Small-molecule TIP60 inhibitors enhance regulatory T cell induction through TIP60-P300 acetylation crosstalk.

Foxp3 acetylation is essential to regulatory T (Treg) cell stability and function, but pharmacologically increasing it remains an unmet challenge. Here, we report that small-molecule compounds that inhibit TIP60, an acetyltransferase known to acetylate Foxp3, unexpectedly increase Foxp3 acetylation and Treg induction. Utilizing a dual experimental/computational approach combined with a newly developed FRET-based methodology compatible with flow cytometry to measure Foxp3 acetylation, we unraveled the mechanism of action of these small-molecule compounds in murine and human Treg induction cell cultures.

Inverting angiogenesis with interstitial flow and chemokine matrix-binding affinity.

The molecular signaling pathways that orchestrate angiogenesis have been widely studied, but the role of biophysical cues has received less attention. Interstitial flow is unavoidable in vivo, and has been shown to dramatically change the neovascular patterns, but the mechanisms by which flow regulates angiogenesis remain poorly understood. Here, we study the complex interactions between interstitial flow and the affinity for matrix binding of different chemokine isoforms.

Computational modelling suggests complex interactions between interstitial flow and tumour angiogenesis.

Angiogenesis, the growth of capillaries from pre-existing ones, plays a key role in cancer progression. Tumours release tumour angiogenic factors (TAFs) into the extracellular matrix (ECM) that trigger angiogenesis once they reach the vasculature. The neovasculature provides nutrients and oxygen to the tumour.

A mathematical model of tumour angiogenesis: growth, regression and regrowth.

Cancerous tumours have the ability to recruit new blood vessels through a process called angiogenesis. By stimulating vascular growth, tumours get connected to the circulatory system, receive nutrients and open a way to colonize distant organs. Tumour-induced vascular networks become unstable in the absence of tumour angiogenic factors (TAFs).

Tissue-scale, personalized modeling and simulation of prostate cancer growth.

Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis.

A Mathematical Model Coupling Tumor Growth and Angiogenesis.

We present a mathematical model for vascular tumor growth. We use phase fields to model cellular growth and reaction-diffusion equations for the dynamics of angiogenic factors and nutrients. The model naturally predicts the shift from avascular to vascular growth at realistic scales.

Capillary networks in tumor angiogenesis: from discrete endothelial cells to phase-field averaged descriptions via isogeometric analysis.

Tumor angiogenesis, the growth of new capillaries from preexisting ones promoted by the starvation and hypoxia of cancerous cell, creates complex biological patterns. These patterns are captured by a hybrid model that involves high-order partial differential equations coupled with mobile, agent-based components. The continuous equations of the model rely on the phase-field method to describe the intricate interfaces between the vasculature and the host tissue.