Hongju Wu, PhD
Associate Professor of Medicine-Endocrinology
Education & Affiliations
Areas of Expertise
Biography
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 Ph.D in Neurobiology at the University of Alabama at Birmingham (UAB) in 2001. She continued her postdoc training at UAB in the field of gene therapy, and became a faculty member in 2003. She is an Associate Professor in the Department of Medicine, Section of Endocrinology, and an Adjunct Associate Professor in the Department of Physiology at Tulane University. 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 beta cell regeneration, and GLP-1 regulation of glucagon secretion from alpha cells.
Research
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:
1) 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.
2) To investigate the role of GLP-1 and GLP-1 receptor in pancreatic α cells. GLP-1, through its receptor GLP-1r, plays essential roles in regulating blood glucose homeostasis. We are interested in how GLP-1/GLP-1R regulates glucagon secretion from pancreatic alpha cells. Thus far, we have demonstrated GLP-1R expression in alpha cells, and generated alpha-cell specific GLP-1R knockout mice. Using the mouse models and isolated islets, we discovered that GLP-1/GLP-1R not only suppresses glucagon secretion at fed state, but also stimulates glucagon secretion under hypoglycemic condition. Our current study aims to delineate the molecular mechanisms underlying how GLP-1/GLP-1R regulates glucagon secretion in a glucose-dependent bidirectional manner.
Contributions
- Fava GE., Dong EW, and Wu H. (2016) Intra-islet glucagon-like peptide 1. Journal of Diabetes and its Complications, 30(8):1651-1658. (PMID: 27267264)
- Zhang Y, Fava GE, Wang H, Mauvais-Jarvis F, Fonseca VA, and Wu H. (2016) Pax4 gene transfer induces α-to-β cell phenotypic conversion and confers therapeutic benefits for diabetes treatment. Molecular Therapy, 24 (2): 251-260.(PMID: 26435408)
- Zhang Y, Wu M, Htun W, Dong EW, Fonseca VA, and Wu H. (2017) Differential effects of linagliptin on human islets isolated from non-diabetic and diabetic donors. Scientific Reports, 7(1): 7964. (PMID: 28801559)
- Zhang Y, Fava GE, Wu M, Htun W, Klein T, Fonseca VA, and Wu H. (2017) Effects of linagliptin on pancreatic α cells of type 1 diabetic mice. Journal of the Endocrine Society, 1 (10): 1224-1234. (PMID: 29264448).
- Dong S, and Wu H (2018) Regenerating β cells of the pancreas – potential developments in diabetes treatment. Expert Opinion on Biological Therapy, 18(2): 175-185. (PMID: 29130349).
- Kim DS., Song L, Wu H, Wang J, Gou W, Cui W, Kim JS, and Wang H. (2018) Carbon monoxide inhibits islet apoptosis via induction of autophagy. Antioxidants and Redox Signaling, 28(14): 1309-1322. (PMID: 28826228)
- Dong S, Bluher M, Zhang Y, Wu H, and Alahari SK. (2019) Development of insulin resistance in Nischarin mutant female mice. International Journal of Obesity, 43 (5): 1046-1057. (PMID: 30546133)
- Zhang Y, Parajuli KR, Fava GE, Gupta R, Xu W, Nguyen LU, Zakaria A, Fonseca VA, Wang H, Mauvais-Jarvis F., Sloop KW, and Wu H (2019) GLP-1 receptor expressed in pancreatic α cells regulates glucagon secretion in a glucose-dependent manner. Diabetes, 68 (1): 34-44. (PMID: 30389749).
- Parajuli, KR, Zhang Y, Cao, AM, Wang H., Fonseca VA, and Wu H (2020) Pax4 gene delivery improves islet transplantation efficacy by promoting β cell survival and α-to-β cell transdifferentiation. Transplantation, in press.
Full list of publications for Dr. Hongju Wu.
