Back to Main

Faculty Detail    
Name GUANLAN XU
 
Campus Address SHEL 1272 Zip 1200
Phone  (20-5) -930
E-mail  gxu@uab.edu
Other websites
     

Education
Graduate  Fudan University, Shanghai, China    2008  Ph.D 
Fellowship  University of Wisconsin-Madison, Madison, WI    2010  Postdoctoral Fellow 
Fellowship  University of Alabama at Birmingham, Birmingham, AL    2014  Postdoctoral Fellow 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Medicine  Med - Endocrinology, Diabetes & Metabolism Instructor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Instructor

Biographical Sketch 
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.

Society Memberships
Organization Name Position Held Org Link
American Diabetes Association  Member   



Research/Clinical Interest
Title
Instructor
Description

Selected Publications 
Publication PUBMEDID
https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/56166057/?sort=date&direction=descending   
1. Xu G, Thielen LA, Chen J, Grayson TB, Grimes T, Bridges SL Jr, Tse HM, Smith B, Patel R, Li P, Evans-Molina C, Ovalle F, Shalev A. Serum miR-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss. Am J Physiol Endocrinol Metab. 2019 Aug 13. doi:10.1152/ajpendo.00122.2019. [Epub ahead of print] PMID: 31408375
2. Ovalle F, Grimes T, Xu G, Patel AJ, Grayson TB, Thielen LA, Li P, Shalev A. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med. 2018 Aug;24(8):1108-1112. PubMed PMID: 29988125; PubMed Central PMCID: PMC6092963.
3. Jo S, Chen J, Xu G, Grayson TB, Thielen LA, Shalev A. miR-204 Controls Glucagon-Like Peptide 1 Receptor Expression and Agonist Function. Diabetes. 2018 Feb;67(2):256-264. PubMed PMID:29101219; PubMed Central PMCID: PMC5780066.
4. Jing G, Chen J, Xu G and Shalev A. Islet ChREBP-β is increased in diabetes and controls ChREBP-α and glucose-induced gene expression via a negative feedback loop. Mol Metab. 2016. Dec. 5 (12), 1208-1215.
5. Xu G*, Chen J, Truman G, Jing G and Shalev A*. MiRNA-204 targets PERK and regulates unfolded protein response signaling and beta cell apoptosis. Mol Endocrinol. 2016. 30 (8), 917-924. (*Corresponding author)
6. Hong K, Xu G, Truman G, Shalev A. Cytokines regulate beta cell TXNIP via distinct mechanisms and pathways. J Biol Chem. In press.
7. Filios SR, Xu G, Chen J, Hong K, Jing G, Shalev A. MiR-200 is induced by thioredoxin-interacting protein and regulates ZEB1 signaling and beta cell apoptosis. J Biol Chem. 2014 Dec 26;289(52):36275-83..
8. Chen J, Jing G, Xu G and Shalev A. TXNIP stimulates its own expression via a positive feedback loop and ChREBP. Mol Endocrinol. 2014 May;28(5):674-80.
9. Jing G, Westwell-Roper C, Chen J, Xu G, Verchere B and Shalev A. Thioredoxin-interacting protein promotes islets amyloid polypeptide expression through miR-124A and FOXA2. J Biol Chem. 2014 Apr 25;289(17):11807-15.
10. Xu G, Chen J, Jing G, Shalev, A. Thioredoxin-interacting protein regulates insulin transcription through microRNA-204. Nat Med. 2013 Sep;19(9):1141-6.
11. Kibbe C, Chen J, Xu G, Jing G, Shalev A. FOXO1 competes with ChREBP and inhibits TXNIP transcription in pancreatic beta cells. J Biol Chem. 2013 Jun 26. 2013 Aug 9;288(32):23194-202.
12. Cha-Molstad H*, Xu G*, Chen J, Jing G, Young ME, Chatham JC, Shalev A. Calcium channel blockers act through nuclear factor Y to control transcription of key cardiac genes. Mol Pharmacol. 2012 Sep;82(3):541-9. (*Contributed equally to this work)
13. Xu G, Chen J, Jing G, Shalev A. Preventing beta cell loss and diabetes with calcium channel blockers. Diabetes. 2012 Apr;61(4):848-56.
14. Xu G, Pan Y, Wang B, Huang L, Tian L, Xue J, Chen J, Jia W. TTRAP is a novel PML nuclear bodies-associated protein. Biochem Biophys Res Commun. 2008 Oct 24;375(3):395-8.
15. Xu G, Ren J, Ding N, Ai H, Guo Y, Chen C, Huang L. Genetic analysis of the KIT and MC1R genes in Chinese indigenous pigs with belt-like coat color phenotypes. Anim Genet. 2006 Oct;37(5):518-9. 
 

Keywords
Diabetes, beta cell, insulin, microRNA.