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Nigeria HIV Research Training Program

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NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Women comprise about 50% of the 36.7 million people living with HIV worldwide and in many sub-Saharan African countries including Nigeria, ~2 out of 3 HIV infected adults are women. Even more worrisome is the observation that overwhelming number of new infections in Nigeria occur among young women of childbearing age, and as such, one-third of all global cases of mother-to-child transmission of HIV occurs in the country. Not only is the burden of HIV higher in women, the impact of its scourge is far more reaching. HIV is the leading cause of morbidity and mortality among women of reproductive age in Nigeria. HIV complicates every aspect of health across a woman’s lifespan, including reproductive health where it impacts partner sero-sorting and sexual habits, fertility desires and contraceptive choices, pregnancy and delivery, menopause and aging. Tackling the myriads of health challenges confronting women living with HIV is a necessary step to achieving the WHO global strategy for women’s, children’s and adolescent health. It will require nurturing a critical mass of local health scientists and equipping them with the skills to conduct valid research that addresses the local health needs of women living with HIV. To address these needs, we established the Emory-Nigeria HIV Research Training Program (EN-RTP). The EN-RTP leverages the research education infrastructure at Emory University and the partnering Nigerian institutions (Nigerian Institute of Medical Research (NIMR); University of Lagos (UNILAG); and AIDS Prevention Initiative Nigeria (APIN)) to provide state-of-the-art in-country research training with focus on methodologies, rigorous mentorship, and grant management capacity building. The EN-RTP training is focused on three main domains of HIV/women’s health research: a) HIV prevention and reproductive health; b) Challenges in HIV therapeutics unique to women living with HIV (WLWH); and c) Complications of chronic HIV infection relevant to WLWH. Preceptors are selected based on their expertise in these areas and their international research education and mentoring experience. We can report that the EN- RTP is now an established program with a cohesive administrative structure and program plan that includes both didactic and mentored research components implemented by a multidisciplinary team of in-country faculty and US-based investigators who have a wide range of mentoring experiences. The short- and medium-term accomplishments include high scholar productivity (over $3M in grant funding, including 3 NIH K 43 awards and more than 150 peer-reviewed publications by trainees), fostering robust scientific networking opportunities, developing emerging in-country scientific leaders, and nurturing the next generation of HIV research mentors. The EN-RTP has demonstrated a potential to be truly transformative in promoting mentored research training and the growth of the HIV biomedical research workforce. Committed to the primary goal of capacity building in HIV research, we look forward with enthusiasm the next cycle – particularly the opportunity to pilot new initiatives and best practices arising from our evaluation processes to enhance program outcomes.

Up to $270K
2028-12-31
health research

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

Nigeria HIV Research Training Program

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FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Women comprise about 50% of the 36.7 million people living with HIV worldwide and in many sub-Saharan African countries including Nigeria, ~2 out of 3 HIV infected adults are women. Even more worrisome is the observation that overwhelming number of new infections in Nigeria occur among young women of childbearing age, and as such, one-third of all global cases of mother-to-child transmission of HIV occurs in the country. Not only is the burden of HIV higher in women, the impact of its scourge is far more reaching. HIV is the leading cause of morbidity and mortality among women of reproductive age in Nigeria. HIV complicates every aspect of health across a woman’s lifespan, including reproductive health where it impacts partner sero-sorting and sexual habits, fertility desires and contraceptive choices, pregnancy and delivery, menopause and aging. Tackling the myriads of health challenges confronting women living with HIV is a necessary step to achieving the WHO global strategy for women’s, children’s and adolescent health. It will require nurturing a critical mass of local health scientists and equipping them with the skills to conduct valid research that addresses the local health needs of women living with HIV. To address these needs, we established the Emory-Nigeria HIV Research Training Program (EN-RTP). The EN-RTP leverages the research education infrastructure at Emory University and the partnering Nigerian institutions (Nigerian Institute of Medical Research (NIMR); University of Lagos (UNILAG); and AIDS Prevention Initiative Nigeria (APIN)) to provide state-of-the-art in-country research training with focus on methodologies, rigorous mentorship, and grant management capacity building. The EN-RTP training is focused on three main domains of HIV/women’s health research: a) HIV prevention and reproductive health; b) Challenges in HIV therapeutics unique to women living with HIV (WLWH); and c) Complications of chronic HIV infection relevant to WLWH. Preceptors are selected based on their expertise in these areas and their international research education and mentoring experience. We can report that the EN- RTP is now an established program with a cohesive administrative structure and program plan that includes both didactic and mentored research components implemented by a multidisciplinary team of in-country faculty and US-based investigators who have a wide range of mentoring experiences. The short- and medium-term accomplishments include high scholar productivity (over $3M in grant funding, including 3 NIH K 43 awards and more than 150 peer-reviewed publications by trainees), fostering robust scientific networking opportunities, developing emerging in-country scientific leaders, and nurturing the next generation of HIV research mentors. The EN-RTP has demonstrated a potential to be truly transformative in promoting mentored research training and the growth of the HIV biomedical research workforce. Committed to the primary goal of capacity building in HIV research, we look forward with enthusiasm the next cycle – particularly the opportunity to pilot new initiatives and best practices arising from our evaluation processes to enhance program outcomes.

Up to $30K
2028-12-31
health research

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

Non-canonical BRAF mutations in AML development and therapeutic response

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NCI - National Cancer Institute

Project Summary/Abstract Acute myeloid leukemia (AML), the most common type of adult acute leukemia, originates from somatic mutation(s) which results in impaired differentiation and aberrant proliferation of hematopoietic stem/progenitor cells. We recently identified recurrent mutations in the gene BRAF, which encodes an integral kinase in the RAS/MAPK/ERK signaling pathway, in AML patients. Divergent from other cancer subtypes, the majority of the BRAF mutations we identified were outside of the well-characterized V600 codon hotspot and therefore, noncanonical mutations. Moreover, the presence of a BRAF mutation correlated with dismal survival outcomes for these AML patients, regardless of therapeutic regimen, suggesting that BRAF mutations may drive therapeutic resistance to front-line AML therapies. This is in contrast with other RAS/MAPK pathway mutant AMLs, which typically respond to the front-line chemotherapy regimens. Our preliminary data in novel BRAF-mutant mouse models indeed confirms these findings from our BRAF-mutant AML clinical cohort. Therefore, our understanding of how BRAF and more broadly, the RAS/MAPK pathway, can contribute to AML pathogenesis and drive therapeutic resistance remains incomplete. In this proposal, state-of-the-art approaches and models will be applied to interrogate innovative concepts in novel, genetically engineered mouse models (GEMM) and patient derived xenografts (PDX). Specifically, we will delineate the contributions of BRAF mutations to leukemogenesis, disease phenotype, and therapeutic response through a combination of single cell multiomic analysis of primary AML samples and functional dissection of BRAF-mutant GEMMs and BRAF-mutant AML PDXs. We expect to elucidate aberrant BRAF-driven signaling pathways and how these mechanisms alter hematopoietic output and cellular response to therapeutic agents. To achieve this, we will discover and examine abnormal hematopoietic output, dysregulated transcriptional programs, and rewired signaling pathway that are specific to leukemic clones harboring BRAF mutations (Aim 1). Next, we will interrogate mechanisms in BRAF-mutant cells that lead to resistance to front-line AML therapies and assess potential efficacious therapies for BRAF-mutant AML (Aim 2). The use of genetically engineered mouse models provides critical isogenic systems to dissect the contribution and impact of BRAF mutations in AML development without the vast heterogeneity and complexity observed in AML patient samples. Moreover, therapeutic studies in BRAF-mutant PDX models in vivo allow for insight into systemic effects of therapies in a native context and uncover important contributions of the bone marrow niche to therapeutic response. In sum, the proposed work will dissect critical contributions of BRAF mutations, and more broadly aberrant functions of RAS/MAPK pathway proteins, to AML pathogenesis and response to therapy to inform and develop novel therapeutic strategies that will improve AML patient outcomes.

Up to $522K
2031-06-30
health research

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

Normal and Pathological Musculoskeletal Loss and Repair

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NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

Project Summary The purpose of this ‘A1 Single-Year NIAMS/NCI R13 Research Conference Grant’ is to host the highest impact scientific and mentoring conference on “Bone: Musculoskeletal Tumor Perspectives’ that will bring together translational and clinical investigators from diverse specialties. Musculoskeletal Tumor Society (MSTS) is the primary host organization that will partner with OREF, ORS, AAOS, and JOR. Musculoskeletal Oncology is a distinct hybrid clinical and research field that requires the solution to 3 distinct problems: ‘Diagnosing’ and ‘Treating’ molecular oncogenesis of MSK tissues and ‘Reconstructing’ afflicted tissue structures to restore limb function. Due to underlying oncological pathophysiology and massive skeletal defects, traditional orthopaedic treatments using trauma or arthroplasty disciplines were associated with high rate of complications. Furthermore, no cross-disciplinary research and mentoring endeavors on bone tumors have not been offered. Many bone and osteoclast-associated molecules were discovered from bone diseases and tumors such as the giant cell tumor of bone. The last AAOS-initiated R13 Conference was in 2017. There is a serious issue of discontinuation of clinician scientists and basic scientists who conduct cross-disciplinary research on bone and reconstruction science from a perspective of musculoskeletal tumors. There is an urgent need to host a R13 conference to offer mentorship for emerging investigators and to develop new collaborations. Our innovative meeting format features sessions addressing challenging clinical problems with plenary overview talks by experts on state-of the art techniques (spatial biology, artificial intelligence, novel signaling & targeted therapies, novel skeletal stem cells, RNA/DNA therapeutics, 3D printed custom device, and mixed reality). We will invite junior surgeon-scientists to present their innovative solutions in mentoring sessions where a panel of established investigators will critique proposed strategies and Specific Aims in a live multi-disciplinary “study section”. ESI selection criteria are based on one-page Specific Aims that summarizes clinical barriers, hypothesis-/technology-driven scientific and clinical investigation plans, and specific needs for mentorship. A meet-the-mentors session will be set up to foster multi-disciplinary collaboration among mentors and emerging surgeon-scientists, engineers, and basic scientists. In order to facilitate networking and matching mentors- mentees, the meeting phone Apps and website will list mentors and participants with well-prepared research ideas (Specific Aims) and other scientific abstracts. Two Specific Aims are Aim 1. Innovative Mentorship for Emerging Clinicians and Scientists; and Aim 2. Dissemination of Cross-Disciplinary New Knowledge and Techniques for New Collaborations and Enhanced Patient Care. A stand-alone R13 conference could be ideal but too costly for meeting space rent, audio/visual services, and support for young investigators. The R13 Conference will be strategically held immediately prior to the 50th MSTS Annual Meeting for cost reduction and improved participation from clinicians, scientists, allied health care workers, and industry R&D staffs.

Up to $20K
2027-05-31
health research

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

Nothing about us without us: Integrating the voices of people who use drugs into HIV resource allocation using large language models

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NIDA - National Institute on Drug Abuse

This project will develop and apply a novel, data-driven modeling approach to guide HIV and hepatitis C virus (HCV) prevention resource allocation among people who use drugs (PWUD) in the United States. Despite advances in HIV prevention and treatment, including long-acting injectable ART, the United States continues to fail to meet the needs of PWUD, a population central to intersecting HIV, HCV, and overdose crises. A key reason is the absence of a rapid, scalable, and comprehensive way to capture and act on the preferences and behaviors of PWUD. Revolutionary advances in large language models (LLMs) now make it possible to create highfidelity “digital twins” — artificial-intelligence powered simulations of individuals that reflect their intervention preferences and even behaviors. Using a community-based participatory process, we will train an LLM on data from multiple PWUD cohorts to generate PWUD digital twins that simulate locally-specific intervention preferences. These digital twins will be integrated into an epidemic and economic model that simulates HIV and HCV transmission, overdose, and related complications, across numerous jurisdictions in the United States. The integrated modeling framework will be used to evaluate the impact and cost-effectiveness of different HIV/HCV prevention and treatment strategies, including responses to potential funding constraints. Epidemic model outputs will be shared through an interactive dashboard designed in consultation with public health departments. Ultimately, our project aims to improve intervention implementation and reduce HIV, HCV, and overdose. Our project includes the following activities: 1) Co-design, development, and validation of a PWUD-informed LLM. 2) Digital twin simulations within a HIV/HCV transmission and overdose model to inform resource allocation. 3) Dissemination and implementation of the epidemic and resource allocation dashboard to county health departments. The proposed research will enable rapid, data-driven evaluation of prevention strategies and resource allocation options. It aligns with the NIH Office of AIDS Research priority to reduce new HIV infections and address HIV coinfections.

Up to $1.1M
2031-03-31
health research

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

Novel Approaches for Gestational E-Cigarette Vaping-Induced Neuronal Adaptations

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NIEHS - National Institute of Environmental Health Sciences

PROJECT SUMMARY Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and is perpetuated by the perception that e-cigs are less harmful than traditional combustible cigarettes. Recent estimates show 7% of women use e-cigs in pregnancy, and 45% view them as less harmful and may help them quit or reduce combustible cigarettes in pregnancy. An extensive knowledge gap persists regarding their health impact when aerosolized, especially during pregnancy. Using our well-established pregnant rat model, we obtained preliminary data utilizing a state-of-the-art e-cig system with a commercial e-cig unit and atomizer that offered a translational inhalation delivery and generated vapor profiles directly comparable to human vaping. Our preliminary data demonstrated that a cardinal outcome of e-cig use was a significant fetal and neonatal growth deficit. Concomitant with growth restriction, our exciting preliminary data provides direct evidence that e-cig vaping significantly alters developmental brain hippocampal mTOR system. As a critical node, mTOR regulates essential brain metabolic activities, including protein synthesis and autophagy. Interestingly, our new preliminary data indicate that these mTORC1 and mTORC2 signaling adaptations were accompanied by altered fetal hippocampal dendritic morphology and hippocampal-dependent long term memory deficits. We subsequently generated critical preliminary data that demonstrated that optimizing mTORC1/C2 activity via in vivo administration of the 3rd gen mTORC1/C2 blocker (RapaLink-1) concomitant with e-cig aerosol exposure reversed specific e-cig-induced fetal developmental phenotypes. Thus, we hypothesize that the mTOR system plays a central role in e-cig induced alterations in fetal brain hippocampal adaptations. To test this hypothesis, we will (1) seek to answer fundamental questions about the impact of e-cig aerosol exposure on hippocampal mTORC1/C2 system using novel mechanistic in vivo studies, (2) assess the role of mTOR in e-cig-induced fetal brain hippocampal developmental adaptations using morphometric, stereological and behavioral approaches, and (3) identify e-cig-induced protein signal propagation pathways leading to activation of mTOR and signal propagation downstream of mTORC1/C2 utilizing mass spectrometry- based phosphoproteomics followed by stochastic optimization and reinforcement learning algorithms. We will then compare and interpret the signature pathways impacted by e-cig vaping with and without mTOR blocker using machine learning models. Upon successful completion of these aims, we will have comprehensively characterized the mTOR signaling cascade as it transduces cues from e-cig vaping into molecular action, enabling the identification of potential strategies to mitigate e-cig-induced neurodevelopmental deficits in the hippocampus. The proposed studies develop a strong etiological framework and directly address a “major research area” of developmental impacts under Theme One of NIEHS Strategic Plan 2018-2023, titled “Advancing Environmental Health Sciences”.

Up to $2.1M
2030-05-31
health research

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

Novel approaches to predict strength and breadth of influenza vaccine response

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NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Influenza vaccines remain the most cost-effective tool for reducing infection and disease burden. However, despite decades of research and development, the protection they provide is often suboptimal. A key challenge is the wide variability in vaccine induced immune responses among individuals, which is poorly understood. Addressing this knowledge gap is crucial for improving vaccine efficacy and vaccination strategies. Predictive modeling, with its demonstrated success in advancing medical research and public health, holds significant promise in this regard. By harnessing predictive models, we can tailor vaccination strategies to individuals, optimizing protection and improving outcomes. Current predictive models, however, suffer from critical limitations. Most rely solely on static, pre- vaccination data and focus narrowly on antibody responses to a single vaccine component (in current vaccines, these are H3N2, H1N1 and one or two of the B lineages). Existing models do not account for the dynamic nature of the immune system or the role of heterologous, non-vaccine-specific antibody responses, reducing their accuracy and practical utility. These shortcomings hinder the development of more comprehensive, adaptable models for predicting vaccine efficacy across diverse populations and viral strains. This project aims to overcome these limitations by developing and validating advanced predictive models for influenza vaccine responses. Our approach integrates systematically collected, longitudinal data with state-of-the-art statistical and machine-learning methods. Specifically, we will: 1. Develop predictive models that incorporate long-term antibody response trajectories and heterolo- gous strain data to improve predictions for vaccine strain responses. 2. Expand the scope of these models to predict heterologous breadth and overall antibody responses, offering a more complete understanding of vaccine-elicited immunity. 3. Generate and analyze high-throughput antibody landscape data to further refine and enhance our predictive models. By combining these innovations, we aim to establish a new framework for individualized vaccine re- sponse prediction. This framework will significantly improve upon existing models, enabling tailored vac- cination strategies designed to optimize protection for each individual. Ultimately, this work will provide a robust scientific foundation for guiding future influenza vaccination efforts, contributing to better public health outcomes worldwide.

Up to $806K
2031-04-30
health research

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

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