Current PhD work

Genetics changes in high tumor mutational burden tumors

Tumors with high tumor mutational burden (TMB), which is composed of mainly passenger mutations that affect protein folding and stability, suffer from protein folding (PF) stress. This can in turn reduce tumor fitness. I am interested in using human genomics data to identify genes that can potentially alleviate the protein folding stress in order to maintain tumor growth and survival.

Establishing novel protein folding stress mouse models

Currently, there is no genetically engineered mouse models that imitate high TMB tumors. I am interested in establishing novel mouse models in order to assess the impacts of PF stress in cancer.

Systematic investigation of tumor suppression and stress-dependent lethality under protein folding stress

Some tuomor suppressor inactivation might be crucial in overcoming the PF stress. As well, the context-dependent essential genes could be promising therapeutic targets. I am interested in systematically investigate the functional impact of these genes.

Previosu work

My previous research was focused on the binding mechanism between a ubiquitin ligase and its substrate. This reveals a conserved strategy of how cells sense and alleviate reductive stress. The key players in this reductive stress response have been found mutated frequently in cancer.

Publications

Manford AG, Rodríguez-Pérez F, Shih KY, Shi Z, Berdan CA, Choe M, Titov DV, Nomura DK, Rape M. A Cellular Mechanism to Detect and Alleviate Reductive Stress. Cell. 2020 Oct 1;183(1):46-61.e21. doi: 10.1016/j.cell.2020.08.034. Epub 2020 Sep 16. PMID: 32941802.

Manford AG, Mena EL, Shih KY, Gee CL, McMinimy R, Martínez-González B, Sherriff R, Lew B, Zoltek M, Rodríguez-Pérez F, Woldesenbet M, Kuriyan J, Rape M. Structural basis and regulation of the reductive stress response. Cell. 2021 Oct 14;184(21):5375-5390.e16. doi: 10.1016/j.cell.2021.09.002. Epub 2021 Sep 24. PMID: 34562363; PMCID: PMC8810291.