Cell and Systems Biology

The Cell and Systems Biology Program is focused on basic cell biological processes critical to tumorigenesis and malignancy. CSB is multidisciplinary, extending from biochemical and molecular cell biological analyses, including an increasing emphasis on systems biology and computational approaches, to mouse models of cancer and application to human patient material.

Major themes include:

1. mechanisms of cell adhesion, cell motility and migration and their connections to invasion and metastasis. The altered adhesive and migratory properties of malignant cells allow them to invade underlying tissues, to penetrate the vasculature and lymphatics and to establish themselves in new microenvironments during the formation of metastases. These processes also play important roles in the host response to cancer (immune cell traffic and targeting, angiogenesis, etc.)

2. mechanisms and signal transduction networks important in mitogenesis, cell growth and division and their roles in tumor progression. Signal transduction networks control how cells respond to and affect their environment. Many initiators of cancer affect signal transduction and many of the responses of cells to oncogenic stimuli and to their microenvironment can only be understood by detailed analyses of these pathways. The application of proteomics, phosphoproteomics and high-throughput analyses of signal transduction molecules plays a crucial role in our deepening understanding of these pathways.

3. responses to DNA damage and genotoxic stress, both at the level of DNA and chromatin and in downstream signaling pathways. This area of interest is fundamental to many areas of cancer biology, including the molecular basis for mutation and genomic instability, and the development, evolution and pathogenesis of tumors. DNA damage and subsequent cellular responses form the basis for human cancer therapy, since most successful treatments, such as conventional chemotherapy and radiation treatment, function by the direct induction of DNA damage.

4. stem cell biology, including studies of adult and embryonic stem cells and the epigenetic programming of differentiated, pluripotent and tumor cells. The nature of pluripotency and of cellular programming underlies many fundamental questions in biology, including cancer. There is increasing interest in the idea that cancer-initiating cells share many properties with stem cells.

Members:

Richard O. Hynes and Michael B. Yaffe, Program Leaders
Paul Chang
Frank B. Gertler
Piyush Gupta
Michael T. Hemann
Angela Koehler
Douglas A. Lauffenburger
Stephen J. Lippard
Leona D. Samson
Graham Walker
Robert A. Weinberg
Forest M. White