The goal of this subproject is to dissect the complex interactions between cancer cells and cells of the host microenvironment and model how these diverse interactions contribute to cancer progression and invasion, both in primary tumors and in metastasis. Tumor cells co-opt their local environment through secretion of stimulating growth factors and cytokines, recruiting stromal cells to the tumor site and promoting growth of new blood vessels. In turn, the locally activated host microenvironment provides growth factors and matrix degrading enzymes to modify the proliferation and invasion of the tumor cells. Currently, our understanding of the complex and reciprocal interplay between the tumor and host cells is limited, particularly with regard to the diversity of metastatic tissue microenvironments that can be colonized by cancer cells.
We aim to address this significant knowledge gap by combining innovative experimental and computational approaches that ultimately should revolutionize our understanding and treatment of primary cancers and metastases.
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|Jena, Prakrit V; Roxbury, Daniel; Galassi, Thomas V et al. (2017) A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux. ACS Nano 11:10689-10703|
|Vogel, Robert M; Erez, Amir; Altan-Bonnet, Grégoire (2016) Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single-cell analysis. Nat Commun 7:12428|
|Quail, Daniela F; Bowman, Robert L; Akkari, Leila et al. (2016) The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science 352:aad3018|
|Argyropoulos, K V; Vogel, R; Ziegler, C et al. (2016) Clonal B cells in Waldenström's macroglobulinemia exhibit functional features of chronic active B-cell receptor signaling. Leukemia 30:1116-25|
|Gao, Sizhi P; Chang, Qing; Mao, Ninghui et al. (2016) JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors. Sci Signal 9:ra33|
|Prill, Robert J; Vogel, Robert; Cecchi, Guillermo A et al. (2015) Noise-driven causal inference in biomolecular networks. PLoS One 10:e0125777|
|Buffie, Charlie G; Bucci, Vanni; Stein, Richard R et al. (2015) Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517:205-8|
|Voisinne, Guillaume; Nixon, Briana G; Melbinger, Anna et al. (2015) T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens. Cell Rep 11:1208-19|
|Korkut, Anil; Wang, Weiqing; Demir, Emek et al. (2015) Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. Elife 4:|
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