Publications de Kuan-Ting Huang

Electrophilic Metabolite/Drug-Target Discovery and Investigations into On-target Signaling Mechanisms Leveraging Larval Zebrafish and Cultured Cells

This thesis presents novel methodologies and discoveries in the study of reactive electrophilic metabolites and electrophilic drugs, using mammalian cells and live zebrafish larvae as models. Chapter 1 details our current understanding and strategies for s ...

EPFL2024

Toward decoding spatiotemporal signaling activities of reactive immunometabolites with precision immuno-chemical biology tools

Yimon Aye, Kuan-Ting Huang

Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs—e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly ...

2024

Z-REX: shepherding reactive electrophiles to specific proteins expressed tissue specifically or ubiquitously, and recording the resultant functional electrophile-induced redox responses in larval fish

Yimon Aye, Sruthi Raja, Kuan-Ting Huang

This Protocol Extension describes the adaptation of an existing Protocol detailing the use of targetable reactive electrophiles and oxidants, an on-demand redox targeting toolset in cultured cells. The adaptation described here is for use of reactive elect ...

NATURE PORTFOLIO2023

Monitoring On-Target Signaling Responses in Larval Zebrafish- Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites

Yimon Aye, Jesse Poganik, Kuan-Ting Huang, Phillippe Ly

Reactive metabolites and related electrophilic drugs are among the most challenging small molecules to study. Conventional approaches to deconstruct the mode of action (MOA) of such molecules leverage bulk treatment of experimental specimens with an excess ...

JOURNAL OF VISUALIZED EXPERIMENTS2023

Keap It in the Family: How to Fish out New Paradigms in Keap1-Mediated Cell Signaling

Yimon Aye, Kuan-Ting Huang

Keap1 is associated with cytoprotective signaling. These roles of Keap1 typically focus on its role as a degrader of the antioxidant response (AR) transcription factor, Nrf2, and the inhibition of this process upon Keap1 labeling by electrophiles. However, ...

Wiley-V C H Verlag Gmbh2023

Z-REX uncovers a bifurcation in function of Keap1 paralogs

Yimon Aye, Xuyu Liu, Jesse Poganik, Yi Zhao, Alexandra Krina Van Hall-Beauvais, Kuan-Ting Huang

Studying electrophile signaling is marred by difficulties in parsing changes in pathway flux attributable to on-target, vis-& agrave;-vis off-target, modifications. By combining bolus dosing, knockdown, and Z- REX & mdash;a tool investigating on- target/on ...

eLIFE SCIENCES PUBL LTD2022

Wdr1 and cofilin are necessary mediators of immune-cell-specific apoptosis triggered by Tecfidera

Yimon Aye, Sruthi Raja, Jesse Poganik, Kuan-Ting Huang, Yi Zhao

The mechanism-of-action of many electrohilic drugs remains poorly understood. Here, the authors use a redox-targeting approach to elucidate the basis for the innate immune cell toxicity of dimethyl fumarate, showing that it modifies Keap1 to trigger mitoch ...

Nature Portfolio2021

The not so identical twins: (dis)similarities between reactive electrophile and oxidant sensing and signaling

Yimon Aye, Kuan-Ting Huang

In this tutorial review, we compare and contrast the chemical mechanisms of electrophile/oxidant sensing, and the molecular mechanisms of signal propagation. We critically analyze biological systems in which these different pathways are believed to be mani ...

Royal Society of Chemistry2021