Biology subjects

Suarez, E.

Publications and source records attributed to Suarez, E..

7 recordsLinked to original sources

bioRxiv2026

EPHA4 Regulates the Transition between Mesenchymal and Hybrid States in TNBC

Metastatic progression in triple-negative breast cancer (TNBC) is strongly influenced by epithelial-mesenchymal plasticity (EMP), which enables transitions between epithelial, hybrid epithelial/mesenchymal (E/M), and mesenchymal cell states. While mesenchymal cells are highly invasive and resistant to therapy, hybrid E/M states confer advantages during metastatic colonization. Both mesenchymal and hybrid states therefore contribute to tumor aggressiveness through distinct mechanisms. However, the molecular regulation governing transitions between mesenchymal and hybrid E/M states remains poorly understood. Here, we identify EPHA4 as a regulator of this transition in TNBC. EPHA4 expression is enriched in mesenchymal TNBC cells, and genetic knockout of EPHA4 in MDA-MB-231 xenograft and 4T1 syngeneic models induces a shift toward hybrid E/M phenotypes. This transition reduces cellular invasion while enhancing metastatic colonization, consistent with the clinical observations of decreased EPHA4 expression in secondary metastases compared to primary tumors. Despite compensatory changes in other Eph/ephrin family members following EPHA4 loss, EPHA4 deficiency is sufficient to drive this phenotypic shift. These findings identify EPHA4 as a regulator of cancer cell plasticity in TNBC and highlight the therapeutic complexity of targeting pathways that govern metastatic state transitions.

cancer biology↗

bioRxiv2023

Latitudinal gradients in predation persist in urban environments

Urbanization can profoundly disrupt local ecology. But while urban areas now stretch across latitudes, little is known about urbanizations effects on macroecological patterns. We used standardized experiments to test whether urbanization disrupts latitudinal gradients in seed predation, a macroecological pattern that shapes community assembly and diversity. Using >56,000 seeds, we compared predation in urbanized and natural areas across 14,000 km of latitude, spanning the Americas. Predation increased 5-fold from high latitudes to the tropics, and latitudinal gradients in predation persisted in urban areas despite significant habitat modification. Urbanization reduced predation by vertebrates, but not invertebrates, and seemed to increase ant predation specifically. Our results show that macroecological patterns in predation intensity can persist in urbanized environments, even as urbanization alters the relative importance of predators. One-Sentence SummaryAcross 56,000 seeds and 112{degrees} of latitude, latitudinal gradients in seed predation are equally strong in natural vs. urban areas

ecology↗

bioRxiv2023

Single-cell Transcriptomic Analysis of Salivary Gland Endothelial Cells

Vascular endothelial cells have important functions in fibrosis via direct and indirect methods and in regeneration through secretion of tissue-specific, paracrine-acting angiocrine factors. In the salivary gland, endothelial cells are required for proper development, but their roles within adult glands are largely unknown. The goal of this work was to identify ligand-receptor interactions between endothelial cells and other cell types that are important during homeostasis, fibrosis, and regeneration. To model salivary gland fibrosis and regeneration, we utilized a reversible ductal ligation. To induce injury, a clip was applied to the primary ducts for 14 days, and to induce a regenerative response, the clip was subsequently removed for 5 days. To identify endothelial cell-produced factors, we used single-cell RNA-sequencing of stromal-enriched cells from adult submandibular and sublingual salivary glands. Transcriptional profiles of homeostatic salivary gland endothelial cells were compared to endothelial cells of other organs. Salivary gland endothelial cells were found to express unique genes and displayed the highest overlap in gene expression with other fenestrated endothelial cells from the colon, small intestine, and kidney. Comparison of the 14-day ligated, mock ligated, and 5-day deligated stromal-enriched transcripts and lineage tracing were used to identify evidence for a partial endoMT phenotype, which was observed in a small number of endothelial cell subsets with ligation. CellChat was used to predict changes in ligand-receptor interactions in response to ligation and deligation. CellChat predicted that after ligation, endothelial cells are sources of protein tyrosine phosphatase receptor type m, tumor necrosis factor ligand superfamily member 13, and myelin protein zero signaling and targets for tumor necrosis factor signaling. Following deligation, CellChat predicted that endothelial cells are sources of chemokine (C-X-C motif) and EPH signaling to promote regenerative responses. These studies will inform future endothelial cell-based regenerative therapies.

cell biology↗

bioRxiv2020

What Markov state models can and cannot do: Correlation versus path-based observables in protein folding models

Markov state models (MSMs) have been widely applied to study the kinetics and pathways of protein conformational dynamics based on statistical analysis of molecular dynamics (MD) simulations. These MSMs coarse-grain both configuration space and time in ways that limit what kinds of observables they can reproduce with high fidelity over different spatial and temporal resolutions. Despite their popularity, there is still limited understanding of which biophysical observables can be computed from these MSMs in a robust and unbiased manner, and which suffer from the space-time coarse-graining intrinsic in the MSM model. Most theoretical arguments and practical validity tests for MSMs rely on long-time equilibrium kinetics, such as the slowest relaxation timescales and experimentally observable time-correlation functions. Here, we perform an extensive assessment of the ability of well-validated protein folding MSMs to accuractely reproduce path-based observable such as mean first-passage times (MFPTs) and transition path mechanisms compared to a direct trajectory analysis. We also assess a recently proposed class of history-augmented MSMs (haMSMs) that exploit additional information not accounted for in standard MSMs. We conclude with some practical guidance on the use of MSMs to study various problems in conformational dynamics of biomolecules. In brief, MSMs can accurately reproduce correlation functions slower than the lag time, but path-based observables can only be reliably reproduced if the lifetimes of states exceed the lag time, which is a much stricter requirement. Even in the presence of short-lived states, we find that haMSMs reproduce path-based observables more reliably.

biophysics↗

bioRxiv2019

Extensive Evaluation of Weighted Ensemble Strategies for Calculating Rate Constants and Binding Affinities of Molecular Association/Dissociation Processes

The weighted ensemble (WE) path sampling strategy is highly efficient in generating pathways and rate constants for rare events using atomistic molecular dynamics simulations. Here we extensively evaluated the impact of several advances to the WE strategy on the efficiency of computing association and dissociation rate constants (kon, koff) as well as binding affinities (KD) for a set of benchmark systems, listed in order of increasing timescales of molecular association/dissociation processes: methane/methane, Na+/Cl-, and K+/18-crown-6 ether. In particular, we assessed the advantages of carrying out (i) a large set of \"light-weight\" WE simulations that each consist of a small number of trajectories vs. a single \"heavy-weight\" WE simulation that consists of a relatively large number of trajectories, (ii) equilibrium vs. steady-state WE simulations, (iii) history augmented Markov State Model (haMSM) post-simulation analysis of equilibrium sets of trajectories, and (iv) tracking of trajectory history (the state last visited) during the dynamics propagation of equilibrium WE simulations. Provided that state definitions are known in advance, our results reveal that heavy-weight, steady-state WE simulations are the most efficient protocol for calculating kon, koff, and KD values. If states are not strictly defined in advance, heavy-weight, equilibrium WE simulations are the most efficient protocol. This efficiency can be further improved with the inclusion of trajectory history during dynamics propagation. In addition, applying the haMSM post-simulation analysis enhances the efficiency of both steady-state and equilibrium WE simulations. Recommendations of appropriate WE protocols are made according to the goals of the simulations (e.g. to efficiently calculate rate constants and/or generate a diverse set of pathways).

biophysics↗

bioRxiv2018

Developing Future Biologists: creating and assessing a portable short course to engage underrepresented undergraduate students in developmental biology

Many barriers discourage underrepresented students from pursuing science careers. To access graduate education, undergraduate students must first gain exposure to a particular subject and subsequently accumulate related coursework and research experience. Many underrepresented students lack exposure to developmental biology due to limited undergraduate course offerings and finite resources at smaller institutions. To address this disparity, a group of University of Michigan graduate students and postdoctoral fellows created a portable short course focusing on developmental biology, titled \"Developing Future Biologists\" (DFB). This weeklong educational initiative provides hands-on laboratory sessions, interactive lectures, and professional development workshops to teach students about developmental biology and increase awareness of scientific career options. To evaluate course effectiveness, we developed a pre-post assessment, incorporating main ideas from the BioCore Guide. Student understanding of basic concepts and perceived experience in developmental biology increased in DFB participants, despite the abbreviated nature of the course. Here, we provide all course materials and an in-depth analysis of the assessment we created. The DFB portable short course model is an easily adaptable tool that connects undergraduate students with opportunities for advanced study and lowers barriers for underrepresented students in science, technology, engineering, and mathematics.

scientific communication and education↗

bioRxiv2018

Seed predation increases from the Arctic to the Equator and from high to low elevations

Species interactions have long been predicted to increase in intensity towards the tropics and low elevations, due to gradients in climate, productivity, or biodiversity. Despite their importance for understanding global ecological and evolutionary processes, plant-animal interaction gradients are particularly difficult to test systematically across large geographic gradients, and evidence from smaller, disparate studies is inconclusive. By systematically measuring post-dispersal seed predation using 6980 standardized seed depots along 18 mountains in the Pacific cordillera, we found that seed predation increases 18% from the Arctic to Equator and 16% from 4000 masl to sea level. Clines in total predation, likely driven by invertebrates, were consistent across tree-line ecotones and in continuous forest, and were better explained by climate seasonality than by productivity, biodiversity, or latitude. These results suggest that species interactions play predictably greater ecological and evolutionary roles in tropical, lowland, and other less seasonal ecosystems.\n\nOne Sentence SummaryPost-dispersal seed predation increases from the Arctic to the Equator and from high elevations to sea level.

ecology↗