Hans Othmer : A hybrid model of tumor-stromal interactions in breast cancer
- Mathematical Biology ( 139 Views )Ductal carcinoma in situ (DCIS) is an early stage non-invasive breast cancer that originates in the epithelial lining of the milk ducts, but it can evolve into comedo DCIS and ultimately, into the most common type of breast cancer, invasive ductal carcinoma. Understanding the progression and how to effectively intervene in it presents a major scientific challenge. The extracellular matrix surrounding a duct contains several types of cells and several types of growth factors that are known to individually affect tumor growth, but at present the complex biochemical and mechanical interactions of these stromal cells and growth factors with tumor cells is poorly understood. We will discuss a mathematical model that incorporates the cross-talk between stromal and tumor cells, and which can predict how perturbations of the local biochemical and mechanical state influence tumor evolution. We focus on the EGF and TGF-$\beta$ signaling pathways and show how up- or down-regulation of components in these pathways affects cell growth and proliferation, and describe a hybrid model for the interaction of cells with the tumor microenvironment. The analysis sheds light on the interactions between growth factors, mechanical properties of the ECM, and feedback signaling loops between stromal and tumor cells, and suggests how epigenetic changes in transformed cells affect tumor progression.
Susan Holmes : Computational Tools for Evaluating Phylogenetic and Hierarchical Clustering Trees
- Mathematical Biology ( 122 Views )Inferential summaries of tree estimates are useful in the setting of evolutionary biology, where phylogenetic trees have been built from DNA data since the 1960's. In bioinformatics, psychometrics and data mining, hierarchical clustering techniques output the same mathematical objects, and practitioners have similar questions about the stability and `generalizability' of these summaries. I will present applications of the Billera, Holmes, Vogtman (2001) distance to inferential problems both in the frequentist (bootstrap) and Bayesian contexts. I will compare the tree of trees representation to the Euclidean approximations of treespace made available through Multidimensional Scaling of the matrix of distances between trees. We also provide applications of the distances between trees to hierarchical clustering trees constructed from microarrays and phylogenetic trees of metagenomic data of bacteria in the gut. This talk contains joint work with John Chakerian and Alfred Spormann.