Cheryl L Meyerkord's research while affiliated with Emory University and other places

Publications (13)

Article
The Emory Chemical Biology Discovery Center (ECBDC) aims to accelerate high-throughput biology and translation of biomedical research discoveries into therapeutic targets and future medicines by providing high-throughput research platforms to scientific collaborators worldwide. ECBDC research is focused at the interface of chemistry and biology, se...
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Dysregulation of EGFR expression and signaling is well documented to contribute to disease progression and metastasis in many types of cancer including breast cancer. EGF-stimulated EGFR activation leads to receptor internalization and endocytic degradation to control EGFR-mediated signaling. This process is frequently deregulated in cancer cells,...
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The cyclin-dependent kinase 4 (CDK4) amplicon is frequently amplified in numerous human cancers including gliomas. PIKE-A, a proto-oncogene that is one of the important components of the CDK4 amplicon, binds to and enhances the kinase activity of Akt, thereby promoting cancer progression. To define the roles of the PIKE-A/Akt interaction in gliobla...
Article
Chemical genomics projects generate enormous amounts of data in a relatively short period of time. A screening campaign against a single target can produce millions of data points before data refinement is performed [1]. Generated data must then be stored and crosslinked with data from other projects. Informatics plays a critical role in all high-t...
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Advances in chemistry, biology and genomics coupled with laboratory automation and computational technologies have led to the rapid emergence of the multidisciplinary field of chemical genomics. This edited text, with contributions from experts in the field, discusses the new techniques and applications that help further the study of chemical genom...
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The 14-3-3 family of phosphoserine/phosphothreonine-binding proteins dynamically regulates the activity of client proteins in various signaling pathways that control diverse physiological and pathological processes. In response to environmental cues, 14-3-3 proteins orchestrate the highly regulated flow of signals through complex networks of molecu...
Article
Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Dysregulation of autophagy, an intracellular bulk degradation system, is strongly associated with the pathogenesis of a number of diseases, including cancer. Despite the identification of 31 genes that are essential for autophagy, the molecular machineries that regulate...
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Atg9 is a transmembrane protein essential for autophagy which cycles between the Golgi network, late endosomes and LC3-positive autophagosomes in mammalian cells during starvation through a mechanism that is dependent on ULK1 and requires the activity of the class III phosphatidylinositol-3-kinase (PI3KC3). In this study, we demonstrate that the N-...
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Autophagy is an intracellular bulk degradation system that plays a vital role in maintaining cellular homeostasis. This degradation process involves dynamic membrane rearrangements resulting in the formation of double-membraned autophagosomes. However, the driving force for generating curvature and deformation of isolation membranes remains a myste...
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The Rad9-Rad1-Hus1 (9-1-1) cell cycle checkpoint complex plays a key role in the DNA damage response. Cells with a defective 9-1-1 complex have been shown to be sensitive to apoptosis induced by certain types of genotoxic stress. However, the mechanism linking the loss of a functional 9-1-1 complex to the cell death machinery has yet to be determin...
Article
Autophagy is an intracellular system for the bulk degradation of cytoplasmic components enclosed within double-membrane structures known as autophagosomes. To date, many autophagy-related (Atg) genes have been identified by independent genetic screens for autophagy-defective mutants in yeast; however, the molecular machinery required for the biogen...
Article
RPA is an important component of DNA replication, repair and recombination, but its involvement in the signaling of cell-cycle checkpoints is not well understood. In this study, we show that knockdown of RPA1 by siRNA duplexes induces ATM (Ser1981) and Chk2 (Thr68), but not Chk1 (Ser345) phosphorylation and results in p21 upregulation in HeLa cells...
Article
The resistance of cancer cells to traditional chemotherapeutic agents is a major obstacle in the successful treatment of cancer. Cancer cells manipulate a variety of signaling pathways to enhance resistance to anticancer agents; such mechanisms include disrupting the DNA damage response and hyperactivating survival signaling pathways. In an attempt...

Citations

... A parallel assay system was established for this purpose. The uHTS campaign was carried out at the Emory Chemical Biology Discovery Center (ECBDC) [22]. Screening data were analyzed using CambridgeSoft Bioassay software [23]. ...
... TMEM106B has been reported to increase lysosomal hydrolase synthesis in lung cancer cells, which is packaged into lysosomes and enlarge lysosomes (11). A hyperinvasive microenvironment is created as lysosomes secrete their protease cargo into the extracellular matrix under conditions of calcium flux (18)(19)(20). ...
... La BiFC a également l'avantage de pouvoir visualiser les IPP directement in vivo, que ce soit au sein de cellules en culture (Dard et al. 2019), de plantes (Kodama et Wada 2009) ou encore chez la mouche drosophile . Cette technique a permis d'identifier des inhibiteurs d'IPPs, comme par exemple un peptide pouvant perturber la formation d'un complexe oncogène, le dimère PIKE-A/Akt, impliqué dans la survie, l'invasion et la migration des cellules de certains glioblastomes multiformes (Qi et al. 2013). ...
... [20,[22][23][24][25][26] In contrast to plant 14-3-3, a large number of inhibitors and stabilizers for mammalian 14-3-3 have been developed toward cancer and neuropathy therapies. [10,[27][28][29][30][31][32][33][34][35][36] However, it remains very challenging to design isoform-selective modulators that distinguish the highly conserved peptide-binding pocket ( Figure 1). [37][38][39][40] Nevertheless, development of covalent and/or allosteric 14-3-3 binders have provided valuable insight into the isoform-specific modulation. ...
... While many autophagy marker proteins exhibit scattered punctate patterns of subcellular localization, ATG9B exhibited a unique elongated tubular pattern in USCs ( Figure 4). ATG9-positive cytoplasmic structures have been observed in elongated tubular patterns, as Atg9 can be localized to Golgi membranes during fragmentation under serum starvation conditions [25]. Our observations reflect a similar phenomenon in serum-starved USCs. ...
... Protein phase separation forms liquid tissue on the surface of the membrane, which exerts compressive stress on the membrane, thus affecting the curvature of the membrane [16]. Bax interaction factor 1 (Bif-1) was originally identified as a Bax-binding protein, containing N-BAR (Bin-Amphiphysin-Rvs) domain and SH3(SrC-homology 3) domain [17]. As a key regulatory molecule for cell membrane binding and bending activities, Bif-1 could regulate intracellular events by inducing membrane curvature [17,18]. ...
... Given the relatively lower co-localization of endogenous PUMA to the ER marker in MCF-7 cells, we examined localization of endogenous PUMA after the induction of PUMA expression by ER stress (Reimertz et al., 2003;Yu and Zhang, 2008) or genotoxic stress (Meyerkord et al., 2008;Jamil et al., 2015). Previous results suggest that a P53-dependent response to genotoxic stress results resident endoplasmic reticulum membrane markers), Calr-KDEL (recycling between ER and Golgi), ERGIC (ER-Golgi intermediate compartment), GalT (trans-Golgi), Golgin84 (cis-Golgi), MAO (outer mitochondrial membrane), CCO (inner mitochondrial membrane), MAM (mitochondrial associated ER membrane), Rab5A, Rab7A, VAMP2 (transport and secretory vesicles), VAMP5 (Secretory pathway to the plasma membrane), ΔTMD-VAMP1 (cytoplasm), Lamin A (nuclear envelope), PTS1 (peroxisomes), LAMP1 (Lysosomes) (Schormann et al., 2020) in the extension of peripheral tubular ER and promotes the formation of ER-mitochondrial contact sites (Wang et al., 2007) which may be binding sites for PUMA. ...
... Next, we established and tested marker proteins to identify each cell cycle phase of a single cell. This identification can be based on the number of cells in a specific cell cycle phase by protein alterations like translocation (16)(17)(18), differences in expression (17,19,20) and/or changes in the phosphorylation level (14,18,21). Table 1 lists stainings that are commonly used to detect the stage of a cell in the different cell cycle phases via immunofluorescence. ...
... Bax-interacting factor 1 (Bif-1), also known as SH3GLB1 or lipophilic enzyme B1, is present in the cytoplasm, and is a key protein in the process of autophagy and autophagosome formation (19)(20)(21). The loss of Bif-1 may impede the endogenous apoptotic pathway while facilitating tumor development (22,23). Bif-1 exerts inhibitory effects on the production of mitochondrial and glycolytic ATP, and its downregulation contributes to the proliferation of melanoma cells (24). ...