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24 grants worth up to $13.3M match your search

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Our Family, Our Voices: An Efficacy Trial Of An Intervention Utilizing Family-Based Assets To Optimize HIV Prevention And Care Outcomes For Black Sexual and Gender Minorities In House Ball Communities

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NIMHD - National Institute on Minority Health and Health Disparities

Originating within urban Black and Latinx communities, the House Ball Community (HBC) is a gender- and sexuality expansive population facing overlapping hardships such as stigma and family rejection that contribute to their overrepresentation in the HIV epidemic. The HBC population, estimated at 8,000 nationwide, is concentrated in New York City (NYC) with growth in the US South and includes a large proportion of Black Gender and Sexual Minority (BGSM) individuals, primarily Black and Latinx gay men who have sex with men (MSM) and transwomen and men. BGSM remain deeply impacted by the US HIV epidemic, with low uptake of pre-exposure prophylaxis (PrEP) and limited HIV care engagement due to stigma and systemic barriers, particularly in the US South. Despite the HBC’s longstanding role as a site for advocacy and normative change within the broader BGSM community, the HBC has received minimal targeted HIV treatment/prevention efforts and remains severely understudied. Our Family, Our Voices (OFOV) addresses these gaps through a community-driven, HIV status-neutral, gender-expansive, group-level intervention developed in collaboration with the HBC. Leveraging the HBC’s hierarchical family structure (e.g., house mother, house father), OFOV’s intervention format includes a family-based retreat for HBC members to empower them to advocate for their own health, cultivate leadership skills, and improve clinical outcomes. OFOV builds on core elements of Many Men, Many Voices (3MV), the only CDC “best evidence” intervention for Black gay MSM that has demonstrated increased HIV testing rates. Previously adapted in NYC (R34 MH124082), OFOV has shown feasibility, but further research in a powered study is needed to evaluate efficacy and scalability across 3 areas, including NYC: Aim 1 (pre-intervention phase): Tailor OFOV materials to local contexts through collaborations with indigenous Black gay CBOs in Atlanta and Dallas. Aim 1 (intervention phase): Conduct a cluster-randomized stepped wedge trial with 27 HBC houses (≥ 20 members each) to evaluate OFOV’s efficacy. Primary outcomes include engagement and retention in HIV prevention (testing, PrEP) and care (antiretroviral therapy (ART), viral suppression) at baseline, 3, 6, and 12-months post-intervention, with 24- and 36- month maintenance periods. Hypotheses include increased leadership skills and HIV-related self-efficacy. Aim 2 (post-intervention phase): Use a mixed-methods approach to identify contextual factors influencing OFOV adoption and implementation. Aim 2 (post-intervention phase): Explore how leadership training impacts community norms and behaviors, hypothesizing high acceptability and adaptability across geographic and cultural settings. The NIMHD framework will guide qualitative work (in Aims 1 and 2) with HBC members and house leaders (directly exposed and unexposed to OFOV) to assess individual, interpersonal, and community-level barriers and facilitators to sustainability. Collaborations with HBC leaders, CBOs, and a multidisciplinary team will ensure cultural relevance, sustainability, and implementation feasibility across jurisdictions.

Up to $1.3M
2030-11-30
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Pacific Center for Artificial Intelligence and Data Science in Medicine (PAC-AID)

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NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY – Overall It is predicted that virtually every type of clinician will use data science, such as artificial intelligence (AI) and machine learning (ML), in the future. Further, AI/ML is expected to play a dominant role across medical disciplines throughout the human lifespan. The utilization and ultimate training of deep learning models require specialized education and skills. The curation and processing of large datasets from locally sourced patient populations requires a curation and analysis team with specialized knowledge of transferring medical data between sites and potentially federated learning. Adding to this complexity is the potential for bias when diagnostic models are trained on datasets that don’t contain the characteristics of the population utilizing the model. There is a need to develop a talented AI and data science biomedical workforce that is trained in innovative approaches to working with large research datasets. In response to the Notice of Special Interest (NOSI): Supporting Data Sciences Research in IDeA States through the Centers of Biomedical Research Excellence (COBRE) Phase 1 Program (NOT-GM- 23-011), we propose to create the Pacific Center for Artificial Intelligence and Data Science in Medicine (PAC-AID). The long-term goal of the PAC-AID is to form self-sustaining core facilities and an AI and biomedical data science program that continually trains investigators to utilize advanced data science to utilize all available biomedical data sources to improve health outcomes in Hawaii and the Pacific region. The objective is to create a nucleating site for the use of AI/ML data science technologies to further our understanding of human health in communities in Hawaii. Specifically, we will 1) foster a next-generation workforce to conduct biomedical research using Artificial Intelligence and advanced machine learning; 2) develop interactive state-of-the-art research cores and projects that support training opportunities for local investigators and foster collaboration across the national IDeA network; 3) establish a supportive Advisory Committee and Mentoring Team of academic leaders and content experts to provide the investigators and RPLs guidance on the successful completion of the Center’s and RPLs’ goals. The expected outcome of the PAC-AID is to form a synergistic environment for investigators to integrate AI and advanced machine learning into problems that were not solvable before. The positive impact on the state and large US community will be experienced investigators in various fields who can take full advantage of complex clinical, translational, and basic research data using AI and advanced data science methods.

Up to $2.6M
2031-02-28
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Partial Heart Transplantation: Clinically Relevant Aspects of Transplant Biology

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NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Heart valve replacement in children is marred with problems because state-of-the art heart valve implants do not grow. This commits affected children to serial re-operations to replace outgrown valve implants. Partial heart transplantation (PHT) is a new approach to deliver growing heart valve implants that is based on transplantation. PHT differs from heart transplantation (HT) because only the part of the heart containing the necessary heart valve is transplanted, while the native ventricles are spared. Sparing the native ventricles eliminates ventricular dysfunction from chronic rejection or ischemic injury and increases the donor pool. Importantly, PHTs grow adap- tively with recipient children. This avoids morbid re-operations to replace outgrown valve implants. However, PHT transplant biology remains unexplored. This is a critical barrier to progress of the field. Without knowledge of PHT transplant biology, clinical protocols cannot be tailored to children with PHTs. Instead, children with PHTs are empirically treated according to HT clinical protocols because the valves contained in HTs are known to grow. The proposed project seeks to advance the field by exploring clinically relevant aspects of PHT transplant biology. This will contribute the evidence-base for clinical protocols tailored to children with PHTs. The central hypothesis is that the transplant biology of PHT differs from HT, which allows for longer donor ischemia times (Aim 1), less stringent recipient immunosuppression (Aim 2) and ABO incompatible transplantation (Aim 3). This hypothesis is based on preliminary data. The approach for the proposed project leverages a unique piglet model and innovative outcome measures for valve growth including leaflet length echocardiography. The central hy- pothesis will be tested by completing the following specific aims: (1) model the effect of ischemia time on PHT growth potential and function; (2) determine the optimal immunosuppression strategy for PHT; (3) determine the effect of donor antigen variability on PHT growth potential and function. Achieving these aims will contribute evidence-based protocols specifically tailored to PHT. Protocols tailored to PHT will improve clinical practice by decreasing the morbidity and mortality of PHT. This is significant because PHT is a game-changer for children with unrepairable heart valve defects. It is also innovative because it is non-derivative, and a radical departure from the status quo for growing heart valve implants. The proposed project shifts research and clinical paradigms for growing heart valve implants using this new theoretical concept based on transplantation. This new clinical intervention opens new horizons for children who need heart valve replacements because it eliminates the mor- bidity and mortality of serial implant exchanges as the children grow.

Up to $801K
2031-02-28
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Pathways and Mechanisms of Drug Resistance Evolution in HIV

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NIAID - National Institute of Allergy and Infectious Diseases

PROJECTSUMMARY/ABSTRACT There are ~40 million people worldwide living with the Human Immunodeficiency Virus Type 1 (PLWH), commonly referred to as HIV. In the absence of a functional cure, antiretroviral therapy (ART) represents the primary treatment option. However, ART fails over time due to the development of drug resistance, even against latest generation drugs. Thus, there is an urgent need to understand the pathways and mechanisms through which resistance emerges, which can then be harnessed for developing next-gen therapeutics to specifically target drug-resistant variants. The proposed research seeks to elucidate the mutational pathways and molecular mechanisms through which resistance evolves against the latest ART drugs. Firstly, a Potts sequence- covariation fitness landscape model built on HIV sequences from the Stanford HIV database will be used to determine the epistatic interactions modulating drug resistance and to identify the specific sequential order in which mutations arise forming pathways to complex resistant variants. This aim builds directly from the candidate’s doctoral research developing the Potts fitness landscape models for HIV. Secondly, a combination of structural biology using cryogenic electron microscopy (cryo-EM) and multiscale molecular simulations will be employed to determine the atomistic mechanisms of resistance against latest generation ART drugs. This aim builds on the candidate’s ongoing training in cryo-EM and will serve as a vehicle to obtain complementary research skills in protein biochemistry, and hybrid quantum mechanics molecular mechanics simulations. Finally, in the independent phase, the project aims to combine the Potts fitness landscape models, structural biology and molecular simulations within a Reinforcement Learning (RL) framework, a state-of-the art artificial intelligence (AI) method, to forecast the evolution of drug resistance in HIV. The aim will prognostically predict the dominant emerging pathway trajectories and mechanisms in the PLWH population to prospectively inform the design of optimum therapeutic strategies. The principles learned (by the RL model) and the methodology developed can be applied to forecast emerging resistance in other RNA viruses including those with scarce data. This aim builds on the candidate’s ongoing training in AI methods through the Eric & Wendy Schmidt AI-in- Science Fellowship and combines the multidisciplinary research methods and training obtained through his doctoral and postdoctoral tenure. Overall, the project seeks to produce critical insights into the mechanisms of HIV evolution under drug selection pressure that can help design next generation therapeutic strategies targeting resistant strains and lead to the development of surveillance tools to monitor and forecast emerging drug resistance. The career development plan will take place at The Salk Institute and provide an important opportunity for training and development that will prepare the candidate to start his independent research career.

Up to $162K
2028-05-31
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Pathways from Chronic Methamphetamine Use to Neurological Dysfunction in People with HIV: High-Dimensional Fusion of Systems Biology and Multimodal Neuroimaging

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NIDA - National Institute on Drug Abuse

Project Summary/Abstract People with HIV (PWH) remain at an elevated risk of developing cognitive impairments. Such impairments are the most common neurological complication of HIV disease, and research targeting these comorbidities is one of four overarching priorities identified by the Office of AIDS Research (NOT-OD-20-018). Over the past decade, our work has focused on identifying the neurological origins of these impairments and determining the impact of substance use, which has led to the exciting discovery of neurophysiological markers that distinguish cognitively impaired PWH from unimpaired PWH, patients with Alzheimer’s disease or mild cognitive impairment, and healthy aging controls. We now propose to embark on the next stage of this research program through a transformational team science project, which will leverage these markers as primary outcomes in high-dimensional models that include key molecular pathways thought to be aberrant in PWH and methamphetamine use disorder (METH). The molecular precursors and pathways that lead to dysfunction in neural circuits serving cognitive processing in PWH remain poorly understood, and this is a critical barrier to the development of new pharmacotherapeutics. Given the scale and complexity of this barrier, we contend that a team science approach is required to deliver the transformational discoveries that are ultimately needed to significantly advance the field. Thus, we have assembled a multidisciplinary team with expertise in neuroHIV, addiction science, clinical psychology, systems biology, cognitive and computational neuroscience, signal processing, neurophysiology, and machine learning. Our overarching hypotheses are that HIV and chronic methamphetamine use imbalances mitochondrial redox environments, triggering increases in inflammation and elevated subcortical iron levels in key brain structures, which then leads to altered neurotransmitter levels, aberrant oscillations and neurophysiological dynamics, and ultimately, cognitive decline in PWH. To address this, our team science approach will enable the latest tools of systems biology to be integrated with state-of-the-art multimodal neuroimaging using both high-dimensional structural equation modeling and advanced variants of machine learning. We will maximize rigor by using a large, deeply-phenotyped sample of PWH and METH who are demographically matched to three other groups who vary based on HIV and METH status in the context of a longitudinal study. Importantly, if confirmed, treatments aimed at this molecular pathway could have a major impact, as we have repeatedly shown that the end point (i.e., altered brain dynamics) distinguishes cognitively impaired PWH from unimpaired PWH and those with other forms of cognitive dysfunction. In sum, while past studies have provided critical advances on the neural circuitry and dynamics underlying cognitive impairments in PWH who do and do not use illicit substances, the primary mechanisms and pathways leading to such dysfunction have remained beyond reach. Herein, we will use a high- dimensional computational approach to identify the modulatory role of mitochondrial redox environments and inflammation on subcortical brain iron, neurotransmitter levels, neuronal dynamics, and cognitive dysfunction.

Up to $2.2M
2031-03-31
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

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