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NIMH - National Institute of Mental Health

The Psychiatric Genomics Consortium (PGC) has been at the forefront of psychiatric genetics for nearly two decades, massively advancing our understanding of the genomic underpinnings of psychiatric disorders. Building on its success with over 1,700 investigators and 755 impactful publications, the PGC proposes a new phase to harness the forthcoming influx of genetic and functional genomic data from across the US and around the world. This effort aims to deepen understanding of the genetic architecture of psychiatric disorders, address critical gaps in biological mechanisms, catalyze clinical relevance, and accelerate training and outreach on how genetic factors contribute to mental and physical health. We propose three synergistic Specific Aims: (1) Identify genetic variants associated with serious psychiatric disorders that afflict many Americans by rigorous integration and analysis of all available datasets using state-of-the-art methods to analyze common, rare, and structural variants. (2) Dissect heterogeneity of psychiatric and chronic medical disorders by examining shared and distinct genetic influences on risk. (3) Advance mechanistic understanding of psychiatric risk and resilience by fine-mapping genetic loci, identifying relevant biological contexts, and integrating functional genomic annotations. These aims create a cohesive framework where foundational discovery (Aim 1) informs efforts to resolve heterogeneity (Aim 2), and then to elucidate biological mechanisms (Aim 3). We will achieve these aims by leveraging our established analytical infrastructure and efficient organizational structure. This phase of the PGC will drive collaboration, accelerate genetic discovery, and deliver biological and clinical insights into psychiatric disorders, with the ultimate goal of improving patient outcomes. Including foreign sites is scientifically essential: the sample sizes required to detect genetic variants of small effect, variants that can have major public health implications for Americans, can only be achieved through global collaboration and our discoveries will accelerate genetic insights that benefit US patients.

NIMH - National Institute of Mental Health

The Psychiatric Genomics Consortium (PGC) has been at the forefront of psychiatric genetics for nearly two decades, massively advancing our understanding of the genomic underpinnings of psychiatric disorders. Building on its success with over 1,700 investigators and 755 impactful publications, the PGC proposes a new phase to harness the forthcoming influx of genetic and functional genomic data from across the US and around the world. This effort aims to deepen understanding of the genetic architecture of psychiatric disorders, address critical gaps in biological mechanisms, catalyze clinical relevance, and accelerate training and outreach on how genetic factors contribute to mental and physical health. We propose three synergistic Specific Aims: (1) Identify genetic variants associated with serious psychiatric disorders that afflict many Americans by rigorous integration and analysis of all available datasets using state-of-the-art methods to analyze common, rare, and structural variants. (2) Dissect heterogeneity of psychiatric and chronic medical disorders by examining shared and distinct genetic influences on risk. (3) Advance mechanistic understanding of psychiatric risk and resilience by fine-mapping genetic loci, identifying relevant biological contexts, and integrating functional genomic annotations. These aims create a cohesive framework where foundational discovery (Aim 1) informs efforts to resolve heterogeneity (Aim 2), and then to elucidate biological mechanisms (Aim 3). We will achieve these aims by leveraging our established analytical infrastructure and efficient organizational structure. This phase of the PGC will drive collaboration, accelerate genetic discovery, and deliver biological and clinical insights into psychiatric disorders, with the ultimate goal of improving patient outcomes. Including foreign sites is scientifically essential: the sample sizes required to detect genetic variants of small effect, variants that can have major public health implications for Americans, can only be achieved through global collaboration and our discoveries will accelerate genetic insights that benefit US patients.

Seattle Repertory Theatre

Through Public Works Seattle, Seattle Rep will use the art of theatre to connect people with one another and with the city as a whole. Working collaboratively with five non-profits, the project will engage over 150 people to participate in free weekly workshops and attend monthly performances at the Seattle Repertory Theater. The project culminates in an ambitious work of participatory theater featuring a large community ensemble, with four free performances for 3,000 attendees.

Seattle Repertory Theatre

Seattle Repertory Theater will partner with local organizations to share theater experiences and the arts with audiences across Seattle, with an emphasis on engaging populations that face barriers to arts access. A twelve-week series of free workshops, rehearsals, performances and acting intensives will be offered during Fall 2019 to Spring 2020 at 7 different locations. The first workshop will be held at the Ballard Senior Center(5429 32nd Ave NW) and other locations.

Puerto Rico Council on the Arts

Arts and cultural grants for organizations in Puerto Rico, supported by NEA federal funding.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT With an emphasis on the integration of basic, translational and clinical approaches, the 68th annual Aspen Lung Conference (June 9th – 12th, 2026) will focus on answering a central question: Are current advancements in understanding the mechanisms of lung vascular cell dysfunction and lung vascular remodeling sufficient to develop effective strategies for the treatment of pulmonary vascular disease in conditions like pulmonary hypertension (PH), chronic lung disease, sepsis, and acute lung injury. To explore this central question, we structured the program into a series of six thematic sessions, each beginning with an opening keynote address: (1) Novel insights into PH phenotypes and vascular remodeling in the pulmonary circulation; (2) The vascular niche in the pulmonary circulation: Modifying resident cell function to treat pulmonary vascular disease (PVD); (3) The vascular niche in the pulmonary circulation: Modifying circulating and recruited cell function to treat PVD; (4) Understanding cellular interactions in the pulmonary circulation in chronic lung disease: Towards a cure for Group 3 PH; (5) Mechanisms of cardiac adaptation and maladaptation and their effects on heart-lung interactions in PVD; (6) Current and emerging diagnostic and treatment strategies for pulmonary hypertension and PVD. By addressing these topics, we seek to accomplish the following: 1) Provide a forum for leading basic, translational, and clinical researchers to exchange ideas regarding the current state of the field; 2) Stimulate interactions between scientific fields to identify emerging and shared interests leading to more efficient and productive research; 3) Enhance the likelihood of success in translation of preclinical scientific advances into direct patient benefit; and 4) Challenge and stimulate the scientific interests of trainees and attract a new generation of early career investigators into the fields of PVD and right heart failure. We identified outstanding thought leaders to present 12 State-of-the-Art lectures (35 min) on these topics. Lectures will be followed by 25 minutes of moderated discussion, a hallmark of the Conference. The program continues the Conference’s dedication to trainees and early-stage investigators, which will be supported by three Travel Awards (given to top scoring submitted abstracts). Travel Awardees give a 15-minute presentation in sessions that follow each State-of-the-Art speaker (24 total). Two evening poster sessions will provide additional presentation opportunities for trainees, early and established investigators (40 total posters). The final presentation is provided by the Conference Summarizer, who reviews the impact and common themes of the Conference. The Conference Summary is published annually in the Am. J. of Resp. Cell and Mol. Biol. as a “state of the field” review and includes key challenges and future directions for basic, translational, and clinical research. To encourage participation by trainees and early-stage investigators, registration is free for all students, trainees, fellows, Instructors, and Assistant Professors. The Conference is live-streamed and recorded to allow real time participation and/or viewing by investigators unable to attend in person.

Quad Cities Community Foundation

Quad Cities Community Foundation ($150M in assets) supports nonprofits in IL through grants focused on education, community development, arts, health. Awards range from $1,000 to $50,000.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY/ABSTRACT Shifting cannabis policy and access to high potency cannabis products creates an urgent need to evaluate and disseminate data on cannabis exposure and risks among aging people living with HIV (PWH). Higher potency products confer heightened risk of cannabis use disorder (CUD), cognitive impairment, and falls. Because PWH are more frail than people without HIV (PWoH), they may be more susceptible cannabis-associated harms (e.g., geriatric syndromes including falls/fractures, delirium/dementia) and ART failure or non-adherence. Our proposal responds to RFA-DA-26-055 (Accelerating the Pace of Drug Abuse Research Using Existing Data) and NIDA priorities of understanding the role of substance use in HIV pathogenesis. Electronic health record (EHR) data can advance cannabis research; innovative approaches are needed to maximize its utility. We will use longitudinal nested Veterans Aging Cohort Study (VACS) cohorts and our expertise in informatics, cannabis epidemiology/policy research, HIV, and causal inference to estimate causal effects of cannabis use on geriatric syndromes and ART failure/adherence. Specific Aims: Aim 1. Determine the association of CUD and incident geriatric syndromes and ART failure/adherence. In VACS-HIV (N~180,000), we will estimate the association of CUD and incident falls and fractures (Aim 1Ai) and delirium and dementia (Aim 1Aii). Among PWH, we will determine the association of CUD and HIV viral suppression and ART adherence (Aim 1B). We will assess how associations (Aim 1A-1B) generalize to a non-veteran population (Mt. Sinai HIV cohort, N~850,000, Aim 1C-D). We will explore how cannabis legalization alters these associations (Aim 1E). Aim 2. Estimate causal effect of cannabis use (self-reported) on incident geriatric syndromes. In VACS-Survey (N~9000), we will use target trial emulation to determine the effect of past-year cannabis use on incident falls and fractures (Aim 2Ai) and delirium and dementia (Aim 2Aii). Aim 3. Build and validate a novel EHR-based cannabis use ascertainment algorithm (NLPWH) by extending an existing natural language processing algorithm (NLPREOP) and validating NLPWH. We will create NLPWH by retraining NLPREOP on multiple EHR clinical note types (e.g., primary care) from VACS-HIV in 9 U.S. states (Aim 3A); internally validate NLPWH using cannabis biomarker and self-report (Aim 3B); externally validate NLPWH by chart review in the Mt. Sinai HIV cohort (Aim 3C); and assess impact of cannabis legalization on algorithm performance (Aim 3D). Using the target trial approach from Aim 2, we will evaluate the causal association of NLPWH-derived cannabis use with geriatric syndromes, ART failure, and ART adherence. IMPACT: Using data from two healthcare systems we will provide early and increasingly complete evidence identifying and quantifying medical harms from cannabis use among PWH and PWoH. The new NLP tool we validate may help health systems rapidly estimate cannabis exposure in their patients and guide urgently needed policies for CUD screening, diagnosis, and treatment.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Dolutegravir is widely used for HIV treatment globally, yet glaringly little data on integrase resistance after dolutegravir failure among children are available. While dolutegravir is associated with improved efficacy and decreased resistance compared to other antiretroviral therapy (ART) regimens, a recent study from Malawi found that integrase resistance was present in 30% of select adults failing dolutegravir. While this may be an overestimate, children have multiple risk factors that increase the risk of developing integrase resistance including greater reuse and resistance to companion antiretroviral drugs, lower rates of viral suppression, higher viral load at failure, and more severe immunocompromise. To address this knowledge gap we will quantify integrase resistance in a population of children failing dolutegravir in Nigeria and utilize this resistance data to develop and validate a rapid diagnostic in collaboration with colleagues there. The 2021 World Health Organization HIV Drug Resistance Report specifically calls for surveys of integrase resistance in order to provide early signals of emerging dolutegravir resistance. Our population of highly treatment-experienced children who were rapidly transitioned to dolutegravir ART, of which 12% have detectable viremia, represents such a clinical population at increased risk of developing integrase resistance, and will inform nationally representative surveys of drug resistance. Nigeria is home to more children living with HIV than any other country in the world. A national survey of pre- treatment drug resistance among ART-naïve infants ≤18 months of age (2016) shows high rates of resistance, including to the most widely used companion drugs among children: abacavir and lamivudine. Such resistance may predispose children to develop integrase resistance. Since 2004, APIN Public Health Initiatives has provided HIV care and treatment to over 22,000 children in Nigeria, and thus is uniquely positioned to provide critical drug resistance data from multiple pediatric sites/regions across Nigeria. We propose to evaluate integrase resistance among 500 children in Nigeria failing dolutegravir-ART at two different time points to provide critical data on the evolution of integrase resistance. We will further utilize these data to develop rapid diagnostics to detect specific integrase resistance mutations with the goal of making dolutegravir resistance testing accessible globally via rapid, low-cost assays. These studies address a critical gap in knowledge regarding integrase resistance among children failing dolutegravir ART, will inform future surveys of drug resistance, and will support the development and validation of a rapid integrase resistance assay in this setting. This has the potential to impact international guidance on dolutegravir use and resistance testing for this vulnerable population of children.

It Takes a Village

The Queens Healing and Liberation project will be a hub for transformative work, committed to the thriving of Black, indigenous and people of color community members and the liberation of everyone. This project will offer space, resources, and nourishment for changemakers grappling with the challenges of our world. Our organization focuses on 3 core fields- health and healing, art and education, and environment and justice. This project will be completed by February 28th, 2023.

Seattle Poetry Slam

Seattle Poetry Slam will host an all-ages three-day celebration of LGBTQ arts and community on December 8-10 at Capitol Hill venues. The Queer Resurgence on Capitol Hill Poetry Festival will include panel discussions, workshops, and a poetry slam competition. Seattle Poetry Slam will partner with key organizations like Seattle Spit (Seattle's only LGBTQ open mic) and Gay City (Seattle's LGBTQ Center).

NCI - National Cancer Institute

SUMMARY/ABSTRACT Cranial radiotherapy remains a cornerstone for treating primary and metastatic brain tumors. However, it is frequently associated with long-term cognitive decline, particularly in patients who survive beyond six months post-treatment. Despite advances in radiation delivery and neuroprotective strategies, no effective interventions currently exist to prevent or reverse radiation-induced neurotoxicity. The studies outlined in this proposal are based on a novel hypothesis that radiation disrupts neural lineage commitment in the developing human brain, driving aberrant cellular plasticity and transdifferentiation of neural stem/progenitor cells into endothelial-like phenotypes, which is supported by preliminary and published data. These fate shifts impair neurodevelopment and alter synaptic function, contributing to long-term cognitive deficits. The overall hypothesis is that radiation-induced cellular reprogramming in the human brain alters both cellular identity and functional connectivity, and that these effects can be mitigated through targeted inhibition of endothelial-inductive pathways (e.g., VEGF, FGFR, Notch). To test this, we will use mature human iPSC-derived cortical organoids subjected to fractionated radiation and apply single-cell and spatial transcriptomic approaches to define lineage transitions (Aim 1), followed by functional assays including calcium imaging and multielectrode array recordings to assess neural network activity in the presence and absence of pathway inhibition (Aim 2). This R21 project leverages cutting-edge 3D human brain models and state-of-the-art technologies to address a major gap in understanding the cellular mechanisms underlying radiation-induced cognitive impairment. Because the targeted pathways have existing pharmacologic inhibitors already in clinical use, this research has high translational potential for developing radiation mitigators to preserve brain function in cancer patients undergoing radiotherapy.

NHLBI - National Heart Lung and Blood Institute

Project Summary The long-term goal of this research program is to provide the endovascular, minimally invasive practitioner with an entirely novel biomaterial platform technology for metallic implants that optimize the key primary attributes of mechanical strength, radiopacity, and bioabsorbability. Specifically, while the past 15 years of vascular material development research has focused on bioabsorbable biomaterial development for balloon expandable stents, no formal longstanding investigations have focused on engineering fully absorbable, radiopaque, wire-based braided stents, which offer numerous advantages over balloon-expandable devices. These advantages include low delivery profile, outstanding softness and trackability, and high mesh density for closure of arterial defects such as aneurysms. A significant motivation for developing absorbable braided stents is the potential for reduction in imaging artifacts, chronic thrombosis and inflammation, and obstacles during reintervention. Motivated by these clinically relevant issues, our team previously engineered and tested novel bioabsorbable iron (Fe)-based alloy (Iron-Manganese-Nitrogen, or FeMnN) flow diverters and have demonstrated their efficacy in vitro and in vivo. While promising, our previous research demonstrates some shortcomings. The FeMnN material degrades quickly and non-uniformly, leading to fractures that reduced long term aneurysm healing rates, and did not possess stent metrics similar to industry standards. Additionally, no previous implant, bioabsorbable or not, has overcome the need for permanent radiopaque portions of the implant for X-ray guided surgical implantation, which counteracts the bioabsorbable benefit. Radiopacity is a critical issue in all bioabsorbable materials, as most are not radiopaque and rely on permanent metal materials to generate radiopacity. Our recent biomaterial-based investigation has resulted in the discovery and engineering of a new metal composite, galvanically coupled bioabsorbable metal biomaterial system, which utilizes FeMnN alloy filaments filled with radiopaque and bioabsorbable Mo in their cores. Furthermore, we hypothesize that stents made with FeMnN-Mo composites (by drawn filled tubing, or DFT) will be able to perform as well as industry standards, with the added benefit of homogenous absorption over time, a benefit of the DFT core and multi staged material degradation. We will improve the corrosion performance, mechanical properties, radiopacity, and biological behavior of this new biomaterial composite system in Aim 1 by engineering new alloys/composites for in vitro and in vivo mouse aorta testing. We will further assess whether FeMnN-DFT-Mo flow diverting stents can be applied successfully in the treatment of saccular aneurysms in rabbits in Aim 2. The expertise of our multidisciplinary team, which includes metallurgists, vascular biologists, clinical endovascular therapists, and biomedical engineers, is well suited to execute this research program. Our cross-disciplinary utilizes novel elemental imaging, leading preclinical animal models, and state of the art manufacturing is poised to uncover new discoveries in advanced bioabsorbable metal biomaterials.

Friends of Rainier Valley Creative District

The Friends of Rainer Valley Creative District are hosting the 2023 Rainier Valley Community Arts Resource Fair (Arts Resource Fair) will take place on Sunday, August 20, 2023 in Columbia Park (located at the north end of Rainier Valley) from 11AM to 7PM. This is a full day multi-purpose event that will provide arts, culture, education, health, legal, housing, and business resources to the general public with a particular focus on the needs of creative businesses in the Rainier Valley.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ ABSTRACT Although World Health Organization (WHO) guidelines now recommend once‐daily tenofovir‐lamivudine‐ dolutegravir (TLD) for antiretroviral therapy (ART), adherence challenges in taking daily oral ART persist. The rates of virologic suppression (VS) worldwide for those on ART are around 70%, with a lower rate (65%) approximately three years after starting ART. Pharmacologic adherence metrics, where ART levels are directly measured in a biomatrix ‐ such as plasma, urine, dried blood spots (DBS), or hair‐ reflect actual pill‐taking and predict virologic suppression more accurately than self‐reported adherence. Our UCSF research group has helped pioneer the use of small hair samples to measure adherence to ART, but most methods to analyze ART drugs in any matrix involve liquid chromatography/tandem‐mass spectrometry (LC‐MS/MS) which is expensive and cannot be performed in real‐time. Point‐of‐care (POC) adherence monitoring requires the development of a highly selective antibody and subsequent development of an immunoassay to ART. Evidence from other disease states show that real‐time monitoring of drug levels to the needed medication, followed by supportive feedback to the patient, increases adherence and improves outcomes. Our UCSF group has now developed one of the first immunoassays (antibody‐based assay) to detect tenofovir (TFV) in urine, a matrix easily‐accessible for point‐of‐care testing. Work by our team among people with HIV (PWH) in Namibia assessed the effect of the urine assay on VS rates among persistently virally non‐ suppressed adults on ART, despite the application of WHO‐recommended enhanced adherence counseling (EAC). In a pre‐post analysis, we found that VS rates increased from 0% to 92% after urine testing and counseling at monthly ART refills over six months. Now is the time to perform a large, randomized trial to explore the ability of counseling informed by results from the urine TFV assay to increase VS versus standard‐of‐care EAC to provide evidence for incorporating the urine POC test into clinical practice. Aim 1 of this renewal R01 application proposes a large randomized trial (n=500) comparing use of the POC urine test for TFV with tailored counseling versus standard‐of‐care EAC among participants with documented virologic failure on TLD at clinics in South Africa. The primary outcome is VS at six months; secondary outcomes include assessing the sustainability of the 6‐month intervention on VS out to 24 months; development of viral resistance in each arm; and positive urine tests by arm. Aim 2 examines implementation outcomes including acceptability and feasibility, with Aim 3 assessing cost‐effectiveness of the intervention. If the trial is successful, we will have demonstrated that an easy‐to‐use inexpensive POC urine adherence test will increase VS among populations with virologic failure on TLD, which will benefit patients, decrease the development of viral resistance, and prevent forward transmission. The aspiration of this grant is to move the low‐cost urine assay into clinical care and inform WHO ART guidelines (WHO letter of support included).

SPRINGVILLE CENTER FOR THE ARTS, INC.

CNSTR/RHAB

SPRINGVILLE CENTER FOR THE ARTS, INC.

CNSTR/RHAB

NIDA - National Institute on Drug Abuse

ABSTRACT Systems neuroscience is acquiring exponentially more neural activity data in vivo and is employing richer stimuli to study ethologically relevant behaviors. Models of neural dynamics in low-dimensional spaces (‘neural manifolds’) are increasingly state-of-the-art for describing the underlying neurobiological mechanisms to encode rich stimuli and evoke behavior. However, causally testing these theories remains challenging, as it requires dynamic manipulation of activity across neurons and time, conditioned on the individual brain, task, or environment. Here, we propose to build new machine learning methods to construct low-dimensional neural manifolds shaped by external stimuli in real time, and design perturbations of neural dynamics on these manifolds to directly test hypotheses of neural circuit function. We will broadly learn how external stimuli drive ongoing neural dynamics and which neuronal stimulations optimally align with these latent vectors. Our real-time approach will also enable us to consider multiple competing models in parallel and choose stimulations to differentiate between them, causally testing competing hypotheses of neural manifold landscapes. We will validate our models in vivo in the larval zebrafish using high-dimensional visual stimuli concurrently with holographic optogenetic photostimulation. In Aim 1, we will develop real-time dimensionality reduction algorithms to construct neural manifolds shaped by external stimulus information. In Aim 2, we will design probabilistic models for predicting the effects of neural stimulations on latent neural dynamics. In Aim 3, we will develop a method for jointly optimizing external stimuli and direct neural stimulation patterns to shape ongoing neural dynamics in real time. Successful completion of this project will result in generalizable machine learning methods that can automatically learn stimulus-shaped neural dynamics and optimize neural stimulations to drive dynamics on the manifold. These tools will be widely available and broadly useful to many neuroscientists.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

ABSTRACT Neurological studies greatly benefit from functional brain imaging to investigate brain activity and understand the underlying mechanisms of healthy and disordered behavior. Studying non-human primates (NHP) stands at the forefront of neurological research, offering unparalleled insights into complex brain activities and advanced cognitive and behavioral processes. Utilizing optical or ultrasound technologies, researchers have developed various brain imaging methods that are versatile for studying a range of awake and behaving applications. However, these tools have been restricted to only small animal models. Recently, photoacoustic tomography (PAT) has emerged as a promising non-invasive, label-free technique capable of mapping deep brain hemodynamic functions by acoustically probing the brain’s optical contrast. Yet, the efficacy of traditional photoacoustic imaging is compromised by the strong acoustic aberration induced by the NHP’s dense, curved, and thick skull. Furthermore, current PAT systems are ill-suited for awake NHP imaging, due to their unwieldy size and complex operation. In this proposal, we will transcend these limitations by developing a four-dimensional smart epidermal photoacoustic tomography (4D-SEPAT) technology, allowing for real-time, longitudinal, functional brain imaging in behaving NHPs. The proposed 4D-SEPAT technology will leverage state-of-the-art epidermal electronics, which combines soft ultrasound transducer array and high-precision shape mapping. Most importantly, the soft ultrasound transducer array, with integrated shape sensor and high-power laser source, can closely adapt to the contour of the NHP head, effectively mitigating the skull’s aberration effect. Powered by fast 3D image reconstruction, 4D-SEPAT will enable real-time transcranial brain imaging while maintaining its high sensitivity to hemodynamic functions. With full conformability to the head, 4D-SEPAT is insensitive to motion artifacts, can be longitudinally applied to behaving NHPs, and allow for deep-brain analysis of sensory and cognition. To achieve this objective, we will pursue the design, development, and validation of the proposed 4D- SEPAT system in Aim 1 and Aim 2, and demonstrate its imaging performance in awake rhesus macaques during visual-oculomotor behavior in Aim 3. Success of this 4D-SEPAT technology has the potential to revolutionize the way the brain is studied, diagnosed, and treated, by providing non-invasive, longitudinal, real-time mapping of deep brain functions.

NIAID - National Institute of Allergy and Infectious Diseases

Vaccines are the most successful prophylactic measure against pathogens, and their protective capacity depends on the formation of long-lived immunological memory, e.g. memory T lymphocytes (TMEM). Coordination between B and T lymphocytes is required against intracellular pathogens to neutralize pathogens and eradicate infected cells, respectively, as recently highlighted with COVID19 vaccine responses. Individuals living with chronic infections were shown to exhibit inferior responses to subsequent infections and vaccination. Studies in animal models suggested the cause to be the inferior recall responses by the TMEM generated to acute stimuli in hosts with preexisting chronic infection (hereafter termed inflm-TMEM). However, epigenetic imprints of persistent inflammation on inflm-TMEM have not been examined, and interventions to restore efficient protective recall responses by inflm-TMEM are understudied. Previous studies and our preliminary data demonstrated arrested development of inflm-TMEM, especially the central memory subset (TCM). Previous transcriptional profiling and our chromatin-accessibility profiling revealed skewed transcriptional and epigenetic landscapes of antigen-specific inflm-TMEM compared to bona fide TMEM, with enrichment of signatures associated with inflammatory mediators including type I interferon (IFN-I) and interleukin-6 (IL-6), which signal downstream janus kinase 1/2 (JAK1/2). We hypothesize that JAK1/2 inhibition would recover normal TMEM differentiation in hosts with preexisting chronic infection. To investigate this, we will use the same mouse model utilized for our preliminary studies to examine the differentiation of antigen-specific T cells responding to acute infection in the presence of preexisting chronic infection with or without JAK1/2 inhibition (JAKi) treatment. We will dissect the profiles of inflm-TMEM using high- dimensional flowcytometry and combined scRNAseq/scATACseq (MultiOme) profiling. More importantly, we will investigate the functional impact of JAKi-treatment on enhanced pathogen clearance and protection upon rechallenge. Our team has expertise in immunology, mouse models, and MultiOme profiling tools. This puts us in a unique position to address our main objectives which are: (1) to examine the capacity of FDA-approved interventions (JAKi) to recover generation of efficient TMEM in hosts with preexisting chronic infection, and (2) to gain insights into the molecular mechanisms underlying the skewed differentiation of inflm-TMEM., and aspects recovered by JAKi treatment. These studies push the envelope of innovation where we will employ combined state-of-the-art high-dimension flowcytometry, functional assays, and MultiOme profiling, to decipher specific mechanisms associated with lower recall capacity of inflm-TMEM that is understudied to date. We will validate novel therapeutic approaches using FDA-approved medication(s) for enhancing TMEM formation in hosts with preexisting chronic infection. This is of high relevance for enhancing vaccine efficiency in people living with chronic viral infection, and can be extended to benefit other populations living with chronic diseases with underlying inflammation. Summary

Tasveer

Reflections through HEART - a CommUNITY Open Mic Event will delight audiences with South Asian artists presenting prose, poetry, comedy, music, performance art, improv, or other forms of artistic expression. The open mic event will have curated segments and non-curated segments which will give the mic to established artists, while encouraging and inspiring new artists to step up to participate. The event will be at the Broadway Performance Hall,1625 Broadway Avenue, on September 24, 2022 at 7:00 p.m. This project will be completed by December 30, 2022.

Refugee Artisan Initiative

Refugee Artisans Connect is a community arts project consisting of 10 free public workshops on upcycled crafts led by 38 refugee women artisans. The project also includes the creation of a 6-feet-long Peace Dove Sculpture, which will be designed and constructed by a lead artist and a team of artisans, and covered with 1,000 peace-message-feathers made by community members. The project will take place between December 2024 and October 2025 at the RAI Maker Space, and the completed Peace Dove Sculpture will debut in late 2025 at the grand opening of RAI's Arts + Cultural Center, an expansion of the Maker Space which is ready for renovation, and which will also serve as the first refugee arts and cultural center in the State of Washington. The primary purpose of our project is to increase public appreciation of the arts and cultural heritage of their refugee neighbors, while providing equitable and sustainable income for our artisans' unique talents and skill sets.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract Current state-of-the-art immunosuppressive strategies have significantly improved short-term graft survival rates, but they have failed to promote immunoregulation and improve long-term graft outcome. Although much research has been performed on CD4+ T cells in the process of rejection, B cells are well-established to be of great significance in alloimmunity. B cells function as antigen presenting cells to promote alloreactive T cell activation, they interact with activated T cell subsets and they differentiate into alloantibody producing plasma cells that elicit humoral rejection which rapidly accelerates graft failure. Nevertheless, distinct but rare subsets of B cells have also been identified to promote immunoregulation, and these regulatory B cells are postulated to have critical protective functions following human solid organ transplantation. In recently published studies, we observed that a regulatory receptor called Neuropilin-2 (NRP2) is expressed on distinct subsets of human and mouse B cells. In preliminary studies, we find that NRP2-expressing B cells have phenotypic features of B regulatory cells, and further that they have potential to suppress CD4+ T effector cell activation responses. In this R21 proposal, we plan to examine this possibility by profiling NRP2-expressing B cells and assessing their function to suppress alloimmune effector T cell activation. Furthermore, we will examine the effects of the NRP2 ligand Semaphorin3F (Sema3F) by profiling responsive genes in NRP2-expressing human and mouse B cells. The overall objective of this proposal is to evaluate whether Sema3F-NRP2 interactions promote immunoregulatory function in B cells. We will test the hypothesis that Semaphorin-induced signaling within NRP2-expressing B cells results in their differentiation into regulatory subsets that suppress CD4+ T effector cell activation following transplantation. We propose two specific aims in which we will: 1) profile NRP2 expression on subpopulations of human and mouse B cells to identify its function in B regulatory cell activity in vitro, and 2), determine whether NRP2-expressing B cells are of functional significance in the prevention of rejection and/or in long-term graft survival. Collectively, the proposed studies address a clinically relevant problem and our approach provides for cohesiveness to translate in vitro findings using human cells into relevant murine transplant models in vivo.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Although HIV-1 infection can be controlled through long-term treatment with anti-retroviral therapy (ART), a true cure has been elusive. Reservoir cells persist over time and support latent HIV-1 reactivation upon therapy cessation, yet little is known about the underlying molecular mechanisms. Our lab has recently identified previously unknown facets in the HIV-1 transcriptional program that we will explore in this proposal to help fill this knowledge gap, and may offer key insights into HIV-1 biology as well as cure strategies. The major goal of this grant application is to understand the role of transcription factors (TFs) in reservoir cells and Tat in first igniting and then sustaining the HIV-1 transcription reactivation program. We will accomplish this goal by leveraging genetic and genomic approaches to explore HIV-1 transcription at high-resolution in several immortalized cell models of latency and then cross-validate the data in samples from HIV-1 infected participants. Our recent studies have revealed that HIV-1 transcription reactivation proceeds through a previously unknown two-step mechanism: first ignited by transcription initiation through de novo Pol II recruitment (host phase) and later sustained by synchronization of pause release with re-initiation (viral phase). These two steps are the major transcriptional bottlenecks in the HIV-1 transcriptional program for a functional cure. Overcoming these bottlenecks guarantees a transcriptional switch that facilitates efficient latency reactivation. We will focus on defining the molecular mechanisms supporting HIV-1 transcription reactivation throughout the multi-phase HIV-1 transcription program. Specifically, we will explore the unifying central hypothesis that the composition and density of TFs at the proviral genome dictates the initial wave of HIV-1 transcription reactivation directly influencing Tat function and reactivation potential. We will examine the roles of the integration site, ligands stimulating reservoir cells and the interplay between TFs and chromatin accessibility. These goals are reflected in two Specific Aims: to define the relevance of TFs in reservoir cells that initiate and sustain HIV-1 reactivation (Aim 1), and to explore the interplay between TFs and chromatin accessibility during the transcriptional switch that facilitates efficient latency reactivation (Aim 2). If successful, this project will yield a better understanding of the molecular mechanisms by which TFs in reservoir cells and Tat converge to promote efficient HIV-1 transcription and latency reactivation, collectively having a sustained impact in the field. In keeping with NIAID’s mission of ending the HIV-1 epidemic, our long-term objective is to force the basic discoveries to devise alternative cure strategies. Thus, the fundamental knowledge to be gained could be used in future studies beyond the scope of this study, to exploit the transcriptional bottlenecks for functional cure approaches.