Search Grants — Free, No Account Required

Northwest Share

Northwest Share will be hosting the Diwali Lights of India Festival on November 2, 2024, located at the Armory at Seattle Center, 305, Harrison St from 12pm to 6pm. The festival showcases Arts and culture of India through live music, dance performances, workshops, and various arts and crafts. This family friendly event is free and open to the public.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY ADP-ribosylation is a modification used across domains of life to mediate biological conflicts. The covalent attachment of ADP-ribose to diverse substrates ranging from proteins and small molecules to nucleic acids can render the target inaccessible or inactive. DNA targeting ADP-ribosylation has received less attention than the modification of other substrates, but is increasingly thought to be a widespread strategy in both interbacterial conflicts and in anti-phage defense mechanisms. DNA ADP-ribosylation was discovered in bacteria less than ten years ago, and therefore despite the prevalence of this modification, little is known about its biological function. My postdoctoral research provided a major advance for the field by revealing that a widely distributed bacterial DNA targeting ADP-ribosyltransferase (ART) toxin is the effector of a family of phage defense systems, thus ascribing a clear biological function to these enzymes. DNA targeted ADP-ribosylation blocks DNA replication and is accordingly highly toxic in bacterial cells but also potently anti-viral. These bacterial DNA targeting ARTs, a family termed DarT, are normally kept inactive by a cognate, neutralizing antitoxin, DarG, which is a DNA targeting ADP-ribosylglycohydrolase (ARG). Many fundamental questions remain about the biology of DarTG systems, including how the DarT toxin becomes active after phage infection. Phages, a co-evolving biological entity, are also a rich source of anti-DNA ART mechanisms. We recently discovered that some phages have co-opted DarG-like proteins and related DNA ARGs on multiple occasions, and that these “orphan antitoxins” protect these phages from DarTG-mediated defense. Thus, as with DarT, we were able to ascribe a biological function to a widespread family of previously mysterious phage enzymes. The distribution of DNA ARGs across the tree of life further suggests that DNA ADP-ribosylation is almost certainly more widespread than currently appreciated. The major goals of this study are both to investigate the underlying biology of DarTG systems in their biologically relevant context of phage infection, as well as to develop and apply cutting edge bioinformatic approaches to identify novel DNA ART and ARG families. To this end, we will pursue the following aims: 1) elucidate the molecular mechanism by which phage infection activates DarTG1 using genome-wide, single-cell, and in vitro approaches; 2) investigate the specificity and diversity of phage- encoded DNA ARGs and other phage anti-DNA ART counter-defenses, and 3) mechanistically dissect a third, unstudied DarTG family and develop methods for discovery of additional DarT- and non-DarT-related DNA ARTs. The discoveries we make in this bacterial-phage system, with its powerful experimental and genetic tools, will reveal fundamental facets of DNA ART and ARG biology relevant to the bacterial immune system and lay the groundwork for future studies of anti-viral DNA ADP-ribosylation in eukaryotes.

Dept. of the Army -- USAMRAA

<p>The USAMRDC’s mission is to provide solutions to medical problems of importance to the American Service Member at home and abroad, as well as to the general public at large. The scope of this effort and the priorities attached to specific projects are influenced by changes in military and civilian medical science and technology (S&amp;T), operational requirements, military threat assessments, and national defense strategies. Extramural research and development programs play a vital role in the fulfillment of the objectives established by the USAMRDC. General information on the USAMRDC can be obtained at https://mrdc.health.mil/.</p><p>This BAA is intended to solicit extramural research and development ideas using the authority provided by 10 USC 4001. The BAA is issued under the provisions of the Competition in Contracting Act of 1984 (Public Law 98-369), as implemented in FAR 6.102(d)(2) and 35.016 and in Department of Defense Grant and Agreement Regulations (DoDGARs) 22.315. In accordance with FAR 35.016, projects funded under this BAA must be for basic and applied research to support scientific study and experimentation directed toward advancing the state-of-the-art or increasing knowledge or understanding rather than focusing on development of a specific system or hardware solution. Research and development funded through this BAA are intended and expected to benefit and inform both military and civilian medical practice and knowledge. This BAA utilizes competitive procedures in accordance with 10 USC 3012 for the selection for award of S&amp;T proposals/applications. For the purposes of this BAA, S&amp;T includes activities involving basic research, applied research, advanced technology development, and, under certain conditions, may include activities involving advanced component development and prototypes.</p><p>The selection process is highly competitive, and the quantity of meaningful submissions (both pre-proposals/pre-applications and full proposals/applications) received typically exceeds the number of awards that available funding can support.</p><p>This BAA provides a general description of USAMRDC’s research and development programs, including Research Areas of Interest, evaluation and selection criteria, pre-proposal/ pre-application and full proposal/application preparation instructions, and general administrative information. Specific submission information and additional administrative requirements can be found in the document titled, “General Submission Instructions,” which is available on Grants.gov along with this BAA.</p><p>The FY23-FY27 USAMRDC BAA is continuously open for a 5-year period, from October 1, 2022 through September 30, 2027, at 11:59 p.m. Eastern Time. Submission of a pre-proposal/pre-application is required and must be submitted through the electronic Biomedical Research Application Portal (eBRAP) (https://eBRAP.org/). Pre-proposals/pre-applications may be submitted at any time throughout the 5-year period. If the USAMRDC is interested in receiving a full proposal/application, the Principal Investigator will be sent an invitation to submit via eBRAP. A full proposal/application must be submitted through Grants.gov (http://www.grants.gov/). Invited full proposals/applications can be submitted under this FY23-FY27 BAA through September 30, 2027.</p>

Defense Health Agency Contracting Activity - DHACA

The USAMRDC s mission is to provide solutions to medical problems of importance to the American Service Member at home and abroad, as well as to the general public at large. The scope of this effort and the priorities attached to specific projects are influenced by changes in military and civilian medical science and technology (S&amp;T), operational requirements, military threat assessments, and national defense strategies. Extramural research and development programs play a vital role in the fulfillment of the objectives established by the USAMRDC. General information on the USAMRDC can be obtained at https://mrdc.health.mil/.This BAA is intended to solicit extramural research and development ideas using the authority provided by 10 USC 4001. The BAA is issued under the provisions of the Competition in Contracting Act of 1984 (Public Law 98-369), as implemented in FAR 6.102(d)(2) and 35.016 and in Department of Defense Grant and Agreement Regulations (DoDGARs) 22.315. In accordance with FAR 35.016, projects funded under this BAA must be for basic and applied research to support scientific study and experimentation directed toward advancing the state-of-the-art or increasing knowledge or understanding rather than focusing on development of a specific system or hardware solution. Research and development funded through this BAA are intended and expected to benefit and inform both military and civilian medical practice and knowledge. This BAA utilizes competitive procedures in accordance with 10 USC 3012 for the selection for award of S&amp;T proposals/applications. For the purposes of this BAA, S&amp;T includes activities involving basic research, applied research, advanced technology development, and, under certain conditions, may include activities involving advanced component development and prototypes.The selection process is highly competitive, and the quantity of meaningful submissions (both pre-proposals/pre-applications and full proposals/applications) received typically exceeds the number of awards that available funding can support.This BAA provides a general description of USAMRDC s research and development programs, including Research Areas of Interest, evaluation and selection criteria, pre-proposal/ pre-application and full proposal/application preparation instructions, and general administrative information. Specific submission information and additional administrative requirements can be found in the document titled, General Submission Instructions, which is available on Grants.gov along with this BAA.The FY23-FY27 USAMRDC BAA is continuously open for a 5-year period, from October 1, 2022 through September 30, 2027, at 11:59 p.m. Eastern Time. Submission of a pre-proposal/pre-application is required and must be submitted through the electronic Biomedical Research Application Portal (eBRAP) (https://eBRAP.org/). Pre-proposals/pre-applications may be submitted at any time throughout the 5-year period. If the USAMRDC is interested in receiving a full proposal/application, the Principal Investigator will be sent an invitation to submit via eBRAP. A full proposal/application must be submitted through Grants.gov (http://www.grants.gov/). Invited full proposals/applications can be submitted under this FY23-FY27 BAA through September 30, 2027.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Immune tolerance remains the goal of allogeneic human organ transplantation in order to achieve safe and long-term transplant function. If achieved, tolerance would reduce the need for retransplants by substantially prolonging the durability of organ transplants and preventing immunologic rejection. This elusive goal is the aim of this proposal, which is based on observations that T regulatory cells (Treg) are able to downregulate the peripheral immune response to organ transplants in animal models and humans. Harnessing such Tregs for the purposes of donor-specific tolerance may be possible using a combination of recently developed novel approaches. These approaches include administering an IL-2 mutein (mIL-2) to promote Tregs in combination with drugs such as rapamycin, anti-CD154 mAb, IL-6 receptor blockade (Tocilizumab) and complement blockade (anti-C3). The need for donor-specificity to tolerance can be substantially enhanced by the exposure of the organ transplant recipient to chemically treated (ECDI) donor B cells, as well as the administration of CAR-Tregs that confer regulation to a specific donor MHC antigen. Each of these technologies is available to us to apply to what is likely the most relevant and feasible animal model that accurately simulates human biology: namely, a rhesus monkey kidney allograft model. We have considerable experience using this model to develop novel immunotherapies that have been successfully introduced into the clinical transplant arena. Examples include T cell depleting therapy, co-stimulation blockade, and desensitization to MHC. We propose to use a combination of Treg promoting strategies in combination with ECDI-treated donor B cells and CAR- Tregs in controlled experiments and with state-of-the-art mechanistic support to define the immunologic impact of each therapy. These data would guide the rational development of a tolerance-inducing strategy and monitoring tools that would be feasible to apply to an initial human kidney transplant trial of Treg-based peripheral tolerance.

NIDA - National Institute on Drug Abuse

Neurologic complications remain prevalent in nearly 50% of people with HIV (PWH) and persist despite viral suppression with antiretroviral therapy (ART). Though the exact processes mediating HIV neuropathogenesis are not well understood, co-morbidities such as substance use disorders (SUD), which are higher in PWH compared to the general population, exacerbate neuropathogenesis of HIV and worsen outcomes. Multiple substances of misuse are reported to increase HIV replication, induce inflammatory signaling, and amplify neurodegenerative phenotypes. Thus, there is a significant need to understand the intersection between SUD and NeuroHIV to improve longitudinal care and inform the public. The overlapping effects of distinct substances of misuse on HIV pathogenesis in the CNS suggest that a common pathway may be involved through presently undefined mechanisms. All addictive substances increase extracellular dopamine in the central nervous system (CNS), which signals neurons and other nearby glial cells expressing dopamine receptors. Our lab has shown that myeloid cells such as macrophages and microglia, which are major HIV reservoirs in the brain, express dopamine receptors more D1-like receptors (D1 and D5) than D2-like receptors (D2, D3, D4). Treatment of macrophages and microglia with micromolar concentrations of dopamine increased pro-inflammatory signaling, increased viral entry, and potentiated viral secretion in vitro. We recently found that a higher D1-like to D2-like ratio is associated with a more pro-inflammatory response in microglia. Further, we showed that dopamine increases activation of nuclear factor-kappa B (NF-κB) in macrophages, and that inhibition of NF-κB can block the pro-inflammatory effects of dopamine. Together, these data suggest that dopamine-enriched brain regions, such as the cortex and striatum, may be especially vulnerable to HIV and neuroinflammation in PWH and co-morbid addiction through the action of dopamine on microglia. Therefore, the central hypothesis of this proposal is that dopamine D1-like receptor activation promotes HIV infection and NF-κB-mediated inflammation in microglia to worsen neurodegeneration. This hypothesis will be tested using human induced pluripotent stem cell (iPSC)-derived brain human cortical assembloids and several orthogonal assays to explore the dopamine-mediated pathways that modulate HIV neuroimmune pathogenesis. We will use pharmacologic activation of dopamine receptors in cortical assembloids to assess viral kinetics (Aim 1), neuroinflammation (Aim 2), and neuronal degeneration of synapses and dendrites (Aim 3). Together, these studies will significantly advance our understanding of dopamine as an immunomodulatory signaling molecule in the context of substance use and HIV, as well as expand the approaches to studying neuroimmune pharmacology using human micro-physiological systems.

Doris Duke Foundation

Multi-year grants for performing arts organizations building audiences and developing new work in contemporary dance, jazz, and theater.

Dozer Art

Dozer Art will organize a temporary art exhibit at 2507 Beacon Ave S featuring local muralists and painters. An opening event for the exhibit will be held on September 8, 2017 from 5 pm - 10 pm. The free all ages event will feature performance art, music, and food.

NEI - National Eye Institute

ABSTRACT Eye diseases can have a profound impact on an individual’s quality-of-life, overall health, and life expectancy, and impose a tremendous burden on society and public health. There have been many advances in vision research, but there is a need for physician scientists who are highly trained in contemporary multidisciplinary research and can bring cutting-edge expertise in clinical/translational/population-outcomes research to solve contemporary vision impairing challenges. The Duke Ophthalmology Mentored Physician Scientist Program will train the next generation of ophthalmology physician scientists by fostering their career development in state-of-the art multidisciplinary research emphasizing the importance of scientific rigor, innovative scientific methods, appreciation of team science, and translation to improve patient health. The program will provide two qualified early-career physician scientist scholars per year with cutting-edge research experiences in a robust, innovative, career development framework to develop the next generation of physician scientists in ophthalmology. The Program will address gaps in scientific knowledge related to ophthalmology by providing skills, support and resources needed for the physician scientist to innovate and build inter- and cross- disciplinary collaboration within ophthalmology research. In that way, this Program will prepare the Duke K12 Mentored Physician Scientist Scholars to lead their own multidisciplinary teams in clinical/translational and/or population heath eye research, advance the field and ocular health, and become mentors and leaders of tomorrow. Upon completing this program, these vision scientists will have both a fundamental understanding of the clinical impact and the ability to apply rigorous and innovative methods to enable discoveries and translate these into tangible interventions. The impact of the Program will be gauged by their development of a research program and its contribution to the improvement of eye health.

Duluth Superior Area Community Foundation

Duluth Superior Area Community Foundation ($150M in assets) supports nonprofits in MN through grants focused on education, environment, community development, arts. Awards range from $1,000 to $50,000.

NEI - National Eye Institute

PROJECT ABSTRACT Cataracts and glaucoma are the two leading causes of blindness worldwide. Crucial ophthalmic procedures to treat cataract, glaucoma, and other vision conditions require precise visualization of anatomy and microsurgical instruments. Visualization in such surgeries has been limited to stereo optical microscopes since the early 20th century. With advancements in optical coherence tomography (OCT), we can now obtain real-time 3D visualization within the eye. Over the past decade, intraoperative OCT (iOCT) systems have become widely researched and integrated into the latest ophthalmic microscopes built by companies such as Zeiss and Leica. These iOCT systems come with the potential to revolutionize ophthalmic surgery, with an unparalleled ability to resolve key anatomic features at micron-level precision. However, there is a crucial challenge that hampers the clinical utility of iOCT. This challenge stems from the fundamental tradeoff between OCT field-of-view and imaging speed. This tradeoff constrains state-of-the-art systems to operate with a relatively small (e.g. 5x5 mm) field of view to achieve the volume update speeds (~10-15 Hz) required for surgical visualization. Consequently, a trained operator on the surgical team must manually reposition the OCT scan throughout the surgery. The current implementation of iOCT results in a “point-and-shoot” approach to imaging, i.e. using OCT as an intermittent snapshot tool, rather than as a continuous surgical visualization technology. With even small movements of the surgical instruments, the OCT image can quickly lose sight of the surgical region of interest (ROI). Manual tracking of iOCT discards a key advantage of OCT, which is real-time 3D data collection. With advances in deep learning methods for image processing and object recognition, there are new opportunities to tackle this problem. The goal of this project is to engineer a novel computational system for automatic, real- time tracking of the surgical ROI in a clinical iOCT system. Our vision is to develop a system that can be readily applied to existing clinical microscopes, and adaptable to future robotic surgical systems. As part of our preliminary work, we have created a lateral tool tracking OCT system using deep learning models applied to the microscope feed. Our current system utilizes a novel synthetic data approach, making use of 3D-rendered models of eyes and tools to accelerate deep learning model development. In the proposed project, we expand on this preliminary work by developing a system for 3D multimodal surgical ROI tracking of iOCT that can be applied to many different types of ophthalmic surgeries. We will then evaluate our platform via ex-vivo porcine and human cadaver eye studies with wet-lab benchmarking and simulated surgeries with our clinical collaborators. Our immediate application is ophthalmic surgery, but the methodology has relevance to a wide range of 3D imaging systems for microsurgical procedures. By developing this system for dynamic OCT surgical tracking, we hope to improve ophthalmic visualization in both training and surgical practice.

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

PROJECT SUMMARY/ABSTRACT More than 17% of infants born in the United States have motor deficits which restrict their development, daily function, and quality of life. Early intervention can improve outcomes for these infants by effectively retraining the brain and body during a critical period of development. However, motor deficits are often not detected until 1-2 years of age or later, which can reduce the efficacy of interventions due to late initiation and lowered brain plasticity. Current evaluation methods, such as caregiver reports and observation-based clinical assessments, lack the accessibility, objectivity, and precision needed to evaluate early infant movement outside of a clinical setting and screen for atypical motor behaviors. The objective of the proposed study is to develop a fully automated wearable sensor toolkit to detect infant motor deficits within the first few months of life during free- living activities the home and community, and to surveil these deficits over the first year of life. Capturing free- living infant movements would provide a more comprehensive and representative picture of everyday infant behavior compared to current evaluation methods. We will develop the wearable sensor toolkit via the following Aims. In Aim 1, whole-body inertial sensor data will be recorded in the home and community from up to 60 newborn infants across the risk spectrum for motor deficits to curate a pediatric dataset of real-world, early motor development. In Aim 2, this dataset will be used along with state-of-the-art signal processing and machine learning techniques to develop a toolkit that collects and automatically analyzes wearable sensor data to evaluate motor development for infants less than 3 months of age during everyday activities and infant behaviors in the home and community. Finally, in Aim 3, the toolkit will be validated in a separate cohort of 30 newborn infants to evaluate its effectiveness in detecting and describing infant motor deficits over the first year of life compared to traditional clinical assessments. The primary outcomes will be a fully annotated, free-living dataset characterizing infant motor development between birth and 3 months of age, as well as the sensitivity and specificity of the wearable sensor toolkit to detect infant motor deficits during these early ages. Secondary outcomes will include surveillance curves of sensor-based metrics to track motor development over the first year of life, and clinical outcomes of infants tracked and not tracked by the toolkit. This study will revolutionize detection and surveillance of infant motor development and deficits by automatically evaluating early-life movement patterns in the home and community, alerting clinicians and caregivers when further examination is needed. Early, accurate, and accessible methods of identifying infant motor deficits would allow for more widespread developmental screening and earlier, targeted interventions to improve lifelong outcomes.

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is tofurther elucidate the mechanisms of early immune development in utero, during the early post-natal period and during early childhood in neonates, infants, and children and adolescents with or without in-utero exposure to HIV or Anti-Retroviral Therapeutics (ART).This initiative aims to understand intricate mechanisms of immune cells at the maternal-fetal interface, T and B cell development and maturation in offspring, and local immune responses and the role of systemic immunity.

National Institutes of Health

<p>The purpose of this Notice of Funding Opportunity (NOFO) is tofurther elucidate the mechanisms of early immune development in utero, during the early post-natal period and during early childhood in neonates, infants, and children and adolescents with or without in-utero exposure to HIV or Anti-Retroviral Therapeutics (ART).This initiative aims to understand intricate mechanisms of immune cells at the maternal-fetal interface, T and B cell development and maturation in offspring, and local immune responses and the role of systemic immunity.</p>

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY Early life stress (ELS), particularly during fetal development, is a critical risk factor for long-term health, including obesity and metabolic disorders. This project investigates how prenatal stress exposure is biologically embedded, leading to increased vulnerability to abdominal adiposity and metabolic dysfunction. Our long-term goal is to eluci- date cellular and molecular pathways that mediate the developmental origins of metabolic disease, supporting early identification and prevention strategies for at-risk children. Despite known associations between ELS and adult dis- ease, current research is limited by inconsistent findings in early life, inadequate biomarkers of fetal stress exposure, and poor measurement of adiposity in infants. Traditional reliance on weight-based metrics fails to capture fat dis- tribution, which is key to metabolic risk. Moreover, stress exposure during pregnancy is typically estimated from basal circulating biomarkers, neglecting dynamic physiological stress responses. To address these gaps, we employ a translational, multi-level design integrating basic science and clinical research. Using umbilical-derived mesenchy- mal stromal cells (MSCs) from human newborns, we will model individualized cellular vulnerability to ELS. In par- allel, we will track in vivo adipose development using serial MRI assessments and metabolic profiling in infants. Our specific aims are: Aim 1: Determine if biological stress during pregnancy predicts infant adiposity, distribution, and metabolic function using state-of-the-art MR imaging at birth and 5–6 months. Aim 2: Test whether MSCs from high-stress exposed infants exhibit greater cellular vulnerability under in vitro adi- pogenic challenge conditions. Stress exposure will be comprehensively quantified using ex vivo glucocorticoid-cytokine stimulation, diurnal sali- vary cortisol sampling, and maternal blood assays during early and late pregnancy. These data will be synthesized into a composite (PCA) biological stress exposure score. We hypothesize that dynamic, functionally derived measures of maternal stress will better predict infant abdominal adiposity and metabolic function than static bi- omarkers, and that stem cells from high-stress-exposed infants will exhibit greater vulnerability—reflected by in- creased lipid accumulation and hypertrophy—especially under in vitro challenge conditions. This integrated ap- proach will illuminate mechanisms of biological embedding and identify novel markers of metabolic risk. Findings will advance precision health by enabling targeted early-life interventions. This project will also establish a scalable human newborn stem cell biobank for future studies of stress-related disease pathways.

East Bay Community Foundation

East Bay Community Foundation ($800M in assets) supports nonprofits in CA through grants focused on racial equity, economic opportunity, arts, environment. Awards range from $5,000 to $200,000.

East Bay Performing Arts

Support of the vital programs conducted by each of its three divisions: Oakland East Bay Symphony, Oakland Youth Orchestra, and Oakland Symphony Chorus.

East Tennessee Foundation

East Tennessee Foundation ($400M in assets) supports nonprofits in TN through grants focused on education, environment, community development, arts. Awards range from $2,000 to $100,000.

East Tennessee Foundation

East Tennessee Foundation ($400M in assets) supports nonprofits in TN through grants focused on education, community development, arts, environment. Awards range from $1,000 to $75,000.

Edmonton Community Foundation

ECF provides grants to charitable organizations in the Edmonton area for community development, education, arts, environment, and social services.

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

Sickle cell disease (SCD) affects approximately 100,000 Americans, making it the most common inherited blood disorder in the United States. Over 1.2 million people are living with HIV in the U.S. Both chronic illnesses are endemic in overlapping geographic areas and reported in thousands of U.S. patients. A systematic review found conflicting conclusions on the effect of HIV on SCD and revealed numerous knowledge gaps, including the clinical profile of SCD patients living with HIV (PLWHIV), and the impact of HIV infection and HIV treatment on SCD outcomes. The clinical management of the comorbidity is currently uncertain in the U.S. because of lack of evidence. The previous studies were unable to include SCD severity due to the phenotype variability within SCD genotypes that may have different associations with severity of SCD and HIV status. Although the study results will be applicable to the medical care of Americans with HIV and SCD, the study will be conducted in Cameroon because the higher HIV prevalence allows the enrollment of more HIV+ patients with SCD. In addition, four of the five SCD genotypes are found in Central Africa allowing the study of this important covariate. Findings from Cameroon are generalizable in the U.S. because the diagnosis, the pathophysiology, and the ART regimens are similar. Based upon the genotypic, clinical, and biological particularities of SCD the project will address the gap in knowledge on the effects of HIV infection on SCD in two Specific Aims: Aim 1: We shall establish a clinical registry that includes all SCD patients to measure HIV prevalence, demographic and clinical characteristics in Cameroon. This will be a cross-sectional and descriptive study involving all SCD patients registered and followed-up in in the country. The investigators will screen all the 866 patients for HIV to confirm their status and to potentially identify new HIV positive patients. This research phase will describe the baseline clinical profile of SCD, determine the frequency of HIV infection in SCD patients and compare socio-demographic and clinical factors between HIV+ and HIV- SCD patients. Aim 2: Using a sample from the same patient population, we shall conduct a cross-sectional study on a matched random sampling of 48 HIV-positive SCD patients, and 96 HIV-negative SCD patients. Additionally, we shall randomly select 48 consenting HIV positive non-SCD patients among the HIV patients currently followed-up at the YUTH HIV care center as a second control group for the study. We shall measure prospectively the levels of biological markers of thrombosis, hemolysis, inflammation and organ failure and compare them according to HIV status. We shall assess if the SCD genotype will be an effect modifier of the relation between HIV status and SCD biological markers. The medical registry and data collected during this exploratory study will serve as the preliminary data for a future R01 application. The study will provide important data to improve specific ways US care through future interventional studies on immune system modulation, targeted infection prophylaxis, iron management, tailored ART regimens and gene therapy optimization in American SCD patients living with HIV.

NIA - National Institute on Aging

PROJECT SUMMARY Family plays a central role in shaping the experiences of aging. Any health shock not only affects the patient but also reverberates throughout the family unit, taking a physical, emotional, and financial toll on family members. The effect on families is likely to be particularly pronounced for health shocks that lead to a pronounced decline in independence, as, for example, happens with the progression of Alzheimer’s Disease and Related Dementias (ADRD). The ways families manage sharp changes in health can have profound effects on both the patient’s well-being and that of their caregivers. Despite the intricate relationship between family dynamics and health outcomes at older ages, public policies and much of the existing research in the U.S. have predominantly focused on individual patients rather than the broader family context. The dearth of evidence relates not to the lack of interest, but to the absence of datasets that could allow studying the effects of health shocks on families. In this project, we propose to start closing this gap in knowledge by leveraging the new extensive U.S. Census Bureau infrastructure for linking administrative data. We will construct and analyze a novel individual-level database that links the health trajectories of older adults to the physical, mental, and economic well-being of their family members across multiple generations, covering twenty-five years from 1999 to 2024. Using this new database, we will comprehensively examine the interdependencies between the mental, physical, and economic well-being of older adults and their families in the United States. First, we will describe the variation in family circumstances of older adults at the time of different health shocks. We will consider variation across demographic groups, local geographies, and socio- economic circumstances. Second, we will use state of the art econometric techniques for causal inference to quantify how much deaths and major but non-fatal health shocks affect the health and economic well-being of family members, including spouses and adult children.

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

PROJECT SUMMARY Over 1 million women living with HIV (WLWH) give birth annually. With widespread use of combination antiretroviral therapy (cART), vertical transmission has been significantly reduced, resulting in ~16 million HIV- exposed uninfected (HEU) children as of 2023. Despite being HIV negative, these children face increased risks of poor growth, infection-related mortality, and respiratory disease. These outcomes are believed to result from maternal HIV-induced inflammation and/or cART toxicity, as many antiretrovirals cross the placenta and may disrupt fetal immune development. However, distinguishing the effects of HIV versus ART is difficult in clinical studies due to challenges of studying non-HIV infected women receiving ART. Limited access to fetal tissues further hampers mechanistic insight, creating a need for translational animal models. To address this critical knowledge gap, we propose to use a rhesus macaque model of simian immunodeficiency virus (SIV) infection to investigate how maternal HIV and long-acting ART (LA-ART) affect fetal immune development. We hypothesize that despite the absence of vertical transmission, maternal SIV and LA-ART exposure dysregulates immune ontogeny in the offspring via altered hematopoiesis. A novel LA-ART regimen of FDA-approved drugs Lenacapavir (LEN) and Cabotegravir (CAB), shown to provide effective viral suppression in preliminary macaque studies, will be given bimonthly by injection to female macaques that will then undergo time-mated breeding following viral suppression. Three experimental groups will be studied: [1] SIV-infected, LA- ART treated; [2] uninfected, LA-ART treated; and [3] uninfected, untreated controls. Offspring will be delivered naturally and monitored through six months of age. Specific Aim 1 will assess how maternal SIV/LA-ART versus LA-ART alone affects infant immune maturation and function in the periphery and in tissues using flow cytometry, single-cell RNA/ATAC-sequencing, and in vitro stimulation. We will evaluate vaccine responsiveness using Varivax™ and examine B/T cell responses and receptor repertoires. Specific Aim 2 will study the impact of maternal SIV/LA-ART versus LA-ART alone on hematopoiesis in the offspring. We hypothesize that SIV/LA-ART exposure impairs differentiation and maturation of hematopoietic stem and progenitor cells (HSPCs). Bone marrow will be analyzed via flow cytometry, differentiation assays, and single-cell RNA/ATAC-sequencing. Functional HSPC capacity will be tested via transplantation into immunodeficient mice. This study uses a clinically highly relevant primate model for HIV cure research and neonatal immunity, and advanced immunological tools to uncover how maternal HIV and LA-ART exposure alter infant immune development. Findings will guide future strategies to improve immune outcomes in HEU children.

El Paso Community Foundation

El Paso Community Foundation ($400M in assets) supports nonprofits in TX through grants focused on education, health, community development, arts. Awards range from $2,500 to $150,000.