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Lindsey James, PhD



Lab Members

The goal of the James lab is to undertake and lead innovative and novel projects focused on the chemical biology of chromatin regulation, with an emphasis on the development of small molecule chemical probes. Providing such tool compounds to the scientific community has the potential to open new avenues of research in various disease relevant fields and translate to compounds of therapeutic value. Specifically, we are focused on developing compounds to study the domains that recognize the post-translational modification, methylated lysine. Aberrant methylation levels and ensuing changes in gene expression patterns resulting from the altered expression of methyl-lysine (Kme) regulatory proteins is one mechanism by which such epigenetic factors contribute to disease. Kme reader domains have emerged as less precedented epigenetic targets, yet considering the abundant links to cancer genetics, they are well suited to become the next impactful target class of chromatin regulators for intervention.

Our work in this area has pioneered the biochemical assays and medicinal chemistry strategies for high-quality probe development for the methyl-lysine reader target class, as well as the means by which to evaluate probe selectivity, mechanism of action, and cellular activity. Using a variety of approaches, we utilize such chemical tools to improve our understanding of their molecular targets and the broader biological consequences of modulating these targets in disease, particularly cancer. We also think about developing novel methods and screening platforms to discover hit compounds to accelerate Kme reader probe discovery such as affinity-based combinatorial strategies, as well as novel ligand-based tools (see below) such as protein degradation reagents, or PROTACs, as potential therapeutic modalities. We have successfully developed numerous first-in-class chemical probes and currently have compounds in preclinical development (for example, see

Additionally, we collaborate closely with UNC faculty from various disciplines to provide medicinal chemistry and chemical biology expertise to bear on biological targets of therapeutic relevance.

Dr, James is committed to providing an inclusive, safe, and supportive research environment for trainees, teaching trainees to conduct rigorous, ethically sound, and responsible scientific research, and fulfilling the needs of trainees so that they can transition to the next phase of their careers.



Slide-Inhibitor derivatives facilitate chemical biology