Articles by Katelyn E. Connelly in JoVE
Sequential Salt Extractions for the Analysis of Bulk Chromatin Binding Properties of Chromatin Modifying Complexes Elizabeth G. Porter1, Katelyn E. Connelly1, Emily C. Dykhuizen1 1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University Sequential salt extraction of chromatin bound proteins is a useful tool for determining the binding properties of large protein complexes. This method can be employed to evaluate the role of individual subunits or domains in the overall affinity of a protein complex to bulk chromatin.
Other articles by Katelyn E. Connelly on PubMed
CBX Chromodomain Inhibition Enhances Chemotherapy Response in Glioblastoma Multiforme The Yale Journal of Biology and Medicine. Dec, 2016 | Pubmed ID: 28018136 Glioblastoma multiforme (GBM) lacks effective therapeutic options leaving patients with a survival time of approximately one year. Recently, the alteration of chromatin modulators has been implicated in the pathogenesis and chemoresistance of numerous cancers; in particular, the Polycomb Group Proteins have been shown to play a role in glioblastoma progression and maintenance [1-5]. In this study, we aimed to identify drug combinations that decrease GBM cell viability by combining small molecule inhibitors against the Polycomb family with two standard chemotherapies. We identified dual inhibition of the CBX chromodomain with doxorubicin as a novel therapeutic strategy. While treatment with chromodomain inhibitor is non-toxic to cells alone, it dramatically increased the toxicity of standard chemotherapy drugs. We further validated an increase in DNA damage resulting in a G2/M block and subsequent apoptosis using the dual inhibitor treatment.
Compositional and Functional Diversity of Canonical PRC1 Complexes in Mammals Biochimica Et Biophysica Acta. Feb, 2017 | Pubmed ID: 28007606 The compositional complexity of Polycomb Repressive Complex 1 (PRC1) increased dramatically during vertebrate evolution. What is considered the "canonical" PRC1 complex consists of four subunits originally identified as regulators of body segmentation in Drosophila. In mammals, each of these four canonical subunits consists of two to six paralogs that associate in a combinatorial manner to produce over a hundred possible distinct PRC1 complexes with unknown function. Genetic studies have begun to define the phenotypic roles for different PRC1 paralogs; however, relating these phenotypes to unique biochemical and transcriptional function for the different paralogs has been challenging. In this review, we attempt to address how the compositional diversity of canonical PRC1 complexes relates to unique roles for individual PRC1 paralogs in transcriptional regulation. This review focuses primarily on PRC1 complex composition, genome targeting, and biochemical function.