个人简介

B.S., POSTECH (Pohang University of Science and Technology), 1999 M.S., POSTECH (Pohang University of Science and Technology), 2001 Ph.D., New York University, 2007 Postdoctoral Fellow, Johns Hopkins University School of Medicine, 2008-2012

研究领域

Oxidative protein modification/cytoprotection/chemical biology/protein semi-synthesis/small molecule screening/fluorescent probes

The research interest in my laboratory lies in the field of chemical biology. Our goals are 1) to understand the significance of oxidative protein modifications that occur in redox signaling or oxidative stress and 2) to develop small molecules that can provide cellular protection against oxidative damages. To this end, we take multidisciplinary approach at the interface of chemistry and biology, including synthetic organic chemistry, protein biochemistry, and cell biology. It is increasingly recognized that the reactive oxygen and nitrogen species (ROS/RNS) can be transiently generated in physiological conditions in response to various stimuli and they act as signaling molecules in redox signaling that regulates diverse cellular processes. In such condition, ROS/RNS are often sensed by unique redox chemistry of thiol in a protein cysteine residue that undergoes various types of oxidative modifications, such as S-glutathionylation, sulfenylation, S-nitrosylation, and disulfide bond formation. Importantly, these oxidative cysteine modifications profoundly influence physiological functions of many proteins, serving as a regulatory switch of many cellular processes. Consequently, its aberrant regulation often leads to oxidative stress, imbalance between the generation and the removal of ROS/RNS, which correlates with many disease conditions, including diabetes, cancer, cardiovascular and neurodegenerative disease. Chemical Tools to Understand Oxidative Protein Modification We are interested in developing chemical tools that lead to understanding oxidative protein modifications in response to ROS/RNS. We are applying these tools to analyze such protein modifications in disease-simulated cell-based system. Site-specific Oxidative Protein Modification We are also interested in understanding functional significance of oxidative protein modifications. To this end, we use semi-synthetic protein synthesis to introduce the site-specific oxidative protein modification, and evaluate structural and functional alterations by various biochemical, biophysical methods and cell-based systems. Targeting Cytoprotective Pathways We explore two important signaling pathways that can provide cellular protection against oxidative damages: namely, anti-oxidant response and heat shock response regulated by two transcription factors, Nrf2 (nuclear factor E2-related factor 2) and Hsf1 (heat shock factor 1), respectively. Many animal/human model studies indicate that activation of these pathways is an effective strategy of conferring protection against disease conditions that involve oxidative stress and/or protein misfolding, such as cancer and neurodegeneration. We are developing small molecules that selectively regulate these pathways by use of various chemical approaches, including small molecule screening and fluorescent assay.

近期论文

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Zhang, Y., Ahn, Y. H., Benjamin, I. J., Honda, T., Hicks, R. J., Calabrese, V., Cole, P. A., Dinkova-Kostova, A. T. A novel role for sulfhydryl-reactive inducers of the KEAP1/NRF2/ARE pathway: HSF1-dependent upregulation of Hsp70. Chem. Biol. 2011, 18, 1355-1361. Ahn, Y. H., Hwang, Y., Liu, H., Wang, X. J., Zhang, Y., Stephenson, K. K., Boronina, T. N., Cole, R. N. Dinkova-Kostova, A. T., Talalay, P. Cole, P. A. Electrophilic tuning of the chemoprotective natural product sulforaphane. Proc. Natl. Acad. Soc. USA. 2010, 107, 9590-9595. Cho, S. J., Ahn, Y. H., Maiti, K. K., Dinish, U. S., Fu, C. Y., Thoniyot, P., Olivo, M., Chang, Y. T. Combinatorial synthesis of a triphenylmethine library and their application in the development of surface enhanced raman scattering (SERS) probes. Chem. Commun. 2010, 46, 722-724 Ahn, Y. H., Chang, Y. T. Tagged small molecule library approach for facilitated chemical genetics. Acc. Chem. Res. 2007, 40, 1025-1033. Ahn, Y. H., Lee, J. S., Chang, Y. T. Combinatorial rosamine library and application to in vivo glutathione probe. J. Am. Chem. Soc. 2007, 129, 4510-4511.