Grants

City of Richmond

AllRepair.com Service Corporation

NYC Department of Cultural Affairs

Alpha Omega 1-7 Theatrical Dance Company, Inc.

NYC Department of Cultural Affairs

Alpha Workshops, Inc.

NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY Epstein-Barr virus (EBV) is a ubiquitous DNA tumor virus that is causally linked to Hodgkin's and non- Hodgkin's lymphoma, nasopharyngeal carcinoma, stomach cancer, and autoimmune diseases. EBV is particularly problematic in the HIV/AIDS population where EBV-associated lymphomas are especially prevalent. There are two distinct stages in EBV's life cycle: latency and lytic reactivation/replication. The viral lytic replication stage is a key component of the EBV infection cycle that facilitates the spread of the virus not only from host to host but also its dissemination within an infected individual. While EBV latency genes are long known to contribute to the tumor phenotype, EBV lytic replication is a precursor of (through dissemination) and a direct contributor to EBV-associated pathologies including lymphomas and autoimmune diseases. EBV is known to elicit a series of host cellular responses and it can almost always find a way to hijack these host machineries for its own benefits. For instance, EBV infection induces double-stranded breaks (DSBs) and strong DNA damage response (DDR) in host cells. It appears that EBV utilizes a variety of strategies to purposely activate the upstream/early steps of DDR signaling and inactivate the harmful downstream/late steps to ensure cell survival and benefit its own self-preservation. Recently, we have found that EBV lytic replication causes substantial induction of alpha-satellite RNAs (α-SatRNA), a novel host cellular response. This motivates us to further explore its significance in EBV lytic replication. Alpha-satellite DNA (α-SatDNA) is one type of tandem repetitive non-coding (nc) DNA sequences and constitutes 3-5% of the human genome. It also serves as the main building blocks for centromeres and has long been viewed as transcriptionally inert. Surprisingly, these genomic “dark matter” can be actively transcribed by RNA polymerase II to produce non- polyadenylated α-SatRNAs. The unique long repetitive sequence also makes α-SatRNAs a novel class of long ncRNAs. Our preliminary findings show that α-SatRNA levels are substantially induced by EBV lytic replication, accompanied by DNA damage DSBs and ATM activation. We further found that α-SatRNAs are required for efficient EBV lytic replication and α-SatRNAs promote ATM/upstream DDR signaling globally. Based on our published and unpublished findings, we hypothesize that lytic reactivation-induced DSBs on host centromeric α-SatDNA upregulate α-SatRNAs, which subsequently facilitate lytic reactivation by promoting ATM/upstream DDR signaling globally. In this proposal, we will test this hypothesis, we will begin to address the mechanisms through which EBV utilizes α-SatRNAs to facilitate its lytic replication and we will begin to address the mechanisms by which EBV reactivation induces α-SatRNA expression. Together, completion of this work will reveal a novel role of these “understudied” α-SatRNAs and associated underlying mechanisms in EBV lytic replication, and thus add conceptually to our understanding of EBV-host interaction.

Ten Penny Players Inc.

Alternative Consortium for Cultural Literacy

City of Oakland

Alternatives in Action

CDFI

Alternatives-Cooperative CDFI 19

CDFI

Alternatives/ Cooperative CDFI 17

CDFI

Alternatives/ Cooperative CDFI 18

U.S. Mission to Kazakhstan

Alumni Engagement Innovation Fund (AEIF) 2026: Strengthen U.S.–Kazakhstan Partnerships Through Alumni-Led Innovation

Cambridge Community Television

Alumni Media Artist Newtork and Production Group

East Hartford

Alumni Park Improvements - Basket ball courts

City of Richmond

Alvaro Dominguez - Consultant

City of Richmond

Alvaro Martinez

NYC Department of Cultural Affairs

Alvin Ailey Dance Foundation, Inc.

NIA - National Institute on Aging

Alzheimer disease (AD) is the fifth most frequent cause of death in the U.S. and currently affects nearly 55 million individuals of all ancestries worldwide; this number is predicted to double over the next 20 years. Clinical trials for effective therapeutics have almost all failed, and the few currently approved treatments provide only modest slowing of progression for a subset of individuals, with potentially severe side effects. Thus, focusing on additional and alternative therapeutic targets is critical to address this increasing health crisis. Genetically driven targets significantly improve the probability of successful clinical trials, but despite the identification of numerous AD-associated loci through GWAS, few have advanced to potential therapeutic intervention. In part, this is because GWAS itself is a blunt instrument that cannot differentiate among the many genes often underlying an associated locus. This leaves a critical gap where numerous GWAS-identified loci have not been sufficiently examined to support or refute their candidacy as a therapeutic target. ADAPTT aims to fill this knowledge gap by leveraging all available data from the growing datasets of the Alzheimer Disease Sequencing Project (ADSP) and the Alzheimer Disease Genetics Consortium (ADGC). Analyses of these genetic data will be significantly enhanced through integration of the currently separate SNV, indel, and structural variant (SV) data. We will also leverage extant in silico data and use existing and generate new in vitro molecular genetic functional data. Our goal is to identify the most likely functional genes/variations lying under each GWAS- identified locus, providing the foundation for critically needed, and genetically-driven, therapeutic development. We will achieve this goal through three parallel specific aims: Specific Aim 1 will integrate and analyze data for all SNVs, indels, and SVs within 54 AD GWAS-identified loci. We will leverage the increasingly multi-ancestry and diverse ADSP and ADGC datasets to reduce the list of probable functional genes/variations. Specific Aim 2 will assess the impact of these 54 loci on the clinically critical endophenotypes of age-at-onset and disease progression. We will first model disease progression and age-at-onset using harmonized data from the ADSP’s Phenotype Harmonization Consortium and then test the influence of the GWAS-identified loci on these endophenotypes. Specific Aim 3 will integrate extant and new molecular genetics functional data to validate causal genetic variations driving the locus associations. The results of this study will generate a set of genetically-driven potential targets that will accelerate the development of new and better therapeutics for AD.

National Institutes of Health

Alzheimer's Drug-Development Program (U01 Clinical Trial Optional)

NYC Department of Cultural Affairs

Amanda & James, Incorporated

The Dance Complex, Inc.

aMaSSiT Lab and Performance

Buhl Investors

New Construction

Buhl Investors

New construction

Buhl Investors

New construction

Norfolk

Ambulance Building Security Cameras

City of Pocomoke

Ambulance Garage