It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (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

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for the establishment of Research Centers, one of the two units of the Translational and Basic Science Research in the Early Lesions (TBEL) program. The aim of the Research Centers is to integrate basic and translational cancer research studies to iteratively examine the direct causal relationships and interactions of an early lesion, its microenvironment, and host-systemic factors as co-organizers of tumor initiation (or suppression) and malignant progression in conjunction with the clinical characteristics of the lesions. The ultimate goals of the TBEL program are to further understand the biological and pathophysiological mechanisms driving or restraining precancers and early cancers and facilitate biology-backed precision prevention approaches.

The U54 Research Centers will serve as the scientific platform for the TBEL Program. Each Research Center will be comprised of a multi-disciplinary group and conduct basic and translational research projects supported by resource and administrative cores that can collectively enable the investigation of novel hypothesis-driven research questions and development of important resources and models, as well as hypothesis-generating comprehensive molecular and cellular analyses of early lesions in an integrated, iterative and synergistic structure. The Research Centers funded through this FOA are expected to work collaboratively and to facilitate the sharing of results, resources, technologies, materials and expertise within the TBEL network of investigators. TBEL investigators are also expected to develop trans-network collaborative projects that are based on the diverse expertise and capabilities across the TBEL Research Centers. The TBEL aims, among its many goals, to ensure that a broad range of tumor sites are represented in the program. Importantly, ethnic and racial diversity for retrospective and prospectively collected lesions is expected.

In addition to the Research Centers (this FOA), TBEL will include the Coordinating and Data Management Center (CDMC) supported by a companion FOA (RFA-CA-21-055). The CDMC will: 1) provide coordination of consortium-wide meetings and conferences, and cross-consortium collaborative activities; (2) provide statistical and computational analysis support; and (3) serve as a program data hub for data capture, curation and management, and protocol development.

Increasingly sensitive imaging/cancer-screening modalities have led to the detection of a significant number of precancers and early cancers, whose clinical management presents a serious challenge, as it is often not possible without an understanding of the underlying biology to distinguish those that will progress to aggressive disease (and require intervention) from those that will remain indolent (for which active surveillance may suffice). Despite the strong links between early lesions and cancer risk for many tumor types including colon, breast, head and neck and numerous clinical conditions ranging from chronic inflammation to obesity/metabolic disorders, and tissue stiffness/desmoplasia, only limited insights exist on the nexus between early lesion drivers and regulators of malignant progression. Elucidation of the basic mechanisms driving or restraining precancers/early cancers would allow differentiation and stratification between aggressive, potentially lethal cancers ( clinically important cancers ) and indolent types and further personalize care.

There is a strong inter-related basic and clinical justification to pursue a more integrated approach to understand what defines early cancer lesions and drivers or blockers of these lesions. Cancer screening reduces mortality from breast, colon, cervical, and lung cancer. However, screening also increases the likelihood of finding lesions that would have never progressed to cancer which are often over-diagnosed, over-treated and result in unintended morbidity, stress, and health care resource and access issues. For example, the sustained increase in incidence of pre-invasive and early stage breast and prostate cancer had no subsequent impact on late stage or metastatic disease in some populations. Furthermore, many additional lesions are identified incidentally ( incidentalomas ) through the increased use of diagnostic imaging procedures. The fraction of malignant incidentalomas identified by imaging is typically small but varies by organ, ranging from <5% for brain, parotid, and adrenal gland to more than 40% for breast. Regardless of how early lesions are found, the current standard of clinical care requires a determination of how the patient with a detected lesion will be managed. Many lines of evidence suggest that integrating basic biology and translational approaches is essential to understanding lesion dynamics and its progression. This integration will also necessitate expanding the focus beyond the early lesion to include the surrounding microenvironment as a co-organizer and enabler of progression and their dependence on clinical parameters such as age, systemic factors, tissue density/architecture, inflammation and/or immunocompetence. Focusing solely on molecular and genomic alterations in early lesions is insufficient especially if driver mutations commonly found in malignant lesions are also found in early lesions that do not necessarily progress to cancer or in normal tissues.

Validated cellular, molecular and biochemical features that define early non-progressing lesions from early aggressive lesions remain elusive and insufficient for appropriately managing the increased detection of early lesions including DCIS, early-stage prostate cancers, or melanoma precursor lesions and lung nodules. Efforts in systematically characterizing the early lesion more broadly and comprehensively by including microenvironmental components are also limited but will undoubtedly be instrumental in differentiating indolent from progressive lesions. Clinical and epidemiologic data also provide evidence that genetic factors, health conditions and systemic indicators of physiologic status (such as tissue density, inflammatory and other stress responses and immune competence) or the microbiome can act as modifiers and cofactors influencing early lesion trajectories. New -omics technologies (e.g., genomics, transcriptomics, epigenomics, proteomics, and radiogenomics) could yield a more comprehensive analysis of early lesions. Employment of these approaches will enable a multidimensional characterization of lesion heterogeneity and the identification of molecular, histological, and physical/architectural features that distinguish early, non-progressing lesions from those that will evolve to malignancy; and help establish direct causal relationships between cellular and molecular features and disease outcomes. Fortunately, retrospective cohorts of patients with early lesions are available that include longitudinally and serially collected biospecimens, imaging data, and cancer incidence and outcomes information.

The progression of an early lesion to malignancy is a complex process that can occur over a period of many years. At the basic biology level, evidence points to early- and later-stage tumor dynamics being governed by distinct mechanisms and pathways. An example of such context-dependent contradictory roles is transforming growth factor (TGF ), which is known to exhibit both tumor suppressive (early) and tumor promoting (late) roles. Likewise, autophagy can play an early tumor suppressive role via maintenance of tissue homeostasis in contrast to its late-stage cancer promotion role via both cell autonomous and non-autonomous mechanisms. Another example of context driving biology/disease progression is senescence, which can prevent the growth of premalignant cells and support immune surveillance. Senescence can also promote tumor initiation via transition of normal fibroblasts to cancer associated fibroblasts (CAFs) and induction of a field effect that facilitates the conversion of actinic keratosis to squamous cell carcinoma. Establishing early lesion models to study their complex environments, heterogeneities, and cooperativity with the surrounding stroma can potentially outline important biological distinctions for these lesions and ultimately inform their clinical management.

Chronic microenvironmental conditions can contribute to cancer risk, perhaps in a coordinated manner with the incipient mutant tumor cells. For instance, chronic pulmonary inflammation can initially drive DNA damage response, along with nitric oxide synthase and p53 induction in preneoplastic lesions, followed by epigenetic silencing of p16 as the lesion evolves to cancer, without necessarily acquiring classic driver mutations at the early stages of transformation. Also, studies have established links between the acellular stroma/extracellular matrix (ECM)-based microenvironment and epithelial cell survival, fate determination, indicating that both stromal content and architecture can modulate suppression/promotion of malignant conversion or even normalization of tumor cells. It will be important to comprehensively study driver pathways in early lesions within the context of the heterogeneous microenvironment that not only hosts and supports the incipient tumors but could also drive and shape its evolution/fate.

Systematic investigations that integrate basic biology and translational efforts to develop mechanistically informed signatures of early lesions (ranging from incipient lesion to stromal composition and heterogeneity) and their trajectories over time will allow the establishment of direct relationships between different subtypes of lesions and stromal cells, extracellular matrix and biochemical events in a clinically meaningful manner. This will not only provide a deeper understanding of the microenvironmental influencers (including clinically relevant systemic factors) that either block or drive a lesion progression to cancer but, importantly, identify biomarkers that could inform efforts to stratify patients more precisely along a continuum of risk progression and tailored treatment needs. Statistical modeling approaches that use data generated at the basic biological level together with data from omics technologies in patients with early clinical lesions may be also helpful in uncovering pathways and sequences of events that lead early lesions to progress. The TBEL program is designed to foster multi-disciplinary collaborations within each Research Center and across the TBEL Network to promote a deeper understanding of early lesions, their microenvironment, and reciprocal interactions that drive early lesion fate and clinical outcomes.

TBEL Administrative and Governance Structure (For Information Only)

TBEL will be structured around the two main units the Research Centers and the CDMC. Although individual teams of TBEL recipients (Research Centers and the CDMC) will operate independently, they will be required to interact closely with other TBEL recipients and engage in collaborative activities with them.

Steering Committee: The TBEL administrative structure and all activities will be governed by its Steering Committee, which will include representatives of the TBEL recipients and the NCI. The Steering Committee will be the governing body of TBEL that will integrate the efforts of all recipients and will provide oversight of collaborative activities. The Chair and co-Chair of the Steering Committee will be PDs/PIs of TBEL cooperative agreement awards and will be elected by the Steering Committee. Any member of the Steering Committee can offer nominations for the Chair and co-Chair.

Further details of the Steering Committee composition and responsibilities are provided in Section VI.2. Administrative and National Policy Requirements: Cooperative Agreement Terms and Conditions.

All proposed TBEL U54 Research Centers must include the following main attributes (for additional details on the requirements, please see Section IV Application and Submission Information).

Overall Research Focus. Each proposed Research Center must represent a multi-disciplinary basic and translational research program that can align with the scientific areas defined in this FOA.

The Research Center must have a combination of basic and translational projects (totaling 3 projects); and each application is expected to be classified by the applicant as either basic cancer biology research emphasis or translational research emphasis depending on whether the Research Center has a primary basic cancer biology research (and secondary translational) emphasis or primary translational research (and secondary basic cancer biology) emphasis as exemplified in Research Center Structure and Research Objectives below.

The Research Center program must focus on timely progress towards the specific objectives described in this FOA (i.e. better understanding of early lesions, their microenvironment and their reciprocal interactions that drive early lesion fate and biologically inform lesions stratification and clinical outcomes).

Research Team. Each team will have a multi-PI structure with appropriately diversified and complementary expertise spanning the basic-translational spectrum as needed to achieve a common overarching hypothesis and defined goals of the proposed Research Center. The team members must be willing and able to work collaboratively across the diverse scientific areas to ensure integration, synergy, and the successful conduct and completion of the proposed studies through an iterative basic-translational approach to testing and supporting the overarching hypothesis.

Research Center Structure and Research Objectives. Each Research Center will consist of a multi-PI structure and include the following components:

Research Projects - Three synergistic and complementary Research Projects with an overarching hypothesis/theme that emphasizes and integrates research across the basic/mechanistic and translational/prevention spectrum. Options are having two basic projects and one translational project or two translational projects and one basic project. The projects with basic and mechanistic emphasis will focus on the poorly understood and understudied area of early lesion and stromal/microenvironmental biology and identify new pathways of early lesion progression or indolence that shape disease outcomes. Projects with translational emphasis can pursue characterization of one or more aspects of molecular and cellular analyses in a specific tumor type or types to assess the degree to which behavior of these lesions towards indolence or progression to advanced disease and poor outcomes is predictable or stochastic, and to allow better predictions of the fate of such early lesions.

Administrative Core - The Administrative Core will facilitate project management, communications, and dissemination of results within the broader TBEL community and the NCI.

Resource Core(s) - The shared Resource Cores (1-2) will provide expertise and resources (e.g. models, biological specimens, imaging, pathology). The proposed core(s) should serve both basic and translational Research Projects.

Central to TBEL’s structural organization are team science approaches and supporting cores that iteratively bridge basic and translational research along the early lesion and microenvironment continuum to inform new strategies to overcome significant challenges in detecting, distinguishing and managing aggressive from indolent lesions. Examples of translational, basic, and core activities that may help establish multi-disciplinary Research Centers are as follows:

TBEL's early lesion translational research specific interest areas include but are not limited to the following:

• Multi-omic evaluation (genomic, transcriptomic, proteomic or metabolomic) of recurrent and non-recurrent screen-detected lesions, incidentalomas, and interval cancers to determine whether a subset of aggressive, screen-detected lesions shares features with interval cancers that predominantly exhibit rapidly progressing phenotypes.
• Analysis of tumor heterogeneity within lesions, by single cell analyses, to determine whether aggressive lesions can be distinguished based on the extent of their heterogeneity.
• Phenotyping of the cellular components of lesions, including the incipient tumor cells and lesion-associated-cells in the microenvironment with the goal of generating molecular signatures to detect highly proliferative early malignant lesions associated with increased cancer-specific mortality.
• Detection of secreted factors in microenvironment and/or in serum specific to a subset of early lesions.
• Detection and characterization of changes over time in sequential images from patients with lesions to elucidate dynamic changes occurring during progressive disease and provide insights into molecular and cellular events intimately associated with lethal cancer versus non-lethal disease.
• Development of image reproductions using Artificial Intelligence and Deep Learning Language of hard-to-read, early stage-lesion histological and radiological images for better visualization and interpretability.
• Statistical model development and testing to better distinguish indolent from aggressive lesions in certain settings such as routine cancer screening, in groups at high risk of aggressive lesions, and involving other cofactors and modifiers.
• Studies that identify determinants of risk in persons with predisposing medical conditions such as inherited immunologic disorders, pancreatic cysts, liver fibrosis, or gastrointestinal lesions.

TBEL's early lesion basic biology research specific interest areas include but are not limited to the following:

• Mechanisms of cell-cell and cell-ECM-based changes and/or aging-associated tissue/microenvironmental alterations that may influence transformation, malignant progression and/or indolence.
• Stromal/microenvironmental mediators of chronic inflammation, metabolic crosstalk, and/or phenotypic switching/cellular plasticity that may influence transformation and malignant progression.
• Lesion/Stromal/Microenvironmental landscape of lesion drivers and suppressors based on position-dependent functional organization/plasticity/heterogeneity.
• Microenvironment-centered effects on incipient tumor cells related to hormones/growth factors, DNA repair or DNA damage response, cell death and survival pathways, cell cycle regulation, senescence/SASP-induced field effect, epigenetic DNA modification and/or genomic instability.
• Organelle, ECM and extracellular vesicle-mediated dynamics that can facilitate stromal/microenvironmental interaction with the evolving tumor, including mitochondrial function/genomic status and stroma cell-tumor cell transfer.
• Application of systems approaches and modeling using experimental omics data to define disease dynamics ; e.g., trajectories of each lesion(s) growth rate, genetic and phenotypic evolution, and corresponding risk of development of clinically-significant malignancy.
• Early lesion and stromal/microenvironmental collaborations as modulators/fate-determinants of indolence/malignant progression.
• Identification of the unique stromal/microenvironment-tumor blockers and drivers of tumor evolution and heterogeneity at distinct phases of a lesion.
• TBEL's resource core-supported activities include but are not limited to the following:
• Cataloguing the availability of screen-detected lesions and interval cancers from participating components in each Research Center and their institutional resources and from prospectively collected samples.
• Establishing organoid co-cultures or patient-derived xenografts from screen-detected lesions and/or incidentalomas, which maintain the original architecture of the lesion-microenvironment, to allow sufficient expansion for a detailed molecular analysis that could include RNA expression profiles, ncRNA, proteomics, metabolomics, cell surface markers, secreted exosomes, DNA methylation, and others.
• Development of novel or repurposed early lesion platforms to trace and interrogate complex ECM-stromal cell-nascent tumor cell interactions in malignant transformation along with companion human tissues (biopsies from clinical trials, rapid autopsies, or patient-derived models).
• Implementing computational and systems biology infrastructure to develop in silico tumor evolution models.

Each Research Center is expected to work collaboratively with other TBEL-supported Research Centers and the CDMC and to facilitate the sharing of results, resources, technologies, materials and expertise within the TBEL network of investigators. TBEL investigators are also expected to develop post-award trans-network collaborative projects using restricted funds initiated in years 2-5 of the program that are based on the diverse expertise and capabilities across the TBEL Research Centers. Such collaborative projects may include non-TBEL investigators to leverage necessary expertise and resources for achieving the TBEL objectives. The TBEL program aims, among its many goals, to ensure that a broad range of tumor sites are represented in the program. Importantly, ethnic and racial diversity for retrospective and prospectively collected lesions is expected.

Data Science

TBEL program components share a mandate to develop an understanding of mechanisms that drive or restrain early lesions based on integrated basic and translational cancer research studies. Given the high-content data-intensive nature of this work, it is expected that members of the TBEL program will adhere to data management and sharing policies developed in conjunction with NCI staff within the Cooperative Agreement environment that facilitate harmonization and interoperability of multiscale data and diverse data types. This will poise TBEL as a unique contributor of multi-modal precancer/early cancer data at the intersection of both basic cancer biology and translational research to the broader National Cancer Data Ecosystem. In leveraging existing data infrastructures, it is anticipated that TBEL will become increasingly engaged in alliances with other data-intensive programs (e.g., Cancer Systems Biology Consortium, Human Tumor Atlas Network, Acquired Resistance to Therapy Network, Radiation Oncology-Biology Integration Network, Pancreatic Ductal Adenocarcinoma Stromal Reprogramming Consortium, NCI-DOE Joint Design of Advanced Computing Solutions for Cancer) as the network matures, creating additional opportunities for collaboration and scientific discovery consistent with the goals of the cancer data ecosystem.

Applications will be considered non-responsive to this FOA based on the criteria described below. Non-responsive applications will not be reviewed.

• Applications that do not focus on early lesions;
• Applications that lack either basic or translational projects;
• Applications that fail to integrate basic and translational projects as described in Research Center Structure and Research Objectives above.

Note: NCI will hold a pre-application informational webinar for this FOA. When published, the related Notice will be linked with the FOA.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) 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 SF424 (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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Submitted applications in response to this FOA must correspond to different PDs/PIs.

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Elisa Woodhouse, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6220
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Project (use for each project)	12
Core (use for each Shared Resource)	6

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Projects: 3 required (2 basic and 1 translational or 1 basic and 2 translational)
• Core: minimum 1 required; maximum 2

When preparing your application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Describe the overall specific aims of the proposed TBEL Research Center. The Specific Aims should be overarching and distinct from the aims of the individual components. It should be clear how the aims will integrate basic biology and translational perspectives.

Research Strategy: Provide an overview of the proposed Research Center. Address all the specific aspects indicated below using the sub-sections as defined:

Sub-section A: Research Center Framework. Describe the overarching organizational framework and vision of the proposed Research Center, its scientific focus, strengths, and leadership in the research field. The framework must also establish either a primary basic research or primary translational research emphasis as described in Specific Research Objectives and Requirements above.

Sub-section B: Research Team Organization and Integration. Describe the overarching structure of the Research Center team. Describe how the individual expertise of team members (e.g. cancer biology, molecular medicine, clinical/experimental pathology, computational biology, bioinformatics, others) complement each other to support the TBEL Research Center and how the team's diverse expertise translates to a collective capability for accomplishing the goals of the proposed Center's research. Highlight how this team increases the capability for innovation, anticipating new directions and redirecting research if/when needed. Explain how this team allows the integration of the basic and translational projects of the Research Center as one unified entity that is greater than the sum of its individual parts in terms of ability to advance the research area (i.e., how the multi-disciplinary team members will function in an integrated, synergistic, and iterative fashion). Describe collective experience and capabilities in areas pertinent to leading, coordinating, managing and understanding the various needs of the team and the projects; and how the elements of the Research Center, including key personnel, will interact to realize this vision. Provide a strategy for integration of new investigators and/or technologies into the Research Center structure and environment. Without repeating information in other sections, explain how any ongoing grant-support, institutional, and/or private sector resources can augment or complement resources for which funding from this FOA is sought.

Sub-section C: Individual Research Projects. Outline the rationale for the proposed research projects, their innovative thinking, reasons for their inclusions, and how they inform and integrate with one another and the objectives of this FOA. Three research projects with basic/translational focus as outlined in Specific Research Objectives and Requirements must be proposed.

The Research Center project requirements are dependent upon whether the overall emphasis is on basic cancer biology research or translational research for which distinct and non-overlapping criteria apply.

For Basic Cancer Biology Research emphasis Centers:

Applications should describe:

Criteria and justification for early lesion designation involving comprehensive lesion and microenvironmental parameters.

Relevance and proposed use of disease-appropriate models to recapitulate early lesion progression and/or indolence;

Robustness/feasibility of genetic, biochemical, and pharmacologic approaches to mechanistically dissect early lesion-microenvironmental dynamics as co-organizers in fate determination;

Rationale for inclusion and prioritization of regulatory factors, signaling nodes, and paracrine/autocrine communication and their role and biological significance in modulating lesion evolution;

Availability of human platforms for initial proof-of-concept translational potential of putative biological leads (please see first and third bullets below for guidance on how to define early lesions when appropriate and the importance of diversity, respectively).

For Translational Research emphasis Centers:

Applicants must define early lesion within a specific clinical context and establish eligibility in reference to screen-detected, incidentally detected, symptom-detected and/or interval cancers. They may propose the use of retrospective and/or prospective biospecimens. In addition, detailed cohort and clinical information must be provided including length of follow-up, endpoints, and how the endpoints were ascertained (cancer progression, death, cause of death). Autopsy specimens, especially for indolent cases, can also be used in experimental designs. In cases where autopsy series samples are proposed, procedures for acquiring samples and obtaining clearances from State and regulatory authorities, including those from an institutional review board (IRB), must be submitted.

Preclinical model systems (e.g., organoid cultures or xenografts) must be used to complement experimental designs in humans to understand underlying mechanisms driving early lesion biology towards indolence or malignancy.

Demonstrate access to biospecimens from diverse and minority populations that are representative of the race/ethnic diversity in the United States. Address any opportunities that exist and, if implemented, can narrow the gaps in health disparities among racially/ethnically diverse populations, who continue to suffer disproportionately from certain cancers and have higher cancer incidence.

For cancer types where there is no screening program in place, cross-sectional samples derived from routine examinations, e.g., community health providers, health maintenance organizations, etc., can be used, provided there were reasons for examinations, as well as presence of signs (clinical, radiological) and symptoms before the testing event. In case of incidental findings, the case could be considered as screen-detected if there were no associated symptoms.

Describe any employed statistical modeling approaches that use data generated from basic biology studies together with high-throughput -omics data from early clinical lesions to uncover pathways and sequences of events that lead early lesions to progress. The different degree of admixture between aggressive versus indolent disease among screen-detected and interval detected lesions offers a possibility to use statistical modeling to elucidate determinants of indolent versus aggressive disease. Describe any additional information available to further enhance statistical models, such as innovative sampling designs and inclusion of study populations with specific health characteristics, hereditary conditions, demographic characteristics, screening history, outcomes after the cancer was diagnosed, and exposures to potential modifiers of lesion aggressiveness.

Applicants should provide clear statements of how tests for different microenvironment components and other factors related to tumors in screen-detected, symptom-detected, interval and incidental cancers are adjusted for multiplicity. It should be clear whether the proposed design is to control for family-wise Type I error rate or control false discovery rate. Also, there needs to be a clear statement of how statistical power is defined in multiple tests and what sample size is required to achieve this power. In case-control study designs, there need to be clear definitions of whether matching is involved and what confounders are adjusted for and why.

Sub-section D: Shared Resource Core(s). Briefly explain the need for the Shared Resource Core(s) and indicate the specific Research Projects that will be supported by the core(s).

Letters of Support: Include a letter of support from an institutional official endorsing the proposed TBEL Research Center and describing available institutional resources to support the Center Research. Also include letters from investigators who will serve as consultants or collaborators on the project but with no measurable efforts. Do not include letters from investigators who will have committed efforts in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

A Resource Sharing Plan should be provided only under the Overall component, but it should cover all the activities proposed for the TBEL Research Center.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Leader and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The contact PD/PI of the TBEL Research Center should serve as the Administrative Core Leader.
• A qualified Core administrator should be appointed to manage the daily activities of the TBEL Research Center. In additional Senior/Key section, provide the role under 'Other Project Role Category' as 'Core Administrator'
• A senior statistician should be included in this Core to provide statistical support for the Research Center. In the additional Senior/Key section, provide the role under 'Other Project Role Category' as 'Statistician'.

Budget forms appropriate for the specific component will be included in the application package. The budget should account for the efforts of the Core Leader, Core Administrator, Statistician, and other Key Persons.

Leadership Effort Commitment: The TBEL contact PD/PI must commit and maintain through the life of the award a minimum of 2.4 person-months effort if the Research Center contact PD/PI is also an individual Research Project leader. The required levels of effort may reflect an aggregate of effort for the entire TBEL (listed here under Administrative Core) and the efforts for other TBEL components, as applicable.

Collaborative Project funds: The budget should include funds (15% of the overall Research Center annual budget) for collaborative projects between TBEL Research Centers or with external/non-TBEL funded collaborator(s) for years 2-5. The use of collaborative project funds will be restricted and must be reviewed and approved by the TBEL Steering Committee followed by NCI concurrence for the individual awards. The collaborative project funds should be listed in the Other Expenses category under the heading "Collaborative Funds".

Travel Funds: The budget should include travel funds for the PD(s)/PI(s) to attend two semi-annual TBEL Steering Committee meetings per year and participate in other network-related activities.

Other: It is expected that funds will be allocated to open-access publishing.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the goals of the Administrative Core.

Research Strategy: Address the specific aspects indicated below using the sub-sections as defined:

Sub-section A) Core Structure. Outline the organization and function of the Administrative Core. Incorporate the plans for specific administrative activities of the Research Center including, but not limited to, progress reports, monthly meetings and teleconferences, development of a Center advisory group, travel for the PD(s)/PI(s) and team leaders to scientific meetings, and other activities. Describe the plans for coordination and communication with the TBEL Coordinating and Data Management Center and NCI scientific staff. Finally, describe the plans for participation in the TBEL Steering Committee and in cross-TBEL activities.

Sub-section B: Research Center Organization, Communication and Data Integration. Describe strategies for project management that will ensure effective coordination, communication, synergy and integration among the functions of the three research projects and the resource core(s) in the Research Center spanning the translational and basic continuum. Briefly describe plans for coordination and communication among the multi-disciplinary team members. Also describe how the Research Center will interact, integrate and coordinate its activities with other Research Centers, the CDMC, and NCI program staff, including the management, harmonization, and interoperability of the diverse multiscale data to be generated. Mention the lead person for each level of communication.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Project.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• The Project Lead must dedicate at least 1.8 calendar months effort to the project for the life of the award. If the project has multiple leads, then each must dedicate at least 1.2 calendar months effort to the project for the life of the award.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For projects with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other(Specify)' and designate the role under 'Other Project Role Category' as "Project Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Project Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget forms appropriate for each individual research project should be included in the application package. The Project Lead must dedicate 1.8 person-months effort to the project for the life of the award. If the project has multiple leads, then each lead must dedicate at least 1.2 calendar months effort to the project for the life of the award.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the goals of the proposed research project.

Research Strategy: Applicants should use the standard structure of the Research Strategy section (i.e sub-sections Significance, Innovation, Approach)

Within these sub-sections, address the following additional aspects of each project:

Provide a concise description of how the Project is integrated within the Center's research goals and contributes to the overall TBEL research theme.

Indicate how the project team will take advantage of the Research Center infrastructure to allow for new approaches or perspectives to be implemented or tested, especially as it relates to bridging the basic and translational aspects of the Research Center.

If the Research Project will use the Shared Resource Core, describe how the Core capabilities impact the performance of the proposed project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. Resource Sharing Plans should only be provided in the Overall component of the application.

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For Cores with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget forms appropriate for each individual Core should be included in the application package.

The Core Lead(s) must each commit and maintain through the life of the award a minimum of 0.6 person-months effort per year. If there are multiple co-leads, it is not necessary that each commit equal effort to the project.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Outline the specific aims of the Shared Resource Core and list projects that will be supported by the specific Core.

Research Strategy: The Shared Resource Core may be physical or virtual infrastructures providing a biological, pathological, imaging, computational or engineering resource that supports other Center components in their activities. Each Shared Resource is expected to support two or more Research Projects and the services, support, and/or resources to be provided to other Research Center components should be clearly defined. Issues to be addressed include:

Value of the Core services to the Research Center and Research Projects;

Integration between the Core and Research Projects;

Procedures for selecting Research Projects to use the Core, including allocating resources, cost effectiveness, and increased efficiency; and

Quality control measures.

Any proposed new shared resources must not duplicate analogous resources already established in the applicant institutions. If existing cores and resources are to be used, then funding to augment such existing resources may be requested. Description of how work related to the Center will be prioritized within such a core must be provided.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Resource Sharing Plans should only be provided in the Overall Component of the application.

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date 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 SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(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 System for Award Management (SAM). 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 and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this FOA, note the following:

Reviewers will provide an overall impact score for the entire TBEL Research Center (Overall component) and for each individual Research Project. In addition, assigned reviewers will provide individual "criterion scores" for the Overall criteria and the Research Projects criteria, but not for the other components.

All other components of the Research Center [i.e., Administrative Core, Shared Resource Core(s)] will be evaluated but each will receive only one overall adjectival (not numerical) score.

For the evaluation of the TBEL Research Center application, the Research Projects will be assessed as the scientific basis of each Research Center, with additional components enhancing and integrating the overall research program. The overall Impact Score will reflect the synergy and integration across the Research Center, especially integration between the basic and translational aspects.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the TBEL Research Center 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 Research Center 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 Research Project that by its nature is not innovative may be essential to advance a field.

Does the TBEL Research Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the TBEL Research Center 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?

Specific to this FOA: Will the scientific framework, organization, and research focus of the proposed Research Center enable a unique and significant understanding of early lesion biology, including the role of microenvironment, as well as the growth trajectory of a lesion to inform effective approaches to precision intervention? Is the requirement for the Research Center structure to accomplish the proposed goals of the program well-articulated? Are the proposed concepts and studies addressing important challenges that would close current knowledge gaps across the basic and translational spectrum that will helpovercome barriers to clinical management of early lesions? Are the Research Center's basic and translational components well integrated and conducive to an iterative basic to translational and back again framework to collectively support the overarching goal of the Research Center and the vision of the TBEL program? Do the proposed resource cores serve the needs for both basic and translational research projects?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the TBEL Center? If Early Stage Investigators or those 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?

Specific for this FOA: Are the expertise and commitments of the PD(s)/PI(s) and other key persons sufficient for the proposed scope of activities and in line with the goals of the TBEL program? Are the roles and responsibilities of multiple PDs/PIs well defined, adequate, and complementary for achieving the goals of the proposed Research Center? How well do the proposed collaborations between the Research Center's PD(s)/PI(s) and other key persons integrate the Research Center's structure to achieve the overarching research goals?

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?

Specific for this FOA: Does the proposed Research Center employ novel concepts, approaches and/or methods to support a basic-translational cancer research continuum? Furthermore, does it inform future early lesion management/interventions that are biology-backed and comprehensive, multi-dimensional, and appropriate for the degree of malignant potential of the lesions?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Research Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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 managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Research Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA: Does the proposed Research Center take advantage of its multi-disciplinary structure, expertise, and resources to advance the understanding of the biological mechanisms and behaviors underlying early lesions, from biochemical, molecular, cellular, and organismal biology to risk stratification/prevention? Are the overall goals, experimental design, methods, and capabilities sound and well developed? Are effective mechanisms in place to foster strong collaborative interactions and promote "cross-fertilization" among investigators?

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?

Specific to this FOA: Will the scientific environment at the participating institutions stimulate multi-disciplinary research collaborations?

As applicable for the Research Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the 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 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 Guidelines for the Review of Human Subjects.

When the proposed Research Center involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. 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.

Not Applicable

Not Applicable

Not Applicable

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 score.

Not Applicable

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).

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) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

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. Please see more details on the structure of the Research Project in Section IV.2 Overall Component, Sub-section C.

Significance

Does the research project address an important problem or a critical barrier to progress in the basic and translational early lesion field? Is the data that serves as the key support for the proposed project rigorous? If the aims of the Project’s research are achieved, how will it inform the under-explored early lesion and microenvironment basic biology, and improve scientific knowledge, technical capability, and/or clinical practice? How will successful completion of the aims change or inform the concepts, methods, technologies, or preventative intervention that drive this field?

Investigator(s)

Are the Lead investigators, collaborators, and other researchers well suited for the proposed research? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments and collaborations that have advanced their field(s)? If the project is collaborative or multi-Lead, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the project challenge and seek to shift current basic and translational 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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center’s project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed research? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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 managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the research project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done (either at a single institution or in a multi-institutional collaborative arrangement) 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?

Review Criteria-Administrative Core

Reviewers will provide only one overall adjectival impact score for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of the application:

As described for the Administrative Core, are the management and collaborative capabilities of the proposed leadership structure of the Center well in place and evident? How appropriate are the leadership structure and activities of the proposed Administrative Core in terms of facilitating: (a) achievement of the overall goals of the Research Center; (b) integration across the Research Projects and Core(s) participating in the Research Center; and (c) collaboration in cross-TBEL activities?

Reviewers will provide only one overall adjectival impact score for the Shared Resource Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of the application:

• How well is the proposed Shared Resource Core matched to the needs of the overall Research Center? Are the services of the Shared Resource Core essential to the goals of more than one Research Project? Is the core well equipped to develop novel early lesion research platforms in support of the proposed objectives?
• Are the qualifications, experience, and effort commitment of the Shared Resource Core Director(s) and other key personnel adequate and appropriate for providing the proposed facilities or services?
• Will the proposed Shared Resource Core provide cost effective services to the Research Center, prevent duplication, and/or increase efficiency?
• What is the overall quality level of the proposed Core services and technologies and the rigor of the processes for quality control/assurance?

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NCI in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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 Policy Statement.

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 recipient’s 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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Participate in the annual TBEL Steering Committee meetings, monthly conference calls organized by the TBEL Coordinating Center, and collaborative TBEL activities;
• Participate in scientific working groups to facilitate TBEL research and program objectives, including collaborative pilot projects and validation of experimental concepts and observations;
• Promote trans-TBEL and external collaborations to advance early lesion basic-translational research;
• Abide by the governance of the TBEL and all program policies agreed upon by the TBEL Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations;
• Report progress to the NCI Program Officials on all TBEL research and activities annually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by NCI program staff members;
• Ensure that data are deposited in a timely manner in appropriate publicly available databases, and that models, software, and other tools and resources developed as part of this Research Center are made publicly available according to TBEL policies;
• Ensure that results of the Research Projects are published in a timely manner.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
• Awardees will be expected to participate in an external TBEL program evaluation process that will be coordinated by NCI Scientific staff.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

Designated NCI Program Directors serving as Project Scientists/Coordinators will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. Additionally, an NCI program director acting as Program Official will be responsible for the standard scientific and programmatic stewardship of the award and will be named in the award notice. The specific roles of the substantially involved NCI staff members include the following activities:

• Serve as the NCI lead Project Scientists and voting members of the TBEL Steering Committee;
• Serve as a liaison for TBEL in promoting interactions with other ongoing NCI activities and programs that may be relevant to the goals of TBEL;
• Assist in avoiding unwarranted duplications of effort across the TBEL Program;
• Facilitate collaborative research efforts that involve multiple TBEL Research Centers and the CDMC;
• Evaluate the effectiveness of the program and facilitate program-wide adoption of resources, policies, and practices;
• Monitor operations of the TBEL recipients and make recommendations on overall project directions and allocations of TBEL Research Center funds;
• Monitoring the progress of individual Research Centers and the CDMC on the program goals and specific activities shared among the Research Centers and the CDMC;
• Participate in organizing annual TBEL Steering Committee meetings, and other specialized workshops, and webinars;
• Review the compliance of TBEL recipients with the recommendations developed by the Steering Committee;
• Coordinating the external evaluation of the TBEL program;

Areas of Joint Responsibility include:

TBEL will have a Steering Committee as a governing body. The TBEL Steering Committee will consist of the following voting members:

• The PD(s)/PI(s) and Project leaders of each awarded Research Center who will collectively have one vote;
• The PD(s)/PI(s) of the CDMC and a designated senior investigator who will collectively have one vote; and
• The NCI Project Scientists/Coordinators who will collectively have one vote for the NCI.

Additional NIH/NCI program staff and other government staff may participate in TBEL Steering Committee meetings as non-voting members. The structure is designed to allow awarded investigators and NCI staff to work together to facilitate trans-TBEL activities based on synergistic expertise and projects.

Two PD(s)/PI(s), representing two different TBEL awards, will be selected to serve as chairs of the Steering Committee starting at the first meeting of the Steering Committee following award issuance. Chairpersons will be subject to a full rotation to two new chairs midway through the third year of the program. All TBEL Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The Steering Committee will meet twice a year, at locations selected by the Steering Committee in consultation with the NCI.

Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members.

The Steering Committee will have primary responsibility for:

• Establishing sub-committees for specific purposes as necessary to ensure progress of the individual Research Centers, Projects, and the entire Network. The NCI Project Scientists/Coordinators and other NCI program directors will serve on such sub-committees, as they deem appropriate.
• Setting the overall research priorities for the TBEL initiative; and identifying emerging research opportunities which can be best explored through a joint collaborative effort via the Network;
• Reviewing the potential of shared support infrastructure(s) at individual Research Centers to serve the needs of other Research Centers and the TBEL program;
• Developing procedures for soliciting and evaluating ideas for pilot projects across TBEL, as well as criteria for their prioritization and approval;
• Ensuring that the Research Centers and CDMC leverage existing NCI and NIH resources and programs;
• Participating in the development of the agenda for the Steering Committee meetings to present scientific progress and future plans from TBEL investigators;
• Coordinating the dissemination of TBEL findings, data, and resources to the broader cancer research community.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting; one NIH designee; and a third designee with expertise in the relevant area who is chosen by the other two. In the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

For Cancer Biology Research Questions:

Elisa Woodhouse, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6220
Email: [email protected]

Rihab Yassin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6230
Email: [email protected]

For Translational and Prevention Research Questions:

Christos Patriotis, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7134
Email: [email protected]

Sharmistha Ghosh-Janjigian, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7122
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Amy R. Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6912
Email: [email protected]v

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, 45 CFR Part 75, and 2 CFR 200.