National Institutes of Health (NIH)

Slots: Each eligible institution (defined as having a unique UEI number or NIH IPF number) may submit up to a combined total of four applications (one in Cancer Data Science, one in Cancer Control Science, one in Molecular/Precision Cancer Prevention, and one in Other Cancer Research) to any companion NOFO or any combination of companion NOFOs (PAR-23-286, PAR-23-287, and/or PAR-23-288).

Deadlines

Internal Deadline: Friday, March 14th, 2025, 5pm PT Contact RII.

LOI: N/A

External Deadline: June 16, 2025

Recurring Deadlines: October 14, 2025; February 17, 2026; June 15, 2026; October 14, 2026

Award Information

Award Type: Grant

Estimated Number of Awards: The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Anticipated Award Amount: Award budgets are composed of salary and other program-related expenses, as described in “Other Award Budget Information” of the RFA.

Who May Serve as PI: 

NOTE: Candidates for this NOFO are strongly encouraged to obtain confirmation of their eligibility from NCI before seeking institutional nomination. It is incumbent upon the candidate to provide evidence that all eligibility criteria have been met.

Any candidate with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to seek institutional nomination and work with his/her mentor and 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. See, Reminder: Notice of NIH’s Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019. Multiple PDs/PIs are not allowed.

K99/R00 candidates must have no more than 2 years of postdoctoral research experience as of the relevant application due date. Individuals must be in mentored, postdoctoral training positions to be eligible for support under to the K99/R00 program. If a candidate achieves independence (i.e., any faculty or non-mentored research position) before a K99 award is made, neither the K99 award, nor the R00 award, will be issued.

Consistent with the NIH Extension Policy for Early Stage Investigator Status (ESI), NIH will approve an extension of one year for childbirth within the 2 year K99 eligibility window. Applicants with candidates who will be PD/PIs on a K99 application must provide the child’s date of birth in the extension request justification submitted to IC program officials and/or scientific/research contacts listed in the NOFO at least 12 weeks before submitting an application.

In addition, parental, medical, military, or other well-justified leave for personal or family situations of generally less than 12 months duration is typically not included in the 2-year eligibility limit, nor is clinical training with no research involvement (e.g., full-time residency training). Only time dedicated to research activities counts toward the 2-year limit. Part-time postdoctoral research training, related to personal or family situations or occurring during a research residency or fellowship, will be pro-rated accordingly.

Additional clarifications are provided under Frequently Asked Questions. Potential candidates are encouraged to discuss their individual situation with an NCI Scientific Program Contact before applying.

There is no citizenship requirement for K99 applicants. An applicant may be a citizen or a non-citizen national of the United States, have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status), or be a non-U.S. citizen.

For applications submitted on behalf of non-U.S. citizens with temporary U.S. visas, visa status during each phase of the K99/R00 award must allow the PD/PI to conduct the proposed research at the applicant institution. For the K99 phase of the award, the applicant institution is responsible for determining and documenting, in the K99 application, that the candidate’s visa will allow him or her to remain in the U.S. long enough to complete the K99 phase of the award. For the R00 phase of the award, the U.S. institution at which the R00 phase of the award will be conducted is responsible for determining and documenting, in the R00 application, that the PD/PI’s visa will allow the PD/PI to remain in the U.S. for the duration of the R00 award.

Candidates for the K99/R00 award must have a clinical or research doctorate (including PhD, MD, DO, DC, ND, DDS, DMD, DVM, ScD, DNS, PharmD or equivalent doctoral degrees). Clinicians (including those with MD, DDS, DVM and other licensed health professionals) in a clinical faculty position that denotes independence in clinical responsibilities but not in research may also be eligible for the K99/R00 award.

Individuals are NOT eligible if they:

• Have currently or previously held an independent research faculty or tenure-track faculty position, or its equivalent, in academia, industry or elsewhere; or
• Have more than 2 years of related postdoctoral research training at the time of initial application or resubmission; or
• Have been an independent PD/PI on NIH research grants (e.g. R01, R03, R21), NIH career development awards (e.g., K01, K07, K08, K23, K25), or other peer-reviewed NIH or non-NIH research grants over $100,000 direct costs per year, or Project Leaders on sub-projects of program project (P01) or center (P50) grants or the equivalent.

Ph.D. (or equivalent research doctorate degree) candidates in positions other than postdoctoral fellow positions: It is recognized that some institutions appoint postdoctoral fellows in positions with other titles although they are still in non-independent, mentored training positions. Candidates in such positions are encouraged to obtain confirmation of their eligibility from the relevant IC before they begin to prepare their applications. It is incumbent upon the candidate to provide evidence that their position complies with the intent of this eligibility requirement. If a potential applicant is in a position that is not clearly identifiable as a postdoctoral training position, candidate should provide the relevant NIH Institute or Center an official statement of the institution’s policy (e.g. published position description in an official institutional document) which documents the position as a mentored, postdoctoral training position.

Clinicians (including those with M.D., D.D.S, D.V.M. and other licensed professionals) in positions not designated as postdoctoral positions: Following clinical training or fellowship training periods, clinicians often obtain a clinical faculty position that denotes independence in clinical responsibilities but not in research. A clinical faculty member who does not hold an independent research faculty position may be eligible for the K99/R00 award, and should contact a Program Director at the relevant NIH Institute for guidance. Clinicians in such positions are encouraged to obtain confirmation of their eligibility before they begin to prepare their applications. Such individuals may also wish to consider other career awards (see K Kiosk) available for junior faculty development.

The following is provided as an aid to distinguish independent from non-independent positions: However, it is not sufficient merely to cite one or more of the following items to document eligibility.

Evidence for non-independence may include:

• The candidate’s research is entirely funded by another investigator’s grants.
• The candidate’s research is conducted entirely in another investigator’s assigned space.
• According to institutional policy, the candidate cannot hire postdoctoral fellows or technical staff or be the responsible supervisor of graduate students.
• According to institutional policy, the candidate is not allowed to submit an application as the PD/PI of an NIH research grant application (e.g., R01).
• The candidate lacks other rights and privileges of faculty, such as attendance at faculty meetings.

Conversely, evidence for independence, and therefore lack of eligibility, includes:

• The candidate has a full-time faculty position.
• The candidate received a start-up package for support of their independent research.
• The candidate has research space dedicated to their own research.
• The candidate may attend faculty meetings, be the responsible supervisor for graduate students, and/or hire technical support or postdoctoral fellows.
• The candidate is eligible to apply for independent research funding as the PD/PI of an NIH research grant.

Link to Award: https://grants.nih.gov/grants/guide/pa-files/PAR-23-288.html

Process for Limited Submissions

PIs must submit their application as a Limited Submission through the Research Initiatives and Infrastructure (RII) Application Portal: https://rii.usc.edu/oor-portal/. Use the template provided here: RII Limited Submission Applicant Template

Materials to submit include:

• (1) Two-Page Proposal Summary (1” margins; single-spaced; standard font type, e.g. Arial, Helvetica, Times New Roman, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 2-page limit will be excluded from review. You must use the template linked above.
• (2) CV – (5 pages maximum)

Note: The portal requires information about the PIs in addition to department and contact information, including the 10-digit USC ID#, Gender, and Ethnicity. Please have this material prepared before beginning this application.

Purpose

The overall goal of the NIH Research Career Development program is to help ensure that a diverse pool of highly trained scientists is available in appropriate scientific disciplines to address the Nation’s biomedical, behavioral, and clinical research needs. NIH Institutes and Centers (ICs) support a variety of mentored and non-mentored career development award programs designed to foster the transition of new investigators to research independence and to support established investigators in achieving specific objectives. Candidates should review the different career development (K) award programs to determine the best program to support their goals. More information about Career programs may be found at the NIH Extramural Training Mechanisms website.

The objective of the NCI Pathway to Independence Award for Early-Stage Postdoctoral Researchers (K99/R00) is to help postdoctoral researchers complete needed, mentored training and transition in a timely manner to independent tenure-track (or equivalent) faculty positions. The K99/R00 award is intended to foster the development of a creative, independent research program that will be competitive for subsequent independent funding and that will help advance the mission of the NCI.

This program is designed for postdoctoral fellows with research and/or clinical doctoral degrees who do not require extended periods of mentored research training beyond their original doctoral degrees before transitioning to research independence, which is common for those working in cancer control, cancer prevention and cancer data sciences, as defined in Section III. 3. Additional Information on Eligibility. Therefore, researchers from these disciplines are particularly encouraged to work with their institutions to apply.

This K99/R00 award is intended to support individuals who require no more than 2 additional years of mentored research training and career development (K99 phase) before transitioning to the independent stage (R00 phase) of the program. Consequently, the strongest applicants will require and will propose, a well-conceived plan for 1 2 years of substantive mentored research training and career development that will help their investigators become competitive candidates for tenure-track faculty positions and prepare them to launch robust, independent research programs.

Individuals must be in mentored, postdoctoral training positions to be eligible for support under the K99/R00 program. If an applicant’s candidate achieves independence (any faculty or non-mentored research position) before a K99 award is made, neither the K99 award, nor the R00 award, will be made. The K99/R00 award will provide up to 5 years of support in two phases. The initial (K99) phase will support up to 2 years of mentored postdoctoral research training and career development. The second (R00) phase will provide up to 3 years of independent research support, which is contingent on satisfactory progress during the K99 phase and an approved, independent tenure-track (or equivalent) faculty position. The two award phases are intended to be continuous in time. Therefore, although exceptions may be possible in limited circumstances, R00 awards will generally only be made to those applicants’ K99 PDs/PIs who accept independent, tenure-track (or equivalent) faculty positions by the end of the K99 award period.

Pre-Application Webinar: The NCI anticipates holding a pre-application webinar to which all interested prospective candidates, mentors, administrators, and grant managers are invited. An NCI program director will explain the goals and objectives of the NCI Pathway to Independence Award for Early-Stage Postdoctoral Researchers, discuss the eligibility and nomination requirements, explain the peer review process, and answer questions. For details on the nomination letter see Sections III and IV. Information about the pre-application webinar will be available after the publication of the NOFO under the “NCI Early K99 Award” tab of the NCI Cancer Training Branch website.

Note: This Notice of Funding Opportunity (NOFO) is designed specifically for candidates proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary clinical trial, as part of their research and career development. Those not planning an independent clinical trial, or proposing to gain research experience in a clinical trial led by another investigator, must apply to companion NOFO (PAR-23-286).

All applications submitted to this Notice of Funding Opportunity must propose basic science experimental studies involving humans, otherwise referred to in NOT-OD-18-212 as prospective basic science studies involving human participants, that fall within the NIH definition of a clinical trial and also meet the definition of basic research.

NIH defines basic research consistent with the definition of basic research in federal code, the systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind. (32 CFR 272.3).

NIH defines a clinical trial as “A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” (NOT-OD-15-015).

Types of studies that should submit under this NOFO include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind.

For the purposes of this NOFO, specific application towards processes or products refers to the application of biomedical or behavioral products, procedures, or services intended to affect a health-related outcome of the individual or a group of individuals either by better understanding the mechanism of action of an intervention or a measurable improvement in health.

Basic experimental studies in which participants are prospectively assigned to experimental conditions and receive an intervention or experimental manipulation where the effect will be assessed for the purpose of understanding fundamental aspects of phenomena may submit under this NOFO.

Please refer to the table comparing Funding Opportunity Types by Clinical Trial Allowability for additional guidance on the most appropriate NOFO for the type of study.

Prospective studies with humans conducted with specific applications towards processes or products in mind, including FDA Phase 0 or 1 studies, mechanistic clinical trials (e.g., those that examine the mechanisms by which an intervention works or the processes that account for an intervention’s effects on clinical outcome), and safety and efficacy studies should submit under the a ‘Clinical Trials Required’ companion NOFO (PAR-23-287), but not under this NOFO.

Observational studies involving humans should submit under the Clinical Trials Not Allowed companion NOFO (PAR-23-286).

Scientific Areas

• (A) Cancer Data Science: For the purposes of this K99/R00 award, cancer data science is defined as an interdisciplinary field of inquiry in which quantitative and analytical approaches, processes, and systems are both developed and used to extract knowledge and insights from increasingly large and/or complex sets of data. This includes cancer-focused data integration and visualization, systems biology, artificial intelligence, machine learning, informatics, genomics, precision oncology, and developing analytics for epidemiological or biostatistical studies.
• (B) Cancer Control Science: For the purposes of this K99/R00 award, cancer control science is defined as basic and applied research in the behavioral, social, and population sciences to create or enhance interventions that, independently or in combination with biomedical approaches reduce cancer risk, incidence, morbidity, and mortality, and improve quality of life. This includes research in epidemiology, behavioral sciences, health services, surveillance, cancer survivorship, and healthcare policy.
• (C) Molecular/Precision Cancer Prevention: For the purpose of this K99/R00 award, early translational research in cancer prevention is defined as basic research to understand mechanisms of cancer formation, development and progression of cancer precursors, and to translate basic biological knowledge into novel human interventions and human-centered adaption of current interventions with the potential to reduce cancer risk, incidence, and mortality, and improve quality of life. This includes but is not limited to research in molecular and systems biology, diagnostics, vaccine and drug development, pharmacology, and biomedical engineering.
• (D) Other Cancer Research: For the purposes of this K99/R00 award, “Other Cancer Research” includes all scientific fields supported by the NCI that are not included in (A), (B) or (C). Applicants proposing research in (D) “Other Cancer Research” may apply only if it is reasonable to expect their candidates to transition to independence with an abbreviated period of mentored research training beyond their original doctoral degrees.”

Visit our Institutionally Limited Submission webpage for more updates and other announcements.

Slots: Only one NCMRR ECR Award (R03) application may be submitted as a single PD/PI or one of Multiple PDs/PIs per due date. 

Deadlines

Internal Deadline: Friday, March 14th, 2025, 5pm PT Contact RII.

LOI: N/A

External Deadline: June 16, 2025

Recurring Deadlines: October 16, 2025; February 16, 2026; June 16, 2026; October 16, 2026; February 16, 2027; June 16, 2027; October 16, 2027

Award Information

Award Type: Grant

Estimated Number of Awards and Award Amount: The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications

Who May Serve as PI: This NOFO targets Early Career Investigators interested in rehabilitation research. The PD/PI must be an independent investigator, not a postdoctoral fellow, at the time of submission. The PD/PI must be no more than 8 years beyond the date that the first professional, advanced professional, or terminal academic degree was awarded, whichever is most recent. The 8-year eligibility period will be calculated based on the MM/DD/YYYY the degree was awarded and the published application receipt date, regardless of whether it is a new or resubmission application. Attainment of an additional Master’s degree after receipt of a doctoral level degree does not extend the timeline. Formal years of clinical training (Internship, Residency, and Fellowship) are not counted as part of the 8-year limit. The exemption of years for clinical training is not limited to physicians.

Recipients of the Federally-funded National Research Service Award fellowships and traineeships (i.e. F- and T- series awards) or mentored career development awards (i.e. K awards) are eligible for the NCMRR ECR Award grant program, provided there is no overlap in professional commitment or budget.

The following are NOT Eligible: 

• Individuals who, at the time of submission, have served as PD/PI on a peer-reviewed NIH research award (R series) over $100,000 direct costs per year or non-NIH research grants over $150,000 total costs per year,
• Project Leaders on sub-projects of NIH program project (P01) or center (P50) grants or the equivalent
• Recipients of the NIH K99/R00 award

 For Multi-PI applications, all of the PDs/PIs must meet the above eligibility criteria.

Link to Award: https://grants.nih.gov/grants/guide/pa-files/PAR-25-124.html

Process for Limited Submissions

PIs must submit their application as a Limited Submission through the Research Initiatives and Infrastructure (RII) Application Portal: https://rii.usc.edu/oor-portal/. Use the template provided here: RII Limited Submission Applicant Template

Materials to submit include:

• (1) Two-Page Proposal Summary (1” margins; single-spaced; standard font type, e.g. Arial, Helvetica, Times New Roman, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 2-page limit will be excluded from review. You must use the template linked above.
• (2) CV – (5 pages maximum)

Note: The portal requires information about the PIs in addition to department and contact information, including the 10-digit USC ID#. Please have this material prepared before beginning this application.

Purpose

The NCMRR Early Career Research (ECR) Award is different from other NIH R03 programs, including the Parent R03 Announcement (PA-20-200) . It is restricted to clinical and basic scientists who are in the early stages of their independent career in rehabilitation research. For projects supported by an  ECR R03 Award, successful results should provide a solid foundation for further research under the R01 funding mechanism.

Given that the goal is to collect preliminary data, R03 projects may be less immediately impactful or significant compared to the typical R01 or other NIH-funded projects. It is not an expectation that this R03 project will likely “move the field forward” at this stage.

The research must be focused on one or more of the areas within the biomedical and behavioral mission of NCMRR: pathophysiology and management of chronically injured nervous and musculoskeletal systems (including stroke, traumatic brain injury, spinal cord injury, and orthopedic conditions); repair and recovery of motor function; functional plasticity, adaptation, and windows of opportunity for rehabilitative interventions; rehabilitative strategies involving pharmaceutical, stimulation, and neuroengineering approaches, exercise, motor training, and behavioral modifications; pediatric rehabilitation; secondary conditions associated with chronic disabilities; improved diagnosis, assessment, and outcome measures; and development of orthotics, prosthetics, and other assistive technologies and devices.

The proposed project may be technology design-directed, discovery-driven, or hypothesis-driven with the goal of collecting the necessary preliminary data sufficient to apply for an R01 grant. The project may aid in the formulation of hypotheses and may be milestone-driven or descriptive in scope. 

Preliminary data are not required or expected. However, if available, preliminary data are allowed.

A 1-page attachment titled “Plan for Inclusion of People with Lived Experience” must be included with the application or the application will be withdrawn prior to review.  (see Section IV; further below). The Plan will be assessed as part of the scientific and technical peer review evaluation, as well as at the programmatic level with respect to funding decisions. 

Investigators proposing clinical research are encouraged to use the common data elements (CDEs) (https://cde.nlm.nih.gov/home) or justify not using CDEs for rehabilitation if they are not included.

For those applications that generate clinical data, investigators are encouraged to share data via the NICHD DASH (data and specimen hub) Center (https://dash.nichd.nih.gov/).

Applicants are strongly encouraged to contact the Scientific/Research contact for this  NOFO for guidance in advance of submitting an application to ensure their proposed project is in compliance with new NIH human subjects research and clinical trials policies (https://grants.nih.gov/policy/clinical-trials.htm) and consistent with the types of clinical trial projects that NCMRR supports.

Visit our Institutionally Limited Submission webpage for more updates and other announcements.

Slots: 1

Deadlines

Internal Deadline: Friday, March 7th, 2025, 5pm PT Contact RII.

LOI: 30 days prior to application due date, but is not required.

External Deadline: May 15, 2025

Award Information

Award Type: “Other.” A mechanism that is not a grant or cooperative agreement. Examples include access to research resources or pre-applications.

Estimated Number of Awards: Funds are not awarded via the X01 mechanism. The total number of approvals for access to DMCC and Network resources is dependent on the number of meritorious applications and the capacity of the Network.

Anticipated Award Amount: Not Applicable; funds are not awarded via the X01 mechanism.

Who May Serve as PI: Standard NIH requirements.

Link to Award: https://grants.nih.gov/grants/guide/pa-files/PAR-23-171.html

Process for Limited Submissions

PIs must submit their application as a Limited Submission through the Research Initiatives and Infrastructure (RII) Application Portal: https://rii.usc.edu/oor-portal/. Use the template provided here: RII Limited Submission Applicant Template

Materials to submit include:

• (1) Two-Page Proposal Summary (1” margins; single-spaced; font type: Arial, Helvetica, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 2-page limit will be excluded from review. You must use the template linked above.
• (2) CV – (5 pages maximum)

Note: The portal requires information about the PIs in addition to department and contact information, including the 10-digit USC ID#.. Please have this material prepared before beginning this application.

Purpose

Undiagnosed diseases are defined as long-standing symptoms or elusive medical conditions that have not been diagnosed despite extensive clinical evaluation. Undiagnosed diseases are often due to rare conditions and can include: 1) not recognized, previously described diseases due to very low incidence or prevalence; 2) yet-to-be-described disorders; and 3) rare variations of more common diseases. These conditions present difficult problems for patients, their families, and physicians resulting in a high emotional, physical, and financial burden to patients who may spend many years seeking a diagnosis and path to treatment. Diagnoses in these difficult cases require teams of clinicians and scientists with a wide variety of special expertise. Scientific advances springing from these diagnoses require an organized approach to testing, data analysis, and validation in patients with similar rare conditions or in model organisms.

In 2008, the NIH established an intramural Undiagnosed Diseases Program (UDP) to aid individuals plagued by longstanding medical conditions that elude medical diagnosis. Using a team science approach, comprehensive clinical phenotyping and cutting-edge diagnostic and genomic technologies, the UDP was successful in ending the “diagnostic odyssey” for many individuals with rare, challenging, and difficult-to-diagnose diseases. Based on the success of the UDP, the NIH Common Fund announced in 2012 an expansion of the UDP to form a nation-wide network – the Undiagnosed Diseases Network (UDN) – composed of the NIH UDP and extramural Clinical Sites. Phase I (FY2013-2017) of the UDN included seven Clinical Sites including the UDP, a Coordinating Center, and Core Laboratories to facilitate diagnoses (genome sequencing, testing variants in model organisms, metabolomics, and a biorepository). In Phase II (FY2018-2022), the number of Clinical Sites was expanded to twelve. Since the launch of Phase I, the UDN has been very successful in achieving its objectives by: providing over 600 diagnoses; discovering hundreds of novel disease-associated genes and genomic variants, including new diseases and syndromes; and building an international reputation for establishing exemplary clinical practices, standards, and pipelines for genomics-based diagnoses.

In Phase II, the network was tasked to develop a framework that would continue the mission of the UDN after NIH Common Fund support ends in 2023. To have a broader impact on the clinical practice of undiagnosed diseases in the United States (US), the NIH envisions the UDN evolving into a larger, self-sustained network that, with public and private partners, can provide expert diagnostic services for undiagnosed patients across the nation and foster scientific discovery. The network will also seek to implement strategies that will expand equity and access to health disparity populations. In this new model, the new Network (henceforth referred to as the “Network” in this NOFO) will consist of an NIH-supported Data Management Coordinating Center (DMCC), the UDP, highly qualified and collaborative clinical sites, patients with undiagnosed diseases (referred to as “participants” in this NOFO), patient advocacy groups, and the NIH and other stakeholders including external funding providers and/or resource providers (e.g., Cores or private partnerships that conduct genomics sequencing, gene function studies or other diagnostic services).

The purpose of this NOFO is to solicit proposals from highly qualified clinical sites in the US to join the Network through an X01 Resource Access Program award. Accepted sites will be designated as a “Diagnostic Center of Excellence (DCoE)” and will be responsible for generating participant clinical, phenotypic and sequencing data to be submitted to the DMCC through a Data Use Agreement with the Center.  X01 recipients will have access to DMCC resources and infrastructure including access to high-quality phenotypic and genotypic data and collaboration with highly skilled physicians, researchers, and bioinformaticians. Using team science, DCoEs will be able to collaborate with Network members to implement strategies that will expand equity and access to health disparity populations and increase the discovery of new disease-associated genes and genomic variants, immunologic and metabolic abnormalities, as well as environmental insults that are causative in previously undiagnosed patients. DCoEs will be invited to submit their most challenging, unsolved cases for acceptance into the Network, and partner in their evaluation with the Network’s virtual case review committee(s), which will be coordinated by the DMCC.

Successful applicants will demonstrate that they have the appropriate expertise and a track record of diagnosing rare and difficult-to-diagnose disorders, along with the infrastructure and resources needed to conduct the clinical evaluation and DNA sequencing of participants enrolled at their sites. Specifically, applicants will be expected to demonstrate the expertise, independent resources (e.g., institutional support, plans for billing insurance, obtaining support from outside partnerships, etc.), and capacity to:

• Enroll a minimum of 5 participants per year who are accepted into the Network, although some sites may have the capacity to enroll more participants. Typically, only the most difficult, unsolved cases will be accepted into the Network (e.g., those cases requiring specialized, non-routine diagnostic testing procedures or collaboration among a team of clinicians and researchers).
• Perform comprehensive clinical evaluations of undiagnosed participants enrolled at their site including medical record review, routine and specialized diagnostic testing procedures, consultations, and referral to other sites with necessary expertise if appropriate.
• Have the resources (in-house or outsourced) to perform DNA and/or RNA sequencing and re-analysis of existing genome-sequencing data.
• Capability to work with Network data stored in a cloud architecture, such as AnVIL.
• Have the genomics capability including medical genetics and associated informatics expertise needed to identify pathogenic variants from human genomics sequence data. This includes the infrastructure to return genetic results to study participants and provide post-test genetic counseling.
• Demonstrate sufficient clinical metabolomics and other omics expertise to interpret or re-interpret lab and research-grade findings.
• Have sufficient clinical staff to review medical records from applicants (so as to enroll a minimum of five cases per year into the Network) and to rigorously discuss the results to arrive at a diagnosis or to interrogate candidate genes.
• Collect and store DNA, fibroblasts from skin biopsies, and other biological specimens produced by clinical evaluations as needed for the diagnosis.
• Organize incoming records and return results to participants, family members, and referring physicians.
• Support a site coordinator or equivalent position to serve as the DCoE’s point of contact for data sharing, case coordination, collaboration, data retrieval for research projects and patient follow-up.

Additional Information

(1) The X01 mechanism does not provide budgetary support for the proposed activities. Successful X01 applications will receive access to DMCC resources and Network data (discussed above), and will have the option to apply for small research grants issued by the DMCC as subawards to DCoE sites (see: RFA-NS-22-051 for more information). The DMCC will provide at least $500,000 Direct Costs (DC) in year 1 and $1M DC per year in years 2-5 to support Network research activities. The subawards (typically in the range of $25-50K DC each) are intended to support: 1) some of the DCoEs’ costs associated with on-site coordination and submitting data to the Network; and 2) pilot research projects such as very early-stage gene function studies in model systems and clinical genomics/metabolomics investigations that are needed to facilitate a participant’s diagnosis. Subawards cannot support clinical trials.

(2) Successful applicants to this NOFO will be expected to incorporate the Network’s infrastructure and operational procedures into their proposed study plans, including coordination, collaboration, and data management through the DMCC and signing onto any agreements or Memoranda of Understanding established by the Network Steering Committee in the next phase of the UDN (see “Network Governance” below). In addition, DCoEs will be expected to work with the DMCC and Steering Committee to develop Network protocols, a Manual of Operations, and participate in Steering Committee, Case Review, diagnostic consultation, and Working Group meetings as established by the Steering Committee.

(3) Successful applicants will be required to consent participants and use a single-IRB managed by the NIH UDP that is consistent with NIH’s Single IRB Policy as described in NOT-OD-16-094 to ethically review Network-wide protocols involving human subjects research.

(4) To gain access to DMCC resources, X01 recipients will be required to submit relevant participant datasets generated at their Site (e.g., clinical, phenotypic, genomic, environmental, covariates, metadata, etc.) to the DMCC through a Data Use Agreement with the Center.  The Network’s Steering Committee will develop and implement Network-wide approaches for data submission from DCoEs and timelines including data standards and formatting requirements, along with standards for data use by Network members.  The DMCC is responsible for submitting de-identified data to national repositories as required in RFA-NS-22-051.

(5) DCoEs are encouraged to use innovative approaches that increase the efficiency, yield, and cost-effectiveness of the diagnosis (e.g., remote visits, tiered evaluation strategies, use of innovative tools or strategies for record review, etc.), while still providing a comprehensive and expeditious clinical evaluation.

(6) Although DCoEs are encouraged to enroll participants with disorders in any clinical specialty (similar to current UDN operations: UDN Manual of Operations), sites have the option to specialize in one or more areas of clinical practice (e.g., pediatrics, neurology, cardiology, gastroenterology, immunology, metabolism, environmentally-linked or infectious diseases, etc.).

(7) Applicants are strongly encouraged to enroll participants from health disparity populations and/or to partner with medical institutions that serve under/uninsured and health disparity populations.

Visit our Institutionally Limited Submission webpage for more updates and other announcements.

Slots: 1

Deadlines

Internal Deadline: Friday, February 28th, 2025, 5pm PT Contact RII.

LOI: N/A

External Deadline: May 25, 2025

Recurring Deadlines: September 25, 2025; January 25, 2026; May 25, 2026; September 25, 2026; January 25, 2027

Award Information

Award Type: Grant

Estimated Number of Awards: The number of awards is contingent upon NIH appropriations and the number of meritorious applications submitted.

Anticipated Award Amount: Application budgets are not limited but must reflect the actual needs of the proposed project.  

Who May Serve as PI: 

• To provide research training leadership for the program, at least one of the training PDs/PIs should have a record of using rigorous and transparent methods in experimental design, data collection, analysis, and reporting in a biomedical research field applicable to the program.
• Additional PDs/PIs may be included to strengthen the expertise of the PD/PI team. Examples include individuals such as program directors who regularly interact with students, or individuals with expertise in education, relevant social sciences, program evaluation, mentoring, or university administration. 

Any of the PDs/PIs may serve as the contact PD/PI. The contact PD/PI is expected to have a full-time appointment at the applicant organization unless extremely well-justified. If the full-time status of the contact PD/PI changes after the award, the organization must obtain prior program approval to appoint a new PD/PI or request a deviation from the full-time rule. The PD(s)/PI(s) will be responsible for:

• The overall direction, management, administration, and evaluation of the program.
• The day-to-day administration of the program, including direct involvement with trainees.
• The selection and appointment of trainees to the research training program.
• The selection of faculty mentors for the program, assessment of mentor performance, and ensuring the program deals appropriately with substandard mentor performance.
• Monitoring and assessing the program and submitting all documents and reports as required.
• Appointing members of the Advisory Committee (when applicable) and implementing their guidance as appropriate.

Link to Award: https://grants.nih.gov/grants/guide/pa-files/PAR-24-128.html

Process for Limited Submissions

PIs must submit their application as a Limited Submission through the Research Initiatives and Infrastructure (RII) Application Portal: https://rii.usc.edu/oor-portal/. Use the template provided here: RII Limited Submission Applicant Template

Materials to submit include:

• (1) Two-Page Proposal Summary (1” margins; single-spaced; standard font type, e.g. Arial, Helvetica, Times New Roman, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 2-page limit will be excluded from review. You must use the template linked above.
• (2) CV – (5 pages maximum)

Note: The portal requires information about the PIs in addition to department and contact information, including the 10-digit USC ID#, Gender, and Ethnicity. Please have this material prepared before beginning this application.

Purpose

The overall goal of the NIH Ruth L. Kirschstein National Research Service Award (NRSA) program is to help ensure that a diverse pool of highly trained scientists is available in appropriate scientific disciplines to address the nation’s biomedical, behavioral, and clinical research needs. More information about NRSA programs may be found at the Ruth L. Kirschstein National Research Service Award website. The NRSA program has been the primary means of supporting predoctoral and postdoctoral research training programs since enactment of the NRSA legislation in 1974. 

Each NIGMS-funded MSTP award is expected to provide a rigorous, well-designed research training program that includes mentored research experiences, courses, seminars, and additional training opportunities that equip clinician scientists with the following skills required for careers in the biomedical research workforce:

• Technical (for example, appropriate methods, technologies, and quantitative/computational approaches).
• Operational (for example, independent knowledge acquisition, rigorous experimental design, interpretation of data, and conducting research in the safest manner possible).
• Professional (for example, management, leadership, communication, and teamwork).

Through this funding announcement, NIGMS encourages changes in integrated clinical and graduate research training to keep pace with the rapid evolution of the biomedical research enterprise, which is increasingly complex, interdisciplinary, quantitative, and collaborative. Other changes in the biomedical research enterprise include greater diversity in the backgrounds of people participating in biomedical research, the approaches utilized to investigate clinically relevant research questions, and the range of careers that dual-degree recipients are pursuing. Additionally, there is an increasing recognition of the need to enhance reproducibility of biomedical research results through scientific rigor and transparency, and to promote a culture where the highest standards of practice are used to ensure the safety of all individuals in the research environment. This funding opportunity is intended to encourage and enable the scientific community to develop and implement evidence-informed approaches to biomedical research training and mentoring that will effectively train future generations of rigorous clinician scientists to become leaders in biomedical research and clinical medicine.

Programs are encouraged not to simply layer additional activities onto existing structures but to instead use creative and transformational approaches to integrate clinical and biomedical graduate training, including curricular reform, that preserve the best elements of current programs, while enhancing the focus on the development of trainee skills.

NIGMS strives to ensure that future generations of researchers will be drawn from the entire pool of potential contributors and seeks to expand opportunities to support individuals from a variety of backgrounds at multiple training and career stages in a variety of organizations and educational settings across the country. The Overarching Objective of the MSTP is to develop a diverse pool of well-trained clinician scientists (that is, a Ph.D. combined with a clinical degree, such as an M.D., D.O., D.V.M., D.D.S., Pharm.D., etc.) who have the following:

• A broad understanding across biomedical disciplines.
• The skills to independently acquire the knowledge needed to advance their chosen fields and careers.
• The ability to think critically and identify important biomedical research questions and approaches that push forward the boundaries of their areas of study.
• A strong foundation in scientific reasoning, rigorous research design, experimental methods, quantitative and computational approaches, and data analysis and interpretation.
• The skills to conduct research in the safest manner possible, and a commitment to approaching and conducting biomedical research responsibly, ethically, and with integrity.
• Experience initiating, conducting, interpreting, and presenting rigorous and reproducible biomedical research with increasing self-direction.
• The ability to utilize clinical experience and observations to identify biomedical research questions and to develop impactful research programs that push forward the boundaries of their areas of study.
• The skills necessary to integrate research and clinical activities and the capacity to translate scientific research findings into clinical practice.
• The ability and skills to lead changes that promote health equity, reduce health disparities and improve the health of those medically underserved across diseases, disorders, and conditions.
• The ability to work effectively in teams with colleagues from a variety of cultural and scientific backgrounds, and to promote inclusive and supportive scientific research environments.
• The skills to teach and communicate scientific methodologies and findings to a wide variety of audiences (for example, discipline-specific, across disciplines, and for the public).
• The knowledge, professional skills and experiences required to identify and transition into careers in the biomedical research workforce that utilize the dual-degrees (for example, the breadth of careers that sustain biomedical research in areas that are relevant to the NIH mission).

Program Considerations

NIGMS will accept predoctoral training grant applications supporting integrated clinician and graduate research training through this MSTP funding announcement and subsequent reissuances (graduate research training in basic biomedical sciences is supported through PAR-23-228 and subsequent reissuances). Applicants are strongly encouraged to read information about NIGMS predoctoral training grant programs, including the MSTP and Leading Equity and Diversity in the Medical Scientist Training Program (LEAD MSTP) (PAR-23-030), found on the NIGMS website and to contact program staff before preparing or submitting an application  to verify that the proposed program is eligible and in alignment with NIGMS funding priorities.

General Considerations. NIGMS intends to fund applications that propose feasible, rigorous, well-designed and integrated dual-degree research training programs that will build on the most effective elements of successful programs, while encouraging creative and transformational approaches to clinician scientist research training, ranging from curricular reform to changes in the research training environment. Funded programs should implement plans to optimize the time required to earn the dual degree. Programs are expected to limit appointments to individuals committed to research careers that utilize the dual-degree qualifications.

NIGMS encourages programs to devise and test alternative entry pathways in addition to or instead of the direct application and admission to the first year of the dual-degree training program, thus providing opportunities to recruit students from clinician-only or from Ph.D.-only programs.  NIGMS encourages institutions to offer MSTP trainees the opportunity to earn the Ph.D. in a broad range of biomedical, physical, and social and behavioral sciences, and engineering to meet the needs for clinician scientist researchers in all areas of the biomedical workforce.  Programs that provide interdisciplinary research training, incorporate training in data science, or take advantage of clinical research opportunities within nationwide networks and infrastructures such as the NIH Clinical and Translational Science Award program are encouraged to apply.  NIGMS encourages applicants to offer training across the landscape of medical fields and scientific disciplines related to health, and to promote opportunities for the exploration of clinician scientist career options. Funded programs are expected to:

• Be a well integrated dual-degree program  that exerts a strong, positive influence at the organizational level on research training and mentoring practices.
• Have clearly defined training objectives and show evidence of meeting the objectives in progress reports and in renewal applications.
• Implement evidence-informed training and mentoring activities (for example, approaches that are grounded in the literature and evaluations of existing relevant dual-degree research training programs). Programs are expected to be responsive to evaluations, particularly with respect to trainee feedback.
• Provide rigorous, well-designed mentored research experiences, and additional opportunities that will build a strong cohort of dual-degree research-oriented individuals. Training grant funds may not be used solely as a vehicle to provide financial aid for trainees to conduct research.
• Demonstrate effective oversight of dual-degree trainee development and promote retention for the entire time the dual-degree trainee is in the training program. Retention efforts are activities designed to sustain the scientific interests and participation of trainees from all backgrounds. Retention and oversight activities might include monitoring academic and research progress, building strong trainee cohorts, as well as increasing science identity, self-efficacy, and a sense of belonging within research training environments. Programs are expected to make efforts to identify individuals who may need additional academic and social supports to successfully complete the program, and ensure they receive the needed support.
• Promote inclusive, safe, accessible, and supportive research training environments to maximize success for all individuals in the training program. Specifically, funded programs should have organizational and departmental environments where individuals from all backgrounds are welcomed, feel integrated into, and supported by the biomedical research community. Safety in research training should encompass (1) environments free from harassment, discrimination, and intimidation, in which all are treated in a respectful and supportive manner, (2) laboratory and clinical settings where individuals exercise the highest standards of practice for chemical, biological and physical safety, and (3) practices at the organizational leadership and research community levels that demonstrate core values and behaviors to emphasize safety over competing goals.

Trainee Support. The training grant defrays the cost of stipends, tuition and fees, and training related expenses, including health insurance, for the appointed trainees in accordance with the approved NIH NRSA support levels.   NIGMS typically provides full-time support for approximately 25% of the trainees in the training program during any given year.  Individuals may receive up to six years of aggregate Kirschstein-NRSA support at the predoctoral level for dual-degree training, including any combination of support from institutional training grants (for example, T32) and an individual fellowship award (for example, F30 or F31 awards).  Many dual-degree training programs guarantee enrolled students full support for the duration of the dual-degree program (through combinations of federal support, institutional funds, other fellowships, and grants). Training programs may implement institutional policies regarding payback of non-NRSA institutional sources of funds by students who start training but do not complete one or both degrees.  NIGMS does not require nor permit institutions to receive payback NRSA funds from trainees who are appointed to NIH training grants, but do not complete training.

Synergies of Federally Funded Training Programs. Funded research training programs are encouraged to complement and synergize with other ongoing federally supported predoctoral research training programs at the applicant organization (for example, in the development of skills needed for careers in the biomedical research workforce that are not discipline-specific); however, the scientific training goals must be distinct from related programs at the same organization currently receiving federal support. In cases where an organization has multiple NIGMS predoctoral training grants, it is expected that these programs will work together to create administrative and training efficiencies to reduce costs and improve trainee services and outcomes.

Visit our Institutionally Limited Submission webpage for more updates and other announcements.