• Loss of functional beta cell mass is a hallmark of both type 1 and type 2 diabetes. However, the mechanism that mediates this process has not been elucidated, and corresponding therapies have not been developed. MicroRNAs are ~ 22-nt small RNAs that mediate post-transcriptional regulation of gene expression. Dr. Xu found that diabetes induces the beta cell miR-204, which in turn represses insulin transcription by targeting and inhibiting the insulin transcription factor MAFA. His work also showed that miR-204 exacerbates ER stress-induced beta cell death by targeting the UPR protein PERK. His current work aims at inhibiting miR-204 to improve beta cell function and survival in the context of diabetes. In addition, Dr. Xu also works on developing strategies to halt beta cell loss in diabetes. He found that the anti-hypertension drug verapamil can prevent and even rescue beta cell apoptosis by targeting thioredoxin interacting protein (TXNIP) in the context of type 1 and type 2 diabetes. This study is currently in a phase II clinical trial.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetesNature Communications.  13. 2022
    2022 Alpha Cell Thioredoxin-interacting Protein Deletion Improves Diabetes-associated Hyperglycemia and Hyperglucagonemia 2022
    2022 Deletion of Gdf15 Reduces ER Stress-induced Beta-cell Apoptosis and Diabetes 2022
    2021 Human Glucagon Expression Is under the Control of miR-320a 2021
    2020 Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP Expression and Glucagon ActionCell Metabolism.  32:353-365.e8. 2020
    2019 Serum mir-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss 2019
    2018 Verapamil and beta cell function in adults with recent-onset type 1 diabetesNature Medicine.  24:1108-1112. 2018
    2018 miR-204 controls glucagon-like peptide 1 receptor expression and agonist functionDiabetes.  67:256-264. 2018
    2016 Islet ChREBP-β is increased in diabetes and controls ChREBP-α and glucose-induced gene expression via a negative feedback loopMolecular Metabolism.  5:1208-1215. 2016
    2016 MiR-204 targets PERK and regulates UPR signaling and β-cell apoptosis 2016
    2016 Cytokines regulate β-Cell Thioredoxin-interacting Protein (TXNIP) via distinct mechanisms and pathwaysJournal of Biological Chemistry.  291:8428-8439. 2016
    2014 MicroRNA-200 is induced by thioredoxin-interacting protein and regulates Zeb1 protein signaling and beta cellJournal of Biological Chemistry.  289:36275-36283. 2014
    2014 Thioredoxin-interacting protein promotes islet amyloid polypeptide expression through miR-124a and FoxA2Journal of Biological Chemistry.  289:11807-11815. 2014
    2014 Thioredoxin-interacting protein stimulates its own expression via a positive feedback loop 2014
    2013 Thioredoxin-interacting protein regulates insulin transcription through microRNA-204Nature Medicine.  19:1141-1146. 2013
    2013 FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cellsJournal of Biological Chemistry.  288:23194-23202. 2013
    2012 Calcium channel blockers act through nuclear factor Y to control transcription of key cardiac genesMolecular Pharmacology.  82:541-549. 2012
    2012 Preventing β-cell loss and diabetes with calcium channel blockersDiabetes.  61:848-856. 2012
    2012 The 156KELK159 tetrapeptide of HIV-1 integrase is critical for lentiviral gene integration 2012
    2011 Sp100 interacts with phage ΦC31 integrase to inhibit its recombination activityActa Biochimica Polonica.  58:67-73. 2011
    2010 Φc31 integrase interacts with TTRAP and inhibits NFκB activation 2010
    2010 Identification and developmental expression of Dec2 in zebrafishFish Physiology and Biochemistry.  36:667-675. 2010
    2008 TTRAP is a novel PML nuclear bodies-associated proteinBiochemical and Biophysical Research Communications.  375:395-398. 2008
    2008 Daxx interacts with HIV-1 integrase and inhibits lentiviral gene expressionBiochemical and Biophysical Research Communications.  373:241-245. 2008
    2006 DAXX interacts with phage ΦC31 integrase and inhibits recombinationNucleic Acids Research.  34:6298-6304. 2006

    Education And Training

  • Doctor of Philosophy in Molecular Genetics, Fudan University 2008
  • Full Name

  • Guanlan Xu