National Institutes of Health (NIH)
Funding Opportunity Title
Enhancing Tumoricidal Activity of Natural Killer (NK) Cells by Dietary Components for Cancer Prevention (R21)
R21 Exploratory/Developmental Research Grant Award
Reissue of PA-08-132
Funding Opportunity Announcement (FOA) Number
Catalog of Federal Domestics Assistance (CFDA) Number(s)
93.393, 93.396, 93.213
This funding opportunity announcement (FOA) is designed to stimulate research efforts aimed at establishing the physiological significance of dietary components in modulating the tumoricidal cell activity of natural killer (NK) cells for cancer prevention.
March 17, 2011
Open Date (Earliest Submission Date)
May 16, 2011
Letter of Intent Due Date
Application Due Date(s)
Standard dates apply, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Standard dates apply, by 5:00 PM local time of applicant organization.
Scientific Merit Review
Standard dates apply
Advisory Council Review
Standard dates apply
Earliest Start Date(s)
Standard dates apply
May 8, 2014
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This NCI-sponsored Funding Opportunity Announcement (FOA)
promotes research to characterize the significance of dietary components in
regulating the tumoricidal activity of natural killer (NK) cells for cancer
prevention. Specifically, this FOA encourages studies that can establish the
physiological significance of dietary components in modulating the tumoricidal
activity of NK cells. Research projects that are appropriate to this FOA should
focus on defining the minimum quantity and duration of exposure to specific
dietary components to modulate tumoricidal activity of NK cells for cancer
prevention and the underlying mechanism(s) accounting for this response.
Appropriate research projects are encouraged to include animal and/or human investigations. . In vitro models can be used only to support in vivo studies, and therefore, should not constitute the primary focus of the application. Molecular targets for food components may be examined at the sites of: 1) the tumoricidal cell receptors and cancer cell specific ligands; 2) the release of tumoricidal cytokines such as IFN-gamma; and 3) the release of lytic granules such as granulysin, perforin, and serine proteases (granzymes).
Related Funding Opportunity: Investigators, who are interested in proposing exploratory and developmental research projects, should submit applications in response to the partner FOA of identical scientific scope (PA-11-160), which uses the NIH Research Project Grant (R01) funding mechanism.
The growth and spread of cancer depend not only on the
biological characteristics of the tumor per se but also on the host responses.
NK cells represent one significant venue for influencing tumor growth and
metastasis. NK cells are large granular lymphocytes without B or T cell
characteristics; these cells are highly effective killers of both tumor cells
and virally infected cells without the need for prior sensitization or
recognition of a specific antigen. An important characteristic of cancer is
that the disease can overcome the surveillance of the immune system. One
possible explanation for this resistance (to immune surveillance) arises from
the ability of tumor cells to inactivate the tumoricidal activity of hosts NK
cells, thereby evading this first-line immune defense mechanism. Furthermore,
inappropriate changes in microenvironment caused by treatment with various
drugs, such as interferons (IFNs), and Interleukin-2 (IL-2) that can
up-regulate NK cell activity, result in their attacking both self and non-self
cells. Thus, it is extremely important to understand the early stage(s) of
tumor-host interactions, and redirect these events from a pro-tumor to an
anti-tumor state. Diet may represent a subtle approach to regulating NK cells
without losing their self-tolerance mechanism.
Several lines of preliminary evidence suggest that a number of bioactive food components can induce tumor cell death, possibly by enhancing NK cell activity. For example, extracts of the Maitake- (Grifola frondosa) and Brazilian sun- mushrooms (Agaricus Blazei) can enhance the cytolytic activity of NK cells in tumor-bearing mice. Likewise, dietary supplementation with 250 mg vitamin E/day (for 2 weeks) can enhance NK cell cytolytic activity in advanced colorectal cancer patients. In addition, the supplementation of vitamin E (administered at 100 mg/day for 8 weeks) restored NK cell activity in a 16 month-old boy with Shwachman-Diamond syndrome that is classically associated with a persistent reduction in NK cytolytic activity. However, these preliminary findings and rare cases are only suggestive of the involvement of dietary components in regulation of the tumoricidal activity of NK cells. The precise role(s) by which these and other dietary components influence NK cells, such as modulation of receptor-ligand interactions and/or the release of cytokines and lytic enzymes, remains largely unknown.
Both experimental and clinical data indicate an important role for NK cells in early neoplastic development, possibly by either responding to specific ligands generated by cancer cells, or to various types of extracellular or cell-associated proteinases. NK cells are known to exert their activity through a diverse repertoire of activating (e.g., NKG2 receptor family) and inhibitory (e.g., killer immunoglobulin-like receptor [KIR] family) receptors that recognize specific ligands on the surface of target cells. Many of the KIRs recognize major histocompatibility (MHC) class I molecules, which in humans are human leukocyte antigen (HLA) class I molecules. The KIRs provide protection for cells that express normal levels of MHC class1 molecules on their surface. In general, the co-ligation of activating and inhibitory receptors results in a net negative (i.e., no cytotoxicity) reaction. In contrast, the down-regulation of MHC class I in cancer, together with expression of specific ligands for activating receptors such as MICA, MICB, or UL16-binding proteins, enhances the sensitivity of target cells to NK cell-mediated cytotoxicity.
There is some evidence to suggest that certain dietary
components may modulate the NK cell activity in response to antigen stimuli.
For example, when C57BL/6J mice were maintained for eight weeks on Selenium
(Se)-deficient (~0.02 ppm), Se-normal (~0.20 ppm), or Se-supplemented (~2.00
ppm) diets, lymphocyte activity was differentially modulated; lymphocytes
isolated from animals maintained on the Se-supplemented diets had an enhanced
ability to destroy tumor cells compared with lymphocytes from animals that were
maintained on either a normal or Se-deficient diet. While these studies support
the general concept that specific dietary components can modify tumoricidal
activity of NK cells, the evidence largely remains indirect. Therefore, the
underlying mechanisms deserve additional study in order to develop and optimize
future intervention strategies.
Circulating NK cells are mature, as opposed to dendritic cells, which only mature during inflammation or infection. During early onset inflammation, immature dendritic cells secrete a variety of cytokines including tumor necrosis factor alpha (TNF-alpha), IL-2, and IL-12. These cytokines can induce a rapid expression of IFN-gamma and subsequently enhance the intrinsic cytolytic activity of NK cells. However, the response is complex since a T-Helper 2 (TH2) cytokine such as IL-4, which is generally viewed as an antagonist of IFN-gamma expression (in T cells), can induce signal transducer and activator of transcription 6 (STAT6)-dependent IFN-gamma secretion by NK cells. While some evidence suggests that specific bioactive food components (such as those derived from fermentable fibers and mushrooms) can modulate the release of various cytokines, it remains unclear whether these changes accompany a proportional alteration in the NK cell activity. NK cells, which can lyse tumor cells, provide antigenic cellular debris for mature dendritic cells to present to T cells; in later stages, NK cells terminate the process by lysing the dendritic cells and halting their ability for antigen presentation.
The lysosomal release of cytotoxic granules from NK cells, including two membrane-perturbing proteins such as perforin and granulysin, and a family of serine proteases (also known as granzymes), constitutes the main pathway for the immune system-mediated elimination of tumor cells. A number of studies indicate that dietary habits, including caloric restriction and alcohol consumption, may influence the cytolytic activity of NK cells by down-regulating the release, activity, and expression of perforin and granular proteases. Nevertheless, these observations need to be further characterized in mechanistic studies to establish a link between dietary modulation and cancer prevention.
NK cells, once activated, initiate the tumoricidal process through the release of both lytic granules and serine proteases (granzymes) or tumor-suppressive cytokines such as IFN-gamma, to mediate transformed cell death. Support for these findings comes from the inability of cytotoxic T lymphocytes (CTLs) to kill their target cells in either perforin-null or ashen mice that possess impaired granule pathway. Recently, genetically modified mouse cancer models have been extensively used for analyzing the occurrence of molecular events during the tumoricidal process. Analogous studies have also been conducted in humans with diseases caused by defects in tumor cell killing. Since a number of dietary components may influence NK cell tumoricidal activity, it would be prudent to use various models to establish the physiological significance of dietary components as either cancer protectants or modulators of cancer risk.
An example of the usefulness of the defined mouse model systems comes from studies using a recombination activating gene 2-deficient (RAG-2 -/-) mice. These mice fail to produce mature lymphocytes, which are critical for generating active forms of perforin and IFN-gamma. Consequently, RAG-2 -/- mice are highly susceptible to spontaneous development of adenocarcinomas in colon and lungs. Tumor growth in these genetically engineered mice was shown to be suppressed in response to dietary supplementation with Brazilian sun-mushrooms (Agaricus Blazei). A. blazei is an edible mushroom with anticancer activity native to Brazil; oral intake of A. blazei can enhance NK cell activation through IL-12-mediated IFN-gamma production.
Another mouse model includes deficiencies in STAT1 gene that is critical for the function of IFN-gamma. Double knockout animals of STAT1 -/- and RAG-2 -/- not only exhibit early onset of malignancy in colon and lung, but also demonstrate an exaggerated incidence of mammary cancers. In addition, mice with deficiencies in a subunit of IFN receptor expression (IFNAR -/-) were successfully used to demonstrate that endogenous Type 1 IFN is critical for controlling NK cell-mediated anti-tumor responses. These findings suggest that both IFN-gamma and perforin are critical in regulating some solid tumors. Therefore, the use of these models for determining the influence of bioactive food components on NK cell activity warrants further studies, given the literature evidence that several food items can modulate cancer risk, especially in cancers of the colon, lung, prostate, and mammary tissue.
The goal of this FOA is to encourage studies that can establish the physiological significance of dietary components in modulating the tumoricidal activity of NK cells for cancer prevention. The focus of the research should be on defining the minimum quantity and duration of exposure to specific dietary components to modulate tumoricidal activity of NK cells for cancer prevention and the underlying mechanism(s) accounting for this response. Both animal- and human- based investigations are appropriate to this FOA. Highly purified populations of immune cells, specific tumor cell lines, target cell-free systems, or single-cell assays may be used to define the molecular bases for diet-induced changes in NK tumoricidal activity. However, in vitro information can be used only to support in vivo studies, and therefore, should not constitute the primary focus of the application. Molecular targets for food components may be examined at the sites of: 1) the tumoricidal cell receptors and cancer cell specific ligands; 2) the release of tumoricidal cytokines such as IFN-gamma; and 3) the release of lytic granules such as granulysin, perforin, and serine proteases (granzymes).
A variety of technologies including those of genomics, proteomics, and metabolomics can be used to identify and characterize the molecular targets for dietary components, as well as the methods for monitoring tumoricidal activity of NK cells, which correlate with cancer prevention. The use of transgenic and/or conditional knockout mouse models that are associated with alterations in NK cell tumoricidal function is encouraged; several of these mouse models are available through the Mouse Models for Human Cancer Consortium (MMHCC). The efficient utilization of molecular resources such as gene, protein, and metabolome databases may be used to expedite the proposed research studies. Bioinformatics-based approaches may also be necessary to identify the complex patterns of alterations in genes, proteins, and metabolites, which can generate unique fingerprints for any given dietary treatments. Applicants are encouraged to use research information resources available at the NCI Center for Bioinformatics (NCICB).
NCCAM’s research interests relevant to this FOA include, but are not limited to, the following examples:
Natural products research supported by the National Center for Complementary and Alternative Medicine must comply with NCCAM’s Natural Product Integrity policy.
Application Types Allowed
The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year.
Award Project Period
The total project period for an application submitted in response to this funding opportunity may not exceed two years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions:
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For profit Organizations
Foreign (non-U.S.) components of U.S. Organizations are allowed.
Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
All Program Directors/Principal Investigators (PD/PIs) must
also work with their institutional officials to register with the eRA Commons
or ensure their existing eRA Commons account is affiliated with the eRA Commons
account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Project Director/Principal
Investigator (PD/PI) is invited to work with his/her organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the SF424 (R&R) Application Guide, with the following modifications:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.
Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review , NIH. Applications that are incomplete will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.
Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.
As part of the scientific peer review, all applications:
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board . The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
eRA Commons Help Desk(Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
Young S. Kim, Ph.D.
Division of Cancer Prevention (DCP)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 3156, MSC 7328
Bethesda, MD 20892-7328 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-0126
T. Kevin Howcroft, Ph.D.
Cancer Immunology and Hematology Branch
Division of Cancer Biology (DCB)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 5060, MSC 7388
Bethesda, MD 20892-7388 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-7815
Barbara C. Sorkin, Ph.D.
National Center for Complementary and Alternative Medicine (NCCAM)
6707 Democracy Blvd., Suite 401
Bethesda, MD 20892-5475
Bethesda, MD 20816 (for non-USPS delivery)
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Office of Grants Administration
National Cancer Institute (NCI)
6120 Executive Boulevard, EPS Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Phone: (301) 496-3160
George Tucker, M.B.A.
Chief Grants Management Officer
National Center for Complementary and Alternative Medicine (NCCAM)
6707 Democracy Boulevard II, Suite 401
Bethesda, MD 20892 (Courier Service 20817)
Telephone: (301) 594-9102
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
Department of Health
and Human Services (HHS)
NIH... Turning Discovery Into Health®
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.