Center for Cancer Research
The Center for Cancer Research (CCR) was established in 1973 (actually opened in 1974) to study fundamental biological processes related to cancer. The goals of the center's research can be generally stated as developing an understanding of the genetic and molecular basis of cancer, how alterations in cellular processes affect cell growth and behavior, and how the immune system develops and recognizes antigens. These goals are related to the center's major research programs in oncogenes and mammalian genetics, molecular, cellular and developmental biology, and immunology. Approximately 248 people work in the center, distributed among the research laboratories of 13 faculty. In addition, six faculty members in the Whitehead Institute, five in Biology, one in Chemistry and one in the Division of Bioengineering and Environmental Health are Affiliate Members of the CCR.
Financial support for research in the center comes from many sources. The core of this support, which provides much of the funds for administration, partial faculty salary support, and central research facilities (i.e. glass washing facility, specialized laboratories and partial support for new faculty), is a Center Core grant from the National Cancer Institute. The current term extends to April 30, 2005. In addition to the core grant, the center's faculty have a total of 39 fully funded projects (plus >$606,000 of competitive support in fellowships for postgraduate studies). This support comes largely from the National Institutes of Health and the Howard Hughes Medical Institute, from industry, and from a variety of foundations supporting research in particular disease areas (American Cancer Society, Hereditary Disease Foundation, Muscular Dystrophy Association, National Neurofibromatosis Foundation, CaPCURE etc.). This latter type of support is particularly valuable for starting projects which later mature into federally funded grants. The center's success in attracting grant support is a reflection of the excellence of the research and educational activities of its faculty members. The FY2001 research volume was approximately $13.2 million, which does not include $4.25 million in additional support from the Howard Hughes Medical Institute.
Several groups in the center study the identities and functions of oncogenes and tumor suppressor genes. This work includes the recent identification of two genes disposing to acute myeloid leukemia as well as basic molecular studies on other oncogenes and tumor suppressor genes that regulate gene expression controlling the cell cycle and tumor growth. Another focus is on the biochemical mechanisms controlling RNA transcription and splicing, including studies of genes of the AIDS virus, HIV.
The immunologists in the center study the development of cytotoxic and helper T lymphocytes, their antigen-specific receptors, and the molecular mechanisms of antigen presentation and autoimmunity as well as the development and memory properties of B lymphocytes which produce antibodies. Since the immune response to tumors is poorly understood, these basic studies are crucial to a more profound analysis of tumor rejection. Immune cells can destroy cancer cells and it may be possible to stimulate this process. Furthermore antibodies to tumor antigens are proving very successful in tumor therapy.
The cell biologists study cell surface proteins involved in cellular adhesion and migration, as well as cytoskeletal proteins involved in cell motility and shape. Alterations in cell adhesion proteins contribute to the malignant phenotype of tumor cells including involvement in invasion, metastasis and angiogenesis. These proteins as well as cytoskeletal proteins are important targets for antitumor drugs, and deeper understanding of their structure and function should contribute to better therapeutic agents.
Since the cellular processes of development and cancer have much in common, useful insights into the behavior of tumor cells can be obtained from studies of normal embryos; several projects in the center focus on developmental processes. Recent advances in the generation of transgenic mice and mice with mutations in targeted genes are being exploited to investigate the roles of a variety of proteins important in tumorigenesis, including oncogene proteins, tumor suppressor genes, cell adhesion receptors, T-cell receptors and protein kinases. Major recent research advances include:
- The Jacks lab has developed several invaluable mouse models for cancer, including two which undergo metastasis.
- The Hynes lab has used genomic analyses to uncover genes that control crucial cellular processes in metastasis.
- The Chen lab has developed procedures for analyzing memory T cells, the cells that control immune responses and are the basis for immunization.
- The Hopkins lab has developed a new system to identify genes critical for development in the zebrafish, a genetically tractable vertebrate, and is using this system for rapid isolation of such altered genes.
In addition to its strengths in basic research, the CCR performs an important role in training future researchers in biomedical science, including undergraduate and graduate students, postdoctoral and clinical fellows. The faculty of the center fulfill critical roles in the educational programs of the Department of Biology. Extensive collaborations exist with medical schools, hospitals and the biotechnology/pharmaceutical industries. Thus, the research in the CCR has a major impact both on the fundamental understanding of cancer and on translation to and from the clinical arena.
A major strength of the center remains its attractiveness as an environment for the training of young scientists. The Center has 37 graduate and undergraduate students and 50 postdoctoral fellows/associates.
Two new faculty members joined the Center for Cancer Research in the fall of 2000. Luk van Parijs is working on autoimmunity (diabetes, arthritis, lupus). Michael Yaffe is working on signal transduction in growth control using cell biology, structural biology and bioinformatics.
It is a pleasure to report the following honors and awards to faculty of the center during this past year:
Tyler Jacks was promoted to Professor of Biology and will take over as Director of the center in July 2001, replacing Richard Hynes who served as Director for the last ten years.
Jacqueline Lees was promoted to Associate Professor with tenure and will be the center's new Associate Director as of July 2001.
Jianzhu Chen was promoted to Associate Professor with tenure.
Luk Van Parijs received the MIT Surdna Award. He was also selected by the Arthritis Foundation to receive the Satterfield Arthritis Investigator Award.
More information about the Center for Cancer Research can be found online at http://web.mit.edu/ccrhq/www/.