Development of a HT-ATACseq assay to identify epigenetic regulators of Ewing Sarcoma cancer cells (Chemical Biology Consortium/NCI Experimental Therapeutics Collaboration)

在此期间，项目团队致力于开发一种目标不可知的小分子筛选技术，该技术利用肿瘤特异性染色质可及性状态作为相关和直接的功能读数。通过靶向染色质可及性而不是单个转录因子或染色质调节蛋白，可以克服与体外筛选和单个蛋白质靶标鉴定相关的限制。该项目团队专注于优化实验条件，以建立一个高通量筛选平台，该平台能够使用基于酶的方法，即反式染色质测定法（ATAC）来测量细胞中染色质可及性的动态状态。 这种筛选技术代表了肿瘤学药物发现的一种有前途的新范式，它将增加我们对表观基因组中肿瘤特异性变化的机理知识，并扩大可药用靶点的库。 应用这一策略，我们将筛选小分子文库，分析尤文肉瘤特异性区域的染色质可及性。

During this period, the project team has worked towards developing a target agnostic small molecule screening technology that exploits tumor-specific chromatin accessibility states as a relevant and direct functional readout. By targeting chromatin accessibility instead of a single transcription factor or chromatin regulatory protein, the limitations associated with in vitro screening and single protein target identification can be overcome. The project team has focused on optimizing experimental conditions towards a high throughput screening platform capable of measuring dynamic states of chromatin accessibility in cells using an enzyme-based approach, Assay for Transpose-Accessible Chromatin (ATAC). This screening technique represents a promising new paradigm in oncology drug discovery that will increase our mechanistic knowledge of tumor-specific changes in the epigenome and expand the repertoire of druggable targets. Applying this strategy, we will screen small molecule libraries assaying chromatin accessibility at regions specific for Ewing sarcoma.