H. Levine

Pulse Instabilities Can Shape Virus-Immune Co-evolution

This study introduces a stochastic model of viral-host co-evolution showing that pulse instabilities can lead to extended endemic infection patterns in large host populations with finite immune memory.

Regulation of chromatin transcription dynamics by DNA supercoiling

This paper models chromatin torsion and RNAP translocation to show how DNA supercoiling and nucleosome dynamics regulate transcription velocity and gene expression.

RACER-m Leverages Structural Features for Sparse T Cell Specificity Prediction

RACER-m predicts T cell specificity using structural features, requiring fewer training examples than sequence-based methods.

Modeling the role of immune cell conversion in the tumor-immune microenviroment

The paper develops an ecological model of the tumor-immune microenvironment to study immune cell conversion and its impact on tumor-immune coexistence.

Dual role of CASP8AP2/FLASH in regulating epithelial-to-mesenchymal (EMT) plasticity

This study identifies FLASH as a regulator of EMT plasticity, showing it influences hybrid E/M states through its effects on EMT-TFs and cell junction proteins.

The Alternate Ligand Jagged Enhances the Robustness of Notch Signaling Patterns

The paper models Notch-Delta-Jagged signaling using ODEs to show Jagged enhances pattern robustness through synergistic effects with Delta.

Epigenetic memory acquired during long-term EMTinduction governs the recovery to the epithelial state

The paper shows that long-term EMT induction in MCF10A cells can be reversible with longer timescales, and epigenetic memory via miR-200 silencing by ZEB slows recovery to the epithelial state.

Optimal Cancer Evasion in a Dynamic Immune Microenvironment

This paper develops a mathematical framework to model optimal cancer evasion strategies in a dynamic immune microenvironment, showing that adaptive evasion leads to heterogeneous tumor antigenicity.

Infiltration of Tumor Spheroids by Activated Immune Cells

The paper quantifies immune cell infiltration dynamics around tumor spheroids and validates a computational model that reproduces experimental infiltration profiles.

Quantifying the patterns of metabolic plasticity and heterogeneity along the epithelial-hybrid-mesenchymal spectrum in cancer

The paper analyzes metabolic pathway associations with EMT status across cancer datasets, revealing both general trends and heterogeneity in metabolic plasticity.

Three-dimensional Cancer Cell Migration Directed by Dual Mechanochemical Guidance

This study investigates how breast cancer cells migrate in 3D under dual mechanochemical guidance, finding that ECM alignment and chemotactic gradients interact to influence migration efficiency.

Immunosuppressive traits of the hybrid epithelial/mesenchymal phenotype

The paper investigates immune-evasive strategies of hybrid epithelial/mesenchymal (E/M) cells using a regulatory network model and RNA-seq data, showing they can exhibit high PD-L1 levels without full EMT.

Cluster Size Distribution of Cells Disseminating from a Primary Tumor

This study uses a computational model to show how the EMT nature of tumor cells affects the size distribution of migrating clusters, with hybrid cells forming larger clusters and more mesenchymal cells forming smaller clusters.

Nrf2 modulates the hybrid epithelial/mesenchymal phenotype and Notch signaling during collective cancer migration

This study shows Nrf2 stabilizes hybrid epithelial/mesenchymal cells and coordinates Notch signaling during collective cancer migration.

DNA supercoiling-mediated collective behavior of co-transcribing RNA polymerases

The paper presents a theoretical model showing DNA supercoiling mediates long-range cooperation between co-transcribing RNA polymerases, affecting transcription elongation rates and orientation-dependent interactions.

A theoretical approach to coupling the epithelial-mesenchymal transition (EMT) to extracellular matrix (ECM) stiffness via LOXL2

The paper introduces a computational model linking LOXL2 secretion to ECM stiffness and ZEB1 levels, showing a positive feedback loop that locks cells in a mesenchymal state during EMT.

A Mechanistic Modeling Framework Reveals the Key Principles Underlying Tumor Metabolism

This paper presents a mechanistic model of tumor metabolism that identifies key principles governing metabolic heterogeneity and plasticity in cancer cells.

Gene expression profiles of inflammatory breast cancer reveal high heterogeneity across the epithelial-hybrid-mesenchymal spectrum

The paper evaluates gene expression signatures for inflammatory breast cancer (IBC) across multiple datasets, finding low overlap and limited predictive accuracy, but identifying a correlation between IBC samples and the epithelial-hybrid-mesenchymal spectrum.

Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT

This study identifies two mechanisms—epigenetic feedback in the ZEB1/GRHL2 loop and stochastic partitioning during cell division—that can drive resistance to EMT in cancer cells.

Suppressing chemoresistance in lung cancer via dynamic phenotypic switching and intermittent therapy

This study shows that intermittent chemotherapy can suppress chemoresistance in lung cancer by preventing the emergence of tolerant cells through dynamic phenotypic switching.

Rapid Assessment of T-Cell Receptor Specificity of the Immune Repertoire

This paper introduces RACER, a pairwise energy model that assesses TCR-peptide affinity using supervised machine learning, demonstrating its utility in simulating thymic selection and estimating recognition rates for tumor antigens.

A Mechanism for Epithelial-Mesenchymal Heterogeneity in a Population of Cancer Cells

The paper shows that epithelial-mesenchymal heterogeneity in cancer cells arises from noise in RNA and protein partitioning during division and models its implications for therapy.

Calpain-2 regulates hypoxia/HIF-induced amoeboid reprogramming and metastasis

This study identifies calpain-2 as a regulator of hypoxia-induced amoeboid reprogramming and metastasis in breast and head and neck cancers.

Comparative study of transcriptomics-based scoring metrics for the epithelial-hybrid-mesenchymal spectrum

This study compares three transcriptomics-based metrics for quantifying EMT status across tumor types, finding that MLR-based scoring better distinguishes pure hybrid E/M cells from mixed populations.

Targeting the Id1-Kif11-Aurka axis in triple negative breast cancer using combination therapy

This paper investigates how Id1 and Id3 maintain chemoresistant CSCs in TNBC by targeting Kif11 and Aurka, and explores combination therapy to enhance tumor debulking.

Sustained Co-evolution in a Stochastic Model of the Cancer-Immune Interaction

This paper develops a stochastic model of cancer-immune interactions showing immune pressure influences cancer incidence and escape.

Fractal dimension, occupancy and hotspot analyses of B cell spatial distribution predict clinical outcome in breast cancer

The paper analyzes the spatial distribution of B cells in breast cancer tumors using novel statistical methods and finds that their spatial arrangement correlates with clinical outcomes.

A possible role for epigenetic feedback regulation in the dynamics of the Epithelial-Mesenchymal Transition (EMT)

This paper investigates how epigenetic feedback affects EMT dynamics by integrating a feedback term into a computational model and supporting it with experimental data showing prolonged TGFβ exposure impairs reversion to the epithelial state.

NRF2 activates a partial Epithelial-Mesenchymal Transition and is maximally present in a hybrid Epithelial/Mesenchymal phenotype

This study shows NRF2 stabilizes a hybrid epithelial/mesenchymal phenotype by upregulating both E-cadherin and ZEB, and correlates this phenotype with poor survival in cancer.

Ordered Hexagonal Patterns via Notch-Delta Signaling

The paper uses mathematical modeling to show how Notch-Delta signaling can generate hexagonal cellular patterns through a system of differential equations and bifurcation analysis.