Cancer by Regulation of Androgen Receptor Transcriptional Activity. Cancer Cell, 23(3), 332-346. DOI: 10.1016/j.ccr.2013.02.016
by Heather Buschman, Ph.D. in Beaker
3D structure of HNF-4α, a protein mutated in a rare, inherited form of diabetes, reveals new pockets that could be targeted with therapeutic drugs... Read more »
Chandra, V., Huang, P., Potluri, N., Wu, D., Kim, Y., & Rastinejad, F. (2013) Multidomain integration in the structure of the HNF-4α nuclear receptor complex. Nature. DOI: 10.1038/nature11966
by Heather Buschman, Ph.D. in Beaker
Researchers use skin cells from patients with an inherited heart condition to recreate the adult-onset disease in a laboratory dish—producing the first maturation-based disease model for testing new therapies.... Read more »
Kim, C., Wong, J., Wen, J., Wang, S., Wang, C., Spiering, S., Kan, N., Forcales, S., Puri, P., Leone, T.... (2013) Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature. DOI: 10.1038/nature11799
by admin in Beaker
Researchers find that certain types of drug-resistant leukemia stem cells are vulnerable to sabutoclax, a novel cancer stem cell-targeting drug based on Sanford-Burnham research.... Read more »
Goff, D., Recart, A., Sadarangani, A., Chun, H., Barrett, C., Krajewska, M., Leu, H., Low-Marchelli, J., Ma, W., Shih, A.... (2013) A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition. Cell Stem Cell. DOI: 10.1016/j.stem.2012.12.011
by Sanford- Burnham in Beaker
First fruit fly model of diet-induced type 2 diabetes shows how high-sugar diet affects the heart and reveals new therapeutic opportunities... Read more »
Na, J., Musselman, L., Pendse, J., Baranski, T., Bodmer, R., Ocorr, K., & Cagan, R. (2013) A Drosophila Model of High Sugar Diet-Induced Cardiomyopathy. PLoS Genetics, 9(1). DOI: 10.1371/journal.pgen.1003175
by Sanford- Burnham in Beaker
A new computational model of sugar transport in the pancreas reveals a metabolic "tipping point” in type 2 diabetes—a discovery that may form the basis for new efforts to prevent and treat the disease.... Read more »
Luni, C., Marth, J., & Doyle, F. (2012) Computational Modeling of Glucose Transport in Pancreatic β-Cells Identifies Metabolic Thresholds and Therapeutic Targets in Diabetes. PLoS ONE, 7(12). DOI: 10.1371/journal.pone.0053130
by Sanford- Burnham in Beaker
Researchers discover that the genes active in a person’s belly fat are significantly different than those in his or her thigh fat, a finding that could shift the way we approach unwanted belly fat—from banishing it to relocating it.... Read more »
Karastergiou K, Fried SK, Xie H, Lee MJ, Divoux A, Rosencrantz MA, Chang RJ, & Smith SR. (2013) Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. The Journal of clinical endocrinology and metabolism, 98(1), 362-71. PMID: 23150689
by Bruce Lieberman in Beaker
Sanford-Burnham researchers show that protein p62 balances metabolism in fat tissue—making it an attractive target for anti-obesity therapies.... Read more »
Müller TD, Lee SJ, Jastroch M, Kabra D, Stemmer K, Aichler M, Abplanalp B, Ananthakrishnan G, Bhardwaj N, Collins S.... (2013) p62 Links β-adrenergic input to mitochondrial function and thermogenesis. The Journal of clinical investigation, 123(1), 469-78. PMID: 23257354
by Bruce Lieberman in Beaker
Dr. Lutz Tautz and colleagues show how the breakup of two proteins interferes with the immune system and demonstrates that inhibiting one of the errant proteins restores proper function. ... Read more »
Vang T, Liu WH, Delacroix L, Wu S, Vasile S, Dahl R, Yang L, Musumeci L, Francis D, Landskron J.... (2012) LYP inhibits T-cell activation when dissociated from CSK. Nature chemical biology, 8(5), 437-46. PMID: 22426112
by Sanford- Burnham in Beaker
Dr. Matt Petroski and colleagues outline a new method to test a tumor’s resistance to an experimental therapy and pinpoint the genetic culprit before testing the drug in patients—providing a new path toward personalized medicine.... Read more »
Toth JI, Yang L, Dahl R, & Petroski MD. (2012) A gatekeeper residue for NEDD8-activating enzyme inhibition by MLN4924. Cell reports, 1(4), 309-16. PMID: 22832224
by Sanford- Burnham in Beaker
Sanford-Burnham researchers convince transplanted stem cell-derived neurons to direct cognitive function—getting us a step closer to using these cells to treat Alzheimer’s disease and other neurodegenerative conditions.... Read more »
Piña-Crespo JC, Talantova M, Cho EG, Soussou W, Dolatabadi N, Ryan SD, Ambasudhan R, McKercher S, Deisseroth K, & Lipton SA. (2012) High-Frequency Hippocampal Oscillations Activated by Optogenetic Stimulation of Transplanted Human ESC-Derived Neurons. The Journal of Neuroscience, 32(45), 15837-42. PMID: 23136422
by admin in Beaker
Dr. Hudson Freeze and colleagues are using whole-exome sequencing to diagnose severe metabolic diseases.... Read more »
Jones MA, Ng BG, Bhide S, Chin E, Rhodenizer D, He P, Losfeld ME, He M, Raymond K, Berry G.... (2012) DDOST Mutations Identified by Whole-Exome Sequencing Are Implicated in Congenital Disorders of Glycosylation. American journal of human genetics. PMID: 22305527
by Sanford- Burnham in Beaker
In 11 independent studies, a consortium of ALS researchers shows that transplanting neural stem cells into the spinal cord of an ALS mouse model slows disease onset and progression, improves motor function, and significantly prolongs survival.... Read more »
Teng YD, Benn SC, Kalkanis SN, Shefner JM, Onario RC, Cheng B, Lachyankar MB, Marconi M, Li J, Yu D.... (2012) Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis. Science translational medicine, 4(165). PMID: 23253611
by Sanford- Burnham in Beaker
Dr. Mark Mercola and his team discovered that microRNAs play an important role in germ layer formation--the process that determines which cells become which organs during embryonic development.... Read more »
Colas AR, McKeithan WL, Cunningham TJ, Bushway PJ, Garmire LX, Duester G, Subramaniam S, & Mercola M. (2012) Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. Genes . PMID: 23152446
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