KOSEN 한인과학기술자네트워크

Cancer Biology Primary Sponsor: Department of Health and Human Services Deadline: 4/1/2001; 8/1/2001; 12/1/2001 KEYWORDS The Division of Cancer Biology (DCB) plans and directs, coordinates, and evaluates a grant- and contract-supported program of extramural basic and applied research on cancer cell biology and cancer immunology, and cancer etiology, including the effects of biological, chemical and physical agents, in the promotion of cancer; maintains surveillance over developments in its program and assesses the national need for research in cancer biology, immunology and etiology; evaluates mechanisms of biological, chemical and physical carcinogenesis and subsequent tumor growth and progression to metastasis; tests for carcinogenic potential of environmental agents; serves as the focal point for the Federal Government on the synthesis of clinical, epidemiological and experimental data concerning biological agents relating to cancer; and maintains the necessary scientific management capability to foster and guide an effective research program. For additional information, please visit our home page at http://www.nci.nih.gov/dcb/dcbhom.htm. A. Biological Carcinogenesis. The Biological Carcinogenesis Branch (BCB) supports research that seeks to determine the role of microbiological agents as factors or cofactors in the etiology of human and animal cancer. The biological agents of primary interest are DNA viruses, RNA viruses, AIDS and AIDS-associated viruses, although the research may encompass all forms of life including bacteria and other microbial agents associated with cancer and use animal models of cancer and cancer vaccines. A wide range of approaches are supported, including basic biochemistry and molecular biology of oncogenic and suspected oncogenic agents, viral oncogenes and associated tumor suppressor genes, pathogenesis and natural history studies, animal models, and preventive vaccine research. The development of technologies to facilitate studies relating to biological carcinogenesis research is also encouraged. Specific research and technologies supported by BCB in this solicitation include but are not limited to the following: 1. Development of reagents, probes, and methodologies to evaluate the etiologic role of oncogenic viruses and other microbial agents (such as bacteria) in human cancer. 2. Development of novel in vitro culture techniques for oncogenic viruses or other microbial agents associated with or suspected of causing human cancer. 3. Development of sensitive, simplified diagnostic kits or reagents for the detection of oncogenic viruses or other microbial agents. 4. Development and characterization of animal models for studies of the mechanism of cancer induction by viruses or other microbial agents. The animals should faithfully mimic the human diseases associated with the virus or other microbial agent. 5. Development of methods (e.g., new-anti-microbial compounds, new vaccine approaches) to avert the induction of neoplasia in humans and animals by oncogenic viruses or bacteria. 6. Development of other novel technologies, methodologies or instrumentation to determine the role of biological agents, especially viruses, in the etiology of cancer. B. Cancer Cell Biology. The Cancer Cell Biology Branch (CCBB) seeks to understand the biological basis of cancer at the cellular and molecular level. This research utilizes lower eukaryote and animal models, and animal and human tumor cells and tissues to analyze the mechanisms responsible for the growth and progression of cancer. Specific research and technologies supported by CCBB in this solicitation include but are not limited to the following: 1. Development of novel methods to study apoptosis. 2. Development of methods to identify tissue-specific stem cells. 3. Development of markers associated with specific cellular processes or differentiation. 4. New techniques to transfer functional genes, proteins, antibodies, etc. into intact cells or organisms. 5. Development of new in vitro cancer models which closely parallel in vivo conditions. 6. Improved methods to isolate and preserve human cancer cells appropriate for research. 7. New or improved technologies for efficient microdissection of tumor tissue sections. Among other uses, these approaches would be useful for isolation of DNA from tumor tissues at defined stages of tumor progression. 8. Development of human tumor cDNA library banks to study gene expression in cancer. 9. Development and distribution of genomic resources suitable for genomic manipulation or cytogenetic studies. 10. Establishment of new or improved animal models or non-mammalian models (e.g., flies, worms) as research tools to study gene mutations important in human cancers. Among other uses, such models could be used to study the role of cancer genes or for analysis of complex traits. 11. Generation of new inbred genetic animal models that transmit defective or altered cancer-related genes. 12. Development of other novel technologies, methodologies or basic instrumentation to facilitate basic cancer research (research tools). C. Cancer Immunology and Hematology. The Cancer Immunology and Hematology Branch (CIHB) supports a broad spectrum of basic research focused on the earliest stages of hematopoiesis and tracing the molecular events that lead to the development of all the functional elements of the immune system and, when errors occur, to the development of leukemias and lymphomas. Most research of interest falls into three major areas. The first is the immune response to tumors to include studies of all of the cells (T, B, NK, antigen-presenting, and other myeloid cells) and secreted molecules (antibodies and cytokines) of the immune system that can recognize and affect tumor growth. Emphasis is placed on the regulatory mechanisms responsible for the failure of immune response to eradicate most tumors under normal conditions, and the development of strategies to circumvent these mechanisms. A second major area of interest examines the biology of hematopoietic malignancies to describe the detailed reasons underlying cell's failure to respond to normal growth controls and to develop novel approaches to prevention or therapy. The third distinct area supported is the basic biology of bone-marrow transplantation, including studies of host cell engraftment, graft-versus-host disease, and the basis of the graft-versus-leukemia effect. Specific research and technologies supported by CIHB in this solicitation include but are not limited to the following: 1. Development of improved or novel monoclonal antibody technologies including improvements of methodologies for fusion, production of novel cells as fusion partners, selection and assay of antibody producing clones, and production of new and improved monoclonal antibodies. 2. Synthesis, structure and function of antibodies capable of reacting with tumor cells, agents that induce tumors, agents used in the treatment of tumors, and agents used in the treatment of tumors. 3. Development of in vivo animal models systems that can be used to study the immune response to tumors and the mechanisms of immunotherapy. 4. Development of technology for large-scale production of specific immune modulators (e.g., lymphokines). 5. Synthesis, structure and function of soluble factors that participate in, activate and/or regulate hematopoietic cell growth and the immune response to tumors, including interferons, other lymphokines and cytokines (interleukins), hematopoietic growth factors, helper factors, suppressor factors and cytotoxic factors. 6. Application of biochemical, molecular biological and immunological techniques for identifying tumor antigens that are good targets for the development of vaccine-type strategies of cancer immunotherapy. 7. Development of techniques to enhance the immune response to tumors, including modification of tumor cells and/or antitumor lymphocytes to facilitate cancer vaccine strategies. 8. Development of improved methodology for manipulating bone marrow inoculum to decrease the incidence of graft-versus-host disease without increasing the risk of graft failure or leukemic relapse. 9. Development of improved methodology for increasing the number of peripheral blood stem cells available for harvest for use in transplantation, including improved methods of identifying and removing residual leukemic cells in the autologous transplant setting. 10. Development of methods to identify and define human minor histocompatability antigens. 11. Development of novel techniques for antigen identification and protein identification in human tumor cells. 12. Development of novel culture systems to improve the expansion of lymphocytes. 13. Development of combinatorial cell culture research tools to better understand expansion of human hematopoietic stem cells. 14. Development of improved techniques for computational simulation/modeling of biological processes involved in immunologic defenses against tumor cells such as signal transduction, cell cycle progression, and intracellular translocation. 15. Development of other novel technologies, methodologies or instrumentation to facilitate basic research (research tools) in cancer immunology and hematology. D. Chemical and Physical Carcinogenesis. The Chemical and Physical Carcinogenesis Branch (CPCB) supports basic and applied research concerned with cancers caused or promoted by chemical or physical agents. Carcinogenesis research is supported at the molecular level in areas such as the genetics of cell transformation, mutagenesis, tumor promotion, and DNA damage. Mechanistic studies are encouraged in areas such as metabolism, toxicity and physiological distribution of carcinogens, genetics and regulation of enzymes, biochemical and molecular markers, and organ and cell culture systems and animal models. Also of interest are studies on cancer etiology by environmental chemicals, tobacco consumption and exposure, nutritional hazards, alcohol, asbestos, silica, and man-made fibers. CPCB supports studies on endogenous exposure to steroid hormones and the generation of oxygen radicals during normal metabolism, studies on phytoestrogens and xenoestrogens and their impact on the metabolism of endogenous estrogens are also supported, and work on carcinogenicity/mutagenicity, testing procedures and the development of analytical technologies for use in carcinogenesis research. Specific research and technologies supported by CPCB in this solicitation include but are not limited to the following: 1. Development and validation of methods for food treatment, preparation, or processing that will reduce or eliminate carcinogen/mutagen content. 2. Development of rapid analytical techniques for the qualitative and quantitative detection and screening of xenobiotics, chemical contaminants, and carcinogens/mutagens in human foods and biological and physiological specimens. 3. Development of in vitro and in vivo models for basic studies of carcinogenesis in specific organ systems, such as the pancreas, prostate, ovary, central nervous system, kidney, endometrium, stomach, and upper aerodigestive tract. 4. Development of methods for the production of carcinogens, anticarcinogens, metabolites, biomarkers of exposure, oxidative damage markers, and DNA adducts, both labeled and unlabeled, which are neither currently available commercially nor offered in the NCI Chemical Carcinogen Reference Standard Repository. The production of these compounds, in gram quantities, is desired for sale/distribution to the research community. 5. Development of methods for detection, separation, and quantitation of enantiomeric carcinogens, metabolites, adducts, and biomarkers of carcinogen exposure. 6. Development of monoclonal antibodies that are specific for different carcinogen-nucleoside adducts and demonstration of their usefulness in immunoassays. Of particular interest are antibodies to alpha-beta unsaturated carbonyl compounds (such as acrolein and crotonaldehyde) which can form exocyclic nucleoside adducts with DNA, and immunoassays for carcinogen/protein adducts as potential biomarkers of exposure. 7. Development of immunoassays using monoclonal antibodies that are specific for different polymorphs of Phase I and II carcinogen-metabolizing enzymes and repair enzymes. Included, but not limited to, are antibodies to the cytochrome P450 isozymes, glutathione S-transferases, and N-acetyl transferases. 8. Development of rapid, sensitive, and quantitative assays for the identification and measurement of androgens, estrogens, phytoestrogens, and xenoestrogens in complex biological matrices. 9. Development of rapid analytical techniques for the direct measurement of ligand-protein receptor interactions and determination of binding coefficients. 10. Development of analytical instrumentation for the detection and quantitation of extremely low levels of Tritium (3H) or 3H and Carbon-14 (14C) from biological samples. Of particular interest is the development of small-sized, accelerator-based mass spectrometry equipment capable of measuring down to, or below, contemporary background levels of 3H and 14C that would make this sensitive technique more widely available to research groups. The design and development of technologically improved and miniaturized individual components, including ion source, sample preparation (autosampling apparatus), accelerator, and mass spectrometric detectors, are also solicited. 11. Isolation and development, from natural sources and/or synthesis, of potentially anticarcinogenic flavonoids, isoflavonoids, lignans, Vitamin D analogs, hormonal agonists/ antagonists, bioavailable protease inhibitors, and terpene compounds. 12. Synthesis of selective suicide inhibitors of cytochrome P450 isoforms and selective arachidonic acid pathway inhibitors/enhancers for basic biochemical studies and anticarcinogenic potential. 13. Development of invertebrate animal models (such as Drosophila, C. elegans, clam, and sea urchin) for the study of environmental chemicals and/or hormonal carcinogenesis. 14. Development of more efficient and reliable methods of preserving valuable animal model gene stocks by innovative in vitro techniques. 15. Development of a defined diet for support and maintenance of aquatic and marine fish models of cancer including but not limited to swordtail, zebrafish, medaka, mummichog, guppy, Fugu, and Damselfish. 16. Development of serum free tissue culture media for aquatic and marine fish models of cancer. E. DNA and Chromosome Aberrations. The DNA and Chromosome Aberrations Branch (DCAB) seeks to study the genome at the DNA and chromosome level, including discovery of genes at sites of chromosome breaks, deletions, and translocations, DNA repair, structure and mechanisms of chromosome alterations, epigenetic changes, radiation- and chemical-induced changes in DNA replication and other alterations, and analytical technologies. Specific research and technologies supported by DCAB in this solicitation include but are not limited to the following: 1. Development of new, improved technologies for characterization of chromosomal aberrations in cancer. 2. Development of new, improved, or high throughput technologies for whole genome scanning for chromosome aberrations in cancer; spontaneous, chemical or radiation induced. 3. New or improved technologies to increase accuracy of karyotypic analyses of tumor specimens. 4. New or improved methods to mutate genes at specific sites, or to replace genes, in intact cells. 5. Development of novel gene technology (e.g., microarray, differential display technology) for measurement of differential gene expression levels and functional genomic studies. 6. Development and distribution of genomic resources suitable for genomic manipulation or cytogenetic studies. 7. Technologies for assaying for mammalian genes relevant to repair of damage induced by exposure of mammalian cells to ionizing and non-ionizing radiations, with special emphasis on human cells. 8. Methods/approaches to study the repair of DNA lesions induced by exposure of mammalian cells to ionizing radiations (both high- and low-LET). 9. Development and characterization of human cell lines with specific DNA-repair deficiencies. 10. Development of genetic constructs that utilize radiation-responsive regulatory genes to control the expression of targeted structural genes in mammalian cells. F. Mouse Models of Human Cancers Consortium. The Mouse Models of Human Cancer Consortium is a program based in the Office of the Director, DCB. The Consortium has the important goal of providing mouse cancer model-related resources and infrastructure to the research community, in part through various outreach activities. The outreach requirement generates the need for innovative educational or informational materials that convey the content of Consortium meetings and symposia, or document hands-on workshops in which models or techniques that are pertinent to mouse modeling are demonstrated. The instructional materials may be CD-ROMs, videotapes, Web-based interactive programs, or other media. G. Structural Biology and Molecular Applications. The Structure Biology and Molecular Applications Branch (SBMAB) focuses on structural and molecular studies to explore the processes of carcinogenesis and tumorigenesis. Areas of interest include structural biology, genomics, proteomics, molecular and cellular imaging, enzymology, bio-related and combinatorial chemistry, and bioinformatics, as they apply to cancer biology. Interests also include modeling and theoretical approaches to cellular and molecular dimensions of cancer biology. Specific research and technologies supported by SBMAB in this solicitation include but are not limited to: 1. Development of new technologies to facilitate the analysis and determination of the molecular structure of macromolecules associated with cancer. 2. Development of new, improved, or high throughput technologies for whole genome scanning for gene identification. 3. Development of systems that will automate the technology of culturing or assaying single cells. 4. New or improved technologies for efficient microdissection of tumor tissue sections and the development of tissue arrays. 5. Improved extraction techniques for tumor specimens for subsequent DNA, RNA, and protein analyses. 6. Rapid methods to isolate intact complexes of regulatory proteins and to separate and identify the proteins. 7. New or improved technologies for the preservation of small amounts of DNA/RNA/protein samples 8. Development of new techniques and vectors for transfer of genes, proteins, and antisense molecules into cells. 9. Generation of software and computer models for the prediction of macromolecular structure and function. 10. Development new methodologies for the generation and automation of tumor cDNA libraries. 11. Development of bioinformatic tools for the study of cancer biology including facilitating genome data, gene "mining", cluster analysis and data base management. 12. Development of novel gene technology (e.g., microarray, differential display technology) for measurement of differential gene expression levels and functional genomics studies. 13. Development of novel proteomic tools for the analysis of protein expression in cancer biology. 14. Combinatorial library approaches for gene function analysis. 15. Computer based methodologies to assist in the understanding of signal transduction and cancer biology. 16. Methodologies and techniques for the imaging of marcromolecues in vitro and in vivo. 17. Development of in vivo imaging technologies for developmental model organisms. 18. Development of other novel technologies, methodologies or instrumentation to facilitate basic research (research tools) in cancer biology. H. Tumor Biology and Metastasis. The Tumor Biology and Metastasis Branch (TBMB) supports research focused on the interaction of the tumor with its local environment, the mechanism of tumor cells' acquisition of aggressive malignant behavior, and the influence of hormonal factors on tumor progression. Special emphasis is given to the development of appropriate animal and cellular models of metastasis. Research in tumor biology includes studies on: (1) the role of cell adhesion molecules; (2) the role the extracellular matrix and the basement membrane in development, tissue morphogenesis, wound healing, invasion, and metastasis; (3) the role of cytoskeleton, and nuclear matrix in cell proliferation, migration, and invasion; and (4) studies on gap junctional structures. Research in tumor progression and metastasis includes studies on: (1) the role of oncogenes and tumor suppressor genes in angiogenesis, matrix degradation, and metastasis; (2) the glycobiology of epithelial cell surfaces and functional consequences of aberrant glycosylation on cell adhesion, tumor progression, and metastasis; and (3) the role of steroid hormones and their receptors in transformation, tumor growth, and in the development of hormone independence during tumor progression. Models utilized in these studies may include animals, tumor tissues/cells, their components or their products. TBMB also focuses on the role of steroid hormones and their receptors during tumor growth and progression. Specific research and technologies supported by TBMB in this solicitation include but are not limited to: 1. New technical strategies to identify and assess the function of components of the extracellular matrix. 2. Development of new in vitro cancer models to study the pathology and biology of solid tumors and tumor bearing animals. 3. Development of technologies to identify novel factors that modulate angiogenesis. 4. Identification of genes associated with the process of metastasis. 5. Development of improved techniques for computational simulation/modeling of biological processes involved in malignant transformation, persistence, or invasion, such as signal transduction, cell cycle progression, and intracellular translocation. 6. Development of other novel technologies, methodologies or instrumentation to facilitate basic cancer research (research tools). ************************************************************ Other Research Topic(s) Within Mission of Institute Rheumatic Diseases Dr. Susana Serrate-Sztein National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-5032; Fax: (301) 480-4543 Email: ss86e@nih.gov Cartilage and Connective Tissue Dr. Bernadette Tyree National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-5032; Fax: (301) 480-4543 Email: bt16w@nih.gov Muscle Biology Dr. Richard Lymn National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-5128; Fax: (301) 480-4543 Email: rl28b@nih.gov Skin Diseases Dr. Alan N. Moshell National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-5017; Fax: (301) 480-4543 Email: am40j@nih.gov Orthopaedics Dr. James Panagis National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-5055; Fax: (301) 480-4543 Email: jp149d@nih.gov Bone Biology Dr. William Sharrock National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-5055; Fax: (301) 480-4543 Email: ws19h@nih.gov Bone Diseases Dr. Joan McGowan National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-5055; Fax: (301) 480-4543 Email: jm106v@nih.gov For administrative and business management questions, contact: Ms. Florence Turska National Institute of Arthritis and Musculoskeletal and Skin Diseases (301) 594-3507; Fax: (301) 480-5450 Email: ft7p@nih.gov NOTE: The Solicitations listed on this site are partial copies from the various SBIR agency solicitations and are not necessarily the latest and most up-to-date. For this reason, you should always use the suggested links on our reference pages. These will take you directly to the appropriate agency information where you can read the official version of the solicitation you are interested in. The official link for this page is: http://grants.nih.gov/grants/funding/sbir.htm. Solicitation closing dates are: April 1, August 1, and December 1, 2001.