Phenotypic plasticity plays a key role in cancer progression and metastasis, enabling cancer cells to adapt and evolve, but precisely how distinct axes governing phenotypic plasticity interact to shape tumour progression and patient outcomes remains unclear. We investigated five major interconnected axes of plasticity in ER-positive (ER+) breast cancer: Metabolic Reprogramming,...
Cancer cell adaptation to their physical tumor microenvironment is a key driver of malignancy. Recent experimental evolution experiments show that the soft extracellular matrix (ECM) can impose a selection pressure on genetically variable tumor populations. Over months of sustained culture, the selection pressure leads to enrichment of specific genetic variants with high fitness, but the...
In this talk, I will introduce four systems of ODEs to identify the most plausible model and the key reactions governing the dynamics of the tumor microenvironment (TME) in estrogen receptorโpositive (ER+) breast cancer. All models quantitatively fit the experimental data for radiation therapy (RT) and endocrine therapy fulvestrant (Fulv) in TC11 ER+ cells, as well as RT and immune checkpoint...
Integrating high-dimensional biological data into mechanistic models requires practical identifiability for reliable inference. We develop a computational framework that reveals scaling laws for identifiability via asymptotic analysis, combining Fisher information with perturbed Hessians to quantify identifiability and uncertainty in non-identifiable subspaces. Validated on several benchmark...
Intermediate filaments are key components of the cytoskeleton, playing essential roles in cell mechanics, signaling and migration. Their spatiotemporal organization, which supports these functions, results from the interplay between assembly and disassembly processes, as well as retrograde actin flow and motor proteinโdriven transport. Investigating the different mechanisms involved in the...
Recent experimental work has shown that dynein transports cargo faster in vivo than in vitro, although counter intuitive, the results are consistent with other experimental data \cite{Torisawa:2025:AFC}. Typically, it is assumed that the cytoplasm, a more viscous and complex environment, should slow down transport compared to in vitro experiments. It is postulated that the catch bond nature...
Resistance to immune checkpoint inhibitors (ICI), including anti-PD-1 and anti-PD-L1 therapies, remains a major limitation in cancer treatment, with most patients relapsing despite initial responses. Previous studies have shown that inhibition of TNF-alpha or TGF-beta overcome resistance to anti-PD-1. Here, we develop a mathematical model to investigate a mechanism of ICI resistance driven by...
Mathematical modelling and computation allow for quantitative testing of proposed hypotheses and estimation of important physical and biological parameters. Combining experiments with mathematical modelling allows a rigorous validation of model hypotheses, thereby providing a powerful investigation tool in biology and medicine. The focus of this session will be on applications of mathematics...
