Center for Cancer Research
The Center for Cancer Research (CCR) 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 members. In addition, 6 faculty members in the Whitehead Institute, 4 in Biology, 1 in Chemistry and 2 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 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 has a total of 41 fully funded projects. 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 that 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 FY2003 research volume was approximately $13 million, which does not include $4.25 million in additional support from the Howard Hughes Medical Institute.
Research
The nature of basic cancer research has changed radically in the 30 years since the CCR was founded. The sequencing of the human genome as well as those of multiple other species has broadened our focus from individual genes to gene networks and genome-wide approaches. Likewise, comprehensive proteomic methods and sophisticated computational tools are beginning to allow for the charting of intracellular signaling pathways with much greater refinement than could have been imagined just a few years ago. Meanwhile, it is now possible to manipulate gene function in cells in culture or in intact animals in unprecedented ways. CCR researchers have helped to affect these changes, and they remain extremely well positioned to take advantage of these developments and apply them to the study of cancer.
Animal Models of Cancer
Using gene targeting in the mouse, several CCR investigators have developed powerful mouse models of tumorigenesis. These models are being used both to elucidate the contributions of individual genes to tumor initiation and progression and to study the interactions between normal cells and the emerging tumor (including tumor-stromal interactions, tumor vasculature, and tumor immunology). Increasingly, such models will be used for developing and screening novel anti-cancer agents as well as improved methods for early detection and cancer prevention. The post-genomic tools being developed in the Broad Institute will be very useful in the investigation of these models. CCR investigators Jacks, Hynes, Lees, Jaenisch, Housman, van Parijs, Chen, Gertler, Sorger, Samson, Lander, and Weinberg are all engaged in the development and/or characterization of mouse models of cancer.
Stem Cells, Development and Cancer
Tumorigenesis is intimately linked to normal embryonic development and homeostasis of adult tissues. Such links have been strengthened with the discovery and characterization of embryonic and adult stem cells. CCR researchers have performed fundamental research in this area to date, and the further elucidation of relationship between stem cell biology, normal developmental processes, and tumorigenesis will be an important theme in the center in the future. Several CCR investigators have active research programs in this area, including Jaenisch, Lodish, Hopkins, Horvitz, Hynes, Sherley, Lees, and Jacks.
RNAi Technology
The discovery of RNA interference (RNAi) and related processes has led to the development of powerful new methods to manipulate gene function. Almost overnight, RNAi methods have revolutionized the ways in which the functions of individual genes and pathways are being interrogated, both in cell-based systems and, increasingly, in the whole animal. RNAi-based technologies are being used to study many biological processes and diseases, including cancer. CCR investigators have been critical to the development and deployment of these technologies, and they will remain a cornerstone of our investigation of cancer-associated pathways in the future. The following CCR investigators have active programs in RNAi and related processes: Sharp, van Parijs, Sabatini, Gertler, Lander, and Horvitz.
Integrative Analysis of Cancer Pathways
The availability of genome sequences from human, mouse, and other organisms plus the development of sophisticated postgenomic, proteomic, and biocomputational tools has greatly accelerated the pace of discovery in cancer research. However, while much has been learned about the component parts of relevant pathways and processes, the challenge remains to translate the flood of new information into a more complete and integrated understanding of normal and transformed cells. Such insight will be critical to efforts in basic cancer biology as well as for understanding the basis of existing cancer therapeutics and for designing improved therapies. A key to addressing this challenge is to apply mathematical and computational modeling methods to biological problems. Within their own research programs and through interactions with the Broad Institute and the CSBi initiative, CCR investigators are actively pursuing both the acquisition of large data sets and the development of new approaches to interpret and utilize the information. These activities currently include gene expression array analysis, systematic genetic and proteomic approaches to the cell cycle and other cell biological processes, transcription factor profiling, and signal transduction network analysis. CCR investigators involved in these projects include Lander, Yaffe, Lauffenburger, Sorger, Young, Jaenisch, Samson, Amon, Bell, Jacks, Lees, van Parijs, and Hynes.
Education
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 Boston area, on June 12, 2003 the CCR hosted its second annual scientific symposium on the molecular basis of cancer, entitled Stem Cells, Development and Cancer and featuring eight renowned cancer researchers, including the 2002 winner of the Nobel Prize in physiology or medicine, H. Robert Horvitz of MIT's Department of Biology, the McGovern Institute for Brain Research, and a member of the Cancer Center.
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 59 postdoctoral fellows/associates.
Honors and Awards
It is a pleasure to report the following honors and awards to faculty of the center during this past year.
Angelika Amon received the Eli Lilly Company Award and the Allan T. Waterman Award from the National Science Foundation.
Nancy Hopkins was awarded the UCSF Medal and the MIT Gordon Y. Billard Award.
Tyler Jacks received the Chestnut Hill Award for Excellence in Medical Research.
Phillip Sharp was elected honorary fellow of the Royal Society of Edinburgh, Scotland, and received the Fourth Annual Biotechnology Heritage Award from the Biotechnology Industry Organization and the Chemical Heritage Foundation.
Michael Yaffe was promoted to associate professor without tenure.
More information about the Center for Cancer Research can be found on the web at http://web.mit.edu/ccr/.