Microsoft word - nih stimulus rfa- revised.doc
Below are all cancer-related topics, including the Challenge Topics the NCI is focusing on. This information is also available at http://grants.nih.gov/grants/funding/challenge_award/ and http://challenge.nci.nih.gov/.
Please note that asterisked items have been deemed as the highest priority topics by NIH.
(01) Behavior, Behavioral Change, and Prevention
Research to Inform FDA Regulation of Tobacco Products.
The “Family Smoking Prevention
and Tobacco Control Act” includes numerous provisions for which timely research is needed to expand the evidence-base for implementation. Topic areas for research include but are not limited to: product and constituent standards reporting and testing; product marketing and sales, including health related claims; product labeling and advertising; consumer perception studies; regulation of menthol; potential reduction of nicotine levels in tobacco products; extended use or additional indications of medications to treat nicotine dependence; and preventing youth’s tobacco use. Proposals should specify the specific provision or provisions of the legislation the research will address and how the proposed research will inform FDA regulation of tobacco products. Contact: Dr. Cathy Backinger, 301-435-8638, [email protected]
The Role of Nutrition in Cancer Biology.
Diet and nutrition have fundamental effects on
health. The exact associations and mechanism involved are poorly understood. Example of topics include: Diet associated differences in the microbiome – how does that affect the composition of the microbiome, inflammation, immune repertoire; the effect of nutrition on adaptive and innate immunity; application of multiscale modeling to linking effects of nutrition from the molecular to cellular to organism to population studies. Contact: Dr. Barbara Spalholz, 301-496-7028, [email protected]
The role of health behaviors in cancer prevention.
High priority domains of behavior change
include tobacco use, diet, physical activity, sun exposure and adherence to recommended cancer screening. Behavior change studies among cancer survivors also are encouraged. In addition, interventions targeted to health care providers to improve the delivery of high quality cancer care are welcome. Contact: Dr. Linda Nebeling, 301-435-2841, [email protected]
Examining the Use and Impact of New Genomic Technologies in Clinical Practice.
Studies that examine the physician utilization and/or patient acceptability of new cellular, molecular and genomics technologies in clinical and public health settings and the potential impact of these technologies on cancer outcomes such as incidence, progression, mortality, survival, and quality of life. Contact: Dr. Andrew Freedman, 301-435-6819, [email protected]
Unified informed consent document for biobanking and subsequent analysis of human
Obtaining adequate informed consent from research participants for broad future research use
of biospecimens remains a challenge that impedes efforts related to biobanking as well as downstream
research that uses biospecimens. Development of a unified informed consent document that describes the
risks and benefits of both biobanking and potential downstream analyses such as genomics or proteomics
would be of broad use to the research community. Development of such an informed consent document would
include synthesis of existing empirical data on informed consent for biobanking with current recommendations
in the ethics literature. In addition, all documents related to informed consent would be evaluated using focus
groups and other techniques in order to ensure patient understanding. Contact: Dr. Nicole Lockhart, 301-496-
0556, [email protected]
Optimizing the Timing of Consent for Biobanking to Achieve Ethical and Research
In order to promote both ethical and research objectives the informed consent process must
provide opportunities for biospecimen contribution to all appropriate patients while at the same time ensuring a
robust consent process that allows research participants to carefully consider risks and benefits. In response to
this challenge, two alternative models have been proposed: a “front-door” consent model in which an institution
actively invites all patients to contribute to a biospecimen resource and a post-operative consent model which seeks consent from patients who have appropriate biospecimens for banking after surgery has occurred. In order to determine which approach would best meet ethical and research objectives, empirical research must be performed to assess how the timing of informed consent affects: patient understanding of the proposed research, the psychological state of the patient; and accrual rates of biospecimens. Ideally, both approaches would be piloted and compared for these and other key parameters. Contact: Dr. Nicole Lockhart, 301-496-0556, [email protected]
Unique Ethical Issues Posed by Emerging Technologies.
biotechnology and biomedical science raise novel ethical, legal, and social issues. Research in this area is needed to understand the unique ethical concerns related to emerging technologies (e.g. biotechnology, tissue engineering, nanomedicine, and synthetic biology). These include issues such as dual use research, privacy, safety, intellectual property, commercialization and conflict of interest, among others. Research is also needed to assess how these novel issues are addressed under current oversight and regulatory structures and identify where there may be gaps and/or need for revised or new oversight approaches. OD(OSP)Contact: Abigail Rives, 301-594-1976, [email protected]
; NCI Contact: Dr. Jerry Lee, 301-594-0255, [email protected]
Ethical Issues in Health Disparities and Access to Participation in Research.
Research is needed to assess the under-representation in biomedical and clinical research of U.S. minority populations, underserved populations, and populations who may be vulnerable to coercion or undue influence, to identify barriers to participation in research and to develop approaches for overcoming them. Additionally, studies are needed to assess the impact and ethical considerations of conducting biomedical and clinical research internationally in resource-limited countries. OD(OSP)Contact: Abigail Rives, 301-594-1976, [email protected]
; NCI Contacts: Dr. Alexis Bakos, 301-443-0542, [email protected]
; Dr. Martha Hare, 301-594-1908, [email protected]
; Dr. Shobha Srinivasan, 301-435-6614, [email protected]
Ethical Issues Associated with Electronic Sharing of Health Information.
development of an electronic health information infrastructure and the sharing of health information for patient
care and research offer enormous promise to improve health care and promote scientific advances. However,
the broad sharing of such data raises numerous ethical issues that may benefit from additional studies (e.g.
those related to privacy and confidentiality). Examples include studies to assess risks associated with health
information technology and the broad sharing of health information for research, and novel approaches for
mitigating them. Examination could also include analysis of current oversight paradigms and suggestions for
enhancements, as well as assessments of how privacy risks may change in the future. OD(OSP) Contact:
Abigail Rives, 301-594-1976, [email protected]
; NCI Contacts: Dr. Chris Kinsinger, 301-436-1550, [email protected]
; Dr. Marsha Reichman, 301-534-7032, [email protected]
Ethical Issues in the Translation of Genetic Knowledge to Clinical Practice.
Genetics and genomics have great promise for the development of personalized medicine, yet the ethical, legal and social implications of both the research and application of genetic and genomic knowledge and technology are far reaching. Studies are needed to better understand the factors that influence the translation of genetic information to improved human health and the associated ethical issues. Examples of studies include those to address ethical issues related to broad sharing and use of new genetic information and technologies for research to improve human health, human subjects protection in genetic and genomic research, the identifiability of genetic/genomic information and how our understanding of identifiability is evolving, return of research results and incidental findings to subjects, alternative models of informed consent for broad data sharing for research, and the impact of intellectual property (IP) issues on development of new technologies. OD(OSP) Contact: Abigail Rives, 301-594-1976, [email protected]
; NCI Contacts: Dr. Mehdi Mesri, 301-496-1550, [email protected]
; Dr. Leah Sansbury, 301-435-4910, [email protected]
Ethical Issues Raised by the Blurring between Treatment and Research.
distinction between clinical practice and research is growing less clear, a trend that may be more pronounced with respect to genetic information and medical records research. Studies are needed to better understand the ethical issues associated with this trend. Examples of studies include those to identify how this blurring in roles
affects traditional human subjects protections, including, for example, essential practices such as informed consent, conceptions of the doctor/patient and investigator/subject relationship, and privacy protections. OD(OSP) Contact: Abigail Rives, 301-594-1976, [email protected]
; NCI Contact: Dr. Paul Han, 301-594-6642, [email protected]
(03) Biomarker Discovery and Validation
Fingerprints for the Early Detection and Treatment of Cancer.
Early detection is a proven
approach to successfully preventing and treating cancer. Because cancer arises through a complex interaction of multiple molecular signals and pathways often confounding the eventual effect, we need to identify key pathways or profiles that better reflect the underlying transforming processes. These “fingerprints”, which could include a myriad of indicators including mutations, proteins and metabolites, would have biological relevance and be appreciate in the detection and management of the disease. Contact: Dr. Dan Gallahan, 301-496-8636, [email protected]
Biological Predictors of Progression in Barrett’s Esophagus.
The incidence of
adenocarcinoma of the lower esophagus and esophagogastric junction has increased at an alarming rate in the last few decades. Risk factors including obesity, alcohol consumption, smoking, and gastroesophageal reflux disease (GERD) have contributed to the increase in this cancer. Research is needed on Barrett’s transformation to cancer to identify unique biological pathways that predict the progression of Barrett’s epithelium to adenocarcinoma and lead to an understanding of their relation to lifestyle risks such as obesity and GERD. The goal is to increase our understanding of Barrett’s associated cancer, facilitate the development of more translational strategies for early detection, and benefit the clinical management of Barrett’s patients at increased risk for esophageal cancer perhaps through lifestyle changes. Contact: Dr. Rihab Yassin, 301-496-7028, [email protected]
Reagents for rapid screening of human tumor cells for defects in DNA repair and/or
. A surprisingly high percentage of human tumors are showing mutations in DNA repair that make
them overly dependent on alternative backup DNA repair pathways for survival. As a consequence, cancer
cells from such tumors tend to be highly vulnerable to the inhibition of the backup pathway(s). Such effects
have been observed for Fanconi anemia mutation in breast and ovarian cancer but similar mutations in other
pathways are likely to exist also but are difficult to predict a priori. What is needed is a systematic screening of
large numbers of patient samples from a variety to human tumors to identify such patterns of DNA repair
mutations and consequent vulnerabilities from the over-dependence on compensatory pathways. This would
be followed by confirmatory validation of putative targets in cultured human cancer cells and animal models.
Contact: Dr. Dick Pelroy, 301-496-9326, [email protected]
Enhancing Biomarker Discovery Through Mass Spec Spectral Libraries.
emerging field of proteomics has reached a development point where it now needs a catalog or map of all detectable peptides. Such a map would unite researchers across the field to common metrics for detection, identification, and quantitation of proteins. Ultimately, this national resource would enable discovery of biomarkers as well as their translation to clinical validation. Contact: Dr. Christopher Kinsinger, 301-496-1550, [email protected]
Enhancing Biomarker Discovery Through Targeted Antibody Production.
affinity capture reagents against the National Institute of General Medical Sciences’ Protein Structure Initiative project. This program will explore the mapping of affinity reagents to a subset of proteins in the PSI. This global resource will empower the biomarker discovery field with critical resources (reagents and data) on translating basic science to clinical utility. Contact: Dr. Henry Rodriguez, 301-496-1550, [email protected]
Utilizing data from the TCGA and TARGET projects to support a large scale
bioinformatics effort to identify biomarkers that lie within a pathway or are epi-pathway indicators of
tumor formation or progression.
Epi-pathway markers lie outside of typical pathways but can be identified as
indicators when statistically significant numbers of tumors are characterized as is being done in these projects. Potential markers would be validated under other funding mechanisms. Contact: Dr. Joseph Vockley, 301-435-3881, [email protected]
Biospecimen Research to Improve Biomarker Identification and Validation
. The human
biospecimens that form the basis of medical research are collected, processed and stored under very different, non-standardized methods in multiple institutional settings. The molecular changes induced by these pre-analytical biospecimen variables can significantly confound research studies, particularly in the study of disease biomarkers. New biospecimen research is needed to better understand the contribution of biospecimen pre-analytical variables to molecular profiles. Potential topics under this research area are: 1) How do differences in how blood biospecimens are collected, processed and stored affect molecular profiles?; 2) How can the relative molecular integrity of banked biospecimens be assessed?; and 3) Normal human tissues are needed for studies that seek to understand early development of disease. How do differences in methods for obtaining normal human tissues affect resulting molecular profiles? How does post-mortem interval affect the molecular integrity of different tissues? Contact: Dr. Helen M. Moore, 301-496-0206, [email protected]
Biomarker Discovery and Validation among racial and ethnic minority Populations
Support community-targeted prevalence studies in co-morbidities (co-occurring conditions) and design research pilots to educate and engage these communities in participating in studies to identify and validate biomarkers of stress-related changes in immune function. Link the value of this research to the health of the community. Contact: Dr. Ken Chu, 301-435-9213, [email protected]
Enhancing biomarker discovery and validation using high quality, unbiased PLCO
The current process for cancer biomarker development is hindered by unsuitable specimens. The
problem is two-fold: the lack of specimens specifically collected for biomarker development; and the lack of
attention to potential sources of biases in the samples. These biases have resulted in numerous false positive
results, leading to wasted efforts and funds invested in those early phase discovery research efforts. The
PLCO biospecimens resource is designed for prospective studies of early detection biomarkers and cancer
etiology. It is ideal for nested case control design for biomarker discovery and validation. We propose that this
resource should be used for coordination of projects of discovery and validation of early detection biomarkers.
Specifically, samples will be divided into two identical aliquots. One will be used for laboratory discovery, and
one will be used for validation of the biomarkers. This design will eliminate many confounding factors that may
lead to false discovery. Contact: Dr. Christine Berg, 301-496-8544, [email protected]
Validation of Known Biomarkers.
Biomarkers in cancer prevention, detection and treatment
continue to challenge the scientific community from realizing its potentials and translating them into clinical use. The pathway to clinical application remains elusive. The challenge grants will ask researchers to take up validation studies of known biomarkers with clearly defined milestones with measurable outcomes in a two-year period. The outcomes may include proof-of-principle studies for select risk groups, cohorts, and populations that may benefits from risk assessment, and early detection and diagnosis. Contact: Dr. Sudhir Srivastava, 301-435-1594, [email protected]
(04) Clinical Research
Enhanced infrastructure for Brain Cancer Research.
Progress in the treatment of brain
metastases has been hampered by a lack of focus on the clinical problem over many years. The most critical need is for coordinated efforts toward creating infrastructure for biospecimen collection, banking, and distribution of clinically annotated tissue available for research focused on all aspects of the process by which a tumor cell metastasizes to the brain are needed. Multidisciplinary approaches should be encouraged to explore: the molecular signature of tumors that metastasize to the brain, homing of tumor cells to the brain microenvironment, the blood brain barrier, the role of brain microenvironment in successful growth of brain metastases and the use of novel imaging and other technologies to target and validate novel therapeutics. Contact: Dr. Judy Mietz, 301-496-9326, [email protected]
Understanding the Impact of Cultural Beliefs on Biospecimen Collection and Use.
Research is needed to understand the impact of cultural beliefs on biospecimen collection and use, and begin to build the interdisciplinary scientific teams and community partnerships that will be required to stimulate an effective, high quality biospecimen collection, processing and banking and analysis system within diverse communities. Building on current research (in CNP and PNRP), focused studies in this area will not only contribute to jobs within multi-ethnic communities, but also help ensure that advances in personalized cancer care among racially and ethnically diverse communities keep pace with broader national biospecimen collection and research efforts. Contact: Dr. Mary Ann S. Van Duyn, 301-451-4284, [email protected]
Augment Clinical Trial Recruitment/Retention of Multi-Ethnic Patients through Patient
Support research to increase representation of multi-ethnic patients in clinical trials through the
development and testing of innovative, multi-pronged, multi-cultural, and incentivized approaches to enhancing
multi-ethnic accrual to and retention within clinical trials. Promising approaches, based on current research,
include employing navigators to help patients through the system and engaging the community. Further
studies are needed to define the role of navigators and the community, as part of broader multi-ethnic outreach
approaches, to improving access to clinical trials among underserved populations with unusually high cancer
rates. Contact: Dr. Martha L. Hare, 301-594-1908, [email protected]
Policy for Challenge Grants: Incorporation of Analysis of Race/Ethnicity Differences into
Applicants for Clinical Research Challenge Grants must set forth race/ethnicity-based
hypotheses based on a consideration of the relevant literature if the proposed study has the potential for such
consideration. The purpose of this requirement is three-fold: to ensure compliance with NIH strategic focus on
eliminating health disparities; to capitalize on the growing body of research demonstrating race/ethnicity
differences in all areas of NIH research; and to ensure that any race/ethnicity-specific solutions/answers to the
stubborn questions are not overlooked, thus resulting in incorrect conclusions. If these requirements are not
relevant to the proposed research, applicants would be required to provide scientific justification for why
racial/ethnic analysis would not be relevant. Contact: Jane L. MacDonald-Daye, MA, 301-594-5946, [email protected]
Oversampling Minority populations in Clinical Research.
incentives/supplements to NCI-supported clinical trials where oversampling for minority populations would be feasible. Efforts to reach minority populations and barriers to access trials should be documented for further study, e.g., non-participation by choice, ineligible based on study design and/or health condition. Contact: Dr. Martha L. Hare, 301-594-1908, [email protected]
Designing Clinical Research Studies based on unique health characteristics of a Minority
Community Cohort with regard to Co-morbidities (domestic and international).
Support the development
of treatment protocols for co-morbid conditions including the development of clinical guidelines, development of
effective low cost diagnostic and treatment techniques, upgrading surveillance and tracking systems in these
communities that are effective in capturing critical information in disease tracking and surveillance, designing
patient navigation networks to support the needs of patients and families, etc. Particular attention should be
paid to projects that include HIV/AIDS, mental health, tropical diseases, tuberculosis, and cancer. Contact:
Jane L. MacDonald-Daye, MA, 301-594-5946, [email protected]
Developing innovative comprehensive trans-NIH approaches to address global health
. Provide support to stimulate the creation of innovative comprehensive trans-NIH approaches to
address global health disparities through the development of scientific teams to strengthen the current
international research agenda to include initiatives that provide the region/country with benefits and improve
the impact of the NIH research investment in low to middle income countries, e.g., improve research capacity
and research translation to contribute to the improvement of health outcomes, expansion of in-country
research training efforts, the introduction of community-based participatory research, and health services
research to address cancer and other co-morbidities. Contact: Jane L. MacDonald-Daye, MA, 301-594-5946, [email protected]
Policy for Conducting Clinical Research in low- and middle income countries.
NIH grants proposing to conduct research in low-middle-income countries to demonstrate/articulate what the benefit is to the country being studied, and to what extent the researcher intends to engage in capacity-building during, and/or at completion of the research project, e.g., what would be provided to the country to address disparities, including capacity-building, research training, financial or in-kind support targeted to improve community health, etc. Encourage partnering/collaborating with existing NCI/NIH health disparities programs (CNP, PNRP) to introduce community-based approaches to addressing disparities. US Jobs: Hire pre-and post-docs to develop and manage foreign relations and community networks and develop linkages with other US programs to address critical health gaps found in the targeted country. Contact: Jane L. MacDonald-Daye, MA, 301-594-5946, [email protected]
Biospecimen standardization for Clinical Assays
. Emerging clinical markers for cancer
diagnosis, prognosis, and treatment efficacy need standardized biospecimen collection, processing and storage protocols to reduce assay variability and improve patient care. Systematic studies are needed to determine the most important standardization steps for biospecimen preparation for markers that have shown particular utility, and to determine the specific biospecimen preparation needs of different marker assays. Contact: Dr. Helen M. Moore, 301-496-0206, [email protected]
Treatment of Prostate Cancer.
Currently there is evidence that Androgen Deprivation Therapy
(ADT) may be effective in the palliative management of advanced prostate cancer and may be effective for high-risk patients treated with radiation therapy for localized disease. In other clinical settings the balance of the clinical costs and benefits of ADT, including adverse effects on quality of life, are not well characterized. This project would use the data resources of the HMO Cancer Research Network (CRN) to identify a large, multi-center historical cohort of men with prostate cancer who received some form of treatment for their cancer. Using a broad array of clinical and pathological data, the analysis would compare clinical outcomes among men with similar prognostic characteristics and primary therapy (surgery, radiation, etc.) who received and didn't receive ADT. The cohort will have to be very large involving several sites the budget is likely to $2-3 million over 4-5 years. NCI Contact: Dr. Martin Brown, 301-496-5716, [email protected]
Quality of Cancer Surgery and Outcomes.
This collaborative project would use electronic
data resources in the CRN and the University of Vermont to identify a large cohort of patients operated on to remove breast and colorectal cancers. From national cancer quality measurement initiatives and the literature, a set of quality indicators (e.g., number of lymph nodes removed, necessity for reoperation, etc.) will be determined for each cancer. Using existing databases and electronic medical records, investigators will assess the quality of each patient's surgery on each indicator. The analysis will examine the ability of the quality indicators singly and in combination to predict outcomes such as survival. Because this study plows new ground, we would propose a large pilot involving the University of Vermont's existing breast cancer surgery database and two CRN sites, Marshfield and GHC. NCI Contact: Dr. Martin Brown, 301-496-5716, [email protected]
Appropriate Use of Colony Stimulating Factors.
Studies suggest that colony stimulating
factors (CSF) are not used as approved by FDA label and clinical indication; namely, patients are often given these agents as treatment rather than prophylaxis for chemotherapy-induced neutropenia. Furthermore, in the correct setting, using these agents as prophylaxis could improve outcomes and at the same time be cost-neutral or perhaps minimally cost increasing. These issues represent testable hypotheses, and are of great interest to health plans facing rising costs for cancer-related care. Therefore, the purpose of this Phase IV study is to determine if an intervention designed to improve use of Neulasta as primary prophylaxis improves health outcomes (episodes of grade 4 neutropenia and febrile neutropenia, quality of life) and is cost-neutral compared to standard care for newly diagnosed breast cancer patients undergoing moderately suppressive chemotherapy. NCI Contact: Dr. Martin Brown, 301-496-5716, [email protected]
The Use of Health Informatics to Increase the Effectiveness of Cancer Prevention.
the electronic medical records systems of integrated health care systems to provide feedback to primary care physicians to increase their effectiveness in providing cancer prevention services, such as tobacco cessation.
A proof of principle trial in the Cancer Research Network has shown that this approach is potentially effective for tobacco cessation. But a larger dissemination/implementation study is needed to generalize these results. NCI Contact: Dr. Martin Brown, 301-496-5716, [email protected]
Chemoprevention of Breast Cancer.
In adult women without pre-existing breast cancer, what
is the comparative effectiveness of selective estrogen receptor modulators (SERMs), tamoxifen citrate (Tamoxifen) and raloxifene (Evista), used for the primary prevention of breast cancer on improving short-term and long-term outcomes including: invasive breast cancer; ductal carcinoma in situ (DCIS); breast cancer mortality; osteoporotic fractures ; and all cause mortality. In adult women without pre-existing breast cancer, what is the evidence for harms of tamoxifen citrate and raloxifene? Harms may include but are not limited to: thromboembolism (i.e. deep vein thrombosis, pulmonary embolism); cardiovascular disease (i.e. stroke, myocardial infarction); metabolic disorders (i.e. hypertriglyceridemia); musculoskeletal symptoms (i.e. arthralgia syndrome); mental health (i.e. mood changes); gynecological outcomes (i.e. vaginal dryness, dyspareunia, sexual dysfunction, endometrial hyperplasia/dysfunctional uterine bleeding, and endometrial cancer; ophthalmologic disorders; other adverse events that would impact quality of life such as vasomotor symptoms; and cross-reactively with other medications or therapies. This could include an examination of whether outcomes vary by subgroups such as age, menopausal status, breast cancer risk, race and ethnicity and metabolism status (i.e., CYP2D6 mutation). NCI Contact: Dr. Martin Brown, 301.496.5716, [email protected]
Comparative Effectiveness of Computer Assisted Diagnostic Devices.
For over a decade,
Computer Assisted Diagnostic devices have been developed to aid clinicians in a variety of ways. Many, but by no means all, of these devices have been developed for use with imaging technologies. This supplement proposes studies regarding comparisons between CAD devices and alternative diagnostic approaches. Some of these CAD devices are intended to remove large numbers of likely negative cases to make the radiologists' time more efficient. Others are used to point to regions of an image for special attention. These Computer Assisted Diagnostic devices have been approved by the US FDA with varying degrees of evidence depending on the particular clinical application. There are opportunities to do short term trials (which can be simulated with outcomes and do not need to wait for clinical course to occur) that compare various CAD algorithms to standard of care, to double reading, and to expert panel approaches. Each project would have three phases: Review the clinical and statistical evidence used to place the product on the market and any evidence accrued since marketing application. Develop a standard protocol and data system (unless data already exist) that can be used for future studies of other algorithms or other was of using imaging data to optimize diagnosis. Perform a head-to-head comparison of CAD with standard of care, with double reading, and with an expert panel approach. NCI Contact: Dr. Martin Brown, 301.496.5716, [email protected]
Comparative Effectiveness of Different Modalities for Breast Cancer Screening.
screen mammography was initially established, through randomized clinical trials to be an effectiveness screening modality for breast cancer. Over time other innovative technologies, such as digital mammography and MRI, have become disseminated into the practice of breast cancer screening. The existing NCI sponsored Breast Cancer Surveillance Consortium, which currently contains information on over 7.5 million mammographic examinations, over 2 million women and over 87,000 cases of breast cancer, can be used as a platform to evaluation the comparative effectiveness of these newer modalities. NCI Contact: Dr. Stephen Taplin, 301.402.1483, [email protected]
04-MD-101* Development of effective approaches to increase minority recruitment and retention into
NCMHD will focus on research activities that reduce barriers to diversity and participation in
clinical trials and on initiatives that build partnerships and utilize new and non-traditional recruitment
approaches. Specific health disparity diseases/conditions of concern include but are not limited to diabetes,
obesity, cardiovascular disease, infant mortality, cancer, substance abuse, mental health, and HIV/AIDS.
Contact: Dr. Derrick Tabor, 301-402-1366, [email protected]
(05) Comparative Effectiveness Research
Comparative Effectiveness Research in Cancer Primary Prevention.
A number of
chemoprevention agents have been shown to be potentially effectiveness for the prevention of common cancers. But dissemination of chemoprevention remains low and controversy remains about the side effects associated with these agents. Comparative effectiveness research in this area would have the following aims: to document the level of dissemination of chemoprevention agents and the examine the physician, patient and health system factors that either facilitate or retard this dissemination; to conduct head to head studies of alternative chemoprevention agents and or approaches (e.g. risk stratification) to determine the relative clinical risk and benefits and economic cost of these alternatives. These studies could be conducted as adjuncts to existing controlled trials, as retrospective analysis of health system data or as prospective studies of cohorts of patients and physicians within the context of various healthcare delivery systems. Contact: Dr. Martin Brown, 301-496-5716, [email protected]
Comparative Effectiveness Research on Cancer Screening.
The effectiveness of cancer
screening has been established through randomized trials and other evidence for breast, colorectal and cervical cancer. However since screening for these cancers were initially introduced, there has been rapid and substantial innovation in new early detection technologies. Many of these technologies have disseminated into the practice of screening but without sufficient evidence as to their comparative effectiveness relative to earlier established technologies. In addition newer technologies may influence how the earlier technologies are most effectively used. Comparative effectiveness research in this area would augment evidence from controlled screening trials with: data from observational studies in defined populations of screening, intermediate and final outcomes; head-to-head studies of the technical performance characteristics, physician and patient acceptability and cost of alternative screening technologies, and decision models designed to project the costs and benefits of different screening technologies and strategies over the long-term at the individual, program and policy level. Contact: Dr. Martin Brown, 301-496-5716, [email protected]
Cost-Effectiveness of Patient Navigation.
Patient navigation is currently being tested to
determine if this approach has an impact on the timeliness of diagnostic testing and treatment. While the cost-effectiveness of patient navigation is being modeled by investigators in NCI’s Patient Navigation Research Program (PNRP), studies comparing the costs associated with navigation as compared to usual care are still needed. The purpose of this pilot project would be to implement
a cost effectiveness model that has been developed within PNRP to understand and quantify the costs associated with implementing and maintaining a patient navigation program, and to determine if this model can be applied to varied patient navigation projects (i.e., screening, diagnosis, treatment). Results would help to determine whether patient navigation is providing both clinically sound and cost-effective service. This initiative would involve supplements to current Patient Navigation Research Programs (PNRP). Using data from the nine funded PNRPs, successful applicants will work collaboratively with the other PNRP PIs, CRCHD Project Scientists, and the PNRP evaluator to test the cost-effectiveness model. The results will form a basis for cost-effectiveness studies in future patient navigation research. Dr. Martha L Hare, 301-594-1908, [email protected]
and Dr. Mary Ann Van Duyn, 301-451-4284, [email protected]
Comparative Effectiveness Research on Cancer Treatment.
The results of controlled clinical
trials guide recommendations for many initial cancer treatments. But cancer treatments are also prevalent for cancers for which the evidence base in-complete, not applicable to the patient population (e.g. older patients) or non-existent. Prostate cancer is a prime, but not the only example, of this situation. Comparative effectiveness research in this area would use retrospective data and/or prospective interviews with patients, physicians and policy makers to assess the clinical benefits, risks and economic costs of commonly used treatment approaches and assess patient, physician and health system factors that effect dissemination of these treatment approaches. Contact: Dr. Martin Brown 301-496-5716, [email protected]
The Cancer Intervention and Surveillance Modeling Network (CISNET)
http://cisnet.cancer.gov/) is a consortium of NCI-sponsored investigators whose focus is to use modeling to extrapolate evidence from RCT’s, epidemiologic, and observational studies to help determine the best strategies for implementing prevention, screening, and treatment strategies in the population and clinical practice. CISNET models could be applied to three areas: evaluation of competing early detection technologies, such as MRI vs digital mammography for breast cancer ; evaluation of competing diagnostic technologies, such as PET scans; evaluation of competing treatments, such as aggressive vs. conservative treatment for early stage prostate cancer. NCI Contact: Dr. Eric Feuer, 301-496-5029, [email protected]
Adjunctive techniques for detection of oral premalignant and malignant lesions.
Approximately 35,000 Americans are diagnosed each year with oral cancer, and early detection, usually during
a regular dental check-up, is critical to successful treatment of this disease. Adjunctive techniques have been
developed to enhance visual detection of oral premalignant and malignant lesions. Overall, there is insufficient
evidence to support their effectiveness. Projects that answer this challenge could include planning for
randomized clinical trials that compare visual and tactile oral mucosal examination with adjunct-assisted
examination in dental settings. Projects responsive to this challenge could estimate the effectiveness of
existing adjunctive techniques for detection of oral premalignant and malignant lesions from available datasets
or records, including cost effectiveness analyses. Applicants would need to submit a future NIDCR Clinical
Trial Implementation grant for support of any proposed clinical trials, which could be considered for support
through regular NIDCR appropriated funds. Contact: Dr. Jane Atkinson, 301-435-7908, [email protected] 05-EB-102*
Screening Methodologies for Breast Cancer
– Phase II trials suggest that dedicated breast
CT approaches can detect earlier stage cancer (i.e., smaller lesions) than mammography. Comparative
effectiveness studies are invited to determine if the information obtained from earlier detection can be used to
better treat breast cancer, and improve clinical outcome in terms of survival and quality of life. Contact: Dr.
Alan McLaughlin, 301-496-9321, [email protected] 05-EB-104*
Comparative Effectiveness of Robotic Surgery -
Compared to standard invasive surgical
procedures, minimally-invasive robotic surgical procedures have the potential to provide a safer and more
precise treatment for a variety of conditions including prostate cancer. Comparison of robotic procedures with
standard invasive treatments should demonstrate the comparative effectiveness and comparative cost of
robotic interventions for the clinical treatment of disease.
Contact: Dr. John Haller, 301 451-3009; [email protected]
(06) Enabling Technologies
Enhancing Electronic Patient-Reported Outcomes Assessment in Clinical Research or
Provide support to enhance, and/or validate the use of electronic-based tools for the
assessment of patient-reported outcomes, such as symptoms, functioning, or health-related quality of life,
and/or health behaviors such as physical activity. Proposed research may include a variety of technologies
including wireless, real-time data capture methods and other interactive tools that enhance patient feedback to
facilitate patient centered care, intervention research, or behavior change or maintenance. Contact: Dr. Bryce
Reeve, 301-594-6574, [email protected]
Transient molecular complexes in Cancer.
Aberrant molecular complex formation resulting in
inappropriate biochemical pathway utilization is a hallmark of cancer. While highly accurate methods such as crystallography and NMR have revealed a great deal of information about molecular complexes, much remains to be understood. Detecting, identifying, and cataloguing transient molecular complexes (those that are too rapid or too unstable to be detected using methods like crystallography) is integral to understanding the aberrant reactions which characterize cancer. New methods for detecting and characterizing transient complexes both in vitro and in vivo are needed to complete our understanding of molecular interactions in cancer. Contact: Dr. Randy Knowlton, 301-435-5226, [email protected]
As we increase our understanding of cancer we find ourselves in a unique
position to re-engineer or manipulate fundamental cellular processes in an attempt to control and treat the disease. This type of approach would require an interdisciplinary effort between cancer biology and engineering principals to interrogate, target and integrate at subcellular and cellular levels to generate model synthetic biological systems. Contact: Dr. Dan Gallahan, 301-496-8636, [email protected]
Quantum biology in Cancer Biology.
Cancer involves fundamental biological processes that
involve the manipulation of chemical reactions in the transfer and conservation of energy, using fundamental physical and chemical principles. Quantum biology is an emerging and interdisciplinary field that seeks to apply quantum principles to macroscopic systems rather than the atomic or subatomic realms generally described by quantum theory. Biological interactions are modeled using mathematical computation and physical measurements in light of quantum mechanics effects. Exploratory work is needed to apply this novel field to cancer research. Contact: Dr. Dan Gallahan, 301-496-8636, [email protected]
Structure Determination of Large Cancer-related Complexes.
Many of the fundamental
cellular events utilize large molecular complexes assembled in a timely way for a specific function, such as DNA repair, RNA splicing, and apoptosis. Our understanding of the structures of these complexes is limited. Since structure often reveals information about function, new approaches need to be developed to determine the structures of these complexes. Contact: Dr. Randy Knowlton, 301-435-5226, [email protected]
Data integration and visualization methods and tools.
Cancer research is increasingly
complex and data-rich. In order for biologists to view their data in the context of other similar data and to view it against the complex background of other data types, new data integration and visualization methods are needed. These can be in the form of software modules that can be plugged into existing portals or viewers and can include the adaptation of existing data visualization and integration methods now tailored to cancer research. Contact: Dr. Jennifer Couch, 301-435-5226, [email protected]
In vivo molecular profiling (spatial relationships) and Single cell Analysis.
A great deal of
information has been gained through molecular profiling of cancer cells and specimens. But these profiles, patterns of gene or protein expression for example, have been identified by monitoring purified components. The context and timing of the expression of these molecules is also important and spatial changes in protein and other molecules are often important in the development of cancer. New methods for visualizing gene expression, proteins or other molecules in normal and cancer cells are needed. Methods for single molecule resolution and methodologies that can monitor expression over time in vivo are needed. Contact: Contact: Dr. Jennifer Couch, 301-435-5226, [email protected]
Nanotechnology-based Prevention, diagnostic, and Therapeutic Tools.
expected to radically change the way we diagnose, image, and treat cancer. Novel and multi-functional nanodevices will be capable of detecting cancer at its earliest stages, pinpointing its location within the body, delivering anticancer drugs specifically to malignant cells, and determining if these drugs are effective. Functionalized nanoparticles would deliver multiple therapeutic agents to tumor sites in order to simultaneously attack multiple points in the pathways involved in cancer. Such nano-therapeutics are expected to increase the efficacy of drugs while dramatically reducing potential side effects. In vivo
biosensors would have the capability of detecting tumors and metastatic lesions that are far smaller than those detectable using current, conventional technologies. Furthermore, they will
provide rapid information on whether a given therapy is working as expected. Contact: Dr. Piotr Grodzinski, 301-496-1550, [email protected]
Advanced Tools to Study Mitochondria Energetics.
Development of new technologies for
studying the role of mitochondrial respiration alterations (energetics and oxidative stress) in the context of cancer. This program will explore the working of a mitochondria from different cell and tissue types in different diseases to help understand essential differences that are present in physiological and pathological conditions and to discover new molecular target for drug development and therapeutic intervention. Contacts: Henry Rodriguez, PhD, 301-496-1550, [email protected]
; Dr. Richard Aragon, 301-496-1550, [email protected]
In Silico Cancer Drug Medicine.
For years, researchers have explored the myriad wonders of
the construction of virtual proteins based on gene and protein sequence alignments and the screening of virtual compounds against a database of drug targets. But as is so often the case in drug development, most of these virtual compounds fail to achieve their lofty goals when synthesized and exposed to the harshness of the real world and the complexity of the human body. This obstacle now negatively impacts translation of new chemical entities into the market. Today, an opportunity exists for the NIH to implement a concerted effort that develops transformative tools (virtual and physical) that test drugs in real-world scenarios, while still in the virtual phase of human physiology. Contact: Dr. Henry Rodriguez, 301-496-1550, [email protected]
Integrative analysis of genomic data sets generated by TCGA and TARGET.
the unsupervised analysis of large and varied data sets that are predictive of cancer formation and can determine regulatory points in pathways and circuits. Contact: Dr. Joseph Vockley, 301-435-3881, [email protected]
Development of high throughput mechanisms for genomic analysis.
methods to improve the throughput of next gen methods for genomic analysis. Methods could be either laboratory based or bioinformatics based improvements with the goal of decreasing the amount of time it takes to analyze a sample. Contact: Dr. Joseph Vockley, 301-435-3881, [email protected]
Pre-Clinical Diagnostic and Prognostic Technologies For the Early Detection of Cancer.
Technologies intended for pre-clinical cancer detection and diagnostics, prediction of progression from preneoplastic lesions to cancer, early detection of cancer, and technologies for risk assessment are badly needed to facilitate the early, effective, and more accurate detection of cancer. Specific technologies of interest include technologies and associated methods to significantly improve cancer biomarker discovery, multiplexing platforms to accurately measure low abundance biomarkers, including those from bodily fluids (serum, plasma, buffy coat cells, urine, sputum, saliva) or cells within these fluids, integrated technological platforms for enabling multiplexed biomarker assays, and cellular imaging technologies to detect preneoplastic lesions. Contact: Dr. Richard Aragon, 301-496-1550, [email protected]
Integrated Clinical Technologies.
Novel devices, instrumentation, and tools intended for
potential clinical application and those for the prediction of response to therapy or for therapy monitoring are needed to facilitate improved clinical outcomes. Such technologies include platforms for comprehensive, high throughput analysis of genomic or proteomic alterations of tumor tissue such as changes in epigenetic profiles, gene copy number, gene expression, post-translational modifications, and tumor-related changes in lipids and carbohydrates. Of particular utility will be the integration of varying technologies for the development of analytical or point of care devices, including microfluidics, nanotechnology, micro or nanofabrication devices, or the multiplexing thereof. Technologies designed for the targeted delivery and retention of anticancer agents or for the surveillance or monitoring of such agents are also needed to facilitate better interventions for cancer treatment and diagnosis. Contact: Dr. Richard Aragon, 301-496-1550, [email protected]
Molecular and Population Epidemiology and Health Disparities Reduction.
significantly improved technologies are needed for high-throughput, non-invasive analysis and to help facilitate the movement of discoveries and improved technologies from the basic sciences arena to studies in human populations and the transfer of information from cancer-related health outcomes to practices in clinic and public health settings. Technologies applicable to cancer etiology, epidemiology, and health disparities reduction, including the novel identification and validation of functional or ancestral biomarkers for risk susceptibility in large or multiple populations with a high degree of specificity, sensitivity, cost-efficiency, predictive value, reproducibility and low variability are needed . Also sought are improved technologies in glycomics, proteomics, epigenetics, haplotyping and genotyping (both nuclear and mitochondrial), pharmacogenomics, toxicogenomics, and nanotechnology suitable for application to human populations, populations exhibiting differential health disparities, or in epidemiologic settings. Contact: Dr. Richard Aragon, 301-496-1550, [email protected]
Physical Sciences and Cellular Mechanics.
Technologies designed to elucidate, interrogate,
and model the role of physical forces on varying cellular functions, including cellular metastasis, metastatic potential, or motility need to be developed in order to facilitate an increased understanding of the role that physical forces play in cancer pathology and metastasis. Of particular need are technologies to quantitatively and temporally model, monitor, track, and/or characterize changes that occur at the level of the cell, including the development of cell-based bio and nanosensors. Technologies for targeted measurements made at the level of the cell, including cell-cell adhesion, cellular motility, and/or cellular adherence properties are also of interest, as are technologies to quantitatively measure cytoskeletal changes and the impact of such changes on elements of metastatic potential, including increased/decreased motility, changes in intracellular mechanics, and ability of cells to interact with the environment. Contact: Dr. Jerry SH Lee, 301-496-1045, [email protected]
Cancer Development, Pathology, and Pathological Progression.
Technologies that provide
new tools and insights for basic research with increased speed, cost efficiency, sensitivity, selectivity, or the capability to create new avenues of research into the specific mechanisms can lead to a better understanding of the development and progression of cancer. Of interest are technologies for molecular, subcellular, cellular and extracellular structure/function studies; capture, separation, and characterization of biomolecules, molecular complexes, sub-cellular complexes, cells, and complex mixtures; and technologies to facilitate the development of more accurate in vitro and in vivo cancer models (especially mouse models for human cancers). Of specific interest are new technologies that enhance understanding of the tumor microenvironment, cancer stem cells, complex pathways, and the role of pathogens in cancer development. Contact: Dr. Richard Aragon, 301-496-1550, [email protected]
Development of minimally invasive image-guided systems.
Target areas include (1)
improving the accuracy of biopsy sampling / staging of disease such as in the evaluation for prostate cancer, (2) reducing the incidence of complications such as in improving prostate nerve bundle sparing, (3) reducing recovery time such as in thoracic cancer resection and (4) improving the safety of interventional procedures such as in lead placement in deep brain stimulation. Contact: Dr. John Haller; 301 451-3009; [email protected]
(07) Enhancing Clinical Trials
Novel Agents for Cancer Treatment.
Initiate early phase clinical trials of novel agents in three
areas: 1) targeting the tumor stem cell by evaluating the sonic hedgehog smoothened antagonist, GDC-0449, and the pan-notch inhibitor, RO4929097, in collaboration with Genentech and Roche, respectively, in trials of breast, lung, colon, leukemia and ovarian cancer; 2) testing Anti-IGFR-1 Monoclonal Antibody IMC-A12 (ImClone) in pediatric tumors such as rhabdomyosarcoma, osteosarcoma, and neuroblastoma, as well as studies in breast, small cell lung, adrenocortical and pancreatic cancer; and 3) testing PARP inhibitor ABT-888 in breast, ovarian, and pancreatic cancer. Contact: Dr. Jeff Abrams, 301-496-2522, [email protected]
Augmenting Genome-Wide Association Studies.
Genome-wide association studies (GWAS)
represent the starting point for a variety of experimental and epidemiological approaches designed to identify the functional gene variants and gene-environment interactions that increase or decrease the risk of cancer, and may thus provide new insights into risk prediction as well as preventive and therapeutic interventions. Linking genomic and molecular alterations within tumors (the Applied Molecular Pathology Lab and the Cancer Genome Atlas) with the germline variants uncovered by GWAS will further catalyze downstream biological research, and speed the translation of genomic discoveries into clinical practice. Furthermore, studies of the “dark matter” in the human genome that are not captured by the SNP-based GWAS (e.g., structural and rare gene variants, micro-RNAs, and epigenetics) are needed to fully understand the inherited component to cancer. Contact: Dr. Daniela Gerhard, 301-451-8027, [email protected]
The Role of Gene-Environment Interactions in Cancer Health Disparities Research.
Minority and underserved communities usually depict higher incidence and mortality rates for a number of different cancers (e.g. breast and prostate). Most research in this area have focused on the social factors that lead to these disparities, however, racial or ethnic disparities in cancer cannot be explained by poverty, access to healthcare or behavior alone. Understanding the etiology of cancer requires the knowledge of how the social and physical environments affect biological pathways/processes at a molecular level. This presents one of the most challenging issues in health disparity research. Studies are needed to delineate how the social/physical environment interplay with biology to affect genetic pathways or mechanisms that contribute to cancer disparities and to help create interventions that would eliminate/reduce them. Contact: Dr. Damali Martin, 301-451-1956, [email protected]
Micro-RNAs in Cancer.
MicroRNAs are recently identified small non-coding RNAs that have
been shown to be both ubiquitous in the mammalian genome but also exerting control over many cancer genes and processes. New technologies and informatics tools are needed to survey the micro-RNAs in cancer and their role in its development. Contact: Dr. Chamelli Jhappan, 301-435-1878, [email protected]
Regulatory functions of small RNAs.
Recent genome wide expression studies have revealed
the existence of small RNAs, transcribed from nearly all genes in both the sense and antisense orientation from promoters. The role of these small RNAs in normal and aberrant gene regulation remains is not known. Research is needed to understand their control and function in normal and cancer cells. Contact: Dr. Chamelli Jhappan, 301-435-1878, [email protected]
Development of a project that evaluates tumors that do not qualify for TCGA or TARGET.
This includes the expansion of TCGA and TARGET to include tumors that are either too small (physically) to make it possible to isolate sufficient RNA and DNA for analysis or are so rare that a statistically significant number of samples can be obtained for characterization under these programs. These “orphan tumors” will miss the genomic revolution as it is applied to other cancers. Methods for the genomic characterization of these tumors exists however, there is no funding to include them in these projects. Expansion of TCGA and TARGET to include these is critical to a comprehensive identification of diagnostic and therapeutic targets as well as understanding the basic biology of these tumors. Contact: Dr. Joseph Vockley, 301-435-3881, [email protected]
Development of methods for the validation of gene discoveries as they relate to cancer.
This includes high throughput methods for validation of targets and the analysis of these data. This may be cellular based approaches to validation. The key is high throughput capacity. Contact: Dr. Joseph Vockley, 301-435-3881, [email protected]
Bioinformatic pipeline for rapid genomic analysis.
Development of bioinformatics tools and
analytical pipelines that will significantly decrease the amount of time it takes to analyze data from TCGA, TARGET and other high throughput projects. Contact: Dr. Joseph Vockley, 301-435-3881, [email protected]
Genomic changes introduced by Biospecimen Pre-Analytical Variables.
tissues are needed for studies that seek to understand early development of disease. The human biospecimens that form the basis of medical research are collected, processed and stored under very different, non-standardized methods in multiple institutional settings. The molecular changes induced by these pre-analytical biospecimen variables can significantly confound research studies. New biospecimen research is needed to better understand the contribution of biospecimen pre-analytical variables to molecular profiles. Potential topics may include: 1) How do differences in methods for obtaining normal human tissues affect resulting molecular profiles?; 2) How does post-mortem interval affect the molecular integrity of different tissues?; 3) How do differences in methods for obtaining normal human tissues affect resulting molecular profiles?; 4) How does post-mortem interval affect the molecular integrity of different tissues? Contact: Dr. Helen M. Moore, 301-496-0206, [email protected]
Genome-wide Association Studies in Cancer Prevention.
The multi-step, multi-factorial
process of carcinogenesis involves mutations in oncogenes, or tumor suppressor genes, as well as the influence of environmental factors. In addition, common DNA polymorphisms in low penetrance genes have also emerged as genetic factors that seem to modulate an individual’s susceptibility to malignancy. Genetic studies, which lead to a true association, are expected to increase understanding of the pathogenesis of each malignancy and to be a powerful tool for prevention and prognosis in the future. Here, we propose integrating such genomic approaches in existing clinical and translational research portfolio and utilization of existing DCP biospecimen resources to promote genome wide association and also gene-environment interactions as they apply to prognostic and diagnostic opportunities in cancer prevention research. Contact: Dr. Asad Umar, 301-594-7671, [email protected]
Human Proteome Atlas (HPA).
This genomic-centric approach will focus on chromosomes that
have been fully mapped and implicated in diseases. This way the proteomic mapping of known genomic aberrations will be able to lead the development of functional assays that could be employed in disease detection. Contact: Dr. Sudhir Srivastava, 301-435-1594, [email protected]
Proteomics programs for Cancer Prevention and Early Detection.
Foster new technology to
rapidly detect proteins in the serum, urine, saliva, and other accessible fluids/cells for the purpose of identifying high risk cohorts for prevention trials and possible surrogate endpoints for Phase II Trials. It would also fund some back validation from trials where samples are available and outcomes known. Contact: Dr. Vernon Steele, 301-594-0420, [email protected]
Identifying Noncoding RNA Targets for Cancer Early Detection and Prevention.
objective of this funding opportunity is to promote research on microRNAs (miRNAs) and other small noncoding RNAs (ncRNAs) in preneoplastic lesions, examine the usefulness of these RNAs to predict progression to cancer and determine whether ncRNAs in body fluids can be used for early cancer detection. The purpose of this initiative is to promote research on the discovery and characterization of ncRNAs in preneoplasias and early stage cancers to (1) improve early cancer detection, intervention, and prevention, (2) predict risk of progression from preneoplasia to cancer, and (3) distinguish benign lesions from precancerous lesions. Contact: Dr. Sudhir Srivastava, 301-435-1594, [email protected]
Enhance genomic studies with social determinants of disparities.
Genomic studies to
study disparities need to include social determinants of disparities, such as SES, access to care, cultural issues, and environmental data, to give context to the genetic factors for disease. Using multidisciplinary teams within a community-based participatory research framework, these studies will integrate the genomic data with the social determinants to gain a fuller understanding of how these factors can affect cancer health disparities. Contact: Dr. Ken Chu, 301-435-9213, [email protected]
Genomics Research targeting Minority Populations.
Support epigenetic and gene-
environment interaction research targeting specific communities with an excess burden of disease. Projects should collaborate with other Federal programs in the targeted community, including HRSA centers, CDC, NCI and NIH community-based programs to improve outreach and education efforts, provide updates, etc. Community leaders/representatives should be a part of the ancillary research support team. New jobs needed at community level to manage and monitor community education and outreach programs, e.g., patient navigation programs. Contact: Jane L. MacDonald-Daye, MA, 301-594-5946, [email protected]
Planning Grants for Genome-wide Studies of Understudied Oral and Craniofacial
Diseases and Disorders [Temporomandibular Joint Disorder, Oral Cancer, Sjögren’s Syndrome,
]: Genome-wide studies have yielded significant insights into the genetic etiologies of
many common complex diseases, but this approach has not been widely adopted for highly complex oral and
craniofacial diseases such as TMJ disorder, oral cancer, Sjögren’s syndrome, or periodontal disease. Goal
Assessment of the adequacy and consistency of clinical, risk factor, endophenotype, behavioral and
demographic data of participants from different research groups; adequacy of tissue specimens for genome-
wide technologies; and feasibility of the initial genome-wide study and follow-up studies. [High Priority Topic for
Dr. Emily Harris, 301-594-4846, [email protected]
(09) Health Disparities
The Basis for Differences in Cancer Incidence.
There is profound difference in the incidence
and outcomes of cancer in various populations. This is also reflected in gender and age demographics. Efforts are needed to better understand the genetic and environmental mechanisms behind these differences so that they can be prevented and more effectively treated. Contact: Dr. Phil Daschner, 301-496-1951, [email protected]
Building Transdisciplinary Regional Capacity in Cancer Health Disparities Research and
Eliminating cancer health disparities can be accelerated through enhanced cooperation,
collaborations and partnerships across the cancer research enterprise. Provide support to stimulate
transdisciplinary planning for the creation of state-of-the-art regional networks of scientists working in cancer
health disparities research and care. An initial phase will encourage information sharing and gathering on
region-based cancer epidemiology, existing cancer research, diversity training, and resources, and begin to
establish the capacity and infrastructure needed to support region-specific pilot research programs in one of
the following areas: clinical trials, bioinformatics, minority biospecimens or biobanking, and emerging or
advanced technologies, and establish new transdisciplinary research partnerships. Contact: Dr. Mary Ann S.
Van Duyn, 301-451-4284, [email protected]
Communication, Bio-Behavior and the Physical Environment: Exploring Interactions to
Address Health Disparities.
Disparities in cancer outcomes continue to grow despite interventions to
increase screening, access to treatment, and preventive strategies. Contributing factors include constraints
within the built environment. Recent studies show that we can increase the reach and effectiveness of health
information through the identification of optimal settings, improved connections and enrichment of the
information and physical environment, and that multi-factor, biobehavioral interventions can positively impact
cancer patients. Further studies and new approaches that consider multiple levels of factors that contribute to
disparities need to be tested among multi-ethnic cancer patients whose physical environment contributes to
health disparities. Contact: Dr. Mary Ann S. Van Duyn, 301-451-4284, [email protected]
Basic cancer research in cancer health disparities.
The role of biological factors in cancer
health disparities is now a reality with studies that show that genetic risks to cancer varies by racial/ethnic groups. Basic research is needed in cancer cell biology, cancer etiology, cancer immunology and hematology, DNA and chromosome aberrations, structural biology, and the tumor microenvironment to examine variation among racial/ethnic groups. This will create the knowledge base for understanding the role of basic cancer mechanisms in cancer health disparities. Contact: Dr. Ken Chu, 301-435-9213, [email protected]
Cost effectiveness analysis of patient navigation.
The Patient Navigation Research Program
(PNRP) has developed models for determining the cost-effectiveness of patient navigation within that program. Further studies will allow a formal cost-effectiveness analysis of the PNRP to be undertaken. This research will allow various patient navigation models, such as the use of lay navigators, nurse navigators and social work navigators, to be compared both in effectiveness and cost. This cost-effectiveness analysis will occur among the 8 PNRP sites. Contact: Dr. Martha L. Hare, 301-594-1908, [email protected]
Designing a systems approach to address health disparities.
research projects in targeted community settings where disparities exist. Projects should demonstrate a clear systems approach to the research design that weaves education and outreach into the research intervention, and where formal partnerships across the current network of community-based participatory research programs supported by NIH Institutes and Centers and among a wide range of Federal departments and agencies are developed. Contact: Jane L. MacDonald-Daye, MA, 301-594-5946, [email protected]
(10) Information Technology for Processing Health Care Data for Research
Cyber-Infrastructure for Health: Building Technologies to Support Data Coordination and
The National Science Foundation has identified research based on
” as the single most important challenge confronting the nation’s science laboratories
(http://www.nsf.gov/news/special_reports/cyber/index.jsp). The challenge is based on a “grand convergence”
of three trends: (a) maturation of the Internet as connective data technology; (b) ubiquity of microchips in
computers, appliances, and sensors; and (c) an explosion of data from the research enterprise. The NIH, for
example, has invested millions within its Genes, Environment, and Health Initiative (GEI) to develop new
technologies for measuring environmental exposure to accompany the millions already spent on data from
Genome Wide Association studies. The DHHS is spending millions to catalyze the deployment of
interoperable electronic health records as a springboard for research (i.e., in the “learning health system”).
Relatively little has been spent on accommodating the petabytes
(i.e., 10 15 bytes of data) of data expected
from these investments. What is needed is a focused concentration of resources to stimulate the creation of
new technologies to accommodate these data and accelerate knowledge discovery through computational
means. Such a stimulus should help bootstrap a new sector of the knowledge economy, one that is dedicated
to accelerating the pace by which data are turned into population health benefits. Contact: Dr. Bradford Hesse,
301-594-9904, [email protected]
Predictive Mathematical Models of Normal and Cancer Processes.
Develop and verify
mathematical models or computer simulations of cancer processes towards integration into basic and translational research. Contact: Dr. Jerry Li, 301-435-5226, [email protected]
Cell Behavior Ontology.
Descriptions of various processes and behaviors of cells are still
crudely described and quantified. This type of description makes it difficult to compare and integrate this type of research into various aspects of biological research. Approaches and nomenclatures are desperately needed to better understand, describe, and utilize the vast amount of information about these critical processes in the transforming environment. Contact: Dr. Jerry Li, 301-435-5226, [email protected]
Infrastructure for the Application of In Silico Models in Cancer.
As mathematical models of
biological functions begin to populate the literature there is a need for a bio-informatics infrastructure to promote and enhance their usage. Components of this can be a repository, web based tools and annotation features. Contact: Dr. Jerry Li, 301-435-5226, [email protected]
Databases for Shared Nanomaterials Characterization.
Nanotechnology is rapidly
developing tools and materials for novel therapeutic applications. Since it is new and emerging field, several solutions are available, with most of them being developed in university laboratories. The information sharing through the development of common databases and portals enabling the selection of most appropriate and useful constructs is critical for the progression of this field. Contact: Dr. Piotr Grodzinski, 301-496-1550, [email protected]
National Cancer Database Integration
. The American College of Surgeons Commission on
Cancer (CoC) and its empirical arm, the National Cancer Data Base (NCDB), have been identified as a key resource from which to obtain demographic characteristics of the patient and information describing the clinical management of a patient’s disease and the outcomes associated with that patient. These data are a critical piece in adequately describing biospecimens used in molecular studies. Contact: Dr. Helen M. Moore, 301-496-0206, [email protected]
Expand Spectrum of Cancer Surveillance through Informatics Approaches.
projects using informatics approaches to facilitate electronic transmission of clinical, EMR, administrative and claims data to facilitate cancer surveillance. Data may originate at physician offices, hospitals, HMOs, third party payers, radiology facilities, pathology facilities, laboratories, etc. Use of data linkage and natural language processing to auto-populate data fields taking into account data coding schemes and quality assurance measures is highly encouraged. Treatment and co-morbidity data are high priorities. Collaboration among epidemiologists, bioinformaticians, health services researchers, etc is necessary to achieve these goals. Projects that develop caBIG compliant tools that can be deployed on the caGRID are especially
welcome. The overall goal is to increase the spectrum of data elements routinely used for cancer surveillance in an efficient, cost effective, state of the art fashion. Contact: Dr. Marsha Reichman, 301-594-6776, [email protected]
(11) Regenerative Medicine
For this RFA, there is no NCI-specific Challenge Topic in this Challenge Area.
(12) Science, Technology, Engineering and Mathematics (STEM) Education
Cross Science Training in Cancer.
Joint projects in STEM disciplines and cancer biology.
Contact: Jennifer Couch, PhD, 301-435-5226, [email protected]
Bringing New Mathematical Methods into Cancer Biology.
Cancer is inherently a complex
system involving many types of interactions and many scales both spatial and temporal. Mathematical methods for modeling, analyzing and understanding complex systems are applied across a wide range of complex systems from transit networks to social systems. Some of these methods have been adapted and applied to the study of cancer risk, initiation and progression. However many cancer processes remain difficult to model and analyze; new methods and methods adapted from the studies of other complex systems analysis are needed to better model cancer processes. Contact: Dr. Jennifer Couch, 301-435-5226, [email protected]
Modeling and Predictive Tools for Development and Testing of Nanotechnology-based
Diagnostics and Therapeutics.
Accurate predictive modeling tools can aid researchers in designing and
deciding future experiments, thereby saving valuable time and resources. Such tools have been successfully
developed in several industries (e.g., semiconductor device fabrication) and have become indispensable to
accelerate the design process as well as provide standardization to the developments for different companies.
The development of such predictive and modeling tools can make a major impact on the nanobiotechnology
efforts to recommend suitable surface functionalization and structural improvements, which can then be
incorporated into the design of nanomaterials. As a result, the nanoparticle circulation times, non-specific
binding, aggregation, and cellular uptake can be assessed and optimized prior to the development of the actual
material and ultimately lead to the optimization of the diagnostic and/or therapeutic nanotechnology-based tool.
Contact: Dr. Piotr Grodzinski, 301-496-1550, [email protected]
Developing the Workforce in Emerging Technologies CURE.
The overarching goals of the
Emerging Technologies Continuing Umbrella of Research Experiences (ET CURE) initiative are to: 1) Create a pipeline of underserved students and investigators in the fields of emerging and advanced technologies; 2) Increase the number of scientists from underserved populations with training in the elective disciplines of focus, such as nanotechnology, clinical proteomics, bioinformatics, biophotonics and cancer health disparities across the cancer research continuum; 3) Enhance the application of emerging technologies to cancer research through increased training and educational opportunities; and 4) Foster academic, scientific and multi-disciplinary research excellence. This training program provides employment opportunities for the public health sector, academic institutions and the next generation of clinicians and scientists. The program is comprehensive and can be augmented at training sites nationwide and has a steadfast commitment to diversity and to the underserved populations that are impacted. It is paramount that we enhance the application of emerging technologies to cancer research through increased training and educational opportunities and increase the number of individuals with diversity in the pool of future investigators, by the creation of training and employment opportunities such as ET CURE. It is believed that the provision of resources, the joining of committed partners and the utilization of the above opportunities in concert will bring to fruition a positive impact on diversity in the areas of advanced and emerging technologies and reduce cancer health disparities. Contact: Dr. LeeAnn Bailey, 301-496-7344, [email protected]
(13) Smart Biomaterials - Theranostics
A great deal of information about cancer has come to light through the
generation of molecular data, including gene and protein expression data that differs between cancer and normal cells. But also of critical importance is the mechanics of the cells themselves: adhesion strength, motility, and shape deformation changes have all been identified in cancer cells compared to normal. High throughput methods for capturing the physical properties of cells are needed to help complete our understanding of cancer processes. Contact: Dr. Randy Knowlton, 301-435-5226, [email protected]
Nanotechnology-based multi-functional materials for theranostic applications.
Nanotechnology provides a unique opportunity to develop multi-functional constructs carrying targeting moiety, therapeutic construct, and imaging agent. Such constructs will enable entirely new category of clinical solutions which permit early recognition of the disease through the use of novel contrast agents combined with one of the existing imaging modalities (MRI, ultrasound, optical imaging) followed through tailored release of the therapeutic. This new category of solutions – theranostic will provide a path for personalized medicine in oncology. Contact: Dr. Piotr Grodzinski, 301-496-1550, [email protected]
Chemoprevention Using Pharmacogenomic Profiles.
Studies that focus on chemopreventive
interventions based on pharmacogenomics profiles are sought. Examples include: chemoprevention clinical trials that utilize specific genomic polymorphisms or proposals that will obtain this information as part of their secondary objectives. Contact: Dr. Asad Umar, 301-594-7671, [email protected]
(14) Stem Cells
Tumor Stem Cells.
The role of cancer stem cells remains a controversial and poorly
understood area of biology. Some of the pending questions include: the existence and characteristics of tumor stem cells in different tissue types; the relationship between stem cells, tumor cells and dormant cells; role of the microenvironment in the development and harboring of stem cells; the effect of cancer stem cells on treatment. Contact: Dr. Allan Mufson, 301-496-7815, [email protected]
Understanding the Heterogeneity of Cancer and its Environment.
Cancer is not a disease
of a single cell but multiple cells interacting in a timely way to develop and progress through the cancer continuum. These cells make up the greater cancer micro-environment and can include transformed cells, tumor stem cells, differentiating cells and associated stromal cells. Efforts are needed to identify and characterize this cellular milieu so that we can better understand the biology. Contact: Dr. Suresh Mohla, 301-435-1878, [email protected]
Cancer\ Stem Medicine.
Development of new technologies to identify and understand
intracellular and intercellular communication, algorithms and processes of cancer stem cells (CSCs). This will enable the biomedical community to understand whether CSCs are responsible for the development and spread of cancer and why the disease is resistant to many conventional treatments and able to reestablish itself after therapy. Contact: Dr. Henry Rodriguez, 301-496-1550, [email protected]
Resource Development for Stem Cells Research.
There is increasing evidence that cancers
may originate in tissue stem or progenitor cells through dysregulation of the normally tightly regulated process of self renewal (1). Further genetic and epigenetic alterations in these cells generate tumors that are driven by a cellular sub-component that retains stem cell properties. These tumor initiating or “cancer stem cells” have been identified in an increasing number of human cancers. This suggests that tissue stem cells or their products might serve as valuable biomarkers for early cancer detection. Furthermore, if cancers originate in these cells then these biomarkers may also prove useful in chemoprevention studies. The identification of cancer stem cells in multiple tumor types has facilitated an initial characterization of molecular pathways which regulate these cells. Interestingly, a number of developmental pathways appear to play a common role in the regulation of both normal and malignant stem cells in multiple organs. Contact: Dr. Sudhir Srivastava, 301-435-1594, [email protected]
Stem Cells for Chemopreventive Interventions.
Cancer stem cells that display tumor-
initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective targeted therapeutic strategies for the most difficult and aggressive cancers. Translational science and genomic studies are needed to validate this hypothesis, as well as to develop a comprehensive understanding of the molecular differences that constitute cancer stem cells. Focus of research in the area will include targeting cancer stem cells to develop effective chemopreventive interventions. Premalignant lesions such as ductal carcinoma in situ of the breast, villous adenomas of the colon and atypical nevi are lesions that are thought to be generated and maintained by progenitor stem cells. Identification of the progenitor stem cells in premalignant lesions and characterization of targetable pathways for elimination of progenitor stem cells in premalignant lesions constitute a challenge area with great potential for cancer prevention. Contacts: Dr. Asad Umar, 301-594-7671, [email protected]
; Dr. Karen Johnson, 301-402-3666, [email protected]
(15) Translational Science
The Role of Cellular Architecture in Normal and Tumor Cell Biology.
The size and shape
of a cell, as well as the placement of organelles and the arrangement of chromosomes within the nucleus are highly regulated and ordered. Changes in cell shape or rigidity of the microenvironment affect the patterns of gene expression and cell growth. These findings indicate that extracellular mechanical forces can alter a cell’s behavior. Recent studies have demonstrated that genes are differentially positioned within the nucleus when they are silent or expressed. Furthermore, the genome is organized into chromosomal domains whose composition changes in different cell types and in cancer. These studies indicate that cellular architecture plays a critical role in regulating cell phenotype. Further studies are needed to define the relationship between cellular architecture and cell function, in both normal and tumor cells. Contact: Dr. Suresh Mohla, 301-435-1878, [email protected]
Understanding mechanisms of hormone refractory cancers for therapeutic targeting.
Steroid receptors continue to play a major role in controlling the growth of hormone-refractory cancers and appear to accomplish this by: the activation of steroid receptors by alternate ligands; local production of steroid hormone; stabilization of steroid receptors and mutations that render steroid receptors hypersensitive to very low levels of the ligands. In addition, recent findings demonstrate that in patients treated with herceptin, ER levels and ER-mediated signaling is enhanced, while in patients treated with antiestrogens, Her 2-mediated signaling is enhanced. Furthermore, at least 25% of the genes modulated in these cancers are via non-genomic signaling. A comprehensive understanding of the molecular underpinnings of steroid receptor dependence of hormone-refractory tumors as well elucidating the subtleties of these regulatory pathways and their crosstalk will support personalized, predictive and preemptive medicine in human breast and prostate cancer. Contacts: Dr. Judy Mietz, 301-496-9326, [email protected]
; Dinah Singer, PhD, 301-496-8636, [email protected]
Thyroid Cancer Cell Line Project.
Thyroid cancer is poorly understood and managed. One of
the challenges is model experimental systems. The community needs a set of well defined human thyroid cell lines reflecting the different thyroid diseases and disease states. Contact: Dr. Rihab Yassin, 301-496-7028, [email protected]
Use of novel mouse genetic resources to elucidate determinants of drug toxicities.
major limitation of human clinical trials is occurrence of toxicities not anticipated from preclinical studies; one example is cardio-toxicity associated with non-steroidal anti-inflammatory drugs. No preclinical studies at present accurately model the important conditions of clinical trials (e.g., metabolic status, genetic heterogeneity). The NCI [and probably NIDA, NIEHS, and NIAAA] invites projects that exploit new mouse genetic resources to disclose the genetic loci, subtle interactions among them, and interactions with environmental effectors (e.g., diet, activity level, stress) that underlie development of toxicities to common therapeutic and preventive agents. Contact: Dr. Cheryl Marks, 301-594-8778, [email protected]
The Biology of Cancer in Adolescents and Young Adults.
A Progress Review Group,
involving the NCI, the Lance Armstrong Foundation and the LIVESTRONG Young Adult Alliance, identified the
need to determine if unique biological and molecular differences underlie adolescent and young adult cancer with respect to prognosis and therapeutic outcome and differentiate it from the disease in younger or older patients. Studies are encouraged using existing tissue samples to investigate whether definitive biological and genetic differences exist in cancers in the 15-39 year age group and whether any such differences could account for the different disease outcomes experienced by this group. Appropriate topics of investigation could include epigenetic differences, developmental influences or microenvironment changes. Contact: Dr. Don Blair, 301-496-9740, [email protected]
Understanding the Molecular Basis of Cancer Cachexia.
Cachexia is a major problem in
cancer patients and a clear understanding of the molecular mechanisms by which this occurs would be of substantial benefit. Cachexia is a pathological state where loss of muscle or muscle and fat and occurs and contributes to significant morbidity and mortality. The most prominent clinical feature of cachexia is weight loss, but it is distinct from starvation and age-related muscle loss. Inflammation and anorexia are frequent characteristics, but they are non-obligatory criteria for the diagnosis of cachexia. Much work is needed to reveal the underlying triggers for cachexia and the metabolic pathways that are disrupted. Development of animals for cachexia would greatly enhance our ability to investigate this process which complicates effective treatment of cancer. Contact: Dr. Barbara Spalholz, 301-496-7028, [email protected]
Multi-scale Modeling: from Molecules to Populations.
At a molecular level cancer can
develop from the aberrant expression of critical cancer genes. One of the challenges in modeling cancer is how these mechanistic alterations can be reflected across scales and dimensions. What is the effect of these changes in a cellular or tissue environment? And moving up the scale how can these changes be monitored or study at the patient or population level? Contact: Dr. Jennifer Couch, 301-435-5226, [email protected]
Application of Novel Biological Model Systems to Cancer
. The use of Drosophila, Zebrafish,
and embryonic microenvironments for the study of cancer progression and for testing paradigms in cancer. Contact: Dr. Judy Mietz, 301-496-9326, [email protected]
Role of lymphangiogenesis in tumor invasion and metastasis.
While the research in the
area of tumor cell dissemination via tumor angiogenesis have become a fertile area of basic research resulting in the development of novel therapeutics such as Avastin, our knowledge in understanding the role of lymphatics and lymphangiogenesis in lymph node metastasis is extremely sketchy. Investigations that result in generation of novel lymphangiogenic models as well as deciphering novel signaling pathways of lymphangiogenesis and the role of lymphatics in distant or nodal metastasis is encouraged. Contact: Dr. Suresh Mohla, 301-435-1878, [email protected]
Application of the Microbiome to Cancer Understanding.
As the inventory of biological
agents in humans becomes realized it will be important to determine the role of these potential agents have in the development and progression of cancer. Contact: Dr. Kevin Howcroft, 301-496-7815, [email protected]
Infectious Disease and Inflammation in Cancer.
A number of infectious agents have been
directly implicated in cancer development. Research is needed to not only examine other potential biological agents but also how these agents can interact with the host to develop an environment of transformation. Contact: Dr. Kevin Howcroft, 301-496-7815, [email protected]
Cancer Cell Energy Metabolism and Cancer Causation.
Nutrients such as glucose and
amino acids are key signals of the signaling network that regulates the survival, growth, and proliferation of mammalian cells. Through a mechanism generally known as “nutrient sensing”, nutrients activate various signal transduction pathways that turn on or off cellular machineries to adapt accordingly. Defects in these signal transduction pathways often uncouples nutrient uptake and proper cellular response, which leads to physiological conditions including obesity that are cancer contributing factors. The objectives of this initiative are to identify metabolic networks distinct to cancer cells; to define the major regulatory nodes for cancer cell energy metabolism; to identify critical steps in adaptation of cancer cells to nutrient deprivation, for example
hypoxia; to define differences in metabolic pathways among cell and tissue types; to begin to understand the relationship between the incidence of cancer and the energy networks disregulated in diabetes and obesity. Contact: Dr. Barbara Spalholz, 301-496-7028, [email protected]
Chromosome Structure in Cancer Biology
. DNA is packaged in the nuclease in a
sophisticated way in order to control its transcription. New tools and imaging approaches are needed to characterize and understand these processes in the developing cancer. Contact: Dr. Judy Mietz, 301-496-9326, [email protected]
Telomere dysfunction in the development and progression of cancer.
Cancer cells have
lost their ability to manage the telomeric ends of their chromosomes leading to the inappropriate addition of telomere repeats by the maintenance enzyme telomerase and to genomic instability resulting from altered telomere structures. Understanding the mechanisms by which telomere dysfunction arises and contributes to the formation and progression of cancer can lead to the development of novel therapeutic treatments for cancer. Contact: Dr. Dick Pelroy, 301-496-9326, [email protected]
Cancer as a systemic disease.
In addition to the local changes in the tumor microenvironment,
several studies suggest that tumor cells induce systemic changes in the host that may promote tumor growth and accelerate metastatic dissemination. Understanding the molecular mechanisms of these pathways will provide novel prevention and therapeutic strategies. Key areas of priorities include: Genotype specific differences in angiogenesis, tumorigenesis susceptibility and risk of metastatic spread. Mechanisms to understand mobilization of bone marrow derived or mesenchymal stem cells by tumors. Mechanisms and clinical relevance of early cancer dissemination and tumor dormancy. Contact: Dr. Suresh Mohla, 301-435-1878, [email protected]
The role of bone marrow derived cells (BMDCs) in tumor initiation, progression and
Recent evidence suggests that the bone marrow derived or mesenchymal cells can contribute to
early tumorigenesis or promote or enhance organ specific metastasis. However the exact mechanism by
which this is accomplished is poorly understood. Investigators are encouraged to address critical issues in
understanding the role of BMDCs in promoting tumor growth in the primary site as well as promoting
metastasis in distant organs such as brain, lung, liver and bone. Contact: Dr. Suresh Mohla, 301-435-1878, [email protected]
Many investigators have demonstrated that tumor cells from the primary
organs can disseminate to distant sites early in cancer development and lie dormant for long periods of time before they can be activated to form distant metastases. However, there is a paucity of information as to nature of these dormant cells as well as mechanisms of their activation. There are several key issues in tumor dormancy, an increased understanding of which will help investigators design novel ways to block activation of dormant tumor cells or induce dormancy in active tumor cells. Our major areas of interests are to (1) delineate mechanisms of tumor dormancy in the bone marrow and other organs, and identify critical pathways of activation of dormant tumor cells; (2) identify novel pathways to induce dormancy in aggressive tumor cells and delineate mechanisms of dormant tumor cell activation in the brain microenvironment resulting in brain metastasis. Contact: Dr. Suresh Mohla, 301-435-1878, [email protected]
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NeuroImage 11, 334–340 (2000) doi:10.1006/nimg.1999.0536, available online at http://www.idealibrary.com on Differential Effects of Muscle Contraction from Various Body Parts onYung-Yang Lin,*,†,‡ Cristina Simo˜es,* Nina Forss,* and Riitta Hari* *Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, P.O. Box 2200, FIN-02015 HUT Espoo, Finland; † Neu