Molecular Mechanisms of Epigenetic Crosstalk between Histone Modifications and DNA Methylation in Cancer: New Avenues for Drug Development

2022 Emerging Leader Award

Karim-Jean Armache, PhD, New York University

Karim-Jean Armache, PhD

Dr. Armache is investigating how patterns of DNA methylation are established and maintained in chromatin. His laboratory uses structural biology and functional approaches to decipher how key DNA methyltransferases are selectively recruited to particular sites and regulated. In this project, he will study the crosstalk between the ubiquitination of histone H2A and cytosine methylation by DNMT3A1. These studies will lay the foundation for rational design of inhibitors that specifically target aberrant DNA methylation in cancer.

Dr. Armache completed his graduate work at the University of Munich, studying basic mechanisms of transcription, and his postdoctoral research at Massachusetts General Hospital and Harvard Medical School, studying epigenetic gene silencing. Since starting his laboratory at NYU Grossmann School of Medicine his work has focused on structural and functional understanding of chromatin-mediated regulation of gene expression.

published research

Thomas JF, Valencia-Sánchez MI, Tamburri S, Gloor SL, Rustichelli S, Godínez-López V, De Ioannes P, Lee R, Abini-Agbomson S, Gretarsson K, Burg JM, Hickman AR, Sun L, Gopinath S, Taylor HF, Sun ZW, Ezell RJ, Vaidya A, Meiners MJ, Cheek MA, Rice WJ, Svetlov V, Nudler E, Lu C, Keogh MC, Pasini D, Armache KJ. Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1. Sci Adv. 2023.

Abini-Agbomson S, Gretarsson K, Shih RM, Hsieh L, Lou T, De Ioannes P, Vasilyev N, Lee R, Wang M, Simon MD, Armache JP, Nudler E, Narlikar G, Liu S, Lu C, Armache KJ. Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1. Mol Cell. 2023.