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OD - NIH Office of the Director

The goal of this S10 Instrumentation Grant application is to acquire a state-of-the-art Cytek® Aurora Full Spectrum 5-laser with automated sample loader flow cytometer for the Flow Cytometry and Cell Sorting (FCCS) Core Facility at the Tulane University School of Medicine (SOM), housed and administered in the Department of Microbiology & Immunology. This instrument will support the research of a minimum of 12 NIH-funded investigators at Tulane SOM and serve as a research and educational resource for regional investigators. The Tulane SOM is an NIH-supported institution with a mission that integrates research, training and service in biomedical research to improve human health through basic and applied biomedical research. In this application we present research projects from 10 Major users and 3 Minor users whose work is performed at the Tulane SOM. These projects are focused on infectious diseases, immunology and inflammation, which are areas of expertise at Tulane SOM. This work attracts national collaboration. Each of the profiled users has a strong history of NIH funding and needs for advanced flow cytometry technology. The existing Cytek® Aurora (3 laser, 38 parameter) and BD LSRII (4 laser, 13 detectors) flow cytometer cell analyzers have been in continuous operation for a nearly decade. While these instruments were state-of-the-art when purchased, they are no longer sufficient to meet future needs with respect to high parameter capability, resolution and versatility. We propose purchasing a Cytek® Aurora equipped with an ultraviolet, violet, blue, yellow/green, and red laser permitting detection of 64 parameters and a high-throughput system. The Cytek® Aurora offers several advantages over our existing instruments to meet investigators’ future needs. The inclusion of multiple lasers ensures addition of at least 20 more parameters than are possible with our existing flow cytometry analyzers, which can detect up to 38 and 13 parameters respectively. Compared to other premiere systems on the market, the Cytek® Aurora offers the best overall system in terms of number of parameters, service and price. The availability of a high-parameter and versatile instrument such as the Cytek® Aurora is expected to attract additional investigators that require this technology, leading to new collaborations that will expand the scope of research at the Tulane SOM and the greater New Orleans area.

NIDCR - National Institute of Dental and Craniofacial Research

ABSTRACT Amyloid was identified in the context of pathology but does not always represent aberrant protein folding. Functional amyloid is now recognized in all kingdoms of life. Amyloid aggregates possess evolutionarily conserved cross -sheet quaternary structures with common biophysical properties enabling their detection and study. Microorganisms are now known to produce purposeful amyloid within biofilm environments, but, considering their prevalence, little is known regarding molecular events influencing amyloid formation. Dental caries is a biofilm-dependent disease caused by dysbiosis and overgrowth of acidogenic and aciduric bacteria, particularly Streptococcus mutans. Amyloid is observed in vivo within dental plaque. Our group was first to discover oral amyloids, and we have identified four amyloid-forming proteins in S. mutans. P1 (AgI/II), WapA, and Cnm are sortase-localized adhesins and virulence factors. The fourth protein, Smu_63, negatively regulates biofilm cell density and genetic competence. Extensive tertiary and quaternary structural characterization of P1 is in hand, with characterization of the other proteins underway. Our X-ray fiber diffraction evidence proved a classical stacked -sheet amyloid structure for S. mutans amyloids, and our work revealed a new paradigm for multiple streptococcal and staphylococcal amyloids in that naturally occurring adhesin truncation products play two key roles within the organisms' biofilm life cycles. First, in monomeric form by promoting adherence to cognate ligands via quaternary interactions involving the cell surface-linked parent proteins, and second in amyloid form by quenching adhesive function and apparently facilitating detachment of aging biofilm cultures. The left-handed Z-conformer of extracellular DNA was recently associated with bacterial biofilm stability whereas right-handed B-DNA is associated with detachment. Of interest, the amyloid but not the monomeric form of neuropathologic A drives conversion of Z- to B-DNA. Also, membrane lipids impact amyloidogenesis by an unknown mechanism. Cardiolipin-rich mitochondrial membranes modulate amyloidogeneis of Parkinson and Huntingtin Disease-associated -synuclein and Htt, respectively. Cardiolipin is a prevalent anionic lipid in S. mutans cytoplasmic membranes and extracellular membrane vesicles, particularly under stress conditions. In this application we will define reciprocal mechanistic influences of amyloid-forming proteins on B- and Z-forms of DNA in vitro and in vivo in mono- and multi-species biofilms (Aim 1), determine the impact of membrane lipid composition on amyloid levels during biofilm progression and assess mechanistic interactions of specific lipids of interest on amyloidogenesis of known virulence-associated proteins (Aim 2), and continue to use state-of-the-art methods including solution and solid-state NMR spectroscopy to identify and characterize structural transitions reflective of monomer to amyloid conversion and determine changes in amyloid signatures for each protein upon exposure to different DNA conformers, amyloid-modulatory lipids, and other amyloidogenic proteins (Aim 3).

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

PROJECT SUMMARY/ABSTRACT Assisted reproductive technologies (ART) have revolutionized fertility treatments, yet implantation success rates remain suboptimal. Emerging evidence reveals that maternal tubal fluid, specifically extracellular vesicles (EVs), nanoscale membrane-bound carriers rich in bioactive molecules that play a pivotal role in embryo-maternal communication essential for early embryo development and implantation. EVs transport lipids, proteins, and regulatory RNAs, including miRNAs, which influence embryo physiology and developmental competence. Although in vitro studies demonstrate embryo uptake of EVs from reproductive tract cells across species, the physiological relevance of maternal EVs during natural embryo development in vivo remains largely unexplored. Critically, EV populations and cargo profiles differ markedly between in vivo and in vitro conditions, underscoring a pressing need to investigate EVs in their native environment. Our innovative study leverages oviductal epithelial cell-specific CD9-green fluorescent protein (GFP) reporter mice to directly visualize and track maternal EVs within preimplantation embryos in vivo. We have discovered CD9-GFP+ EVs localized in the perivitelline space of 4- to 8-cell stage embryos, providing the first direct in vivo evidence of maternal EV-embryo communication during early development. Building on this, our research pursues two complementary aims: (1) to comprehensively map EV distribution and profile miRNA cargo in oviductal and uterine luminal fluid throughout early pregnancy stages, illuminating dynamic changes in EV-mediated signaling; and (2) to elucidate the functional significance of epithelial cell- derived EVs by employing pharmacological inhibitors to disrupt EV biogenesis and release in vivo, assessing consequent effects on embryo development, implantation, and pregnancy outcomes. This study offers a significant advance in reproductive biology by uncovering the in vivo role of maternal EVs in supporting embryo development and implantation. Our innovative use of epithelial-specific CD9-GFP reporter mice to directly visualize EV transfer to embryos provides valuable new insight into natural embryo-maternal communication. By combining cutting-edge molecular profiling with functional inhibition of EV biogenesis in vivo, this research is uniquely positioned to identify key EV cargos that influence embryo viability and pregnancy outcomes. The results will deepen our fundamental understanding of early developmental processes and enable the development of novel, clinically relevant strategies to improve assisted reproductive technologies. Leveraging maternal EVs as biomarkers or therapeutic agents holds strong potential to enhance ART success rates and promote healthy pregnancies, addressing critical challenges in fertility treatment.

NIAID - National Institute of Allergy and Infectious Diseases

PROPOSAL SUMMARY Autoimmune diseases remain challenging to treat due to a lack of therapies that specifically target immune dysregulation without inducing generalized immunosuppression. Dysregulated immunoregulatory networks drive autoimmune disorders and are often associated with imbalances in regulatory T (Treg) and effector T (Teff) cells. Treg cell therapy or selective expansion of Treg cells in vivo can shift the Treg/Teff balance towards Treg cells to resolve ongoing inflammation and promote tissue repair to restore function and improve overall quality of life. However, selective and functional expansion of Treg cells during ongoing autoimmune conditions (i.e., therapeutic use) has been challenging. This is mainly because immune regulatory networks are complex, and our knowledge of the cellular and molecular choreography of Tregs in tissues is still evolving, particularly in the context of autoinflammatory disorders of the central nervous system (CNS). Treg cells hold tremendous potential to not only stop the course of the disease but also to restore neuronal function by inducing the repair of damaged axons. Therefore, our main objective is to investigate key principles of expansion of Treg cells to limit the pathophysiology of CNS autoimmunity and promote myelin repair. Capitalizing on the multiphoton imaging, state-of-the-art ratiometric calcium indicator, Salsa6f, label-free detection of myelin lesions, we aim to identify the role of combinatorial activation of T cell receptor (TCR), IL-2 signaling, and TGF-beta signaling for expansion of Treg cells in vivo. Using immunomodulatory Treg expanding biologics (TREBs) and experimental autoimmune encephalomyelitis (EAE), a model of MS-like disease, we will determine target engagement, biodistribution, and immunosafety of combinatorial Treg-expanding biologics (Aim 1); and define cellular and molecular determinants of Treg expansion and evaluate therapeutic efficacy in models of CNS autoimmunity (Aim 2). We postulate that selective expansion of Treg cells is an ideal strategy to curb ongoing autoinflammatory responses while preserving the immune system’s ability to fight new infections and promoting tissue repair for functional recovery. Although our exploratory/developmental project aims to establish a mechanistic link between Treg expansion and clinical improvement during CNS autoimmunity, in a broader context, our studies will guide the rational design of Treg-targeting immunotherapies, accelerating translation into effective and safe treatments for MS and several other autoimmune conditions.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary Hypersensitivity to touch is common in neurodevelopmental disorders including autism spectrum disorder (ASD). Individuals with ASD can have aversive responses to certain textures or human touch, which can lead to emotional distress, social withdrawal, and difficulties accomplishing everyday tasks. In humans and rodents, aberrant touch sensitivity perinatally is predictive of ASD-linked traits later in life. The molecules and mechanisms underlying touch sensation are just being elucidated, and little is known about how they relate to ASD. Touch sensation begins with the activity of mechanically activated PIEZO2 channels that transduce forces into electrical signals. The overall objective of the proposed research is to investigate the role(s) of the Ca2+ sensing protein caldendrin in regulating PIEZO2, touch sensation, and neurodevelopmental processes controlling cognition/affective behaviors. Our project builds on our discovery that mice lacking caldendrin (Cabp1 KO) display tactile hypersensitivity and increased activity of PIEZO2 in dorsal root ganglion neurons (DRGNs). Neurite outgrowth, which depends on PIEZO2 as well as Cav1 L-type Ca2+ channels, is abnormal in Cabp1 KO DRGNs and differs in cultures from males and females. Moreover, Cabp1 KO mice exhibit ASD-like phenotypes, such as anxiety and anti-social behavior, which are more severe in males than females. Considering that genetic silencing of some ASD-related genes in DRGNs of neonatal mice causes tactile hypersensitivity and ASD-linked behaviors in adulthood, our central hypothesis is that caldendrin modulates PIEZO2, Cav1, and the structural maturation of DRGNs early in development, which has sex-specific effects in driving synaptic plasticity in the brain and cognitive, affective, and social behaviors in adulthood. We will use state of the art methods in biochemistry, electrophysiology, and optical imaging to test the following specific aims: (1) elucidate the mechanism whereby caldendrin modulates the activity of PIEZO2; (2) define the contributions of caldendrin to sex- specific patterns of neurite development; and (3) determine how loss of function of caldendrin leads to aberrant cognitive/affective behaviors.

Fundacao Calouste Gulbenkian

Portuguese foundation supporting art, charity, science, and education internationally.

National Park Service

1. Create a science and technology showcase for art conservators to expose more conservators to scientific methods. The showcase will lead to better conservation of cultural heritage. 2. Create a research opportunity for youth, students, and new professional conservators to be exposed to and undertake research in an art conservation science laboratory. Research opportunities will lead to a new generation of conservators with an understanding of research within the art conservation practice. 3. Disseminate preservation technology information.

Bureau Of Educational and Cultural Affairs

ECA announces an open competition for a cooperative agreement to develop and implement a program that will convene cultural ministers from key countries at an iconic location in the United States for high level discussions on cultural heritage and cultural property protection as part of the State Department s programming to mark America s 250th birthday. The implementing partner will work closely with ECA to develop the program s one-to-two-day exchange agenda, including showcasing innovation and new technologies of the U.S. private sector and other American institutions in the cultural heritage field; strengthening cooperation in combatting art and antiquities trafficking; and using cultural heritage to amplify global narratives on America s foundational values. The convening will feature U.S. models, standards, and best practices; strengthen relationships with key countries in the cultural heritage field; and produce concrete follow-on steps to advance the program s agenda. Two to three virtual sessions with working level representatives of the selected cultural ministers will precede the U.S. program, helping gain input into and solidify the agenda. Participants will include 25-40 cultural ministers or equivalents/designees from select countries; representatives from the U.S. government, U.S. companies and other institutions involved in cultural heritage preservation and protection; and U.S. law enforcement focused on combatting art and antiquities trafficking. The program will introduce the foreign participants to U.S. advancements in cultural property protection and preservation, strengthen commercial diplomacy, and accelerate coordination between ECA and U.S. law enforcement, thereby enhancing border security and reducing financing from trafficked art and antiquities. Please see the Notice of Funding Opportunity for additional Information.

Bureau Of Educational and Cultural Affairs

The U.S. Creative Tech Exchange (U.S.CTX) is a new international arts exchange program that drives economic growth by connecting U.S. creative professionals and technologists with international peers working at the intersection of the arts and emerging technologies, especially artificial intelligence (AI). The goal is to position American technology as a key driver of American innovation, economic, and cultural influence in art and technology, For the purposes of this program, arts refers specifically to architecture, creative coding and gaming, fashion, graphic design, music and immersive art such as virtual reality (VR), augmented reality (AR), and mixed reality (MR); but excludes film and television. U.S.CTX will support up to 30 participants through short-term, hands-on activities such as collaborative labs, fellowships, workshops, and public showcases. ECA will award one U.S.-based nonprofit or educational organization $1.32 million to design and implement the program in close coordination with ECA and U.S. embassies. Applicants should propose a concept that leverages their strengths and includes clear plans for recruitment, program delivery, and measurable outcomes in creative arts, economic impact, and public diplomacy. Please see the Notice of Funding Opportunity for additional information.

Bureau Of Educational and Cultural Affairs

The Office of Academic Exchange Programs of the Bureau of Educational and Cultural Affairs (ECA), U.S. Department of State, announces an open competition for one cooperative agreement to design, implement, and oversee the Office's Fulbright Teacher Exchange Programs in Fiscal Year (FY) 2027. Fulbright Teacher Exchanges advance American competitiveness by engaging K-12 educators in international exchanges that allow them to learn cutting-edge educational practices and develop innovative programs that prepare their students for careers that support U.S. economic and security interests at home and abroad. For more than 80 years, Fulbright Teacher Exchanges have offered opportunities for American K-12 educators to demonstrate U.S. prominence and expertise to peers abroad in areas including the arts, humanities, STEM and technology. Furthermore, U.S. Fulbright Teacher Exchanges advance American interests by providing upskilling to American teachers to increase K-12 expertise in technology, especially AI and the critical minerals industry, and to prepare their students for careers in fields critical to U.S. security and prosperity. Programming supports American teachers to expand STEM coursework in fields such as earth science, data analysis, and geology to meet the need for student specialization in critical minerals and rare earths in the U.S. market. The program also integrates a wide range of fields that advance the Administration s America First priorities and related Executive Orders, including expanding career readiness programs, promoting digital freedom, and increasing K-12 expertise in technology education, especially the use of American-designed AI.Through Foreign Fulbright Teacher Exchanges, U.S. university schools of education showcase American leadership in education and educational technology to visiting teachers who return home with enhanced pedagogy, leadership skills, and technology training. Foreign teachers expand the use of American-designed AI and other U.S. technology in the global market, promoting digital freedoms and developing leaders who value America as their partner of choice. Fulbright Teachers participation in these programs has a powerful multiplier effect, influencing millions of students around the world over the course of their careers. Fulbright Teacher Exchanges comprise a suite of shorter and longer-term program models to accommodate the schedules of U.S. and international educators. The Presidentially appointed J. William Fulbright Foreign Scholarship Board (FFSB) is responsible for the Fulbright Teacher Exchange Program and establishes policies and procedures that govern the Fulbright program, including overall policy guidelines and selection criteria. The FFSB is responsible for the final selection of all Fulbright candidates. Organizations must ensure compliance with all FFSB policies and procedures and fully and properly identify this program as both a Fulbright Program and a U.S. Department of State Program in all communications. ECA reserves the right to fully fund, partially fund, or not to fund a given program component, and to adjust or request new program models if foreign policy priorities change. The amounts listed for each component are provided below to enable applicant organizations to prepare budgets for planning purposes only and are subject to change, pending the availability of FY 2027 funds. Please see the Notice of Funding Opportunity for additional information.

National Park Service

The intern will be part of the Cultural Landscape Inventory team for the National Park Service and based at the Olmsted Center for Landscape Preservation in Boston, Massachusetts. Responsibilities and learning opportunities include: creating field maps to document cultural landscape characteristics and features, field measurements and photography, meetings and interviews with park staff, archival research for historic photographs and maps, writing landscape descriptions, preparing landscape management and maintenance recommendations, and formatting reports for distribution. These responsibilities will be carried out with the guidance of Olmsted Center staff, including landscape architects and horticulturists. The intern will also collaborate with other interns and the Olmsted Center's youth education program. The intern should have skills and enthusiasm for reading and writing; skills in communicating and working as a member of a team; an interest in landscape architecture, horticulture, history, and historic preservation; and an interest in learning graphics programs, including Adobe Illustrator and Photoshop. No previous experience working in digital graphics is necessary, but an interest in art and drawing is helpful. This position is NOT eligible for AmeriCorps.

Patrons of the Trumbull Nature and Arts

FY25-ARPA-Sub Recipient

Bridgeport Arts & Cultural Council

FY25-ARPA-Sub Recipient

NCI - National Cancer Institute

PROJECT ABSTRACT/SUMMARY Neoplasms of the central nervous system (CNS) are the most frequently encountered solid tumors of childhood and remain one of the top causes of death in children. Pediatric high-grade gliomas (pHGGs) and atypical teratoid rhabdoid tumor (ATRT) are particularly aggressive pediatric CNS (pedCNS) tumors associated with poor outcome. Therapy consists of extremely burdensome multi-modal treatment protocols with toxic profiles that cause patients to suffer from detrimental effects, which significantly impact the quality of life during their already limited lifespan. New therapeutic strategies are badly needed to increase the survival benefit and quality of life of patients with pHGG and ATRT. To address this need, we performed initial studies that demonstrated that primary CNS cancers display dysregulated iron homeostasis and that gallium maltolate (GaM), an iron mimetic metallocompound, inhibits the growth of pHGG and ATRT cells in vitro and in an orthotopic rat model, extending overall survival. Cancer iron metabolism is an attractive target for therapeutical intervention. Iron plays a vital role in the pathobiology of many cancers, including brain cancer. Gallium acts as an iron mimetic, enabling it to hijack common iron trafficking pathways to enter cancer cells. However, unlike iron, gallium cannot take part in cellular redox reactions, thus disrupting critical iron-dependent processes and resulting in cell death. Our group has demonstrated the effectiveness of gallium maltolate (GaM), a newer generation compound with high oral bioavailability and therapeutic index, both in vitro and in vivo. In animal studies of adult glioblastoma, the most aggressive type of primary brain tumors, we demonstrated a slower tumor growth rate, a doubling of survival, and an improved quality of life with treatment. Preliminary studies in pHGGs and ATRTs suggest similar benefits. Despite this promising initial step, questions regarding the efficacy of GaM remain. Specifically, we intend to address the knowledge gap as to what drives response to GaM therapy. Therefore, our overall goal is to be able to offer a new treatment strategy to brain tumor patients with few therapeutic options. In Specific Aim 1, we propose a sophisticated multi-pronged approach leveraging behavioral assessments, state-of-the-art MRI-guided biopsy, cellular bioenergetics, and induction coupled plasma mass spectrometry (ICP-MS), to develop a tissue sensitivity profile. In Specific Aim 2, we propose to explore the synergistic potential of combining GaM with radiation therapy, the backbone of many treatment protocols. Preliminary data suggest a potentiating cytotoxic effect, which requires confirmation in vivo. Collectively, these investigations will provide insights regarding how to maximize antineoplastic therapy with GaM to improve both the quality of life and extend survival in children with primary brain tumors.

Garfield Weston Foundation

One of the UK's largest family-funded charitable foundations distributing 90M+ GBP annually across arts, education, community, environment, health.

NIA - National Institute on Aging

PROJECT SUMMARY Microglia are the macrophages of the brain and become activated in response to amyloid. Recently, single cell sequencing has defined multiple activated states of microglia including two states that are robustly induced in animals of Alzheimer’s disease (AD): disease associated microglia (DAM), and interferon responding microglia (IRM). It is now established that in response to amyloid microglia initiate the classical pathway of the complement cascade, and that the complement cascade is a critical mediator of neuronal synapse loss during disease progression. Synapse loss is among the strongest neurobiological correlates of cognitive decline in AD. Global ablation of the C1 complex (via C1qa gene knockout) preserves synapses in AD mouse models, highlighting the importance of determining the mechanisms determining the role of microglia in complement-mediated synapse loss. Yet despite much work, key knowledge gaps remain. First, the relationships among the different transcriptionally defined microglia states have not been determined. Second, all microglia express C1Q and it remains unknown whether microglia belonging to distinct states trigger synapse loss on neurons. Third, the complement cascade requires downstream components such as complement factors C2 through C9 that are not expressed by microglia, but virtually nothing is known about the spatial and temporal coordination of the specific cell types expressing these components in the brain. Filling these knowledge gaps may lead to new therapeutic avenues that prevent or intervene in synapse loss in AD. By leveraging floxed alleles of Csf1r, Trem2, Sting1, C1qa, C3, C5 and C7, microglia state specific Cre driver lines such as Cx3cr1-cre, Tmem119-cre, Itgax-cre, and Mx1-cre, and reporter lines to lineage trace distinct states, we will take a multi-modal approach based on genetic strategies to address these questions with cellular specificity. We will use distinct mouse genetic contexts we have shown are susceptible (C57BL/6J) or resilient (PWK/PhJ) to synapse loss, and we will employ state-of-the- art methodologies including single cell myeloid cell sequencing, spatial transcriptomics and protein visualization, and circuit-specific labeling of synapses. In three aims we will test the model that IRM are an intermediate microglia state necessary to recruit DAM to plaques, and that DAM are the critical state driving complement- mediated synapse loss. In Aim 1, to test whether IRM are the intermediate state between homeostatic microglia and DAM, we will lineage trace IRM, ablate DAM or IRM, and conditionally delete Sting1 (a key mediator of interferon signaling) from DAM. In Aim 2, to determine whether DAM are the primary initiators of complement mediated synapse loss, we will conditionally delete Trem2 from homeostatic microglia, ablate DAM, and conditionally delete C1qa from DAM. In Aim 3, to uncover the cell types producing the downstream components of the complement cascade, we will perform spatial transcriptomics and protein visualization. We will then conditionally delete a downstream component from its parent cell type. Successful completion of these aims will result in the identification of critical cellular and genetic contributors to complement-mediate synapse loss in AD.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Gene editing offers the prospect of directly modifying any nucleotide(s) in the genome, including correction of pathogenic variants underlying disease. These technologies could form the basis of cures for currently untreatable genetic conditions. The work proposed in this application aims to identify genome editing strategies to prevent aortic pathology in Marfan syndrome (MFS). MFS is the most prevalent hereditary connective tissue disorder and is associated with significantly increased morbidity and mortality due to life-limiting thoracic aortic aneurysm and dissection. MFS is caused by heterozygous pathogenic variants in FBN1, the gene encoding the main structural component of extracellular microfibrils, fibrillin-1. Microfibrils are essential for providing structural elasticity and resilience, in addition to having a signaling role, and defects in both features are thought to contribute to elastic lamina fragmentation and aortic wall weakness. We hypothesize that gene editing correction of FBN1 pathogenic variants or genome editing-based upregulation of the structurally related protein FBN2 within aortic vascular smooth muscle will reduce risk of aortic root dilation and dissection, thereby limiting the major cause of morbidity and mortality in this disease. In the first aim, the candidate will identify a prime editing strategy to correct the Fbn1 C1041G pathogenic variant in aortic vascular smooth muscle of a murine model of MFS and will test this therapeutic strategy by monitoring aortic aneurysm. In the second aim, a machine learning model will be used to identify promoter variants, putative enhancers, and transcription factor binding site motifs within the FBN2 promoter region that are predicted to augment FBN2 expression. These elements will be functionally evaluated in a massively parallel reporter assay (MPRA). Finally, in vivo genome editing will be used to introduce an optimized FBN2 upregulatory strategy established through these analyses in the Fbn1C1041G/+ mouse model of MFS for correction of aortic pathology. In addition to establishing potential gene editing treatment strategies for aortic aneurysm in Marfan syndrome, these studies will enable the candidate to obtain expertise in the design and application of state-of-the-art gene editing tools that can be used to generate disease models and investigate therapies for many different genetic disorders, which he plans to pursue throughout his career as a physician-scientist.

NHGRI - National Human Genome Research Institute

Project Summary This proposed MAGen development site aims to develop genomics and multi-modal artificial intelligence (AI) models to transform personalized cancer risk assessment, monitoring, and prevention. A substantial gap exists between the theoretical potential of genomics-based AI predictions and their practical application in clinical and population healthcare settings. The clinical classification of genetic variants is hindered by insufficient data to classify ultra-rare variants, particularly those found in non-European populations. Moreover, despite significant advances in AI across fields, we lack AI models that can combine diverse streams of health data to accurately predict disease risk across a person’s life course. Finally, the real-world effectiveness of these AI models remains untested and their ethical, legal, and social implications (ELSI) are unclear. To address these challenges, our primary goal is to develop state-of-the-art (SOTA) AI models that can accurately identify pathogenic variants affecting DNA repair genes and predict cancer risks over the life course of high-risk carriers, thereby optimizing screening and prevention strategies in an ELSI-informed manner. Our multidisciplinary team comprises experts in computational genomics, AI/ML, health informatics, statistical genetics, medical genetics, population health, oncology, and ELSI research from Icahn School of Medicine at Mount Sinai (ISMMS), Boston Children’s Hospital/Harvard, and Columbia University, and has complementary and extensive experience in consortium and team science projects. In our proposed project for MAGen, Aim 1 will develop robust genomic AI models for identifying protein-disrupting missense variants that confer high cancer risks. Aim 2 will combine other genetic factors, including common and rare variant polygenic risk scores (PRS), and non-genetic factors, including EHR, longitudinal lab markers, SDoH, and digital pathology, to predict cancer risk over the life course and optimize screening recommendations for carriers. Aim 3 will cross-validate AI models in real-world population biobanks and determine their clinical impact. Aim 4 will construct an ELSI framework and conduct ELSI projects to evaluate the multi-faceted impacts of AI-driven genetic diagnostics. Aim 5 will disseminate AI model/predictions, cross-validation data, and ELSI recommendations. The completion of these Aims will bring genomics-based and multi-modal AI closer to the advancement of personalized medicine in real-world settings by more accurately classifying pathogenic variants, optimizing the timing of screening, and identifying key lifestyle and medical prevention strategies that could ultimately save lives from cancer.

Georgetown Merchants Association

The Georgetown Carnival is a free, one-day, arts & music-focused street fair centered in Georgetown’s historic business district. The 2025 Carnival will take place on June 14, 12-10 pm, on Airport Way S between 12th Ave S & Corson Ave. The Carnival is a celebration of the neighborhood and its unique place as an artistic and small business haven surrounded by large-scale industry. It brings visibility to the neighborhood artists and businesses, and gives our small residential community a day of fun focused on our special neighborhood. With a residential population of only 1700, Georgetown’s small businesses rely on customers from other parts of Seattle to remain viable. Events like Carnival are vital in increasing the visibility of our local artists and businesses, and create a lasting economic impact by introducing new people to the neighborhood and encouraging them to return. In 2023, we welcomed over 5,000 people to the Carnival, many of whom were first time visitors to Georgetown.

Georgetown Merchants Association

Our project is the revival of the annual Georgetown Carnival. Carnival has been a tradition going on 14 years, with 2023 being it's official return post-COVID. Carnival is a one day music and arts festival, taking place from 12pm - 10 pm along Airport Way S, and 12th Ave S in the Georgetown Neighborhood. Featuring live performances on three stages, booths for local vendors and artists, industrial art displays, and children's activities. The purpose of Carnival is to increase visibility of businesses in Georgetown. The businesses in Georgetown cannot be sustained by our small residential population alone.

Georgetown Steam Plant CDA

The Georgetown Steam Plant Science Fair is a two-day, community-driven celebration of SHTEAM – science, history, technology, engineering, art, and math. Curated to spark curiosity, connection, and critical thinking for all ages, this event empowers participants by moving them from the role of “observer” into “active contributor” to community development. Hosted at the historic Georgetown Steamplant, the fair blends hands-on experiments, scientific demos, community dialogue, data visualizations, interactive exhibits, art installations, and more to inspire makers, thinkers, and problem solvers. With the theme “Break the System,” this year’s fair challenges participants to reimagine outdated systems and structures – industrial, social, or ecological – and explore bold and regenerative solutions for the future. Along with exhibits, there will be food trucks, performances, and more! The event is free, family-friendly, and rooted in the values of community and collaboration.

Georgia Council for the Arts

Georgia Council for the Arts provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across GA.

Georgia Council for the Arts

Georgia Council for the Arts Arts Education grants support in-school and community arts education programs, artist residencies, and initiatives that bring arts experiences to Georgia students and youth.

Georgia Council for the Arts

The Georgia Council for the Arts provides operational support grants to Georgia nonprofit arts organizations, enabling them to sustain programming, build organizational capacity, and deliver arts and cultural experiences statewide.