Annual Report 2024

Tsuruoka Metabolomics Laboratory

Akihiko Yokoyama, Yosuke Komata, Tomoaki Fujii, Hagumu Sato, Ikuko Yokoyama, Ayako Yokoyama, Kanae Ito

Introduction

 Our focus is on molecular pathology of childhood cancers such as refractory leukemia.

The Team and What We Do

 Our team investigates the molecular mechanisms of leukemia and Wilms tumor using mouse disease models, proteomics approaches, and epigenome analytical tools. We aim to identify novel molecular targets for drug development by elucidating the molecular mechanisms by which oncoproteins cause aberrant self-renewal.

Research Activities

 We studied and revealed some of the oncogenic roles of histone acetyltransferases in leukemia. HBO1 histone acetyltransferase and its cofactor JADE2 fuse with NUP98 to constitute leukemia oncogenes. We showed the molecular mechanism by which these NUP98 fusion proteins associated with their target chromatin. We also discovered that MOZ histone acetyltransferase and its oncogenic mutant bound to the target DNA and p300 histone acetyltransferase through the same structure.

1. *Yokoyama A, Niida H, *Kutateladze TG, *Cote J. HBO1, a MYSTerious KAT and its links to cancer BBA-Gene Regulatory Mechanisms (REVIEW) (2024) (1867:3:195045) doi.org/10.1016/j.bbagrm.2024.195045

2. #Gaurav N, #Kanai A, #Lachance C, Cox KL, Liu J, Grzybowski AT, Saksouk N, Klein BJ, Komata Y, Asada S, Ruthenburg AJ, Poirier MG, *Cote J, *Yokoyama A, and *Kutateladze TG. Guiding the HBO1 complex function through the JADE subunit Nature Structural & Molecular Biology 31, 1039-1049 (2024) DOI:10.1038/s41594-024-01245-2

3. Becht DC, Kanai A, Halawa M, Biswas S, Shi X, Yokoyama A, and Kutateladze TG. The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300 iScience 27, 109367 (2024) doi.org/10.1016/j.isci.2024.109367

Clinical Trials

 A novel drug for leukemia that we developed with Sumitomo Pharma is now in the phase II clinical trial worldwide.

Education

 Training:Researchers and technicians

Future Prospects

 We aim to identify novel therapeutic targets, which may lead to the development of new therapies, through the deep understanding of the molecular mechanisms of childhood cancer.