Sudhanshu Raikwar, Ph.D. (Associate Member) Assist. Res. Sci., Dept. of Internal Medicine, University of Iowa
Research Interest
Dr. Riakwar's research interests include: 1) the development of stem cell- and gene therapy-based approaches for the treatment of type 1 diabetes, and 2) the development of real-time noninvasive and minimally invasive molecular imaging modalities for monitoring the fate of transplanted cells and viral vectors in vivo. In particular, his research involves understanding the molecular mechanisms that underlie the differentiation of embryonic stem cells (ESC) into insulin-producing cells. Towards achieving this aim, Dr. Raikwar has established new protocols for the efficient differentiation of mouse ESC into insulin-producing cells. This involved developing feline immunodeficiency virus (FIV)-based gene transfer vectors (pseudotyped for the vesicular stomatitis virus envelope) from which the pancreatic beta cell-specific transcription factors Pdx1 and Pax4 are expressed. The transduction of ESC-derived Nestin+ cells with FIV-Pdx1 was found to significantly enhance the generation of insulin-producing cells while FIV-Pax4 transduction was not as efficient. However, cotransduction of Nestin+ cells with FIV-Pdx1 and FIV-Pax4 at half the multiplicity of infection improved the generation of insulin producing cells. The group has further observed that the treatment of these FIV-transduced Nestin+ cells with a PI3 kinase inhibitor LY294002 leads to a significant increase in the generation of insulin-producing cells. These studies suggest that multiple pancreatic beta cell-specific transcription factors and signaling pathways are involved in the differentiation of mouse ESC into insulin producing cells. The group is currently working on optimizing the enrichment of insulin-producing cells and testing their therapeutic efficacy in mouse models of diabetes.
Selected Publications:
Raikwar, S.P., Temm, C.J., Raikwar, N.S., Kao, C., Molitoris, B.A. and Gardner, T.A. (2005): Adenoviral vectors expressing human endostatin-angiostatin and soluble Tie2: enhanced suppression of tumor growth and antiangiogenic effects in a prostate tumor model. Molecular Therapy 12 (6) 1091-100.
Li, X., Raikwar, S.P., Liu, Y.H., Lee, S-J., Zhang, Y.P., Zhang, B., Gardner, T.A., Jeng, M.H. and Kao, C. (2006): Combination therapy of androgen-independent prostate cancer using a prostate restricted replicative adenovirus and a replication-defective adenovirus encoding human endostatin-angiostatin fusion gene. Mol. Cancer Ther. 5 (3) 676-684.
Raikwar, S.P., Mueller, T. and Zavazava, N. (2006): Strategies for developing therapeutic application of human embryonic stem cells. Physiology 21:19-28.
Chan, K.M., Raikwar, S.P. and Zavazava, N. (2007): Strategies for differentiating embryonic stem cells (ESC) into insulin-producing cells and development of non-invasive imaging techniques using bioluminescence. Immunol. Res. 39 (1-3) 261-270.
