The epithelial mesenchymal transition (EMT) is a process by which epithelial cells lose their characteristic adhesion and gain the migratory properties associated with mesenchymal cells. Triggered by exogenous factors from the surrounding microenvironment, EMT produces phenotypic and behavioral changes that are maintained even after the cell migrates away from a tumor to form a metastasis. Within the complex system of intracellular signaling pathways associated with EMT, we identify a feedback loop between E-cadherin, a transmembrane protein involved in cellular adhesion, and Slug, a transcription factor associated with the mesenchymal phenotype. Here we present a simple mathematical model using ordinary differential equations (ODEs) that examines the relationship between E-cadherin and Slug during EMT in response to exogenous pro-epithelial (cell-cell contact) and pro-mesenchymal (TGF-β signaling) factors. A cell’s ability to maintain the mesenchymal phenotype after leaving the tumor microenvironment suggests that there is a bistable switch underlying EMT. We hypothesize that a bistable switch due to a loss of cell-cell contact is reversible, while a switch due to TGF-β activation is irreversible. This model shows how changes in the tumor microenvironment and intracellular changes via signaling pathways are closely linked and the loss of cell-cell contact and activation of the TGF-β must work together to allow some cells to undergo EMT. The results of this model for E-cadherin and Slug levels are then compared to the experimental data recently generated using MCF7 breast carcinoma cells. Experiments examined changes in cell-cell contact and exogenous TGF-β and data were gathered using qPCR, flow cytometry, and immunocytochemistry (ICC). Our model works well to predict E-cadherin and Slug mRNA expression in low confluence experiments but struggles to predict the expression of either factor in high confluence environments. Ultimately, this work establishes a framework for modeling the influence of multiple factors on EMT, while also highlighting the issues that arise when comparing experimental results to theoretical predictions.
Wednesday, July 19 at 10:30am
MS05-CDEV-1: Connecting mathematical models of pattern formation & organization at cell and/or tissue level with experimental results
Organized by: Diana White
- Kelsey Gasior University of Notre Dame (Department of Applied and Computational Mathematics and Statistics) "Understanding the influence of cell-cell contact and TGF-β signaling on the epithelial mesenchymal transition in MCF7 breast carcinoma cells"
- Ginger Hunter Clarkson University (Biology) "Investigating the rules of cell contact-mediated tissue patterning using the Drosophila peripheral nervous system"
- Veronica Ciocanel Duke University (Mathematics) "Modeling and data analysis for actin-myosin dynamics and organization"
- Diana White Clarkson University (Department of Mathematics) "Understanding the regulation of growth and shedding of disks in the rod cells of zebrafish"
MS05-CDEV-2: The role of the microenvironment in controlling cell phenotypic decisions across scales
Organized by: Laura F. Strube, Adam L. MacLean
- Tian Hong The University of Tennessee, Knoxville (Biochemistry & Cellular and Molecular Biology) "Diverse dynamical systems for understanding nongenetic heterogeneity of cells"
- MeiLu McDermott University of Southern California (Department of Biology) "Characterizing Intermediate States of Epithelial-Mesenchymal Transition in Cancer through Single-Cell RNA Sequencing and Mathematical Modeling"
- Ken J. Oestreich The Ohio State University School of Medicine (Microbial Infection and Immunity) "Regulation of T helper cell programming by the transcription factor Aiolos"
- Rachel A. Gottschalk University of Pittsburgh (Department of Immunology) "Modeling cytokine-induced signaling features and sensitivity to network variation"
MS05-ECOP-1: Population-level impacts of ecological interactions across scales
Organized by: Amanda Laubmeier
- Rebecca Everett Haverford College (Department of Mathematics and Statistics) "Nutrient driven dynamics of ecosystem diseases"
- Mohammad Mihrab Uddin Chowdhury Texas Tech University (Department of Mathematics and Statistics) "Understanding Bsal Transmission Dynamics to Safeguard North American Salamander Populations"
- Joshua C. Macdonald Tel Aviv University (Faculty of Life Sciences) "Forward hysteresis and Hopf bifurcation in a NPZD model with application to harmful algal blooms"
- Omar Saucedo Virginia Tech (Mathematics) "The impact of host movement on mosquito-borne disease dynamics"
MS05-ECOP-2: Mathematical models of community: a journey through the scales
Organized by: Alexander Browning, Sara Hamis
- Pierre Haas Max Planck Institute for the Physics of Complex Systems (Biological Physics) "Impossible ecologies: interaction networks and stability of coexistence in ecological communities"
- Aminat Yetunde Saula University of Bath (Department of Mathematical Sciences) "Immune cell-bacteria interactions in tuberculosis"
- Moriah Echlin Tampere University (Medicine and Health Technology) "Characterizing the Impact of Communication on Cellular and Collective Behavior Using a Three-Dimensional Multiscale Cellular Model"
- Daniel Strömbom Lafayette College (Department of Biology) "Facilitating the emergence of collective biological controls to combat the spotted lanternfly and similar invasive pests"
MS05-IMMU-1: Immunobiology and Infection Subgroup Minisymposium 2023
Organized by: Morgan Craig, Daniel Reeves
- E. Fabian Cardozo-Ojeda Fred Hutchinson Cancer Center (Vaccine and Infectious Disease Division) "HIV-1 reservoir dynamics during hematopoietic stem cell transplantation"
- Jessica M. Conway Penn State (Mathematics) "Modeling on-demand PrEP regimen to prevent HIV transmission"
- Chapin S. Korosec York University, 4700 Keele St, Toronto, M3J 1P3, ON, Canada. (Modelling Infection and Immunity Lab, Mathematics and Statistics) "Within-host evolution of SARS-CoV-2: how often are de novo mutations transmitted?"
- Adnan Khan Lahore University of Management Sciences (Mathematics) "Modeling Antibiotic Resistance and Effective Dosing Regimens"
MS05-MEPI-1: Zoonotic Infectious Diseases Models
Organized by: Rocio Caja Rivera, Iona McCabe, Dana Pittman, Linda J. Allen
- Holly Gaff Old Dominion University (Department of Biological Sciences) "Understanding Ticks and Tick-borne Diseases through Agent-based Modeling"
- Kat Husar & Dana C. Pittman Duke University; Texas A&M University (School of Public Health Epidemiology and Biostatistics) "Lyme Disease Models of Tick-Mouse Dynamics with Seasonal Variation in Births, Deaths, and Tick Feeding"
- Katherine Royce Harvard University (Law School) "Mathematically predicting intermediate host species for emerging zoonoses"
- Iona McCabe; Kaia Smith University of California, Santa Barbara; Scripps College (Department of Mathematics; Department of Mathematics) "Stochastic Models of Zoonotic Avian Influenza with Multiple Hosts, Environmental Transmission, and Migration in the Natural Reservoir"
MS05-MFBM-1: Data-driven methods for biological modeling
Organized by: John Nardini, Erica Rutter, Kevin Flores
- Natalia Kravtsova The Ohio State University (Department of Mathematics) "Scalable Gromov-Wasserstein based comparison of biological time series"
- Yordan P. Raykov University of Nottingham (Statistics and Probability) "Digital disease progression biomarkers for Parkinson's disease: algorithms for passive monitoring"
MS05-ONCO-1: Digital twins for clinical oncology and cancer research
Organized by: Guillermo Lorenzo, Chengyue Wu, David A Hormuth II, Ernesto A. B. F. Lima, Lois C. Okereke, Thomas E. Yankeelov
- Stéphane Bordas University of Luxembourg (Department of Engineering Sciences) "Digital twinning physiological processes: brain metabolism and cancer growth"
- Jesús J. Bosque University of Castilla-La Mancha (Spain) (Mathematical Oncology Laboratory (MOLAB)) "Less is more in glioma treatment: In silico and in vivo evidence towards a clinical trial"
- Renee Brady-Nicholls H. Lee Moffitt Cancer Center & Research Institute (Integrated Mathematical Oncology) "An In Silico Study of Hormone Therapy in Metastatic Prostate Cancer"
- Chase Christenson University of Texas at Austin (Biomedical Enginering) "Fast digital twin construction for modeling the response of breast cancer to therapy using proper orthogonal decomposition."
MS05-OTHE-2: Preparing for the Next Pandemic: Modeling and Simulation in Drug Development
Organized by: Celeste Vallejo
- Sriram Chandrasekaran University of Michigan (Biomedical Engineering) "Drug discovery and repurposing using hybrid machine learning and biochemical modeling"
- Amber Smith University of Tennessee Health Science Center (Department of Pediatrics) "PKPD modeling of Plasmodium falciparum ATP4 inhibitor SJ733 with the pharmacokinetic enhancer cobicistat"
- Celeste Vallejo Simulations Plus, Inc. (DILIsym Services) "Potential application of a mechanistic model of chronic lung disease to the treatment of post-COVID lung fibrosis and other respiratory pandemics"