Daotai Nie, PhD
Dr. Nie is a Professor in the Department of Medical Microbiology, Immunology and Cell Biology at SIU School of Medicine and a member of the SIU Simmons Cancer Institute. Dr. Nie is a member of the American Association of Cancer Research and American Association for the Advancement of Sciences. He serves as an academic editor in PLoS ONE and a member of editorial boards for Journal of Bioanalysis & Biomedicine and Journal of Carcinogenesis & Mutagenesis.
Project 1. Regulation of tumor progression and metastasis by bioactive lipids
Invasion and metastasis represent the most insidious aspects of cancer. We have long term interests in elucidating the roles of bioactive lipids in tumor progression and metastasis. One such bioactive lipid is thromboxane A2 (TXA2). It is a prostanoid produced by thromboxane synthase utilizing prostaglandin H2, the arachidonate product of cyclooxygenases, as the substrate. TXA2 has potent biological activities in platelet aggregation and vessel constriction. It should be noted that thrombosis is a recurrent problem for cancer patients and is a significant cause of cancer death. My colleagues and I were among the first to report a systematic investigation regarding the expression, activities, and functions of thromboxane A2 synthase in cancer cells (American Journal of Pathology, 2004). We also report for the first time an extensive investigation of the TXA2 receptor (TP) in tumor cells (Cancer Research 2008), in which we examined the expression of TPs in prostate cancer cells and its role in reorganization of cytoskeleton during cell migration. Our ongoing efforts are geared toward elucidating the temporal and spatial regulation of TP expression and presentation and rolesof TP in tumor progression and metastasis.
Project 2. Tumor OCT4 in stemness of cancer cells and resistance to chemo-and radio-therapy
This research program was initiated to determine the role of cancer stem cells in resistance to chemo- and radio-therapy as well as in tumorigenicity. Recently we discovered the expression of embryonic stem cell transcription factors, notably Nanog and Oct4, in some cancers. Our recent focus is to determine how OCT4 is expressed in tumor cells, to determine the functionalities of tumor Oct4 in the stemness, tumorigenicity, and resistance of cancer cells toward chemo- and radio-therapy, and to investigate the regulation of Oct4 activities by cellular signaling pathways.
Project 3. Short chain fatty acid (SCFA) inhibition of aberrant activation of mTOR in cancer cells
Aberrant activation of mTOR is common in cancers and represents an attractive target of intervention. Our previously studies found SCFAs, the fermentation products of undigested fibers in hindgut, can damp the aberrant mTOR activation (Cell Death and Differentiation, 2011), raising the possibility of nutritional downregulation of mTOR signaling. Our current efforts are focused on the mechanism involved for SCFAs to suppress mTOR signaling, the difference between normal and neoplastic tissues in responses to SCFAs, and identification of biomarkers to stratify responders to SCFA treatments.
General Laboratory Techniques:
Cell and tumor biology: Cell and tissue cultures, transfection, transduction with recombinant viral particles, assays for cell proliferation, apoptosis, migration and invasion, autophagy assay, various animal models for tumor initiation, growth, and metastasis, cytochemistry and immunocytochemistry, imaging and confocal imaging, FACS and flow cytometry analyses of cell cycles, apoptosis, mitochondrial membrane potentials, and cell surface proteins.
Biochemistry and Molecular Biology: Electrophoresis, Western blot, nucleic acid extraction, PCR and real-time PCR, cloning and subcloning, site-directly mutagenesis, siRNA and shRNA, CRISPR-based genomic engineering.
Nie, D. and Honn, K.V. 12-Lipoxygenase inhibitors as radiosensitizers for prostate cancer radiotherapy. Provincial patent applied. 2005. This technology was licensed to Biomide Corporation.
Nie, D. and Chen, Y. Camptothecin and its analogs as inhibitor of pregnane X receptor and their therapeutic applications. Provincial patent application filed in May, 2011.