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Children's Nutrition Research Center - Faculty

Houston, Texas

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Children's Nutrition Research Center - Faculty
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Ning-Hui Cheng, Ph.D.

Ning-Hui Cheng, Ph.D. Assistant Professor of Pediatrics, Baylor College of Medicine

E-mail: ncheng@bcm.edu

Research Interest

My research interests center on studying redox regulation of insulin signaling in nutrient metabolism with emphasis on metabolic disorders including type2 diabetes and obesity.

Redox regulation incorporates both transcriptional and post-translational mechanisms to modulate gene expression and protein levels. Thiol group modification represents one of redox control mechanisms in insulin action and signaling. There is growing evidence that the glutaredoxin (Grx)/ glutathione (GSH)/ glutathione reductase (GR) system, like the thioredoxin (Trx)/thioredoxin reductase (TR)/NADPH system, plays an essential role in regulating cellular function. It will be important to understand the mechanistic link between Grx-mediated redox signals and insulin signaling pathways and the biochemical nature of those processes.

As an initial step towards this goal, we are currently investigating a novel group of Grxs-monothiol Grxs, which were recently identified and isolated from bacteria, fungi, plants, and animals including mammals. Recent studies from ours and other laboratories indicate that monothiol Grxs contain a conserved PICOT-HD (protein kinase C interacting cousin of thioredoxin homology domain) and have a common function in regulating cellular processes in response to oxidative stresses. By utilizing genetic, biochemical, and cell biology approaches, we are going to determine a), the biochemical properties of those enzymes including their enzymatic activities and substrate specificity; b), how these monothiol Grxs, coupled with GSH and GR, regulate the targeted proteins in response to cellular redox changes; and c), how the PICOT-HD integrates redox signals into insulin/IGF mediated signaling. Elucidating the physiological role of PICOT will lead to an understanding of the complexity of insulin resistance in the pathogenesis of metabolic disorders, such as type2 diabetes and obesity.

Representative Publications

Liu, X., Liu, Shian., Feng, Y*., Liu, J.-Z., Chen, Y., Pham, K., Deng, H., Hirschi, K.D., Wang, X*., and Cheng, N*. Structural insights into the N-terminal GIY-YIG endonuclease activity of Arabidopsis glutaredoxin AtGRXS16 in chloroplasts. Proc Natl Acad Sci USA 2013 June 4, 110, 9565-9570 PMID:23690600 (* denoted corresponding author)

Connorton, J.M., Webster, R.E., Cheng, N, Pittman, J.K. Knockout of Multiple
Arabidopsis Cation/H+ Exchangers Suggests Isoform-Specific Roles in Metal Stress Response, Germination and Seed Mineral Nutrition. PLoS ONE 7 2012 Oct 12, (10): e47455. PMID:23071810

Wu, Q., Lin, J. Liu, J.-Z., Wang, X., Lim, W., Oh, M., Park, J., Rajashekar, C. B., Whitham, S.A., Cheng, N.,* Hirschi, K. D. and Park, S.* Ectopic expression of Arabidopsis glutaredoxin AtGRXS17 enhances thermotolerance in tomato. Plant Biotechnol J 2012 Jul 5, 10, 945–955. PMID:22762155

Cheng, N.-H.,* Liu, J.-Z., Liu, X., Wu, Q., Thompson, S.M., Lin, J., Chang, J., Whitham, S.A., Park, S., Cohen, J.D., and Hirschi, K.D. Arabidopsis monothiol glutaredoxin, AtGRXS17, is critical for temperature-dependent postebryonic growth and development via modulating auxin response. J Biol Chem 2011 June 10, 286, 20398-20406

Cheng, N.*, Zhang, W., Chen, W.-Q., Jin, J., Cui, X., Butte, N.F., Chan, L., and Hirschi, K.D. A mammalian monothiol glutaredoxin, Grx3, is critical for cell-cycle progression during embryogenesis. FEBS Journal 2011 June 2, 278, 2525–2539 PMID: 21575136

Qu, Y., Wang, J., Ray, P.S., Guo, H., Huang, J., Shin-Sim, M., Bukoye, B.A., Liu, B., Lee, A.V., Lin, X., Huang, P., Martens, J.W., Giuliano, A.E., Zhang, N.,* Cheng, N.-H.,* and Cui, X.* Thioredoxin-like 2 regulates human cancer cell growth and metastasis via redox homeostasis and NF-κB signaling. J Clin Invest 2011 Jan 4, 121, 212–225

Conn, S.J., Gilliham, M., Athman, A., Schreiber, A.W., Baumann, U., Moller, I., Cheng, N.-H., Stancombe, M.A., Hirschi, K.D., Webb, A.A.R., Burton, R., Kaiser, B.N., Tyerman, S.D., and Leigh, R.A. Cell-Specific Vacuolar Calcium Storage Mediated by CAX1 Regulates Apoplastic Calcium Concentration, Gas Exchange, and Plant Productivity in Arabidopsis The Plant Cell 2011 Jan 21, 23, 240–257

Li, L., Cheng, N-.H.,* Hirschi, K.D., and Wang, X.Q.* Structure of Arabidopsis chloroplastic monothiol glutaredoxin AtGRXcp. Acta Crystallographica Section D Biological Crystallography 2010 June 3, D66, 725–732

Mei, H., Cheng, N-H., Zhao, J., Park, S., Escareno, R.A., Pittman, J.K., and Hirschi, K.D. Root development under metal stress in Arabidopsis thaliana requires the H+/cation antiporter CAX4. New Phytol 2009 Apr 8, 183, 95-105

Zhao, J, Shigaki, T., Mei, H., Guo, Y.Q., Cheng, N-H., and Hirschi, K.D. Interaction between Arabidopsis Ca2+/H+ exchangers CAX1 and CAX3. J Biol Chem 2009 Feb 13, 284, 4605-4615

Zhao, J., Cheng, N-H., Motes, C.M., Blancaflor, E.B., Moore, M., Gonzales, N., Padmanaban, S., Sze, H., Ward, J.M., and Hirschi, K.D. AtCHX13 is a plasma membrane K+ transporter. Plant Physiol 2008 Oct, 148, 796-807

Cheng, N.-H.* AtGRX4, an Arabidopsis chloroplastic monothiol glutaredoxin, is able to suppress yeast grx5 mutant phenotypes and respond to external stresses. FEBS Lett 2008 Mar 19, 582,848–854

Koren’kov, V., Park, S., Cheng, N.-H., Sreevidya, C., Lachmansingh, J., Morris, J., Hirschi, K.D., and Wagner, G.J. (2007) Enhanced Cd2+-selective root-tonoplast-transport in tobacco expression Arabidopsis cation exchangers. Planta 2007 Jan, 255, 403-411

Cheng, N.-H.*, Liu, Z-J., Brock, A., Nelson, R.S., and Hirschi, K.D. AtGRXcp, an Arabidopsis chloroplastic glutaredoxin is critical for protection against protein oxidative damage. J Biol Chem 2006 Sept 8, 281, 26280-26288

Park, S., Cheng, N.-H., Pittman, J.K., Yoo, K.S., Park, J., Smith, R.H., and Hirschi, K.D. Increased calcium levels and prolonged shelf life in tomatoes expressing Arabidopsis H+/Ca2+ transporters. Plant Physiol 2005 Nov, 139, 1194-1206

Cheng, N.-H., Pittman, J.K., Shigaki, T., Lachmansingh, J., LeClere, S., Lahner, B., Salt, D.E., and Hirschi, K.D. Functional association of Arabidopsis CAX1 and CAX3 is required for normal growth and ion homeostasis. Plant Physiol 2005 Aug 1, 138, 2048-2060

Pittman, J.K., Shigaki, T., Marshall, J.L., Morris, J.L., Cheng, N.-H., and Hirschi, K.D. Functional and regulatory analysis of the Arabidopsis thaliana CAX2 cation transporter. Plant Mol Biol 2004 Apr 7, 56,959-971

Pittman, J., Cheng, N.-H., Shigaki, T., Kunta, M., and Hirschi, K.D. Functional dependence on calcineurin by variants of the Saccharomyces cerevisiae vacuolar Ca2+/H+ exchanger Vcx1p. Mol Microbiol 2004 Nov, 54, 1104–1116

Sze, H., Padmanaban, S., Cellier, F., Honys, D., Cheng, N.-H., Bock, K., Conejero, G., Li, X., Twell, D., Ward, J.M., and Hirschi, K.D. Expression Patterns of a Novel AtCHX Gene Family Highlight Potential Roles in Osmotic Adjustment and K1 Homeostasis in Pollen Development. Plant Physiol 2004 Sept 1, 136, 2532-2547

Cheng, N.-H.*, Liu, J., Nelson, S., and Hirschi, K.D. Characterization of CXIP4, a novel Arabidopsis protein that activates the H+/Ca2+ antiporter, CAX1. FEBS Lett 2004 Feb 13, 559, 99-106

Yang, S., Carter, S., Cole, A., Cheng, N.-H., and Nelson,S.R. A natural variant of a host RNA-dependent RNA polymerase is associated with increased susceptibility to viruses by Nicotiana benthamiana. Proc Natl Acad Sci USA 2004 Apr 20, 101, 6297-6302

Cheng, N.-H., Pittman, J.K., Zhu, J.-K., and Hirschi, K.D. The Protein Kinase SOS2 Activates the Arabidopsis H+/Ca2+ Antiporter CAX1 to Integrate Calcium Transport and Salt Tolerance. J Biol Chem 2004 Jan 23, 279, 2922-2926

Ding, X.,a Liu, J.,a Cheng, N.-H.,a Folimonov, A., Hou, Y., Bao, Y., Katagi, C., Carter, S., and Nelson, S.R. The Tobacco mosaic virus 126-kDa protein associated with virus replication and movement suppresses RNA silencing. Mol Plant-Microbe Interact 2004 June 17, 583-592 (a these authors contributed equally and should be considered co-first authors )

Cheng, N.-H., and Hirschi, K. D. Cloning and Characterization of CXIP1, a Novel PICOT Domain-containing Arabidopsis Protein That Associates with CAX1. J Biol Chem 2003 Feb 21, 278, 6503 - 6509

Cheng, N.-H., Pittman, J.K., Barkla, B., Shigaki, T., and Hirschi, K.D. The Arabidopsis cax1 Mutant Exhibits Impaired Ion Homeostasis, Development, and Hormonal Responses and Reveals Interplay among Vacuolar Transporters. The Plant Cell 2003 Feb 15, 347-364

Cheng, N.-H., Pittman, J.K., Shigaki, T., and Hirschi, K.D. Characterization of CAX4, an Arabidopsis H+/Cation antiporter. Plant Phsiol 2002 Apr, 128, 1245-1254

Pittman, J.K., Shigaki, T., Cheng, N.-H., and Hirschi, K.D. Mechanism of N-terminal autoinhibition in the Arabidopsis Ca2+ /H+ antiporter CAX1. J Biol Chem 2002 Jul 19 277, 26452-26459

Li, X.B., Cai, L., Cheng, N.-H., and Liu, J.W. Molecular characterization of the cotton GhTUB1 gene that is preferentially expressed in fiber. Plant Physiol 2002 Oct, 130, 666-74

Shigaki, T., Cheng, N.-H., Pittman, J.K., and Hirschi, K.D. Structural determinants of Ca 2+ transport in the Arabidopsis H+/Ca2+ antiporter CAX1. J Biol Chem 2001 Nov 16, 276, 43152-43159

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