Matthew M. Parks's research while affiliated with Weill Cornell Medical College and other places
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Publications (30)
The article Implications of sequence variation on the evolution of rRNA, written by Matthew M. Parks, Chad M. Kurylo, Jake E. Batchelder, C. Theresa Vincent and Scott C. Blanchard, was originally published electronically on the publisher’s internet portal (currently SpringerLink).
Ribosome biogenesis is a canonical hallmark of cell growth and proliferation. Here we show that execution of Epithelial-to-Mesenchymal Transition (EMT), a migratory cellular program associated with development and tumor metastasis, is fueled by upregulation of ribosome biogenesis during G1/S arrest. This unexpected EMT feature is independent of spe...
The coronary vasculature is crucial for normal heart function, yet much remains to be learned about its development, especially the maturation of coronary arterial endothelium. Here, we show that endothelial inactivation of ADAM10, a key regulator of Notch signaling, leads to defects in coronary arterial differentiation, as evidenced by dysregulate...
The evolution of the multi-copy family of ribosomal RNA (rRNA) genes is unique in regard to its genetics and genome evolution. Paradoxically, rRNA genes are highly homogenized within and between individuals, yet they are globally distinct between species. Here, we discuss the implications for models of rRNA gene evolution in light of our recent dis...
Prevailing dogma holds that ribosomes are uniform
in composition and function. Here, we show that
nutrient limitation-induced stress in E. coli changes
the relative expression of rDNA operons to alter the
rRNA composition within the actively translating
ribosome pool. The most upregulated operon encodes
the unique 16S rRNA, rrsH, distinguished by
c...
Background
Procedures for controlling the false discovery rate (FDR) are widely applied as a solution to the multiple comparisons problem of high-dimensional statistics. Current FDR-controlling procedures require accurately calculated p-values and rely on extrapolation into the unknown and unobserved tails of the null distribution. Both of these in...
The ribosome, the integration point for protein synthesis in the cell, is conventionally considered a homogeneous molecular assembly that only passively contributes to gene expression. Yet, epigenetic features of the ribosomal DNA (rDNA) operon and changes in the ribosome’s molecular composition have been associated with disease phenotypes, suggest...
Motivation:
A significant difference in the distribution of a feature between two gene sets can provide insight into function or regulation. This statistical setting differs from much of hypothesis testing theory because the genome is often considered to be effectively fixed, finite, and entirely known in commonly studied organisms, such as human....
Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show that Wnt5a rapidly represses rDNA gene...
Author
Synthesis of the translation machinery, including the mega-Dalton, RNA-protein ribosome complex, serves as a key driver of cellular growth and proliferation. It is therefore unsurprising that ribosomal biogenesis is under intricate regulation. The process through which ribosomes are made entails the coordination of components from diverse s...
DVL2 and DVL3 are excluded from nucleoli.
(a) Immunofluorescence and confocal microscopy using antibodies to DVL1 (green) and Fibrillarin (red) merged with DNA (blue) in MCF7 cells and MCF7 cells stably expressing Wnt5a treated with ActD at 1000 ng/mL for 4 hours. (b) Immunofluorescence and confocal microscopy using antibodies to DVL2 (red) and UBF...
Wnt5a decreases nucleoli size via non-canonical Wnt signaling and reduces cell growth.
(a) Immunofluorescence analysis of β-catenin (green) staining after treatment of BT549 cells for 3 hours with vehicle, Wnt3a (200 ng/mL) or Wnt5a (200 ng/mL). The inability of Wnt5a treatment to induce stabilization and nuclear translocation of β-catenin (green),...
Nucleolar localization of DVL1.
(a) Immunofluorescence with rabbit polyclonal antibody for DVL1 (red) merged with DNA (blue) in MCF7 and MDA-MB-231 breast cancer cells. Scale bar, 10 μm. (n = 3). (b) Exogenous DVL1 ectopically expressed in Rat2 cells localizes to the nucleolus. Immunofluorescence of DVL1 (green) and Fibrillarin (red) and their co-l...
Knockdown of endogenous DVL1 does not affect DVL2 or DVL3 levels.
(a) Western blots showing specific reduction of DVL1 protein levels, but no change in DVL2 or DVL3, in BT549 and MCF7 cells transduced with DVL1 shRNA (shDVL1) compared to non-silencing shRNA (Ctrl). Tubulin and GAPDH served as loading controls (n = 3). (b) Nucleofection of MCF7 cell...
Escherichia coli strain MRE600 was originally identified for its low RNase I activity and has therefore been widely adopted by the biomedical
research community as a preferred source for the expression and purification of transfer RNAs and ribosomes. Despite its widespread
use, surprisingly little information about its genome or genetic content exi...
The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover...
Non-allelic homologous recombination (NAHR) is a common mechanism for generating genome rearrangements and is implicated in numerous genetic disorders, but its detection in high-throughput sequencing data poses a serious challenge. We present a probabilistic model of NAHR and demonstrate its ability to find NAHR in low-coverage sequencing data from...
Citations
... Of note, enhanced ribosome biogenesis facilitates the transition of cells from an epithelial to a mesenchymal state, a process known as epithelial-mesenchymal transition (EMT). This EMT-associated ribosome biogenesis is accompanied by a pronounced increase in Rictor's localization in the endoplasmic reticulum (ER), indicating also a regulatory role of mTORC2 in ribosome biogenesis [87]. ...
... We are interested in understanding the evolution of rRNA genes due to the uneven distribution of crossing over, which evolves co-ordinately within but independently between species [25]. Here, we have undertaken the functional characterization of unusual ribosomal gene sequences from Oryza species that showed great diversity but are absent in the present genomic sequence. ...
... While both Etv2 and Sox17-Erg activated a generic endothelial gene program seen by Cdh5 expression or marker gene expression (Hpgd and Igfbp3), Etv2 directed the targeted fibroblasts to an immature endothelial fate seen by the activation and maintained expression levels of Vegfr3 (Fig. 5g). The expression of Vegfr3 was of particular note because it is normally expressed in developing coronary vessels and lymphatic vessels and its expression is shut off in properly matured adult coronary vessels [18][19][20] . Sox17-Erg, however, directly targeted a differentiated arterial fate as seen by the gradual decrease in Cdk1 expression and increase of Gja5, both of which mimic what has been observed in the development of pre-artery and arterial vessels 10,21,22 (Fig. 5g). ...
... Although in this case we cannot rule out that this is intraspecific variation and not a manifestation of HGT, these data demonstrate the power and importance of concerted evolution for the evolutionary dynamics of 16S rRNA. In fact, this variability at the 16S rRNA level has been described previously and its significance appears to be biologically relevant 53 ; but see 54 . In particular, transcriptional upregulation of a variant referred to as rssh 16S rRNA (referred to here as variant B) is associated with a general stress response, activation of starvation related gene pathways and increased antibiotic resistance 53 . ...
... Naturally, such methods are sensitive to the parametric specification. Parks, Raphael, and Lawrence [28] proposed to estimate the local FDR using a kernel density estimator based on the internal negative controls but did not provide theoretical justifications of their method. Other authors suggested heuristic approaches that use the internal negative controls to estimate the FDR [34,42]. ...
... The WGBS data was mapped to a reference genome modified to include a representative copy of the rDNA since the rDNA clusters present on chromosomes 13, 14, 15, 21 and 22 in humans are not included in the genome assembly 5,9 . The sequencing depth of these data (~14x), is sufficient to produce high resolution quantitation of DNA methylation when considering groups of genomic features, or mapping to a consensus for a multi-copy genomic element, such as the rDNA (Table S2). ...
... Differences in stem cell index were determined using the Wilcoxon test and Kruskal-Wallis test for glioma and nontumor tissue and for different clinical features (Parks, 2018). The tumor samples were divided into a high stem cell index group (high) and low stem cell index group (low) according to the median value. ...
... Interestingly, the spliceosome is one of the members of RNPs. Moreover, growing evidence strongly identi es an essential link between the EMT program and Ribonucleoprotein (RNP) biogenesis 32,33 , which leads to tumor cell migration, invasion, and eventual metastasis. Previous studies shows that high expression of DLAT is associated with metastasis in liver and colon cancer, predicting a poor prognosis 34,35 . ...
... Ribosomes were isolated from the E. coli strain MRE600, which does not produce RNase I due to a missense mutation in the rna gene 38 . Several hundred grams of log-phase cells were commercially produced and purchased. ...
... Table 2). This is substantially less frequent than what was observed in pre-translocation bacterial and human ribosomes (28,65). Importantly, spontaneous transitions of pre-translocation ribosomes in complex with tRNAs are fast and occur on the subsecond time scale (28,29,(66)(67)(68). ...