Department of Medicinal Chemistry and Molecular Pharmacology Personnel - Chang-Deng Hu
Specialization: Molecular Biology, Cell Biology, Cancer Biology and Molecular Imaging
EducationM.D. (1984) -Bengbu Medical College, China (Medicine)
M.S. (1987) -Tongji Medical University, China (Cancer Immunology)
Ph.D. (1997) - Kobe University, Japan (Molecular Biology)
Assistant Professor (1997-2000) - Kobe University
Postdoc (2000-2002) - University of Michigan
Research Investigator (2002-2003) - University of Michigan
Research: Molecular Biology, Cell Biology, Cancer Biology and Molecular Imaging
Transcriptional regulation is a key regulatory mechanism that determines how all intracellular and extracellular signals are properly translated into gene expression profiles in cells and how cells reprogram or respond to any extracellular or intracellular changes. This is best exemplified by the fact that introduction of a few transcription factors can reprogram somatic cells into inducible pluripotent stem cells. Because of the importance of transcriptional regulation, deregulation of important transcription factors has been implicated in many human diseases such as cancer, neurodegenerative diseases, diabetes, heart diseases and autoimmune diseases. In fact, many transcription factors are products of oncogenes or tumor suppressor genes. Because transcription factors are subject to regulation at multiple levels and by multiple mechanisms such as protein-protein interactions, post-translational modifications, and changes in subcellular locations, these regulatory mechanisms can be explored to develop novel therapeutics. The goal of our research is to use molecular, cellular, biochemical, genetic, "Omics" and imaging approaches to identify novel and unique molecular targets and pathways in cancer cells and to develop novel therapeutics.
(1) Development of novel technologies to image and target transcriptional and epigenetic regulation. Many transcription factors form dimers among the family members to bind DNA and regulate gene expression. Although genetic approach has been used as a gold standard to analyze the role of genes in vivo, it suffers from several drawbacks when transcription factor-encoding genes are knocked out or knocked down. We have been developing a series of bimolecular fluorescence complementation (BiFC)-based technologies to visualize and target transcription factor dimers, rather than invididual proteins or genes. We will continue to explore novel BiFC applications in the context of cancer. These applications include, but not limited to, biosensors, high throughput screening for protein-protein interaction disruptors and BiFC-based interactomes. We believe the development and application of novel technologies will allow us to identify molecular targets and pathways for the development of novel cancer therapeutics.
(2) Regulation and function of AP-1 in mammalian cells and in C. elegans. We have been applying our novel technologies to investigate how activator protein 1 (AP-1) dimers function in mammalian cells. We are also using C. elegans as a genetic model to assess the roel of AP-1 dimers in vivo. The use of novel technologies has allowed us to make several novel discoveries regarding the role of AP-1 dimers and their target genes in cells and in C. elegans. We are currently investigating the regulation and functional consequences of ATF2 subcellular localization in cancer cells and in C. elegans.
(3) Mechanisms and targeting of therapy-resistant prostate cancer. The ultimate goal of our research is to translate our understanding of how transcription factors such as AP-1 proteins function in cells into clinical settings. We are currently collaborating with basic cancer researchers and clinicians to investigate how AP-1 and several other transcription factors are involved in the development, progression and therapeutic responses of prostate cancer. We are also particularly interested in understanding how epigenetics can be explored to reprogam thereapy-resistant prostate cancer into therapy-sensitive prostate cancer. To learn more about our research, please visit our lab homepage at http://people.pharmacy.purdue.edu/~cdhu/.
Lab Members:Xuehong Deng (Lab Technician VII)
Sarah L. Kelsey (Graduate Student)
Gyeon Oh (Graduate Student)
Yihang Wu (Visiting Scholar)
Suarez, C., Deng, X., and Hu, C.D. Targeting CREB inhibits radiation-induced neuroendocrine differentiation and increases radiation-induced cell death in prostate cancer cells. Am J Cancer Res, 2014 (in press)
Zhang, H.T., Zhang, D., Zha, Z.G., and Hu, C.D. Transcriptional regulation of PRMT5 by NF-Y is required for cell growth and negatively regulated by the PKC/c-Fos signaling in prostate cancer. Biochim Biophys Acta 1839:1330-1340 (2014)
Hsu, C., and Hu, C.D. Transcriptional activity of c-Jun is critical for the suppresson of AR function. Mol Cell Endocrinol 372:12-22(2013)
Ejendal, K.F.K., Conley, J.M., Hu, C.D. and Watts, V.J. Bimolecular fluorescence complementation analysis of G protein-coupled receptor dimerization in living cells. Methods Enzymol 521:259-270 (2013)
Kodama, Y. and Hu, C.D. Bimolecular fluorescence complementation (BiFC): How to calculate signal-to-noise ratio. Methods Cell Biol 113:107-121 (2013)
Kodama, Y. and Hu, C.D. Bimolecular fluorescence complementation (BiFC): A 5-year update and future perspectives. Biotechniques, 53:285-298 (2012)
Young MM, Takahashi Y, Khan O, Park S, Hori T, Yun J, Sharma AK, Amin S, Hu CD, Zhang J, Kester M, Wang HG. Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J. Biol. Chem. 287:12455-12688 (2012)
Hsu, C. and Hu, C.D. Critical role of an N-terminal end nuclear export signal in regulation of ATF2 subcellular localization and transcriptional activity. J. Biol. Chem. 287:8621-8632 (2012)
Deng, X., Elzey, B.D., Poulson, J.M., Morrison, W.B., Ko, S.C., Hahn, N.M., Ratliff, T.L., and Hu, C.D. Ionizing radiation induces neuroendocrine differentiation in vitro, in vivo and in human prostate cancer patients. Am. J. Cancer Res. 1:834-844 (2011)
Xing, J., Wang, S., Lin, F., Pan, W., Hu, C.D., and Zheng, C. A comprehensive characterization of interaction complexes of Herpes Simplex Virus type I ICP22, UL3, UL4 and UL20.5. J. Virol. 85:1881-1886 (2011)
Kodama, Y. and Hu, C.D.. An improved bimolecular fluorescence complementation assay with a high signal-to-noise ratio. Biotechniques, 49:793-805 (2010)
Le, T.T, Duren, H.M., Slipchenko, M.N., Hu, C.D.*, and Cheng, J.X. Label-free quantitative analysis of lipid metabolism in living Caenorhabditis elegans. J. Lipid Res. 51:672-677 (2010) *Co-Corresponding Author
Hiatt, S.M., Duren, H.M. Shyu, Y., Ellis, R.E., Hisamoto, N., Matsumoto, K., Kariya, K., Kerppola, T.K., and Hu, C.D.. C. elegans FOS-1 and JUN-1 regulate plc-1 expression to control ovulation. Mol. Biol. Cell 20:3888-3895 (2009)
Hu, C.-D. and Kerppola, T. Simultaneous visualization of interactions between multiple proteins in living cells using multicolor bimolecular fluorescence complementation analysis. Nat. Biotechnol. 21, 539-545 (2003).
Hu, C.-D. Chinenov, Y., and Kerppola, T Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol. Cell. 9, 789-798 (2002).All publications for Chang-Deng Hu (an Adobe Acrobat file)
Click here for a full CV for Chang-Deng Hu. (an Adobe Acrobat file)
This record was last updated on Oct 28, 2014 at 8:42 PM