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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA148967-05
Application #
8628769
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
City
New York
State
NY
Country
United States
Zip Code
10065
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
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
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
Korkut, Anil; Wang, Weiqing; Demir, Emek et al. (2015) Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. Elife 4:
Klemm, Florian; Joyce, Johanna A (2015) Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol 25:198-213
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

Showing the most recent 10 out of 35 publications