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NCI - National Cancer Institute

Project Summary The overall goal of this application is to establish the University of Arizona Cancer Center (UACC) as a Network Lead Academic Participating Site (LAPS) for the NCI’s National Clinical Trials Network (NCTN). As the only NCI-Designated Comprehensive Cancer Center headquartered in the state of Arizona, the UACC currently provides significant leadership and mentorship in the development and conduct of important translational and therapeutic clinical trials for cancer patients across the state. This application will enhance participation and bolster the UACC’s infrastructure capabilities to continue to provide scientific leadership in the development and conduct of clinical trials and substantial accrual to clinical trials across the state and entire NCTN while simultaneously training the next generation of clinical investigators in state-of-the art clinical trials for the treatment of adult cancer patients. Specifically, this will support the UACC’s infrastructure to increase clinical research activities, protocol development, investigator leadership and junior faculty mentorship. UACC has a strong track record of past and present leadership and participation in the NCTN Program and will continue this participation as a LAPS site. We will achieve our goal through the following Aims: 1) to develop, lead, and participate in scientifically and clinically relevant NCTN clinical trials; 2) to support robust accrual, timely and accurate data reporting and internal monitoring for NCTN trials; 3) to support accrual at satellites sites across the state of Arizona as part of the Arizona Clinical Trials Network; and 4) to serve the community by utilizing a Clinical Trials Oncology Navigation program to assist with trial education and enrollment and retention of patients reflective of our catchment populations and the state of Arizona. We plan to do this through creating a LAPS Leadership Committee for oversight and mentoring, by working with the Clinical Trials Navigator to educate patients on clinical trials, and specifically targeting sites with access to rural and other underserved populations.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Tuberculosis (TB) in humans results from infection with members of the Mycobacterium tuberculosis complex (MTBC). The disease is endemic in many parts of the world. So is bovine tuberculosis (bTB) - a well-recognized zoonotic disease of bovine species (cattle and buffalo) also caused by infection with members of the MTBC. India has the world’s highest TB burden in humans, with more than 2M new cases and 400,000 TB-related deaths each year. India also hosts the largest bovine herd on the planet (~300M animals), and our recent studies suggest that more than 22M of those animals may suffer from bTB. Yet the risk of zoonotic TB (zTB) resulting from transmission of MTBC from bovines to humans in India and other high-TB burden settings is unknown. This is a major knowledge gap, and elimination of TB will be considerably more difficult if there is spillover from a domestic livestock reservoir to humans. This is of particular concern in countries such as India where the frequent consumption of unpasteurized milk and close contact with infected animals likely present additional elevated risks for zoonotic transmission. Because of this, the World Health Organization (WHO) and other supranational organizations have developed a "Roadmap for zoonotic TB" that calls for the establishment of a stronger evidence base to improve understanding of the burden and risk pathways of zTB to guide an effective response. To fill these knowledge gaps, we propose studies with the overall objective of estimating the risk associated with zTB in a high-TB-burden setting. We will accomplish this by applying rigorous quantitative risk assessment augmented by state-of-the-art whole-genome sequence (WGS)-based molecular epidemiology and multi-host transmission modeling. Performed at well-established study sites in Vellore and Tiruvallur districts in Tamil Nadu, India, our Specific Aims are to: 1) Estimate the risk of human TB associated with exposure to cattle, buffalo, or the consumption of raw milk in ~1,750 human cases and ~3,500 controls; 2) Apply WGS-based approaches to define the genetic diversity and molecular epidemiology and perform phylodynamic and phylogeographic analysis of MTBC lineages circulating in human TB cases, sympatric cattle and buffalo, and locally sourced raw milk; and 3) Perform multi-host transmission modeling to quantitatively assess zTB risk to humans and the potential benefits of control. These studies involve the application of innovative and powerful nested case-control epidemiological surveys with WGS-based genotyping and mathematical modeling. The results of our studies will inform and refine estimates of zTB risk, enable identification of transmission chains at a local scale, and transform our understanding of spillover and circulation of MTBC strains between human and bovine hosts. In the long-term, our findings will provide sustained positive impact through the development of evidence-based approaches to quantify and reduce risk of zTB in support of the global efforts to end TB.

East African Arts & Cultural Association

The East African Arts & Cultural Association will celebrate Seattle Ethiopians' Week with a 5 day public celebration to be held July 2-6, 2017. It will take place at King's Hall located at 2929 27th Ave S. The celebration will convene the Ethiopian community to express their heritage, engage Ethiopian youth in relevant community issues, showcase Ethiopian performing and visual arts, and strengthen mutual understanding and respect between a wide variety of cultures.

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.

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.

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.

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.

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.

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.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.<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.

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.

Fargo-Moorhead Area Foundation

Fargo-Moorhead Area Foundation ($200M in assets) supports nonprofits in ND through grants focused on education, community development, health, arts. Awards range from $1,000 to $50,000.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY/ABSTRACT This proposal requests funds for acquisition of an AKTA pure 25 fast protein liquid chromatography (FPLC) system for biomolecule purification at Eastern Washington University (EWU), a primarily undergraduate institute. This instrument will greatly enhance our research and education capacities. At EWU we strive to provide students with hands-on biomedical research experiences through our classes and research labs. The AKTA pure will provide a much needed high quality protein purification system for our biomedical research community. Currently our protein purification projects mainly use gravity flow purification methods with poor yield, and purification quality. With the AKTA pure, we will be able to make use of advanced purification methods, and perform chromatography based biochemical assays, considerably expanding our experimentation capabilities. The instrument will enable us to offer a new class focused on protein purification using the FPLC. We will also incorporate FPLC skills into several current upper-level classes. It will support a diverse range of ongoing research projects, including two NIH funded projects, and allow researchers to gather data for new grant applications. Furthermore, it will enable users to explore new avenues of research, such as small RNA purification and analytical chromatography techniques for protein characterization that we are currently not able to perform. The classes and research projects supported by the AKTA pure will provide a large number of EWU students the opportunity to gain training in a state of the art instrument widely used in biomedical research. Students will gain valuable research experience, and proficiency in using the FPLC will give them a career-ready skill for the biomedical field. The AKTA pure FPLC system will be an invaluable tool for advancing research and education at EWU.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY The production of red blood cells (RBC), known as ‘erythropoiesis’, serves as a paradigm for understanding cellular differentiation and terminal maturation. Defects in erythropoiesis or RBC function cause various forms of anemia, a health burden affecting nearly one-third of the global population. Each step of erythropoiesis, including lineage specification, proliferation, differentiation, and terminal maturation into RBCs filled with hemoglobin for oxygen transport, has unique metabolic requirements with potential opportunities for therapeutic intervention. For instance, recent evidence indicates that hemoglobinopathies can be treated by stimulating glycolysis with pyruvate kinase agonists. We demonstrated previously that glutamine synthesis is uniquely upregulated during erythropoiesis to detoxify ammonium generated by heme synthesis and that enhanced glutamine synthetase activity alleviates -thalassemia. However, the comprehensive metabolic regulation of erythropoiesis remains poorly understood, which limits therapeutic opportunities. To address this knowledge gap, we performed global metabolomic profiling, isotope tracing and transcriptome analysis of staged erythroid precursors from mouse fetal liver and bone marrow. We discovered that distinct, ontogeny-specific metabolic processes govern erythropoiesis. While glucose is the primary nutrient for bioenergetics and biosynthesis in fetal liver erythroid precursors, mitochondrial fatty acid β-oxidation (FAO) becomes more active during postnatal bone marrow erythropoiesis. Surprisingly, isotope tracing showed that long chain fatty acids are essential metabolic precursors for TCA cycle intermediates and heme during adult-type erythropoiesis. Moreover, genetic disruption of FAO enzymes caused impaired erythropoiesis and anemia in adult mice, whereas erythroid FAO was profoundly dysregulated in sickle cell disease (SCD). These findings support our central hypotheses that FAO provides essential nutrients to support erythropoietic energy demands and biosynthetic needs, including heme biosynthesis, and that dysfunctional FAO contributes to the pathophysiology of SCD. Thus, the objective of this project is to elucidate the functional and mechanistic roles of fatty acid metabolism as a new regulatory pathway in erythropoiesis and RBC disorders according to three specific aims: 1) Define the functional roles of FAO in erythropoiesis; 2) Elucidate the mechanistic roles of fatty acid metabolism in erythrocyte development and function; and 3) Determine the role of fatty acid metabolism in the pathophysiology of sickle cell disease. Our hypotheses and the feasibility of proposed studies are supported by extensive preliminary data combining orthogonal, state-of-the-art metabolic and transcriptomic approaches with orthogonal mouse and human models to analyze erythropoiesis in vivo. Now we will elucidate fatty acid metabolism as a critical metabolic regulator of normal postnatal erythropoiesis and a potential therapeutic target for SCD.