Thomas Hanigan

Thomas Hanigan

he/him/his

Harnessing Metabolism for Drug Development

Publications

Small Molecule Inhibitors of Complex IV Induce Imbalanced Pyrimidine Expansion in OXA1L Variant Cells

Published in Preprint, 2024

Discovery of first in class small molecules targeting the mitochondrial insertase OXA1L, and characterization of a common genetic vulnerability mediating selective lethality in non-small cell lung cancer.

Recommended citation: Thomas W. Hanigan, Junichiro Takaya, Haoxin Li, Jarret R. Remsberg, Verena Albert, J.C. Ducom, Christopher M. Joslyn, Scott C Henderson, Kathryn S Spencer, Sabrina Barbas, Melissa A Dix, Kim Masuda, Enrique Saez, Kenji Sasaki, Christopher G. Parker, Benjamin F. Cravatt. Small Molecule Inhibitors of Complex IV Induce Imbalanced Pyrimidine Expansion in OXA1L Variant Cells. In-Preparation (2023)..
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Proteomic discovery of chemical probes that perturb protein complexes in human cells

Published in Molecular Cell, 2023

Novel function-first approach to discover molecules that disrupt multi-protein complexes, with focus on the splicing machinery

Recommended citation: Michael R. Lazear, Jarrett R. Remsberg, Martin G. Jaeger, Katherine Rothamel, Hsuan-lin Her, Kristen E. DeMeester, Evert Njomen, Simon J. Hogg, Jahan Rahman, Landon R. Whitby, Sang Joon Won, Michael A. Schafroth, Daisuke Ogasawara, Minoru Yokoyama, Garrett L. Lindsey, Haoxin Li, Jason Germain, Sabrina Barbas, Joan Vaughan, Thomas W. Hanigan, Vincent F. Vartabedian, Christopher J. Reinhardt, Melissa M. Dix, Seong Joo Koo, Inha Heo, John R. Teijaro, Gabriel M. Simon, Brahma Ghosh, Omar Abdel-Wahab, Kay Ahn, Alan Saghatelian, Bruno Melillo, Stuart L. Schreiber, Gene W. Yeo, Benjamin F. Cravatt. Proteomic discovery of chemical probes that perturb protein complexes in human cells. Bioarxiv. 2022. https://doi.org/10.1101/2022.12.12.520090
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ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth. Nat Chem Biol 17, 856–864 (2021).

Published in Nature Chemical Biology, 2021

Significance: Discovery of first in class inhibitors ABHD17, which selectively block depalmitoylation of N-Ras in a plasma membrane-specific fashion.

Recommended citation: Remsberg, J.R., Suciu, R.M., Zambetti, N.A., Thomas W. Hanigan, et al. ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth. Nat Chem Biol 17, 856–864 (2021).
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Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue.

Published in J Biol Methods, 2019

Significance: This work describes a novel method applying photoreactive HDAC inhibitors for chromatin immunoprecipitation, which permits characterization of genomic loci specifically targeted by HDAC inhibitors.

Recommended citation: Thomas W Hanigan, Jeanne Danes, Taha Taha, Jonna Frasor, Pavel Petukhov. “Histone Deacetylase Inhibitor-Based Chromatin Precipitation for Identification of Targeted Genomic Loci”. J Biol Methods. 2018;5(1):e88. doi: 10.14440/jbm.2018.216.
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Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue.

Published in Chem Med Chem, 2019

Significance: In this study we describe a robust synthetic strategy to access chemically diverse photoreactive probes (PRPs), which we used to prepare PRPs based on seven HDAC inhibitor scaffolds. The selectivity of these PRP chemotypes for HDAC isoforms was characterized by biochemical assays and photolabeling experiments in cell lines and mouse liver tissues, relevant for the design of isoform selective HDAC inhibitors.

Recommended citation: Thomas W. Hanigan, Aboukhatwa SM, Taha TY, Neerasa J, Ranjan R, El-Bastawissy EE, Elkersh MA, El-Moselhy TF, Frasor J, Mahmud N, McLachlan A, Petukhov PA. Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue. ChemMedChem. 2019 Jun 5;14(11):1096-1107. doi: 10.1002/cmdc.201900114
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Divergent JNK Phosphorylation of HDAC3 in Breast Cancer Cells Determines HDAC Inhibitor Binding and Selectivity

Published in Cell Chemical Biology, 2017

Significance: This work demonstrates that histone deacetylase (HDAC) inhibitor selectivity and efficacy is regulated by HDAC phosphorylation and characterizes a novel pathway catalyzing HDAC3 phosphorylation mediated by c-Jun N-terminal kinase, differentially active across breast cancer subtypes. Thus, the selectivity and efficacy of HDAC inhibitors is cell type-dependent, which is not recapitulated in vitro analysis, and provides a strategy to improve HDAC inhibitor efficacy for breast cancer treatment.

Recommended citation: Thomas W. Hanigan, Jonna Frasor, Pavel Petukhov. “Divergent JNK Phosphorylation of HDAC3 in Breast Cancer Cells Determines HDAC Inhibitor Binding and Selectivity. Cell Chemical Biology. 2017 Nov 16;24(11):1356-1367.e8. doi:10.1016/j.chembiol.2017.08.015.
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