Now showing items 1-16 of 16

    • Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones 

      Maianti, Juan Pablo; McFedries, Amanda; Foda, Zachariah H.; Kleiner, Ralph; Du, Xiu Quan; Leissring, Malcolm A.; Tang, Wei-Jen; Charron, Maureen J.; Seeliger, Markus A.; Saghatelian, Alan; Liu, David Ruchien (Nature Publishing Group, 2014)
      Despite decades of speculation that inhibiting endogenous insulin degradation might treat type-2 diabetes, and the identification of IDE (insulin-degrading enzyme) as a diabetes susceptibility gene, the relationship between ...
    • The Biochemistry and Physiology of Peptidases 

      Lone, Anna Mari (2013-03-14)
      Peptidases regulate important physiological processes by controlling levels of bioactive peptides and occasionally through noncatalytic processes. This thesis presents a study of prolyl endopeptidase-like (PREPL), which ...
    • Characterization of Protein-Metabolite and Protein-Substrate Interactions of Disease Genes 

      McFedries, Amanda Kathryn (2014-06-06)
      Discovery of protein-metabolite and protein-substrate interactions that can specifically regulate genes involved in human biology is an important pursuit, as the study of such interactions can expand our understanding of ...
    • Deletion of Prepl Causes Growth Impairment and Hypotonia in Mice 

      Lone, Anna Mari; Leidl, Mathias; McFedries, Amanda K.; Horner, James W.; Creemers, John; Saghatelian, Alan (Public Library of Science, 2014)
      Genetic studies of rare diseases can identify genes of unknown function that strongly impact human physiology. Prolyl endopeptidase-like (PREPL) is an uncharacterized member of the prolyl peptidase family that was discovered ...
    • Discovering Bioactive Peptides and Characterizing the Molecular Pathways that Control Their Activity 

      Mitchell, Andrew (2012-08-15)
      Bioactive peptides constitute a major class of signaling molecules in animals and have been shown to play a role in diverse physiological processes, including hypertension, appetite and sleep. As a result, knowing the ...
    • Discovery and Characterization of Novel Bioactive Peptides and a Natural ERRalpha Ligand 

      Schwaid, Adam (2013-10-17)
      Metabolites and peptides have a central role in biology that is often overlooked. Despite the importance of metabolites in key protein-metabolite interactions (PMIs), the extent and identity of these interactions is not ...
    • Discovery and Characterization of Novel smORF-Encoded Polypeptides (SEPs) 

      Ma, Jiao (2016-01-04)
      Peptides and small proteins have essential physiological roles including metabolism (insulin), sleep (orexin), and stress (corticotropin-releasing hormone). Recent exploration of the human genome and proteome has revealed ...
    • Discovery of bioactive lipids and lipid pathways in cell death and disease 

      Zhang, Tejia (2014-06-06)
      Apoptosis is an intricately regulated cellular process required for the health and homeostasis of living systems. The mitochondrial apoptotic pathway depends on the BCL-2 family of pro- and anti-apoptotic members whose ...
    • Discovery of Novel Lipid Pathways associated with the Metabolic Syndrome 

      Homan, Edwin (2013-02-19)
      The prevalence of obesity and type 2 diabetes has increased at alarming rates in recent decades. These diseases are prominent components of the metabolic syndrome, which is characterized by marked dyslipidemia. Adipose ...
    • Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans 

      Cezairliyan, Brent Orvin; Vinayavekhin, Nawaporn; Grenfell-Lee, Daniel; Yuen, Grace J.; Saghatelian, Alan; Ausubel, Frederick M. (Public Library of Science, 2013)
      Pathogenic microbes employ a variety of methods to overcome host defenses, including the production and dispersal of molecules that are toxic to their hosts. Pseudomonas aeruginosa, a Gram-negative bacterium, is a pathogen ...
    • Macrophage VLDL Receptor Promotes PAFAH Secretion in Mother’s Milk and Suppresses Systemic Inflammation in Nursing Neonates 

      Du, Yang; Yang, Marie; Wei, Wei; Huynh, Hoang Dinh; Herz, Joachim; Saghatelian, Alan; Wan, Yihong (Nature Publishing Group, 2012)
      Mother’s milk is widely accepted as nutritious and protective to the newborn mammals by providing not only macronutrients but also immune-defensive factors. However, the mechanisms accounting for these benefits are not ...
    • The Metabolite α-Ketoglutarate Extends Lifespan by Inhibiting ATP Synthase and TOR 

      Chin, Randall M.; Fu, Xudong; Pai, Melody Y.; Vergnes, Laurent; Hwang, Heejun; Deng, Gang; Diep, Simon; Lomenick, Brett; Meli, Vijaykumar S.; Monsalve, Gabriela C.; Hu, Eileen; Whelan, Stephen A.; Wang, Jennifer X; Jung, Gwanghyun; Solis, Gregory M.; Fazlollahi, Farbod; Kaweeteerawat, Chitrada; Quach, Austin; Nili, Mahta; Krall, Abby S.; Godwin, Hilary A.; Chang, Helena R.; Faull, Kym F.; Guo, Feng; Jiang, Meisheng; Trauger, Sunia A; Saghatelian, Alan; Braas, Daniel; Christofk, Heather R.; Clarke, Catherine F.; Teitell, Michael A.; Petrascheck, Michael; Reue, Karen; Jung, Michael E.; Frand, Alison R.; Huang, Jing (Nature Publishing Group, 2014)
      Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms1, 2. Similar conditions ...
    • Metabolomics Strategies for Discovery of Biologically Active or Novel Metabolites 

      Vinayavekhin, Nawaporn (2013-02-08)
      Along with genes and proteins, metabolites play important roles in sustaining life. There remains much to be learned about the in vivo roles of metabolites. Metabolomics is a comparative tool to study global metabolite ...
    • Peptidomic discovery of short open reading frame-encoded peptides in human cells 

      Slavoff, Sarah A.; Mitchell, Andrew J.; Schwaid, Adam G.; Cabili, Moran N.; Ma, Jiao; Levin, Joshua Z.; Karger, Amir; Budnik, Bogdan A.; Rinn, John L.; Saghatelian, Alan (2013)
      The amount of the transcriptome that is translated into polypeptides is of fundamental importance. We developed a peptidomic strategy to detect short ORF (sORF)-encoded polypeptides (SEPs) in human cells. We identified 90 ...
    • Proteolysis Controls Endogenous Substance P Levels 

      Mitchell, Andrew J.; Lone, Anna Mari; Tinoco, Arthur D.; Saghatelian, Alan (Public Library of Science, 2013)
      Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP ...
    • Therapeutic potential and physiological roles of Insulin-Degrading Enzyme illuminated by a DNA-templated macrocyclic inhibitor 

      Maianti, Juan Pablo (2015-05-19)
      Insulin-Degrading Enzyme (IDE) is a zinc-metalloprotease responsible for the clearance of insulin in peripheral tissues. Despite decades of speculation that inhibiting endogenous insulin degradation might treat Type-2 ...