Faculty & Staff

Chenbo Zeng, PhD

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Research Associate of Radiology
Research Associate, University of Pennsylvania Perelman School of Medicine, Department of Radiology
Department: Radiology

Contact information
Department of Radiology
University of Pennsylvania
3400 Spruce Street
Philadelphia, PA 19104
Office: 215-746-2511
Education:
B.A. (Biochemistry)
Jilin University, Changchun, P.R. China, 1985.
M.S. (Biochemistry)
Jilin University, Changchun, P.R. China, 1988.
Ph.D (Biochemistry)
Iowa State University, Ames, Iowa, 1996.
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Description of Research Expertise

The research highlights during my Ph.D. and postdoctoral studies
During my Ph. D. work I studied structure and function of human brain hexokinase which catalyzes the phosphorylation of glucose, the first step in glycolysis. At that time the interaction of ATP with the active site of hexokinase was unknown since the crystal structure of the hexokinase-ATP complex was unavailable. I read an interesting paper reporting that yeast hexokinase, glycerol kinase, actin, and heat shock protein hsc70 have similar ATP-binding domain structures although there are no overall primary sequence similarities among them. Base on this work I did amino acid sequence comparison between yeast and human hexokinase and identified several amino acid residues in human hexokinase which may be important for ATP binding. I went ahead to mutate these amino acids, purified the mutant enzymes, and did enzyme kinetic characterization on the mutant hexokinase. The data demonstrated that these amino acids indeed bind to ATP and are essential for the catalytic reaction of hexokinase. This work increased our understanding on the catalytic mechanism of human brain hexokinase. In addition, I improved the enzyme purification procedure and increased the yield in half time. As a result I purified a large amount of hexokinase from E. Coli, which overexpressed recombinant human brain hexokinase. Using the pure enzyme I purified, the crystallographer was able to obtain high quality crystals of hexokinase and to solve the first crystal structure of mammalian hexokinase. My Ph D work led to six high quality publications.
I developed interests in signaling transduction pathways in live cells during my Ph.D. studies. I chose to do my post doctorate training in studying signaling pathways. I have investigated Target of Rapamycin (TOR) signaling pathways involved in cell survival, and cytokine-induced Inducible Nitric Oxide Synthase (iNOS) signaling pathways involved in inflammation. By using yeast two hybrid screen, I identified numerous putative TOR-interacting proteins, leading to the findings that TOR signaling regulates microtubule structure and function by interacting with Bik 1 and that TOR regulates Gln3, a transcription factor responsive to the nitrogen nutrients and starvation. Using primary renal mesangial cells of rat, I demonstrated that Interleukin-1beta (IL-1)-induced iNOS expression is regulated by actin cytoskeletal dynamics and is inhibited by serum response factor (SRF). These findings increased our understanding of iNOS-involved pathological and physiological processes. In cultured oligodendrocytes, I showed that amyloid-beta (A) peptide enhances tumor necrosis factor alpha (TNFα)-induced iNOS through neutral sphingomyelinase/ceramide pathway. These results implicate that oligodendrocytes may be involved in free radical production in response to the combination of A deposition and proinflammatory cytokines, contributing to the Alzheimer Disease pathology in brain white matter.

Selected Publications

Zeng, C.,Rothfuss, J.M., Zhang, J., Vangveravong, S., Chu, W.,Li, S., Tu, Z., Xu, J., Mach, R.H.: Functional assays to define agonists and antagonists of the sigma-2 receptor. Anal Biochem. 448C:68-74, 2014.

Izzo, N., Mozonni, K., Silky, C., Rehak, C., Yurko, R., Mach, R. H., Xu, J., Zeng, C., Rishton, G., Safferstein, H., Catalano, S.M.: A pharmacological model for treating Abeta synaptotoxicity at a receptor target. Poster presented at Society for Neuroscience 43rd annual meeting, San Diego,CA 2013.

Mach, R.H., Zeng, C., Hawkins, W. G.: A novel protein for the imaging and treatment of cancer. J Med Chem. 56:7137-7160, 2013.

Zeng, C., Vangveravong, S., McDunn, J.E., Hawkins, W. G., Mach, R.H.: Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer. Br J Cancer 109:2368-2377, 2013.

Xu, J., Cai, X., Yao, J., Spitzer, D., Zeng, C., Hawkins, W.G., Li,S., Wang W., Mach, R. H.: Photoacoustic imaging of pancreatic cancer proliferation via sigma-2 receptor/PGRMC1-eYFP. Poster presented at American Association for Cancer Research, 103rd annual meeting, Chicago, IL. 2012.

Zeng, C., Rothfuss, J., Zhang,J., Chu, W., Vangveravong, S., Tu, Z., Pan, F., Chang, K.C., Hotchkiss, R., Mach, R.H. : Sigma-2 ligands induce tumor cell death by multiple signaling pathways. Br J Cancer 106:693-701, 2012.

Zeng, C., Vangveravong, S., Rothfuss, J. M., Xu, J., Mach, R. H.: Validating sigma-2 receptor ligand as a novel tumor-targeted drug delivery agent for treating ovarian cancer. American Association for Cancer Research, 103rd annual meeting, Chicago, IL 2012 Notes: Poster Presentation.

Spitzer, D., Simon, PO Jr, Kashiwagi, H., Xu, J., Zeng, C., Vangveravong, S., Zhou, D., Chang, K., McDunn, J.E., Hornick, J.R., Goedegebuure, P., Hotchkiss, R.S., Mach, R.H., Hawkins, W.G.: Use of multifunctional sigma-2 receptor ligand conjugates to trigger cancer-selective cell death signaling. Cancer Res. 72:201-209, 2012.

Zeng, C., Vangveravong, S., Jones, L.A., Hyrc, K., Chang, K.C., Xu, J., Rothfuss, J.M., Mark P. Goldberg, M.P., Hotchkiss, R.S., and Robert H. Mach, R.H.: Characterization and evaluation of two novel fluorescent sigma-2 receptor ligands as proliferation probes. Molecular Imaging 10, 420-433, 2011.

Zeng, C., Xu, J., & Mach, R. H.: Imaging the sigma-2 receptor for diagnosis and prediction of therapeutic response. Breast Cancer – Recent Advances in Biology, Imaging and Therapeutics. Susan Done (eds.). Rijeka, Croatia: InTech, Page: 303-318, 2011.

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Last updated: 03/19/2014
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