The goal of this subproject is to dissect the complex interacfions 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 secrefion 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 matrixdegrading enzymes to modify the proliferafion 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 computafional approaches that ulfimately should revolufionize our understanding and treatment of primary cancers and metastases.
|Carmona-Fontaine, Carlos; Deforet, Maxime; Akkari, Leila et al. (2017) Metabolic origins of spatial organization in the tumor microenvironment. Proc Natl Acad Sci U S A 114:2934-2939|
|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|
|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|
|Prill, Robert J; Vogel, Robert; Cecchi, Guillermo A et al. (2015) Noise-driven causal inference in biomolecular networks. PLoS One 10:e0125777|
|Korkut, Anil; Wang, Weiqing; Demir, Emek et al. (2015) Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. Elife 4:|
|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|
Showing the most recent 10 out of 35 publications