Norman H. L. Chiu
One of the limiting factors for studying a biological system is how well the system can be monitored. The focus of Dr. Chiu’s research group is to identify specific analytical challenges in measuring biomarkers, and develop new analytical methods to overcome the challenges. Specifically, we are interested in the analysis of variations in the human genome, transcriptome, and/or proteome. To reduce the complexity of genomics or proteomics samples, specific molecular probes as well as the activity of some unique enzymes have often been used as part of our developed methods. For the end point measurements in our developed methods, the use of different analytical techniques have been explored, which include fluorescence spectroscopy, mass spectrometry, etc.
Dr. Chiu’s achievements have included the development of (1) the first expressible enzyme-coding DNA label for immunoassays and nucleic acids hybridization assays; (2) a microtiter-based immunoassay for monitoring the performance of a bioreactor for wastewater treatment; (3) a new commercial assay for high throughput identification of different bacterial strains by using MALDI-TOF mass spectrometry; (4) a novel enzymatic method for analyzing DNA sequences; (5) an improved tandem mass spectroscopic method for measuring carcinogenic DNA adducts; and (6) a simple method for determining the yield from the extraction of total microRNA in tissue samples.
Current research projects include the development of mass spectroscopic methods for measuring small non-coding RNA biomarkers that are related to cancer disease. In collaboration with Prof. Boris Lau at Baylor University, we are examining the analytical methods for studying the cellular uptake of nanomaterials. Other research collaborators include Prof. Bakhos Tannous at Harvard Medical School, and Profs. Wei Jia, Jie Hu and Zhenquan Jia at UNCG.
The above projects have been supported by funding from NIH, UNCG, NCBC, and NSF.
LIST OF PEER-REVIEWED PUBLICATIONS
- Christopoulos TK, Chiu NH. Expression Immunoassay. Antigen quantitation using antibodies labeled with enzyme-coding DNA fragment. Anal. Chem., 67; 4290 (1995).
- Chiu NH, Christopoulos TK. Hybridization assays using as a label an expressible DNA fragment encoding firefly luciferase. Anal. Chem., 68; 2304 (1996).
- Chiu NH, Christopoulos TK, Peltier J. Sandwich-type DNA hybridization assays based on enzyme amplified time-resolved fluorometry. Analyst, 123; 1315 (1998).
- White SR, Chiu NH, Christopoulos TK. Expression immunoassay based on antibodies labeled with a DNA fragment encoding the alpha-peptide of beta-galactosidase. Analyst, 123; 1309 (1998).
- Chiu NH*, Cantor CR. Mass spectrometry of nucleic acids. Clin. Chem., 45; 1578 (1999).
- Chiu NH, Christopoulos TK. Two-site expression immunoassay using firefly luciferase-coding DNA label. Clin. Chem., 45; 1954 (1999).
- Chiu NH*, Tang K, Yip P, Braun A, Koster H, Cantor CR. Mass spectrometry of single-stranded restriction fragments captured by an undigested complementary sequence. Nucleic Acids Res., 28; e31 (2000).
- White SR, Chiu NH, Christopoulos TK. Expression immunoassay. Methods, 22; 24 (2000).
- Leushner J, Chiu NH. Automated mass spectrometry: a revolutionary technology for clinical diagnostics [review]. Mol. Diagn. 5; 341(2000)
- Shahgholi M, Garcia BA, Chiu NH, Heaney PJ, Tang K. Sugar additives for MALDI matrices improve signal allowing the smallest nucleotide change (A:T) in a DNA sequence to be resolved. Nucleic Acids Res., 29; e91 (2001).
- Tannous B, Chiu NH, Christopoulos TK. Heterobifunctional linker between antibodies and reporter genes for immunoassay development. Analytica Chimica Acta, 459, 169 (2002).
- Wintzingerode FV, Bocker S, Schlotelburg C, Chiu NH, Storm N, Jurinke C, Van den Boom D. Base-specific fragmentation of amplified 16S rRNA genes and mass spectrometry analysis: A novel tool for rapid bacterial identification. Proc. Nat. Acad. Sci ., 99, 7039 (2002).
- S. Schiavo, A. El-Shafey, N. Jordan, C. Orazine, Y. Wang, X. Zhou, N.H. Chiu, and I.S. Krull. Immuno-PCR: an overview of the analytical technique currently pushing the limits of detection [review]. PharmaGenomics. January, 36-45 (2004).
- Li G, Zhou X, Wang Y, El-Shafey A, Chiu NH, and Krull IS. Capillary isoelectric focusing and affinity capillary electrophoresis approaches for the determination of binding constants for antibodies to the prion protein. J. Chromatogr A, 1053(1/2), 253-262 (2004).
- Schiavo S, Yang W, Chiu NH and Krull IS. Comparison of fluorometric detection methods for quantitative PCR. J Immunoassay Immunochem, 26(1), 1-12 (2005).
- Littman M, Chiu NH and Wang J. Specific recognition of non-denatured nitrite-oxidizing system of Nitrospira moscoviensis by monoclonal antibody Hyb 153-3. J Chem Technol Biotechnol 81 (3), 318-21 (2006).
- Qing L, Chiu NH and Vouros P. Investigation of benzonase/alkaline phosphatase digestion of DNA and DNA-adducts using LC-ESI MS. Anal. Chem., 79(5), 1907-17 (2007).
- Barnes CA, and Chiu NH. Accurate characterization of carcinogenic DNA adducts using MALDI tandem time-of-flight mass spectrometry. Int. J. Mass Spectrom., 279, 170-175 (2009)
- Yang W, Chiu NH. Correlation between UV spectrophotometry and quantitative MALDI-TOF MS. Spectroscopy Letters, 43(7), 602-608, (2010).
- Xiaojiao Zheng, Guoxiang Xie, Aihua Zhao, Chun Yao, Weiping Jia, Norman H. L. Chiu, Zhanxiang Zhou, Wei Jia. The footprints of gut microbial - mammalian co-metabolism. Journal of Proteome Research 10(12), 5512-5522 (2011).
- Jack G. Walleshauser III, Trace Kessler, Bakhos A. Tannous, Norman H. L. Chiu. A Simple Approach for Evaluating Total MicroRNA Extraction from Mouse Brain Tissues. Journal of Analytical Sciences, Methods and Instrumentation (2012) Accepted.
- Norman H. L. Chiu and Theodore K. Christopoulos. "Advances in Immunoassay Technology", InTech (In press).
- Walter B. Wilson, Dickson M Wambua, Norman H. L. Chiu. Reduction of Internal Standard Signals in Quantitative MALDI-TOF Mass Spectrometry. Analytical Methods. (Submitted)