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Program 1 has a central focus on the programs governing the cellular state and interactions of cancer cells and other cells within tumors. This emphasis has two main themes—1) the molecular programs and development of cancer cells and 2) the phenotypic diversity among cells that emerges from genetic and metabolic factors, as well as the intercellular networks in which they operate.
The first theme of Program 1 will build on the progress of the Program over the past five years on the foundational principles and mechanisms governing gene expression and regulation in cancer cells. The overall aim of this part of the program is to elucidate molecular mechanisms controlling critical aspects of the malignant cell phenotype and to translate this this knowledge into new therapeutic strategies. Toward these objectives, the following topics are developed in the research sections: 1) the role of phase transition and transcription in gene regulation in cancer cells, 2) designing gene circuits to detect cancer gene expression, 3) chromosomal integrity and modification in development of cancer, and 4) RNA in regulation of cell phenotype and cancer.
The second theme in the Program will focus on the diversity in phenotypes that emerge within cancer as a result of genetic variation, metabolism, or other extrinsic factors within the tumor microenvironment. This part of the program is strengthened by the Program’s effort to develop and advance single-cell sequencing and in situ tissue microscopy technologies. These technological advances are providing an unparalleled layer of resolution to the composition of the tumor and will attain the Program’s goals to further understand the functional impact of genetic variants in cancer, and how cancer cells metabolize nutrients to grow and proliferate. These aspects of cellular programs will be developed in the research sections of 1) cell metabolism and its regulation, 2) genetic variation and risk of malignancy, and 3) heterogeneity among cell populations and environments.
J. Christopher Love and Phillip A. Sharp, Program Leaders
Eliezer Calo, Associate Program Leader
Stephen P. Bell
Matthew Vander Heiden