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The Pattenden lab is focused on the development of innovative techniques in chromatin-based therapeutic target discovery and cancer diagnostics. As Director of Applied Epigenetic Screening Technologies at the Center for Integrative Chemical Biology and Drug Discovery, my goal is to enable collaborators to apply chemical biology to the discovery of novel molecular targets, pathways and mechanisms. Our central strategy exploits tumor-specific changes in chromatin accessibility, a universal feature that is directly linked with transcriptional activation, DNA damage repair, replication, RNA processing, and nuclear organization. Since chromatin accessibility offers a comprehensive overview of the rewiring of transcriptional networks that accompanies processes such as cellular differentiation, tumor growth, metastasis, and therapeutic resistance, it is frequently more reliable in predicting cell behavior than gene expression profiles alone. This strategy has played a critical role in advancing several collaborative projects. With Dr. Michael Jarstfer (UNC, CBMC), we developed a first-in-class screen for inhibitors of the alternative lengthening of telomeres (ALT) pathway in ALT-positive cancers. We developed a chemical biology screening platform for Ewing sarcoma with Dr. Ian Davis (UNC, Genetics), based on chromatin accessibility to gain both mechanistic and therapeutic insight into tumor growth and development. This screening technique represents a promising new paradigm in oncology drug discovery since it is broadly applicable to other cancers and will potentially expand the repertoire of druggable chromatin-focused targets. Along with Dr. Paul Dayton (UNC, Biomedical Engineering), we patented and published a new method for fragmentation of DNA using a cavitation enhancement reagent, and founded Triangle Biotechnology, Inc., a company focused on the development of new sonication technologies. We have expanded the application of our technology to include extraction of chromatin from fixed cells and archived tissues to study changes in chromatin architecture.


UNC AFFILIATIONS:

Other, Pharmaceutical Sciences

CLINICAL/RESEARCH INTERESTS:

Cancer Biology, Chemical Biology, Drug Discovery, Epigenetics and Chromatin Biology, Molecular Biology, Translational Medicine