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NIDA - National Institute on Drug Abuse

PROJECT SUMMARY Early initiation of cannabis use (<16 years of age) increases risk for cannabis use disorder (CUD), mental illness, cognitive impairment, later unemployment, and poor social relationships. Prevention of early initiation is critical for improving social and health outcomes. Precision prevention programs have reduced youth substance use, but no approaches have specifically targeted cannabis use. Furthermore, no studies have comprehensively considered risk factors for early cannabis initiation (genetic, social, behavioral, environmental, and cognitive) to enhance the prediction of early use and inform precision prevention approaches. Comprehensive multivariable prediction models for early cannabis initiation that include genetics and social/environmental factors are needed. Cannabis use is polygenic, influenced by multiple genetic variants with weak-to-moderate effects, and polygenicity makes it difficult to translate genetics for clinical application. One method for clinically applying genetics is through the development of polygenic risk scores (PRS) that are composite scores representative of overall genetic risk. Prior PRS have typically lacked portability to non-European populations; however, a state- of-the-art method has been developed to build PRS with significantly improved risk prediction (34% improvement) across ancestries. There is a need to apply this method to develop cross-ancestry PRS for cannabis use for inclusion of overall genetic risk in comprehensive prediction models. Furthermore, given the complex interplay between genetics and social/environmental factors, research is needed to understand gene by environment (GxE) interactions in which social/environmental factors synergistically impact the risk conferred by genetics. Research into GxE interactions is statistically and computationally challenging, and traditional single-variant and more recent polygenic approaches focus on lower order 2-way interactions. Our logic forest (LF) algorithm efficiently searches all possible interactions up to 8 variables without a priori specification. This study will apply these state-of-the-art computational methods to the Adolescent Brain Cognitive Development (ABCD) Study, which examines childhood risk factors and initiation of substance use from ages 9-10 years to early adulthood in a population demographically reflective of the U.S. Nearly all youth had not used cannabis at recruitment, enabling the prospective measurement of initiation and the development of prediction models integrating genetics with pre-substance use measurements of cognitive, social, and environmental factors. This research will 1) develop cross-ancestry PRS for inclusion in prediction models that comprehensively consider genetic, sociodemographic, behavioral, cognitive, and environmental factors, and 2) apply LF to gene-sets within known biological pathways across the whole genome to identify pathway-specific GxE interactions. Comprehensive models coupled with a more complete understanding of GxE factors influencing early cannabis initiation can identify 1) high risk youth populations for targeted prevention, 2) targetable factors present among high-risk clusters for tailored interventions, and 3) biological pathways for therapeutic development.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT The goal of the studies in this proposal is to establish how disease-associated genetic variation regulates antibody responses at the level of B cell help by follicular helper T cells (TFH). In Aim 1, we will use a powerful combination of state-of-the-art, variant-to-gene mapping approaches in follicular T cells ‘caught in the act’ of helping B cell antibody responses in human lymphoid tissue: 1) chromosome conformation data to reveal physical associations between regulatory variants and gene promoters in the context of the 3D structure of the genome, 2) quantitative expression-trait mapping to reveal statistical associations between disease-associated variants and gene expression in TFH cells, 3) massively-parallel reporter assays to identify expression- modulating variants, and 4) CRISPR interference screens to identify genes regulated by antibody disease variants in TFH cells. In Aim 2, ‘novel’ effector genes prioritized by the approaches in Aim 1 will be assessed for roles in TFH function in an in vitro lymphoid organoid model human humoral immunity and in in vivo mouse models of lupus and influenza vaccination. The proposed studies are supported by the extensive experience and preliminary data of the research team, and will use a confluence of evidence from orthogonal approaches to power discovery of novel mechanisms that regulate T cell-dependent humoral immunity, refine our understanding of how common genetic variation contributes to autoimmune disease susceptibility, and point to novel therapeutic interventions to modulate humoral immunity in the context of vaccines, infectious disease, and autoimmune disorders.

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 Association of Arts and Culture

The Georgetown Halloween Parade is a free community event on October 31, 2024. The family-friendly parade will be open to the public for participation and for viewing. Georgetown Association of Arts and Culture will host a number of free workshops leading up to the parade teaching people to do special effects make-up and prop-building, among other skills that can help them prepare for the parade. Many businesses and venues along Airport Way are coordinating with GTAAC to provide post-parade programming that night. This project will be completed by December 31, 2024.

Urban ArtWorks

The Georgetown Mural Program is an arts-based employment opportunity for up to 10 teens experiencing economic barriers and systemic inequality in the Georgetown neighborhood. This program is a partnership between Urban ArtWorks (UA)s and Mini Mart City Park (MMCP), a new community arts center in Georgetown. Mentored by a UA professional teaching artist, teens will be paid a stipend to design and install a mural at MMCP. The project will culminate in a publicly accessible mural unveiling and solo art exhibit at the new MMCP gallery. The anticipate project completion date is September 30, 2021.

Coltura

On November 5th, 2017, community group, Coltura, will create a Georgetown No-Gas Mural. The mural will be installed at 969 S. Nebraska St. The public will be invited to Georgetown Art Attack Day to dedicate and celebrate the unveiling of the mural on November 11th. The goal of the Georgetown No-Gas Mural is to invite viewers to think about the use of gasoline in all the ways it touches them - the effect on their community and society, and to transform their thoughts to action. This mural is an effort to address community concerns regarding environmental justice through art.

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.

National Institutes of Health

-Purpose. The purpose of this initiative is to provide funding opportunities for the increasing pool of foreign social and behavioral scientists, clinical investigators, nurses and other health professionals, with state-of-the-art knowledge of research methods. It is expected that this program will advance critical issues in global health through behavioral and social sciences research upon return of the investigators to their home countries. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism. -Funds Available and Anticipated Number of Awards. The total amount to be awarded is $300,000 and the anticipated number of awards is six. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award may also vary; however, individual awards are limited to a maximum of $50,000 direct costs per year. The total amount to be awarded and the number of awards will depend upon the quality and costs of the applications received.

Grand Rapids Community Foundation

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

Grand Rapids Community Foundation

Grand Rapids Community Foundation ($400M in assets) supports nonprofits in MI through grants focused on education, community development, health, arts, environment. Awards range from $2,000 to $100,000.

Greater Cedar Rapids Community Foundation

Greater Cedar Rapids Community Foundation ($300M in assets) supports nonprofits in IA through grants focused on education, community development, health, arts. Awards range from $2,000 to $100,000.

Greater Cincinnati Foundation

Greater Cincinnati Foundation ($800M in assets) supports nonprofits in OH through grants focused on education, community development, arts, health. Awards range from $2,500 to $150,000.

Greater Cincinnati Foundation

Greater Cincinnati Foundation ($700M in assets) supports nonprofits in OH through grants focused on education, economic opportunity, health, arts, community development. Awards range from $5,000 to $200,000.

Greater Kansas City Community Foundation

Greater Kansas City Community Foundation ($5.0B in assets) supports nonprofits in MO through grants focused on education, health, community development, arts. Awards range from $2,500 to $300,000.

Greater Milwaukee Foundation

Greater Milwaukee Foundation ($1.0B in assets) supports nonprofits in WI through grants focused on education, workforce development, arts, community development. Awards range from $2,500 to $200,000.

Greater Worcester Community Foundation

Greater Worcester Community Foundation ($200M in assets) supports nonprofits in MA through grants focused on education, community development, health, arts. Awards range from $2,000 to $75,000.

National Institutes of Health

The Genomics Research to Elucidate the Genetics of Rare Diseases:innovation (GREGoRi) initiative seeks to accelerate a paradigm shift in rare disease diagnosis by reimagining the tools, molecular technologies and analytical approaches used to identify the causal gene(s) and/or variant(s) underlying rare genetic disorders. This Notice of Funding Opportunity is intended to stimulate the development and testing of highly innovative experimental or computational approaches for rare disease diagnosis, that have the potential to make transformative improvements to the current state of the art.

National Institutes of Health

The Genomics Research to Elucidate the Genetics of Rare Diseases:innovation (GREGoRi) initiative seeks to accelerate a paradigm shift in rare disease diagnosis by reimagining the tools, molecular technologies and analytical approaches used to identify the causal gene(s) and/or variant(s) underlying rare genetic disorders. This Notice of Funding Opportunity is intended to stimulate the development and testing of highly innovative experimental or computational approaches for rare disease diagnosis, that have the potential to make transformative improvements to the current state of the art.