Professional Education
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Doctor of Philosophy, Cornell University (2019)
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Bachelor of Science, Pennsylvania State University (2012)
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PhD, Cornell University, Biochemistry, Molecular, and Cell Biology (2019)
All Publications
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Cell Size Contributes to Single-Cell Proteome Variation.
Journal of proteome research
2023
Abstract
Accurate measurements of the molecular composition of single cells will be necessary for understanding the relationship between gene expression and function in diverse cell types. One of the most important phenotypes that differs between cells is their size, which was recently shown to be an important determinant of proteome composition in populations of similarly sized cells. We, therefore, sought to test if the effects of the cell size on protein concentrations were also evident in single-cell proteomics data. Using the relative concentrations of a set of reference proteins to estimate a cell's DNA-to-cell volume ratio, we found that differences in the cell size explain a significant amount of cell-to-cell variance in two published single-cell proteome data sets.
View details for DOI 10.1021/acs.jproteome.3c00441
View details for PubMedID 37910793
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Increasing cell size remodels the proteome and promotes senescence.
Molecular cell
2022
Abstract
Cell size is tightly controlled in healthy tissues, but it is unclear how deviations in cell size affect cell physiology. To address this, we measured how the cell's proteome changes with increasing cell size. Size-dependent protein concentration changes are widespread and predicted by subcellular localization, size-dependent mRNA concentrations, and protein turnover. As proliferating cells grow larger, concentration changes typically associated with cellular senescence are increasingly pronounced, suggesting that large size may be a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative, DNA-damage-induced, and CDK4/6i-induced senescence. Size-dependent changes to the proteome, including those associated with senescence, are not observed when an increase in cell size is accompanied by an increase in ploidy. Together, our findings show how cell size could impact many aspects of cell physiology by remodeling the proteome and provide a rationale for cell size control and polyploidization.
View details for DOI 10.1016/j.molcel.2022.07.017
View details for PubMedID 35987199
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Whi5 is diluted and protein synthesis does not dramatically increase in pre-Start G1.
Molecular biology of the cell
2022; 33 (5): lt1
View details for DOI 10.1091/mbc.E21-01-0029
View details for PubMedID 35482510
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Delineation of proteome changes driven by cell size and growth rate.
Frontiers in cell and developmental biology
2022; 10: 980721
Abstract
Increasing cell size drives changes to the proteome, which affects cell physiology. As cell size increases, some proteins become more concentrated while others are diluted. As a result, the state of the cell changes continuously with increasing size. In addition to these proteomic changes, large cells have a lower growth rate (protein synthesis rate per unit volume). That both the cell's proteome and growth rate change with cell size suggests they may be interdependent. To test this, we used quantitative mass spectrometry to measure how the proteome changes in response to the mTOR inhibitor rapamycin, which decreases the cellular growth rate and has only a minimal effect on cell size. We found that large cell size and mTOR inhibition, both of which lower the growth rate of a cell, remodel the proteome in similar ways. This suggests that many of the effects of cell size are mediated by the size-dependent slowdown of the cellular growth rate. For example, the previously reported size-dependent expression of some senescence markers could reflect a cell's declining growth rate rather than its size per se. In contrast, histones and other chromatin components are diluted in large cells independently of the growth rate, likely so that they remain in proportion with the genome. Finally, size-dependent changes to the cell's growth rate and proteome composition are still apparent in cells continually exposed to a saturating dose of rapamycin, which indicates that cell size can affect the proteome independently of mTORC1 signaling. Taken together, our results clarify the dependencies between cell size, growth, mTOR activity, and the proteome remodeling that ultimately controls many aspects of cell physiology.
View details for DOI 10.3389/fcell.2022.980721
View details for PubMedID 36133920
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In-depth and 3-dimensional exploration of the budding yeast phosphoproteome
EMBO REPORTS
2021: e51121
Abstract
Phosphorylation is one of the most dynamic and widespread post-translational modifications regulating virtually every aspect of eukaryotic cell biology. Here, we assemble a dataset from 75 independent phosphoproteomic experiments performed in our laboratory using Saccharomyces cerevisiae. We report 30,902 phosphosites identified from cells cultured in a range of DNA damage conditions and/or arrested in distinct cell cycle stages. To generate a comprehensive resource for the budding yeast community, we aggregate our dataset with the Saccharomyces Genome Database and another recently published study, resulting in over 46,000 budding yeast phosphosites. With the goal of enhancing the identification of functional phosphorylation events, we perform computational positioning of phosphorylation sites on available 3D protein structures and systematically identify events predicted to regulate protein complex architecture. Results reveal hundreds of phosphorylation sites mapping to or near protein interaction interfaces, many of which result in steric or electrostatic "clashes" predicted to disrupt the interaction. With the advancement of Cryo-EM and the increasing number of available structures, our approach should help drive the functional and spatial exploration of the phosphoproteome.
View details for DOI 10.15252/embr.202051121
View details for Web of Science ID 000610988800001
View details for PubMedID 33491328
View details for PubMedCentralID PMC7857435