Research interests

Study the aggregation and misfolding of Tar DNA binding protein TDP-43 (TDP43) in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FLD).

Develop fluorescence-based methodologies, such as Forster resonance energy transfer (FRET) or fluorescence anisotropy, to investigate the interactions between nascent peptides and chaperon proteins. Explore the specific interaction between chaperones and protein aggregates and develop potential treatment.

Studies of in vitro protein folding driven by various effect (turn formation, hydrophobic interaction, solvation and etc.) using various biophysical method (including fluorescence technique, CD, NMR, Mass etc.).

 

In an effort to clarify the physical properties of the C-terminal domain of TDP-43, we have synthesized peptide fragments and shown that only D1 within D1-4 can form twisted fibrils.
(A) PONDR analysis of the full-length TDP-43 (1-414).Calculations use VL3 version of PONDR. EM images of (B) D1, (C) 315T, and (D) G294A incubated in pH 7.0 phosphate buffer at 37℃ for 2 weeks. The scale bars represent 100 nm.

Selected publications

• Koubek, J., Lin, K.-F., Chen, Y.-R., Cheng, R.-P., Huang, J. J.-T.* Strong anion exchange fast performance liquid chromatography as a versatile tool for preparation and purification of RNA produced by in vitro transcription. RNA, 2013 (in press)
• Huang, Y.-C. Lin, K.-F, He, R.-Y., Tu, P.-H. Koubek, J., Hsu,Y.-C., Huang, J. J.-T.* Inhibition of TDP-43 aggregation by nucleic acid binding. PLoS One 2013, 8(5), e64002

• Chang, C.-K., Wu, T.-H., Wu, C.-Y., Chiang, M.-H., Toh, E.-K., Hsu, Y.-C., Lin, K.-F., Liao, Y.-H., Huang, T.-H.*, Huang, J. J.-T.* The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity. Biochem. Biophys. Res. Commun. 2012, 425, 219-224

• Lin, K.-F., Sun, C.-S., Huang, Y.-C., Chan, S.-I., Koubek, J., Wu, T.-H., Huang, J. J.-T.* Cotranslational Protein Folding within the Ribosome Tunnel Influences Trigger-Factor Recruitment. Biophys. J. 2012, 102, 2818-2827.
• Lin, K.-F., Sun, C.-S., Huang, Y.-C., Chan, S.-I., Koubek, J., Wu, T.-H., Huang, J. J.-T.* Cotranslational Protein Folding within the Ribosome Tunnel Influences Trigger-Factor Recruitment. Biophys. J. 2012, 102, 2818-2827.
• Huang, J. J.-T.; Larsen, R.-W.; Chan, S.-I.* The Interplay of Turn Formation and Hydrophobic Interactions on the Early Kinetic Events in Protein Folding. Chem. Comm. 2012, (Feature Article), 48, 487-497.
• Chen, K.-H., Lin, Y.-Y., Xie, Z.-J., Tu, P.-H., Chen, P.-Y., Liao, T.-Y.,Huang, J. J.-T.* Induction of Amyloid Fibrils by the C-terminal Fragment of TDP-43 in Amyotrophic Lateral Sclerosis. J. Am. Chem. Soc.2010, 132, 1186.