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BEGO, Inc.

BEGO, Inc. will host an Ethiopian cultural festival on August 12, 2018 from 10am - 10pm. It will take place on E Cherry St between 23rd Ave and Martin Luther King Jr Way. The free event will feature musicians, dancers, creative artists, vendors, food, and family activities.

Ethiopian Women Mothers & Family

This project will celebrate the empowerment of Ethiopian women in Seattle. This all day event will take place on the street of E cherry between MLK Jr. way S. and 23rd street. This event will celebrate the achievements of Ethiopian women through arts and culture, speakers presentations , family entertainment , and role model awards.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY In the era of modern antiretroviral therapy (ART), cardiometabolic diseases have become a leading cause of morbidity and mortality among people with HIV (PWH). Type 2 diabetes, a major contributor to cardiovascular and kidney disease, now affects approximately one in five PWH. PWH face unique metabolic challenges due to HIV infection and ART, including chronic inflammation and disrupted glucose and lipid metabolism. Despite these distinct metabolic derangements, population-specific evidence guiding the pharmacologic management of diabetes in PWH remains limited. This project seeks to generate real-world evidence addressing critical knowledge gaps on the comparative effectiveness of commonly used glucose-lowering agents—metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, and sulfonylureas. The candidate is an internal medicine physician with a background in pharmacoepidemiology at Johns Hopkins University. During the award period, he will be mentored by a multidisciplinary team whose expertise spans diabetes and cardiometabolic comorbidities in PWH, machine learning, and causal inference methods. His long-term career goal is to become an independent clinician-investigator applying innovative machine learning and epidemiologic methods to improve clinical care for PWH with diabetes and other chronic conditions. The overarching objective of this project is to generate robust evidence to inform the pharmacologic management of type 2 diabetes among PWH. The proposed study will focus on three aims: (1) characterize the utilization of glucose-lowering therapies; (2) evaluate the comparative effectiveness of glucose-lowering therapies on glycemic control; and (3) estimate the effect of different glucose-lowering therapies on cardiovascular and renal outcomes and mortality among PWH with diabetes. This work will leverage the North American AIDS Cohort Collaboration on Research and Design (NA- ACCORD), a large, representative, multi-site cohort of over 190,000 people with HIV in the United States and Canada. Comparing glucose-lowering therapies on key clinical outcomes will generate population-specific evidence to inform clinical care for the growing population with HIV and diabetes. In parallel, the project will support the candidate’s development of the expertise needed to become an independent investigator capable of applying advanced quantitative methods to generate robust clinical evidence and improve the treatment of diabetes and other chronic conditions among PWH.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY The goal of this project is to evaluate telomere length (TL) and epigenetic age (EA), important biomarkers of biological age, in children with perinatally acquired HIV (CPHIV), children who were HIV exposed and uninfected (CHEU), and children who were HIV unexposed and uninfected (CHUU). CPHIV grow into adulthood on effective, lifelong antiretroviral therapy (ART); however, adults with perinatally acquired HIV are at higher risk of chronic health issues. There is evidence that adults with HIV have shorter TL and accelerated EA compared to adults without HIV, but this association is not as clear in pediatric populations. TL and EA have been associated with adverse health outcomes and all-cause mortality. Childhood is a sensitive time for changes to TL and EA. TL decline and EA acceleration are not well characterized in children, and leveraging longitudinal samples to evaluate these biomarkers of biological age in CPHIV – who are higher risk of future adverse age-related morbidities – could inform strategies to improve long-term health outcomes. To better understand biological age in CPHIV, we plan to compare TL decline and EA among CPHIV, CHEU, and CHUU, compare TL decline and EA acceleration between CPHIV who initiated ART early versus later, determine predictors of TL decline and EA acceleration, and evaluate the association between biomarkers of biological age and neuropsychological outcomes. This project will leverage samples and survey data from three unique cohorts enrolled in ongoing studies (R33HD103079, PI: Dr. Grace John-Stewart and R01HD023412, MPI: Grace John-Stewart, Dalton Wamalwa). Two of the parent cohorts have followed CPHIV for over 15 years, which will allow for robust longitudinal analyses of TL decline and EA acceleration. Aim 1 will compare TL decline from infancy through 24 months and EA at 24 months of age among CPHIV, CHEU, and CHUU using linear mixed effects models. In Aim 1, we will also use hierarchical clustering to identify clusters of children with similar biological aging profiles at 24 months and multinomial logistic regression to determine cluster differences among CPHIV, CHEU, and CHUU. Aim 2a will leverage repeated samples collected at 4 and 16 years of age to compare long-term TL decline and EA acceleration between CPHIV who started ART within the first year of life and CPHIV who started ART later. Aim 2b will determine correlates of TL decline and EA acceleration among CPHIV. Correlates evaluated include levels of total and intact HIV DNA, HIV viral load, cytomegalovirus viral load, and interleukin- 6. Aim 3 will determine the association between biomarkers of biological age and neuropsychological outcomes among children in long-term follow up at 7 and 16 years of age. Findings from this project will address gaps and in knowledge of biomarkers of biological age. This research plan will provide the K01 candidate with rigorous training focused on biomarkers of biological age and HIV, machine learning techniques, neuropsychological outcomes of children and adolescents with HIV, and community engagement and equitable partnerships to support her independence.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Broadly neutralizing antibodies (bNAbs) are a promising immunotherapy for the treatment and cure of HIV-1. Clinical trials passively infusing bNAbs have proven their ability to significantly reduce viral loads but pre- existing and de novo resistance remains the limiting factor to their success. Rationally designing improved bNAb combinations that impose stronger constraints on viral resistance is required to achieve bNAb control of HIV. As with antiretroviral therapy (ART), successful bNAb strategies will likely require combinations where resistance can only emerge through multiple mutations that incur a high fitness cost. Targeting Env epitopes less tolerant of mutations is central to achieving this goal. Broadly neutralizing antibodies against the CD4bs function by directly blocking viral binding to cellular CD4 receptors on its primary target, CD4 T cells. Since these bNAbs mimic CD4 interactions, CD4bs bNAbs are advantageous in that escape mutations can carry a fitness cost by impairing viral CD4 receptor binding. Additionally, these bNAbs take longer to escape from than antibodies targeting other Env epitopes. Focusing bNAb strategies on the CD4bs therefore shows promise for increasing the difficulty of viral escape. Importantly, recent data has shown that CD4bs bNAbs can have different, non-overlapping resistance mutations, which indicates that a CD4bs bNAb combination could put distinct selection pressures on the CD4 binding site. Thus, we hypothesize that two CD4bs bNAbs together will exert strong selection pressure on the receptor binding site inducing multiple resistance mutations that either delay escape or severely reduce replication. We will test this hypothesis with 2 specific aims: AIM 1. Quantify the ease of virus escape from multiple CD4bs bNAbs and AIM 2. Identify selection pressures imposed by CD4bs bNAb combinations. First, to identify the bNAb pairing with the least overlap in resistance, we will assess neutralization patterns of 3 clinically relevant bNAbs VRC07-523, 1-18, and N49-P9.6 against CD4bs bNAb resistant viruses. We will quantify the resistance overlap between every bNAb pairing and define an optimal combination. To understand if CD4bs bNAbs with distinct resistance phenotypes can indeed delay or prevent the emergence of viral escape, time to escape from this combination will be quantitated in an in vitro CD4 T cell assay. Finally, to get a mechanistic understanding of viral escape from multiple CD4bs bNAbs, we will map mutational escape pathways from the CD4bs bNAb combinations and quantify the impact of each mutation on viral fitness. These findings will reveal if independent resistance mutations arose in response to each bNAb, as well as if gaining resistance exerts a fitness cost. Successful completion of these aims will reveal if including multiple CD4bs bNAbs in combination regimes is advantageous and greatly expand our understanding of CD4bs bNAb neutralization mechanisms. These findings will directly inform new bNAb combination strategies for the treatment and cure of HIV.

NCCIH - National Center for Complementary and Integrative Health

PROJECT SUMMARY By 2050, 23% of the U.S. population will be aged 65 or older, leading to an increase in chronic diseases and significant burdens on healthcare systems. Physical activity (PA) is essential for preserving whole-person health including physical and cognitive function, independent living, and quality of life in older adults. However, PA tends to decline with age, and currently, about 30% of older adults in the U.S. are physically inactive. Given the protective effects of PA against age-related decline and numerous chronic conditions, developing effective interventions to promote PA in this population is imperative. This project proposes to evaluate the efficacy of an innovative online Mindfulness-based Dance/Movement Therapy (M-DMT) intervention in promoting PA and overall well-being in sedentary older adults. M-DMT integrates mindfulness and dance/movement therapy, fostering holistic health by combining physical activity with mindful awareness and creative expression. Unlike standard PA interventions, M-DMT encourages autonomous engagement in movements that align with participants’ physical and emotional states, enhancing intrinsic motivation and enjoyment. The intervention also leverages group therapy to promote social support and positive emotional states, further enhancing its effectiveness. Our proposal will conduct a randomized controlled trial (RCT) using a mixed methods approach to compare online M-DMT with the Stony Brook Health Education Program (HEP). Quantitative data will measure PA levels and whole-person health outcomes, while qualitative data will explore participants' perceptions of the intervention’s impact and underlying mechanisms. Outcomes will be assessed at baseline, post-intervention, and 3-month follow-up. Our primary aim is to test the efficacy of online M-DMT on PA in sedentary older adults relative to the HEP control. We expect that M-DMT will be associated with greater increase in PA as measured by self-report and accelerometry at post-intervention, and 3-month follow-up. Our second aim will test the effects of online M-DMT versus HEP on multiple dimensions of whole-person health including cognitive, physical, emotional, and social domains, consistent with the NIH whole-person health framework. We expect that M-DMT participants will exhibit greater improvements in these outcomes than those in HEP. Our third aim is exploratory and will examine the changes in mechanisms hypothesized to drive intervention effects, including increases in self-efficacy for PA, intrinsic motivation, mindful awareness, and perceived social support. We expect that changes in these mechanisms will lead to greater increase in PA. This project is significant, innovative, and timely, representing the first application of a remote mind-body and creative arts-based intervention specifically designed to enhance PA and whole-person health among older adults. The study will provide critical evidence for a low-cost, accessible, and scalable PA intervention that can be integrated into home and clinical settings, facilitating large- scale dissemination and further testing.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Background. Hypertension and diabetes are among the most common risk factors for cardiovascular disease among people living with HIV (PLHIV), with prevalence up to 54% in high-income countries, and 46% in lowand middle-income countries. Yet, most people with these comorbidities are undiagnosed or undertreated. In Zambia, only 14% of 750,098 adults living with HIV received blood pressure screening in 2021. Of those, 15% had hypertension, and only 9% received antihypertensive medication. Diabetes screening reached only 8-13% of PLHIV. While many countries recommend integrating non-communicable disease (NCD) screening into HIV care with various self-testing kits to address these shortfalls, there is an increasing number of patients who need both anti-retroviral treatment (ART) and NCD management; Integrating care may overwhelm the health system, especially in high-burden, densely populated areas. To date, however, no study has determined if integrating HIV-NCD screening and care influences overall clinic visits, key health outcomes, and program cost effectiveness. Using the Center for Infectious Disease Research in Zambia (CIDRZ)fs large NIH-funded trial dataset (TASKPEN, NCT05950919) and mathematical modeling, we aim to evaluate the epidemiological impact and cost-effectiveness of integrating NCD screening and treatment at scale for PLHIV in Zambia.one of the earliest adopters of integrated HIV-NCD service delivery.versus the current standard of care. Candidate Overview. My long-term goal is to become an independent investigator specializing in the design and evaluation of integrated service delivery for multimorbidity management. Drawing on my background in health systems research, economic evaluation, and disease modeling, I have developed a training plan with mentorship in HIV and NCD epidemiology, health system dynamics, and model calibration and validation. Research Strategy. My study will 1) determine the effect of an integrated HIV-NCD care model on clinical outcomes among PLHIV with .1 cardiometabolic NCD; 2) estimate the long-term health impact and costs of service integration and multi-month drug dispensing strategies using mathematical modeling; and 3) determine the cost-effectiveness of service integration and multi-month drug dispensing strategies under different health systems' capacities and community disease prevalence conditions. Relevance to U.S. public health. CIDRZ provides access to one of the worldfs most mature HIV treatment programs with a rapidly aging patient population experiencing high burdens of cardiometabolic comorbidities. This setting offers a unique, accelerated opportunity to study multimorbidity patterns, care delivery challenges, and outcomes of integrated service models directly relevant to the growing population of older adults living with HIV in the United States. With 54% of U.S. people living with HIV now aged 50 years or older, and an estimated 60.80% experiencing multimorbidity, this work will inform integrated care models for Ryan White clinics and other safety-net systems, where improving chronic disease care coordination is a national priority.

NINDS - National Institute of Neurological Disorders and Stroke

Summary Genetic ataxias are slowly progressing neurodegenerative diseases causing severe disability for which no disease-modifying therapy exists. Though individually they are rare diseases, together they affect nearly 15,000 people worldwide. Current clinical scales for assessment of ataxia severity and progression are ineffective for evaluation of treatment effects during the timeframe of typical clinical trials, necessitating inclusion of high numbers of patients, which often is not feasible, to achieve statistically meaningful outcomes. These challenges could be addressed if reliable, sensitive, and preferably minimally invasive biomarkers for ataxia severity and progression were available for use in clinical trials. Unfortunately, such biomarkers do not presently exist. Therefore, we propose an initial study combining both biomarker discovery using proteomic and transcriptomic approaches, and testing of several promising candidate biomarkers in blood samples from patients with the most common dominant and recessive types of genetically inherited ataxia. We will utilize state-of-the-art techniques including Olink®’s proximity extension proteomics, NextGen RNA sequencing, and electrochemiluminescence immunoassays. The analyses will be done in patient plasma and neuronal extracellular vesicles isolated from the plasma, increasing the likelihood of discovering biomarkers reporting on specific biochemical changes in the central nervous system. The study will generate an initial set of potential biomarkers, providing the basis for subsequent, larger testing and validation in the context of R01 or U01 applications, addressing a current urgent gap in developing effective therapies for patients with genetic ataxias. Additionally, the proteomic and transcriptomic data will allow pathway analysis that may shed new light on the mechanisms underlying the pathogenesis of specific types of genetic ataxia, including both common and distinct features among them.

Every One Every Day Yesler Terrace

Every One Every Day Yesler Terrace aspires to weave together the socioeconomic and cultural diversity of Yesler Terrace through radically inclusive community initiated pilot projects and events. The pilot projects will be cooking, sewing, and art-based, and be available to both the market-rate and SHA housed residents of Yesler Terrace located at 110 10th Avenue South, Seattle, WA 98104. This project will be completed by November 30, 2025.

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

SUMMARY Reading comprehension (RC) is one of the most complex skills that we utilize daily and is crucial for functioning in modern society, but despite its significance for academic achievement, employment prospects, and mental health, many children and adults do not exhibit proficient RC abilities. New theoretical models aiming to explain variability in RC suggest a dynamic interplay and co-development among ‘precursor’ foundational and cognitive- linguistic skills, interacting with environmental and socio-ecological factors across the developmental timeline of learning to read. Behavioral and neuroimaging studies in school-age children have demonstrated critical mechanistic support for these multifactorial RC models by identifying the developmental trajectories of precursor skills and further showing that brain areas, tracts, and networks typically underlying language and cognitive skills are also involved in RC. Nevertheless, the precursor skills that support RC start developing in infancy and the brain correlates underlying these precursors begin to develop in utero, which suggests that typical and atypical RC developmental trajectories could diverge long before school age. As such, examining RC development using a multifactorial, longitudinal approach that includes brain and behavior starting in infancy is critical for developing theoretical frameworks that can inform early preventative and intervention strategies. Here, we propose a comprehensive longitudinal study of RC development in which we examine direct and indirect effects on RC from brain, behavioral, familial risk, and environmental data from infancy to adolescence. To achieve this goal, we will combine two existing longitudinal cohorts, one ranging from infancy to late childhood (n = 174) and the other from preschool to early adolescence (n = 137). By applying state-of-the-art pediatric neuroimaging analyses, multiple indicator growth model structural equation models, and an innovative behavior- brain co-development measurement index to this unique, combined dataset, we will be able to identify brain and behavioral measures in infancy that directly and indirectly support subsequent RC development (Aim1). We will further characterize how longitudinal trajectories of behavioral measures as well as brain structure, function, and white matter organization contribute to RC development and how familial risk and environmental factors shape these trajectories (Aim 2). Finally, we will examine how the co-development of brain and behavior, as measured with an innovative co-development index, relates to subsequent RC (Aim 3). If successful, we will contribute the first multifactorial longitudinal model of RC development comprising direct and indirect effects from brain, behavior, brain-behavior co-development, familial risk, and environmental measures beginning in infancy. Understanding RC development using a multifactorial longitudinal lens will be crucial for building theoretical models and developing experimental designs focused on early preventative and intervention approaches long before the start of formal schooling.

NIGMS - National Institute of General Medical Sciences

Project Summary/Abstract Mechanistic understanding of living things requires our understanding of how proteins and DNA interact together to generate functional chromosomes. The structure and dynamics of chromosomes ultimately controls all functions of cells, and in turn, multicellular organisms, including humans. Understanding chromosome structure and dynamics and the underlying biochemical interactions defining them are central to preserving human health, dealing with genetic disorders, and fighting pathogenic organisms. Dramatic reorganizations of chromosomes occur throughout the cell cycle: in humans, hundred-million-base-pair long DNAs are genetically deactivated and refolded into the metaphase form to facilitate mitosis, following which are reorganized into cell nuclei harboring once again active gene expression. My laboratory studies chromosome structure and dynamics using a novel combination of cell- and molecule-scale mechanics with state-of-the-art genetic, biochemical, single-molecule and mathematical modeling tools. Chromosome mechanics at the nanonewton scale are central to cell division due to large mitotic spindle forces, and the well-defined elasticity of chromosomes also provides a quantitative readout of internal structural changes. Those micron-scale dynamic reorganizations of chromosomes are controlled by piconewton forces and nanometer steps generated by individual protein machines. Direct mechanistic analysis of chromosome organizational principles and their relation to underlying molecular interactions will transform our understanding of how cells interpret, fold and change their genomes. In turn this will advance understanding of pathologies where those functions are impaired including genetic disorders and cancers and will improve our understanding of how to target those functions in pathogenic organisms. Over the next five years my laboratory will analyze roles Structure of Maintenance of Chromosomes protein complexes (SMCs: condensin, cohesin and SMC5/6 in eukaryotes) and other key genome-acting proteins in organizing chromosomes across the three kingdoms of life, using single- molecule mechanics approaches to directly observe their function. In parallel we will use chromosome and nuclear mechanics studies to study their roles in organizing chromatin at the larger scales of metaphase chromosomes and cell nuclei. The remarkable stability of DNA-protein complexes will be studied using single- molecule and cell-level experiments on “facilitated dissociation” (FD), preliminary studies for which indicate that pathways for spontaneous dissociation – the backbone of our understanding of biochemical interactions – may be kinetically irrelevant compared to competitive binding pathways. This promises a complete revision of how we think about binding affinity in the crowded, competing in vivo environment, replacing the concept of a ligand-receptor affinity with a large competition kinetic matrix, with transformative implications for how we think about regulation of biochemical interaction networks in vivo. Experimental results will be linked to mathematical models and coarse-grained computer simulations of molecular function and genome/chromosome folding.

NIMH - National Institute of Mental Health

ABSTRACT The prevalence of Major Depressive Disorder (MDD) among people with HIV (PWH) is 20-50%, which is 3 times higher than the prevalence of MDD in the general population. Depression is a leading risk factor for continuity of care among PWH, including adherence to anti-retroviral therapy (ART). Complicating clinical decision making and patient care are the overlapping symptoms of depression with those of HIV and side effects of ART (e.g., psychomotor slowing, difficulties thinking, sleep disruption, fatigue, apathy, and other comorbidities (e.g., anxiety). In addition to depression being underdiagnosed, our preliminary machine learning analyses indicate bidirectional associations between HIV and depression: (1) depressive symptoms predict chronic immune dysregulation (e.g., CD4/CD8 inversion) among virally suppressed PWH; and (2) elevated levels of peripheral inflammatory markers despite sustained viral control predict depression incidence and persistence. These findings suggest an urgent need for novel approaches to accurately identify and manage depression in PWH. Aligned with the NIMH’s Research Domain Criteria (RDoC), we propose an innovative paradigm shift to elucidate the interplay between these overlapping constructs by moving away from conventional a priori measurement selection and small single-study, group-level analyses to integrative, multimodal analyses leveraging existing data acquired prospectively across multiple longitudinal studies from 3962 PWH. To maximize research efficiencies, we will harmonize the datasets to the repository of the NIH-sponsored National NeuroHIV Tissue Consortium (NNTC). We will then create a pioneering, multimodal, explainable AI (xAI) framework that uses knowledge graphs to holistically capture individual-level neurobiological, cognitive, sociodemographic, and environmental determinants of depression in PWH. We will prioritize interpretability, scientific rigor (including reproducibility), and clinical relevance. We will ensure ethical and stakeholder-driven development in order to support the vision of this team in translating results into actionable clinical strategies capable of improving treatment outcomes for PWH. Specifically, in Aim 1, we will develop and validate HIV- specific data-driven models that will use knowledge graphs to predict depression from self-report questionnaires (e.g., Beck Depression Inventory-II), neuropsychological testing, and MR images. In Aim 2, we will create xAI capable of forecasting future incidents and non-remitting cases of depression based on longitudinal data in virally suppressed individuals. By sharing our validated explainable AI tools publicly, this research promises immediate, tangible benefits to HIV clinical care, with the potential of enabling precise identification and management of depression risk. Doing so will help refine clinical care strategies to reduce the clinical burden of depression in people with HIV.

NCI - National Cancer Institute

PROJECT SUMMARY Osimertinib (osi), a third-generation EGFR tyrosine kinase inhibitor (TKI), has significantly improved outcomes for patients with EGFR-mutant lung cancer, but resistance is inevitable, and it is not curative. Understanding the mechanisms driving resistance is critical to developing more effective treatments. Emerging evidence suggests that osi induces replication stress. I am investigating ATR, a kinase activated by replication stress, for its role in promoting cell cycle progression after osi treatment. Additionally, osi-induced replication stress may sensitize tumors to DNA-damaging chemotherapy by overwhelming DNA repair machinery. Consistently, recent clinical trials have shown that combining osi with chemotherapy improves progression-free survival, and trastuzumab deruxtecan (TDXd), the only antibody-drug conjugate approved in lung cancer, is effective against EGFR-TKI- resistant tumors. The central hypothesis of this study is that osi-induced replication stress activates ATR to attenuate this stress and promote cell cycle progression, leading to resistance. Furthermore, ATR inhibition and TDXd is expected to delay tumor relapse following osi treatment. Using patient-derived models, this project will: Aim 1) determine if ATR is necessary to promote cell cycle progression during the acquisition of osi resistance and identify ATR-dependent pathways mediating this process. Aim 2) will evaluate if residual tumors persisting after osi treatment exhibit elevated replication stress and ATR activity, and whether ATR inhibition and TDXd can delay relapse. Human tumors treated with EGFR-TKIs, +/- chemotherapy, will also be profiled using imaging mass spectrometry (IMC) to detect if DNA damage repair (DDR) activity correlates with treatment response and predict sensitivity to ATR inhibition and TDXd. This research will address the critical need to understand the role of ATR activity in osi resistance and provide novel insights into the presence of DDR in human tumors. Together these insights will explore the clinical potential of ATR inhibitors and TDXd for treating EGFR-mutant tumors. The project will utilize Yale School of Medicine’s (YSM) state-of-the-art facilities, confocal microscopes from the Yale Center for Cellular and Molecular Imaging (CCMI) and a Cytometry Time-Of-Flight (CyTOF) Helios Imaging Mass Cytometer for the IMC study. Access to patient-derived cell lines (PDCs) and xenograft tissues (PDXs) from the Yale Advanced-Stage Lung Cancer Tissue Collection Study, managed by the Sponsor, will further facilitate this research. This F31 Fellowship will provide the Principal Investigator (PI) with essential training in advanced techniques such as mass spectrometry and IMC while supporting the PI's development in translational research skills and scientific communication. Additionally, acquiring this training is crucial for the PI who intends to pursue a future career studying therapeutic biomarkers, that target synthetic lethal interactions, to bridge gaps in cancer patient care with translational research. Leveraging the F31 Fellowship to maximize resources and training will ensure the project's success and support the PI’s growth into an independent researcher.

NIEHS - National Institute of Environmental Health Sciences

Project Summary The exponential increase in plastic production and extensive usage has led to millions of metric tons of plastic waste accumulating in the environment. Micro(nano)plastics (MNPs) are common environmental pollutants that bioaccumulate in the human brain. Our early findings show that MNPs tend to accumulate more in the human brain than in the liver and kidneys, with their levels rising over time. Initial data from our laboratory also reveal the presence of MNPs as solid particles in human cerebrospinal fluid (CSF) samples. The question remains about the physicochemical forms and molecular interactions of these circulatory particulates within the CSF matrix and central nervous system (CNS), and ultimately the corresponding physiological and pathological events. CSF reflects the essential biochemical aspects of the extracellular brain milieu. A tight concentration of cholesterol can be exchanged between CSF and blood in the form of the oxysterol metabolites, such as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Dysregulation in CNS cholesterol homeostasis is linked to neurodegenerative disorders and cerebrovascular diseases. Nanoplastics are polymer particles that may interact with lipids and proteins. Lipid coating on therapeutic nanoparticles enhances biocompatibility, but cholesterol-containing lipid corona is linked to increased cholesterol hydroxylases, ROS, lysosomal damage, and NLRP3 inflammasome activation, causing glial changes like foam cells. Whether this same process occurs for polymeric plastic to which humans are exposed remains unknown. Our project will address glial inflammation and cholesterol metabolism dysregulation in response to plastic-lipid particles composed of endogenous lipids in simulated human CSF. Aim 1 will assess the molecular interactions of lipid-nanoplastic mixtures in simulated human CSF using state-of-the-art spectroscopy. We will evaluate the size, shape, composition, and surface functional chemistry of the circulatory plastic-lipid nanoparticles that develop through interactions involving real-world nanoplastics and endogenous primary lipid classes (phospholipids, cholesterol, and sphingomyelin) in simulated human CSF. In the second aim of our study, we will evaluate in vitro the inflammatory and lipidomic dysregulation in glial cells in response to plastic-lipid nanoparticles in simulated human CSF. We will assess the astrocyte response to plastic-lipid nanoparticles compared to original non-lipidic nanoplastics by examining cholesterol and lipid metabolism and the NLRP3 inflammasome using transcriptome, lipidome, and proteome analyses. This research offers insight into the molecular and physicochemical characteristics of real-world circulatory nanoplastics. CSF biochemical matrix is more diluted than plasma, offering a simplified view of the molecular interactions that might occur between endogenous lipids and circulatory nanoplastics. Knowledge of astrocyte-secreted proteins and oxidized cholesterol will serve as biomarkers in human CSF cohort studies.

NIA - National Institute on Aging

People living with HIV (PLWH) in the U.S. and globally are aging, and they are at higher risk for neurocognitive decline despite successful antiretroviral therapy (ART). UNAIDS (2023) estimated that 8.1 million of the 40 million PLWH in the world were 50 years or older, with 41% of PLWH in the U.S. are at least 55 years old. While the majority of aging PLWH globally are infected by subtype C HIV-1, little is known about its neuropathogenesis in this population, representing a critical research gap. Extended lifespan, poor ART penetration of the brain, neuroviral replication, and chronic neuroinflammation with HIV-1 infection may increase the risk for the early onset of age-related neurodegenerative diseases like Alzheimer disease (AD) in PLWH. In 2022, 32 million people globally had AD dementia. However, little is known about whether chronic HIV-1 infection accelerates AD-associated neuropathology due to brain tissue access barriers. Our autopsy program has collected full-body autopsy tissues from 459 decedents with and without HIV-1 to study the size and distribution of HIV-1 tissue reservoirs and the potential effects of cannabis use. We demonstrated that HIV-1 tissue reservoirs were significantly reduced in cannabis users, and the reduction correlates with a decrease in pro-inflammatory cytokines in their tissue reservoirs. In addition, our preliminary study on some collected brain tissues suggests increased AD-associated tauopathy in several PLWH brain tissues analyzed. Our findings support other reports showing an increased risk of AD among PLWH. Interestingly, we found AD-associated neuropathology in PLWH at a younger age than in uninfected individuals. This suggests that HIV-1 may be a potential risk factor for the early onset of AD, with inflammation potentially playing a key role. Our overall goal is to further analyze our archived and additional procured tissues to determine the extent of differential AD-associated neuropathology in PLWH, whether HIV-1 infection and inflammation are associated with the onset of AD at an earlier age (symptom onset before 65), whether cannabis use can mitigate such an effect, and the potential mechanisms involved. We hypothesize that AD- associated neuropathology manifests earlier in PLWH due to HIV-driven neuroinflammation/vascular injury, and can be mitigated by cannabis. Our specific aims are: 1) Determine whether HIV infection enhances and exacerbates AD-associated neuropathology across ages (35-65); 2) Determine whether cannabis use is associated with reduced burdens of AD-associated neuropathology and neuroinflammation in PLWH; 3) Uncover mechanisms linking HIV-1 infection, neuroinflammation, vascular dysfunction, and AD-associated neuropathology. This study will map the spatial distribution of AD-associated neuropathology across age groups in PLWH, identify neurodegeneration mechanisms, and evaluate the potential therapeutic effects of cannabis use. Insights from this research will inform targeted interventions to mitigate brain aging and neurodegeneration in PLWH in the U.S. and throughout the world.

Eyebeam

Residency grants for artists working at the intersection of art, technology, and social justice.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY/ABSTRACT The University of Puerto Rico at Aguadilla (UPR-Aguadilla) requests funding to acquire a Nikon AX Galvo Confocal Laser Scanning Microscope (LSCM) with a TI2-E inverted platform and a four- laser configuration (405/488/561/640 nm) to establish transformative imaging capabilities at our resource-limited institution serving 96% Pell Grant recipients. This state-of-the-art instrument addresses a critical infrastructure gap, enabling high-resolution fluorescence imaging, live-cell microscopy, and quantitative analysis essential for competitive biomedical research and undergraduate education. The LSCM will directly support four active research projects spanning parasitology (monogenean host-specificity studies), plant pathology (coffee biocontrol development), environmental chemistry (metalloprotein biomarkers), and neuroscience (astrocyte dysfunction in diabetic epilepsy) while integrating into core laboratory courses including Immunology (BIOL 4009) and Undergraduate research courses (BIOL 3108 and QUIM 4999). Our multidisciplinary faculty, in partnership with the Neuroimaging and Electrophysiology Facility (NIEF) Excellence Imaging Center, offers expertise in confocal microscopy, encompassing advanced imaging and specialized sample preparation techniques. This collaboration ensures effective implementation of the technology, sustained technical support, and high-quality training programs that will enhance research productivity and broaden educational impact. The broad, long-term objective is to transform UPR-Aguadilla from a primarily teaching institution into a research-active campus capable of producing graduate-school-ready students equipped with cutting-edge technical skills. Access to advanced confocal microscopy will stimulate new research collaborations, enhance faculty productivity, and provide 30-40 students annually with hands-on experience in modern imaging technologies currently absent from our curriculum. The instrument will strengthen our partnership with the emerging Natural History Museum of Puerto Rico for specimen digitization and support comprehensive outreach programs targeting 25-50 high school students annually through "Seeing Science Up Close" workshops. Expected outcomes include 1- 2 peer-reviewed publications within three years, establishment of 1-2 new institutional collaborations, and measurable enhancement of biomedical research capacity. This investment will significantly advance STEM education and research opportunities at UPR-Aguadilla while expanding access to cutting-edge scientific instrumentation for students pursuing biomedical careers and contributing to the development of skilled researchers in the biomedical sciences.

U.S. National Science Foundation

To facilitate fundamental research in the atmospheric sciences, the Division of Atmospheric and Geospace Sciences (AGS) supports state-of-the-art instruments and facilities through the Facilities for Atmospheric Research and Education (FARE) Program. The FARE Program includes the Lower Atmosphere Observing Facilities (LAOF) and the Community Instruments and Facilities (CIF). Lower Atmospheric Observing Facilities The National Science Foundation (NSF) Division of Atmospheric and Geospace Sciences (AGS)Lower Atmospheric Observing Facilities (LAOF) Program oversees a portfolio of multi-user national facilities that are sponsored by NSF for use by the geosciences research community. Program management resides within AGS in the NCAR and Facilities Section (NFS) which provides a single point for coordination of planning and resources.<br /><br />The LAOF program enables geoscience research through the provision of specialized facilities, instrumentation, and field support services necessary to carry out the scientific field work associated with investigations of a wide range of geophysical phenomena. The program is actively involved in oversight of LAOF facilities and decisions about the acquisition, operation, maintenance, upgrading and replacement of these facilities based on input from the scientific community. LAOF funding supports both the planning for scientific field programs (e.g., experimental design, operational plans, logistical support) and the deployment of NSF-sponsored facilities. Proposals to the LAOF program are acceptedby invitation only. Please contact the FARE program director if you intend to submit a proposal to this program. Community Instrumentation and Facilities (CIF) The CIF program provides the NSF-sponsored atmospheric sciences research community with access to specialized instrumentation for field and laboratory-based studies.The program requests proposals from instrument and facility providers who will make their equipment available for community use through an NSF-defined request process.Support will be provided for limited technician time, minor upgrades, and travel for outreach.

U.S. National Science Foundation

To facilitate fundamental research in the atmospheric sciences, the Division of Atmospheric and Geospace Sciences (AGS) supports state-of-the-art instruments and facilities through the Facilities for Atmospheric Research and Education (FARE) Program. The FARE Program includes the Lower Atmosphere Observing Facilities (LAOF) and the Community Instruments and Facilities (CIF). Lower Atmospheric Observing Facilities The National Science Foundation (NSF) Division of Atmospheric and Geospace Sciences (AGS)Lower Atmospheric Observing Facilities (LAOF) Program oversees a portfolio of multi-user national facilities that are sponsored by NSF for use by the geosciences research community. Program management resides within AGS in the NCAR and Facilities Section (NFS) which provides a single point for coordination of planning and resources.The LAOF program enables geoscience research through the provision of specialized facilities, instrumentation, and field support services necessary to carry out the scientific field work associated with investigations of a wide range of geophysical phenomena. The program is actively involved in oversight of LAOF facilities and decisions about the acquisition, operation, maintenance, upgrading and replacement of these facilities based on input from the scientific community. LAOF funding supports both the planning for scientific field programs (e.g., experimental design, operational plans, logistical support) and the deployment of NSF-sponsored facilities. Proposals to the LAOF program are acceptedby invitation only. Please contact the FARE program director if you intend to submit a proposal to this program. Community Instrumentation and Facilities (CIF) The CIF program provides the NSF-sponsored atmospheric sciences research community with access to specialized instrumentation for field and laboratory-based studies.The program requests proposals from instrument and facility providers who will make their equipment available for community use through an NSF-defined request process.Support will be provided for limited technician time, minor upgrades, and travel for outreach.

NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

Polyethylene (PE) wear and implant-related failure remain leading causes of revision in total shoulder arthroplasty (TSA), a procedure which now surpasses the growth rate of hip and knee arthroplasty. Both anatomic (aTSA) and reverse (rTSA) TSA outcomes are heavily influenced by complex interactions between rotator cuff function, scapular motion, implant design, and patient-specific loading—factors not adequately captured in current preclinical implant testing standards. Emerging evidence suggests that PE wear progression in TSA is highly dependent on shoulder kinematics, joint loading, implant positioning, and individual patient factors. Nonetheless, data on in vivo motion and load profiles remain sparse, and few tools exist to link these profiles to clinically relevant wear patterns or associated periprosthetic inflammatory tissue responses. Accordingly, the primary objective of this project is to develop validated, patient-specific models that predict PE wear in TSA and identify modifiable surgical, design, and rehabilitation targets to improve implant longevity and restore patient mobility. Additionally, we will establish histopathological hallmarks that indicate TSA failure caused by PE wear debris. Our central hypothesis is that specific shoulder kinematics and joint loading drive distinct PE wear patterns in TSA associated with mechanical failure or inflammatory-mediated osteolysis, depending on implant design and positioning. To achieve the overall objective of this work, shoulder motions and muscle excitations across 25 activities of daily living will be collected at pre-op and post-op (>6 months) in both aTSA and rTSA patients, with long-term follow-up of patient-reported outcomes via validated surveys (5 years). Unsupervised machine learning will categorize patients into movement-based phenotypes, which will then inform a multi-scale modeling framework to estimate in vivo shoulder joint loads and implant wear across the varying movement strategies. Predicted wear patterns will be validated using state-of-the-art preclinical wear simulators. Simultaneously, we will quantify how patient, surgical, and implant factors contribute to wear in retrieved TSA components (>400 samples), correlating imaging-based wear patterns with clinical outcomes, patient-reported function, inflammatory tissue responses, and radiographic indications of loosening. For that purpose, we will establish benchmarks of TSA wear rates and introduce a new histopathological approach augmented by infrared spectroscopic imaging. This work is innovative because we are linking patient-specific movement patterns following TSA with multi-scale computational models to predict PE wear, breaking the current approaches of using generic motions and loads in existing testing standards. This work will produce the first integrated, publicly available database of TSA kinematics, joint loading, and PE wear patterns and rates, along with validated computational tools to inform implant design, surgical planning, rehabilitation strategies, and personalized risk assessment. Ultimately, these advances will improve functional outcomes and long-term success for TSA patients and enable better preclinical testing methods and standards.

Fairfield County's Community Foundation

Fairfield County's Community Foundation ($400M in assets) supports nonprofits in CT through grants focused on education, economic opportunity, health, arts. Awards range from $2,500 to $100,000.

Freeway Park Association

The Freeway Park Association will organize a community lantern installation and Fall Festival event on Friday, October 26, 4-7pm, at Freeway Park, 700 Seneca St. Communities neighboring the park will be invited to help make lanterns and participate in the festival. The lanterns will hang throughout the fall and winter as a way to bring light, movement, color and community art into the park, making people feel safe and invested in Freeway Park.

Arts Corps

Arts Corps will organize a series of arts-based family workshops to strengthen intergenerational and community connections. Three workshops will be held between January and May 2019. They will take place at Martin Luther King Jr Elementary School located at 6725 45th Ave S. All workshops will be held during non-school hours to ensure public accessibility.

Group for Promotion of Family Entertainment in Seattle

To improve the accessibility of the arts to everyone, regardless of age or income, we propose producing twelve monthly family friendly variety shows to take place over a year. We will focus on including the many different kinds and nationalities of performing arts, circus arts, and musical styles in Seattle.