Federal Health Grants

The primary purpose of the NIH Mentored Clinical Scientist Research Career Development Awards (K08) program is to prepare qualified individuals for careers that have a significant impact on the health-related research needs of the Nation. This program represents the continuation of a long-standing NIH program that provides support and "protected time" to individuals with a clinical doctoral degree for an intensive, supervised research career development experience in the fields of biomedical and behavioral research, including translational research.

Notice of Funding Opportunity Description Background The accumulation of misprocessed and aberrant proteins is a defining characteristic of various neurodegenerative conditions, such as AD and frontotemporal lobar degeneration (FTLD). These atypical proteins may arise from various factors, such as somatic mutations, environmental changes, genomic instability, irregular RNA processing, and proteolytic cleavages, as well as incorrect folding and post-translational modifications. For instance, many recent proteome and transcriptome profiling of AD brains reveals RNA splicing dysfunction and abnormal accumulation of U1 small nuclear ribonucleoprotein (snRNP) and transactive response DNA-binding protein 43 (TDP-43). In AD, U1-70K and its N-terminal 40-KDa fragment (N40K) is one of the most abundant proteins in the insoluble fraction of cell lysates. TDP-43 is an RNA-binding protein. In AD, TDP-43 pathology is observed in approximately 25-50% of cases, particularly in cases with co-morbidities such as Lewy body dementia or hippocampal sclerosis. However, the relationship between U1snRNP/TDP-43 and AD pathology is complex and not fully understood. The disruption of RNA processing is thought to be one possible mechanism to cause the accumulation of misprocessed proteins, which can lead to altered expression of genes involved in AD pathology, including amyloid precursor protein (APP), tau, and synaptic proteins. Understanding the mechanisms underlying the dysregulation of misprocessed proteins in neurodegenerative diseases will be important for developing effective therapies. Approaches that target the production or aggregation of misprocessed proteins, or that promote their clearance or degradation, may be effective in preventing or slowing disease progression. Purpose This NOFO invites innovative research proposals to explore the accumulation of misprocessed proteins in Tauopathies within specific brain regions and cell types. This NOFO encourages collaborative efforts to create advanced single-cell or single-cell type proteogenomic platforms. These platforms aim to shed light on dynamic changes in protein-misfolding responses in neuronal proteomes and their potential biological consequences during aging and the development of AD/ADRD. Research Objectives This NOFO aims to provide a proof-of-principal for a novel strategy to identify misprocessed and aberrant proteins in Tau diseases using the proteogenomic approach. Proteogenomics is an integrated approach that combines proteomics and genomics data. In proteogenomics, genomic and transcriptomic experiments are more closely integrated to identify potential protein coding and non-coding regions in the genome. These regions are then validated using mass spectrometry-based proteomics. Proteogenomics has emerged as a powerful tool for investigating the role of protein homeostasis in AD pathogenesis, especially in the context of mis-translated and mis-repaired proteins. However, relying solely on misprocessed protein levels to draw conclusions about biological processes is unlikely to be reliable. Therefore, an intermediate layer of functional validation is essential to transform proteogeomic data into meaningful biological information. As a result, the objective of this NOFO is not only to confirm changes in protein abundance using other methods, but also to assess the biological effects of those changes in some model systems, especially in the area of tauopathies, to ensure high interlaboratory reproducibility. Using the proteogenomics approach, this NOFO aims to accomplish the following: Create a comprehensive database of misprocessed and aberrant proteins in selected mouse models of human Tau diseases. Cross-validate the presence of misprocessed and aberrant proteins in human AD/ADRD brains. Identify new molecular pathways and novel misprocessed protein-protein interaction networks that are not currently in most datasets. Define novel mechanisms through which misprocessed and aberrant proteins influence the onset and progression of neurodegeneration in tauopathies. Identify disease specific therapeutic targets in neurodegenerative diseases. It is expected that applications responding to this initiative will use the latest cell-type-specific labeling and proteogenomic techniques with suitable model systems to understand the etiology of tauopathies in aging and AD.

This funding opportunity provides financial support to healthcare systems and organizations to implement a comprehensive suicide prevention model aimed at improving mental health outcomes and reducing suicide rates.

This funding opportunity supports researchers exploring the mechanisms of Treponema pallidum, the bacteria responsible for syphilis, to address the rising rates of sexually transmitted infections and improve understanding of its pathogenesis.

This grant provides funding for research projects that test strategies to reduce suicide risk by promoting safe storage of lethal means, such as firearms, in healthcare and community settings.

The "Innovation Grants to Nurture Initial Translational Efforts (IGNITE)" program supports the development of in vitro and ex vivo assays to identify and characterize new therapeutic agents for neurological and neuromuscular disorders, with a focus on creating robust screening methods for promising neurotherapeutics.

This funding opportunity supports exploratory preclinical studies to evaluate the effectiveness of therapeutic agents for rare diseases affecting fewer than 200,000 people in the U.S., aiming to advance these treatments toward clinical trials.

The "NIDCD's Mentoring Networks to Enhance Clinician-Scientists' Participation in Research" grant aims to support educational and mentoring activities that encourage individuals, especially those from diverse backgrounds, to pursue research careers in biomedical, behavioral, and clinical sciences, with a particular focus on improving the recruitment, preparation, and retention of clinician investigators.

This grant provides funding to early-career researchers in mental health to support innovative projects that advance the understanding and treatment of mental illnesses.

This grant provides funding to statewide networks focused on improving maternal and infant healthcare quality, particularly for underserved populations, by implementing best practices and ensuring equitable care in birthing facilities.

This program will constitute a national CBA Provider Network (CPN) to deliver CBA services to an interdisciplinary HIV prevention workforce (e.g., professional, technical, clinical, and managerial staff) within CDC-funded state and local health departments and CBOs. In the United States, an estimated 1.2 million people are living with HIV. In recent years, the number of people with HIV (PWH) has increased while deaths have declined. Of PWH, about 87% were aware of their HIV status. In 2021, among people with diagnosed HIV, an estimated 75% received HIV medical care and 66% were virally suppressed. Promising progress has been made in HIV prevention as the estimated annual new HIV infections were 12% lower in 2021 (32,100 infections) compared to 2017 (36,500 infections). This decline was largely driven by a substantial decrease (34%) in new infections among 13- to 24-year-olds, mostly among gay and bisexual males. However, HIV prevention efforts must go further, and progress must be faster, for gains to equitably reach all populations and end the HIV epidemic. The National HIV/AIDS Strategy (NHAS) for the United States focuses on four goals: preventing new HIV infections, improving HIV-related health outcomes of people with HIV, reducing HIV-related disparities and health inequities, and achieving integrated, coordinated efforts that address the HIV epidemic among all partners. Successful HIV programs must recognize the syndemics that affect the people and places disproportionately affected by HIV. A syndemic is population-level clustering of social and health problems. In the context of HIV, a syndemic is when HIV clusters with one or more other diseases or health conditions within a specific population, driven by the contextual, structural and social factors that increase the adverse effects on the health of people and communities. Syndemics may include HIV, STIs, TB, viral hepatitis, overdose, and substance use, and other existing and emerging conditions or factors that may be related to or impact HIV. The Ending the HIV Epidemic in the US (EHE) initiative focuses on scaling up four sciencebased strategies in communities most affected by HIV across the country. The strategies are to diagnose all people with HIV as early as possible; treat people with HIV rapidly and effectively to result in sustained viral suppression; prevent new HIV transmissions by using proven interventions, including condom distribution, pre-exposure prophylaxis (PrEP), postexposure prophylaxis (PEP), and syringe services programs (SSP); and respond quickly to potential HIV outbreaks to get vital prevention and treatment services to people who need them. Toward achieving national HIV prevention goals, the Centers for Disease Control and Prevention (CDC) funds state and local health departments and community-based organizations (CBOs) to plan, integrate, implement, evaluate, and sustain HIV prevention and surveillance programs, prioritizing people disproportionately affected by HIV including gay, bisexual, and other men who have sex with men, in particular Black, Latino, and American Indian/Alaska Native men, Black women, transgender women, youth aged 13-24, and people who inject drugs. Racism, HIV stigma, discrimination, homophobia, poverty, and barriers to health care continue to drive disparities in HIV prevention. Building individual competencies and technical expertise among staff, strengthening organizational capacities, and enabling supportive structural environments are critical strategies Page 5 of 81 in addressing operational challenges for more effective HIV prevention and surveillance programs. Reflecting CDC’s continued investment in improving the performance of the nation’s HIV workforce, this NOFO will support the provision of capacity building assistance (CBA) services, including training and technical assistance (TA).

The goal of the Activity is to improve the health, well-being, and protection of children and adolescents (and their families) living with, affected by, and vulnerable to HIV through high-impact service delivery and social service system strengthening to sustain an effective response for children, adolescents, and their families through locally led solutions in North West Province. The United States Agency for International Development (USAID) is seeking applications for acooperative agreement from qualified entities to implement the Children, Adolescents, andFamilies in the HIV Epidemic in North West Province Activity. Subject to funding availabilityand at the discretion of the Agency, USAID intends to provide up to $20 million in total USAIDfunding over a five (5) year period. Eligibility for this award is restricted to local entities (seeSection C.1 of this notice of funding opportunity (NOFO) for eligibility requirements of localentities). USAID encourages applications from potential new local partners. The Activity will beimplemented in the North West Province of South Africa.

The purpose of this program is to provide training and technical assistance (TTA) to domestic public and private non-profit entities that provide or support services intended for people who are experiencing challenges related to a substance use or co-occurring condition. Recipients will be expected to develop, implement, and maintain a TTA center that aligns with SAMHSA’s National Recovery Agenda.2 TTA activities will range from outreach and engagement to promotion of recovery and peer support. The vehicles used to deliver the TTA vary along a continuum from universal TTA (broad in scope; limited in depth, such as webinars), to more specific group-focused (such as learning collaboratives), to intensive (limited in reach, but deeper in-depth, such as onsite regular consultation or policy academies). The recipient will also partner with national, state, and local organizations and experts, including peer-run organizations and experts with lived experience to achieve required activities.

"Fluctuating cognition can occur in many types of dementia and is a core clinical feature of Dementia with Lewy Bodies. Cognitive fluctuations can last from seconds to days, are unpredictable (e.g., do not just occur in the evenings, as with sun-downing), and are associated with poor daily functioning for the patient. A number of small studies have suggested that cognitive fluctuations in subjects with dementia may be related to epileptiform discharges and impaired oscillatory activity on EEG, but it is not clear that these are the only factors involved in patient populations that often experience dysautonomia, orthostasis, and sleep disturbances. The etiology of cognitive fluctuations may be multi-factorial and may vary in different dementia populations. Understanding the physiology related to cognitive fluctuations is a critical next step to the development of treatment approaches and improving quality of life for these patients. This initiate would encourage research that will better characterize the physiology responsible for cognitive fluctuations in ADRD populations. Given their variable appearance and time course, it is anticipated that wearable digital devices will be important for capturing fluctuations in a timely fashion, and applicants should consider incorporating those device(s) capable of acquiring the relevant data to support the hypothesized mechanism(s). Applicants may focus on assessing multiple mechanisms in a specific ADRD population, or may chose to compare mechanisms across multiple types of ADRDs. "

This funding opportunity supports research on the ethical, legal, and social implications of human genetics and genomics, particularly focusing on diverse perspectives and community engagement.

This funding opportunity supports early-stage postdoctoral researchers in cancer research by providing resources for structured training and professional development to advance their scientific careers.

(Reissue PAR-21-056) The purpose of this Program Announcement (PAR) is to enable analytical validation of strong candidate biomarkers for neurological diseases and conditions. Specifically, the goal of this PAR is to enable the rigorous validation of analytical methods for biomarker measurements, including evaluation of the detection method, its performance characteristics, and the optimal conditions that will generate reproducibility and accuracy consistent with FDA guidelines. This PAR assumes that 1) a candidate biomarker has already been identified, 2) detection method technology has already been developed, and 3) the research and/or clinical need and potential context of use has been identified.

This grant provides funding for researchers to study how HIV and substance use disorder affect brain cell function, with the goal of uncovering new treatment strategies for individuals facing these combined challenges.

This funding opportunity supports researchers in conducting multi-site clinical trials to investigate the effects of natural products, such as botanicals and dietary supplements, on health, requiring a comprehensive plan for trial management and data analysis.

The purpose of the NINDS Postdoctoral Mentored Career Development Award is to support the ability of outstanding, mentored postdoctoral researchers to develop a potentially impactful research project with a comprehensive career development plan that will enable them to launch an independent research program. Candidates are encouraged to apply for support from this NINDS K01 any time between the second through fourth year of cumulative mentored postdoctoral research experience, and may be supported by this NINDS K01 within the first 6 years of cumulative postdoctoral research experience. Because the completion of a strong, well-planned, thorough career development plan, in addition to development of an impactful research project, is a critical aspect of this K01, applications are strongly encouraged early in the postdoctoral eligibility window. By the end of the proposed K01 award period, the candidate should be poised to begin an independent research career with a well-developed, impactful research project and the expertise required to become a leader in the field.This Funding Opportunity Announcement (FOA) is designed specifically for applicants proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary study to an existing trial, as part of their research and career development.