Young Hoon Ahn

Young Hoon Ahn

Department

Chemistry

Research interest(s)/area of expertise

• Protein post-translational modifications, proteomics, cysteine redox biology, chemical biology,

Research

The research in the Ahn Laboratory is centered around protein oxidative modifications that occur in response to endogenous reactive species, including reactive oxygen species (ROS) and reactive nitrogen species (RNS). We use various interdisciplinary approaches, including synthetic chemistry, protein engineering and biochemistry, enzyme kinetics, and cell biology.

1) Protein Glutathionylation

Our recent research focused on the investigation of protein glutathionylation. Glutathionylation is disulfide bond formation of a protein cysteine residue with intracellular glutathione that occurs in response to oxidative stimuli. There are many examples that highlight the significance of protein glutathionylation in human health and disease.

A chemical approach to investigating protein glutathionylation

We have developed a biochemical approach, called clickable glutathione, that labels glutathione with a clickable group to identify and characterize protein glutathionylation. The clickable group provides a chemical tag that allows for sensitive, selective, and versatile detection of glutathionylation. We are applying our approach to protein identification in various ROS-relevant disease models.

Identification and functional studies of glutathionylated proteins

ROS are significant factors that contribute to heart and muscle diseases, neuronal damage, and cancer development and progression. It is widely accepted that an intracellular level of ROS is significantly influenced by cellular metabolic state, or nutrient and oxygen availability. We are currently investigating two biological systems, cardiomyocytes and cancer cells, for identification and functional analysis of glutathionylated proteins under metabolic stress, including hypoxia, nutrition-deprivation, ischemia, and ischemic reperfusion. We use various approaches, including protein biochemistry, proteomics, and cell biology, to investigate the functional significance of glutathionylation in individual proteins.

2) Targeting Cysteines in Redox-Sensitive Enzymes

We are interested in developing small-molecule or peptide-derived inhibitors for redox-sensitive enzymes that contain the reactive cysteine residues and are implicated in cancers. We are developing the potential inhibitors by employing various approaches, including the synthetic organic chemistry, molecular modeling, the rational-design, the peptide-library screening, and the phage-display screening.
 

Education

• B.S., Pohang University of Science and Technology
• M.S., Pohang University of Science and Technology
• Ph.D., New York University
• Postdoctoral Fellow, Johns Hopkins University School of Medicine

Selected publications

Gurusingha Arachchige, H. S., Herath Mudiyanselage, P. D. H., VanHeck, G. C., Patel, K., Cheaito, H. A., Dou, Q. P., Ahn, Y. H. Synthesis and Evaluation of Tiaprofenic Acid-derived UCHL5 Deubiquitinase Inhibitors, Bioorg. Med. Chem. 2020, In press.

VanHecke, G. C.,ª Yapa Abeywardana, M.,ª Huang, B., Ahn, Y. H. Isotopically-labelled Clickable Glutathione to Quantify Protein S-Glutathionylation, ChemBioChem, 2020, 21, 853-859. ª equal contribution

VanHecke, G. C., Yapa Abeywardana, M., Ahn, Y. H. Proteomic Identification of Protein Glutathionylation in Cardiomyocytes, J. Proteome Res. 2019, 18, 1806-1818.

Munkanatta Godage, D. N. P., VanHecke, G. C., Samarasinghe, K. T. G., Feng, H. Z., Hiske, M., Holcomb, J., Yang, Z., Jin, J. -P., Chung, C. S., Ahn, Y. H. SMYD2 Glutathionylation Contributes to Degradation of Sarcomeric Proteins. Nature Commun. 2018, 9, 4341

Samarasinghe, K. T. G., Munkanatta Godage, D. N. P., Zhou, Y., Ndombera, F. T., Weerapana, E., Ahn, Y. H.* Clickable Glutathione Approach for Identification of Protein Glutathionylation in Response to Glucose Metabolism. Mol. Biosyst. 2016, 12, 2471-2480.

Ndombera, F. T., VanHecke, G. C., Nagi, S., Ahn, Y. H.* Carbohydrate-based Inducers of Cellular Stress for Targeting Cancer Cells. Bioorg. Med. Chem. Lett. 2016, 26, 1452-1456.

Samarasinghe, K. T. G., Ahn, Y. H.* Synthesizing Clickable Glutathione by Glutathione Synthetase Mutant for Detecting Protein Glutathionylation. SynLett. 2015, 26, 285-293.

Samarasinghe, K. T. G., Munkanatta Godage, D. N. P., VanHecke, G. C., Ahn, Y. H.* Metabolic Synthesis of Clickable Glutathione for Chemoselective Detection of Glutathionylation. J. Am. Chem. Soc. 2014, 136, 11566-11569.

Currently teaching

• CHM 5998 Honors Thesis Research in Chemistry, F2020

  CHM 5999 Research in Chemistry, F2020

  CHM 6610 Biological Chemistry Laboratory, F2020

  CHM 8840 Seminar in Biochemistry, F2020

Courses taught

CHM 1030 Survey of Organic and Bioorganic Chemsitry

CHM 5600 Survey: Biochemistry

CHM 6270 Advanced Bioorganic Chemistry and Drug Design

CHM 6620 Metabolism: Pathway and Regulation: Biochemistry

CHM 6610 Biological Chemistry Laboratory

CHM 7600 Structure & Function: Biomolecules

CHM 7620 Metabolism: Pathway and Regulation: Biochemistry