Center for Cancer Research
The Center for Cancer Research was established in 1973 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 leading to cancer and other diseases, and how the immune system develops and recognizes antigens. These goals are related to the center's major research programs in cancer-associated genes 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, four in Biology, one in Chemistry and two in the Division of Bioengineering and Environmental Health Sciences 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 support for new faculty, and central research facilities (i.e. glass washing facility, media preparation and other specialized laboratories), 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 >$809,000 in sponsored funds, primarily in the form of fellowships for postgraduate studies). This competitive 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, Arthritis Foundation, 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 FY2002 research volume was approximately $12.7 million, which does not include $4.7 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 development of sophisticated mouse models of cancer development 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 and the newly discovered process of RNA interference (RNAi).
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. The development and memory properties of B and T cells is also under study as well as the process of tolerance defects which can lead to autoimmune disease. 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. A large-scale insertional genetics strategy in zebrafish is yielding new genes with essential roles in early vertebrate development.
The center has been instrumental in establishing the BiomicroCenter and several research projects are using increasingly powerful tools in gene expression analysis, proteomics and bioinformatics to address complex mechanisms in proliferation control, checkpoint function, and tumorigenesis.
The Jacks lab continues to develop important new mouse models for cancer, including a powerful new model of lung cancer.
The Yaffe lab has used a combination of biochemistry and bioinformatics to define a function for the PX domain of proteins involved in phagocytic cell function. Their work explains the effects of mutations in patients with granulomatous disease.
The Hynes lab has shown that tumors comprised of cells lacking a key cell surface receptor have reduced blood vessels and growth properties.
The Sharp lab has used RNA interference methods to inhibit the replication of the virus that causes AIDS, HIV.
The Amon lab has discovered a new regulatory network in yeast cells that controls a critical transition in the cell division cycle.
The Hopkins lab has completed their insertional mutagenesis screen in zebrafish and has identified seventy-five genes involved in early development in this vertebrate organism.
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. To further the center's goal of bringing cutting edge research to the cancer research community in the greater Boston area, on June 21, 2002 the CCR hosted its first annual scientific symposium on the molecular basis of cancer entitled Invasion and Metastasis. This inaugural symposium featured eight internationally renowned cancer researchers and was dedicated to Dr. Richard Hynes in recognition of his accomplishments in the field of cancer research and in appreciation of the decade of service and leadership he provided as director of the center from 1991–2001.
A major strength of the center remains its attractiveness as an environment for the training of young scientists. The center has 41 graduate and undergraduate students and 57 postdoctoral fellows/associates.
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 investigator of the Howard Hughes Medical Institute and was appointed director of the center in July 2001. He received the director's service award for his service to the National Cancer Institute and the Board of Scientific Advisors and was the seventh annual Verne M. Charpman lecturer at the Rosewell Park Cancer Institute. Jacqueline Lees was appointed associate director of the center in July 2001. Phillip Sharp received the fourth annual biotechnology heritage award from the Biotechnology Industry Organization (BIO) and the Chemical Heritage Foundation (CHF) and was elected an honorary fellow of the Royal Society of Edinburgh, Scotland. Angelika Amon was promoted to associate professor. Jianzhu Chen was appointed guest professor at Institute of Microbiology, Chinese Academy of Sciences. Luk Van Parijs received the MIT Westaway award.
More information about the Center for Cancer Research can be found on web at http://web.mit.edu/ccrhq/www/.