Dr. Hongju Wu obtained her BS in Biochemistry from Wuhan University (China) in 1992, a MS in Molecular and Cell Biology from Shanghai Institute of Cell Biology, Chinese Academy of Science in 1995, and a PhD in Neurobiology at the University of Alabama at Birmingham (UAB) in 2001. She continued her postdoctoral training at UAB in the field of gene therapy, and became a faculty member in 2003. She is an Associate Professor of Medicine in the Department of Medicine, Section of Endocrinology at Tulane University School of Medicine since 2011. Her laboratory explores genetic therapy and islet transplantation strategies for the treatment of diabetes. In addition, she is interested in islet cell biology involving the mechanisms of islet cell regeneration, and GLP-1 action in glucagon-producing alpha cells.
My research has been focused on exploring novel strategies for diabetes treatment and investigating the underlying mechanisms. My laboratory is equipped with sophisticated techniques for diabetes research, which include molecular and cellular assays, immunohistochemical and biochemical assays for pancreas, surgical techniques (islet transplantation, bile ductal injection, islet purification), FACS-based purification of primary islet cells, mouse breeding, diabetes animal models, physiological assays for diabetes, and so on. Currently my laboratory is working on two major projects:
- To explore novel strategies to protect and to regenerate the insulin-producing β-cells. Type 1 diabetes (T1D) is caused by insulin deficiency, which is largely due to the lack of insulin-producing β-cells. Cell-based therapies such as islet transplantation and β-cell regeneration emerged as a promising cure for T1D. Islet transplantation has demonstrated clinical benefits for T1D treatment in recent years. However, a few issues have to be addressed before this treatment strategy can be applied to a broader patient range, and to achieve better therapeutic outcome. Our efforts have been focused on two therapeutic genes, Akt1 and Pax4. Akt1 is a potent survival and proliferation-stimulating gene, whereas Pax4 is a β-cell specific transcription factor able to transdifferentiate the glucagon-producing α cells into β cells. We are also interested in stem cell-based β cell regeneration strategy.
- To investigate the role of GLP-1 and GLP-1 receptor in pancreatic α cells. The glucagon-like peptide 1 (GLP-1), a peptide hormone encoded by the proglucagon gene together with glucagon, plays important roles in regulating blood glucose. GLP-1 stimulates insulin secretion from β-cells, and suppresses glucagon secretion from α-cells. More and more evidence suggests GLP-1 is not only expressed in the gut by L-cells, but also in the pancreatic islets by α cells. How GLP-1 acts on α-cells, however, is not clear. Our preliminary studies have demonstrated the expression of GLP-1 receptor (GLP-1R) in α cells, and we hypothesized that α-cell expressed GLP-1R mediates a negative feedback and/or glucagonostatic effect of GLP-1. An α-cell specific GLP-1R knockout (αGLP-1R-/-) mouse model has been generated in our lab, which will provide a valuable tool for our research endeavor.
- Kim DS, Song L, Wang J, Wu H, Gou W, Cui W, Kim JS, Wang H. Carbon Monoxide Inhibits Islet Apoptosis via Induction of Autophagy. Antioxid Redox Signal. 2018 May 10;28(14):1309-1322. doi: 10.1089/ars.2016.6979. Epub 2017 Nov 27. PMID: 28826228
- Kim DS, Song L, Wang J, Wu H, Gu G, Sugi Y, Li Z, Wang H. GRP94 Is an Essential Regulator of Pancreatic β-Cell Development, Mass, and Function in Male Mice. Endocrinology. 2018 Feb 1;159(2):1062-1073. doi: 10.1210/en.2017-00685. PMID: 29272356
- Dong S, Wu H. Regenerating β cells of the pancreas - potential developments in diabetes treatment. Expert Opin Biol Ther. 2018 Feb;18(2):175-185. doi: 10.1080/14712598.2018.1402885. Epub 2017 Nov 13. PMID: 29130349
- Zhang Y, Fava GE, Wu M, Htun W, Klein T, Fonseca VA, Wu H. Effects of Linagliptin on Pancreatic α Cells of Type 1 Diabetic Mice. J Endocr Soc. 2017 Aug 31;1(10):1224-1234. doi: 10.1210/js.2017-00253. eCollection 2017 Oct 1. PMID: 29264448
- Zhang Y, Wu M, Htun W, Dong EW, Mauvais-Jarvis F, Fonseca VA, Wu H. Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-diabetic and Diabetic Donors. Sci Rep. 2017 Aug 11;7(1):7964. doi: 10.1038/s41598-017-08271-9. PMID: 28801559
Full list of publications in PubMed