Untangling chromatin to find novel anti-cancer targets
Our lab is a part of the oldest cancer research center, Roswell Park Cancer Institute, which was founded by surgeon Dr. Roswell Park in in 1898. The lab was started in 2008 within the Department of Cell Stress Biology, and according to Google, is the only department with this name. The major goal of our research is the identification of a way to gain control over cancer, i.e. finding novel targets for anti-cancer treatment and approaches to modulate these targets. Several novel small molecules with anti-cancer properties were identified in our lab. One of them, curaxin CBL0137, is currently being tested in clinical trials.
Curaxins were discovered in a cell-based screening for novel type of activators of tumor suppressor p53. The search for the mechanism of action of curaxins brought us to the field of chromatin biology, since curaxins appeared to be the “first in the class” – pure “chromatin damaging” compounds. The current focus of our research is understanding the chromatin alterations in cancer, the reasons chromatin destabilization is more toxic for tumor than for normal cells, how chromatin stability is regulated, and whether it is possible to utilize some chromatin remodeling factors, e.g. histone chaperone, as targets for anti-cancer treatment.
Long-awaited review about FACT: "Structure and function of the histone chaperone FACT –
Resolving FACTual issues" is finally published today in BBA!
The first paper about generation of mice with conditional knockout of FACT is published!!! This paper is not yet about the consequences of FACT inactivation in mammals but about underwater stones of using genetic recombination in mice: Uncovering the fine print of the CreERT2-LoxP system while generating a conditional knockout mouse model of Ssrp1 gene. We thought that discolsure of this problem is very important for the community. Congratulations Poorva and other coauthors!
Two of our papers were recently accepted for publication, one in eLife "TRAIN (Transcription of Repeats Activates INterferon) in response to chromatin destabilization induced by small molecules in mammalian cells," and another one in Cancer Research "Role of chromatin damage and chromatin trapping of FACT in mediating the anticancer cytotoxicity of DNA-binding small molecule drugs".
Cancer Research with our cover image was published today!
Poorva got her PhD diploma. Congratulations!!!