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.
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.
1. Wu, H., Reuver, S. M., Kuhlendahl, S., Chung, W. J. and Garner, C. C. (1998) Subcellular targeting and cytoskeletal attachment of SAP97 to the epithelial lateral membrane. Journal of Cell Science, 111, 2365-2376. (PMID: 9683631)
2. Wu, H., Reissner, C., Kuhlendahl, S., Coblentz, B., Reuver, S. M., Kindler, S., Gundelfinger, E. D. and Garner, C. C. (2000) Intra-molecular interactions regulate SAP97 binding to GKAP. EMBO Journal, 19 (21), 5740-5751. (PMID: 11060025)
3. Mehta, S., Wu, H., Garner, C. C. and Marshall, J. (2001) Molecular mechanisms regulating the differential association of kainate receptor subunits with SAP90/PSD-95 and SAP97. Journal of Biological Chemistry, 276(19): 16092-16099. (PMID: 11279111)
4. Seki, T., Dmitriev,I., Suzuki, K., Kashentseva, E., Takayama, K., Wu, H., Uil, T. and Curiel, D. T. (2002) Artificial extension of adenoviral fiber shaft improves the specificity of transgene expression in CAR negative tumors both in vitro and in vivo. Gene Therapy, 9(16): 1101-1108. (PMID: 12140738)
5. Wu, H., Nash, J., Zamorano, P. and Garner, C. C. (2002) Interaction of SAP97 with minus-end directed actin motor myosin VI: implications for AMPA receptor trafficking. Journal of Biological Chemistry, 277(34): 30928-30934. (PMID: 12050163)
6. Wu, H., Seki, T., Dmitriev, I., Uil, T., Kashentseva, E., Han, T., and Curiel, D. T. (2002) Double modification of adenovirus fiber with RGD and polylysine motifs improves CAR-independent gene transfer efficiency. Human Gene Therapy, 13: 1647-1653. (PMID: 12228019)
7. Wu, H., Dmitriev, I., Kashentseva, E., Seki, T., Wang, M., and Curiel, D. T. (2002) Construction and characterization of a novel hexon chimera: adenovirus type 5 encapsided by type 3 hexon. Journal of Virology, 76 (24): 12775-12782. (PMID: 12438602)
8. Contreras, J. L., Wu H., Smyth, C. A., Eckstein, C. P., Young C. J., Seki, T., Bilbao, G., Curiel, D. T., and Eckhoff, D. E. (2003) Double genetic modification of adenovirus fiber with RGD polylysine motifs significantly enhances gene transfer to isolated human pancreatic islets. Transplantation, 76 (1): 252-261. (PMID: 12865820)
9. Wu, H., Han, T., Lam, J. T., Leath, C. A., Dmitriev, I., Kashentseva, E., Barnes, M. N., Alvarez, R. D. and Curiel, D. T. (2004) Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy. Gene Therapy, 11 (10): 874-878. (PMID: 14999229)
10. Rein, D. T., Breidenbach, M., Wu, H., Han, T., Wang, M., Kirby, T., Dall, P., Alvarez, R. D., Curiel, D. T. (2004) Gene Transfer to cervical tumors with fiber modified adenoviruses. Internation Journal of Cancer, 111 (5): 698-704. (PMID: 15252838)
Full list of publications in PubMed