Grants

Lighthouse for the Blind

Upgrade assistive technology to current standards. This will allow Lighthouse to improve computer training and access to technology to Deaf-Blind adults with varying needs.

NIDCD - National Institute on Deafness and Other Communication Disorders

Project Summary/Abstract Despite historical reports of lower reading outcomes of deaf and hard-of-hearing (DHH) high school students, evidence from eye-tracking suggests that skilled DHH adults who learned a signed language before learning to read are uniquely efficient: They read faster and rereading less than matched hearing readers without a negative impact on comprehension. What factors lead this subset of DHH children to become highly skilled adult readers? For hearing mono- and bilingual readers, vocabulary knowledge of the target language strongly correlates with reading ability. However, while studies have pointed to the emergence of reading efficiency in young DHH readers, the role of first- (L1) and second-language (L2) vocabulary knowledge has yet to be established empirically. We use eye-tracking and behavioral language testing to assess the degree to which L1 American Sign Language (ASL) vocabulary knowledge transfers to L2 English reading comprehension and supports eye- movement control during reading. L1 ASL vocabulary knowledge may be particularly important for this group of developing bilinguals for several reasons. First, they do not have typical access to the speech sounds of the language they are learning to read. Thus, their path to successful literacy may lie in the connection between visual form in text and word meaning in ASL. Second, they only read in their L2 as ASL has no written form. As such, while hearing L2 readers are typically less efficient than L1 readers, the exclusive experience processing text in English, compounded by visual linguistic processing expertise from extracting language information from visual forms in their L1, may result in highly efficient reading behaviors for DHH signers. To achieve our goal, we will predict DHH readers’ comprehension on a standardized measure of reading by L1 and L2 vocabulary skill as well as nonverbal IQ, working memory, print spelling recognition, and fingerspelling recognition (Aim 1). We will also use eye-tracking to assess the role of L1 ASL vocabulary knowledge while controlling for L2 English vocabulary knowledge as well as (finger)spelling ability, nonverbal IQ, and working memory on measures of eye- movement control during reading (L2). We further assess the emergence of adultlike reading efficiency, particularly regarding the information in text to which they attend (Aim 3). This project will provide insight into the successful path to literacy for DHH students, as well as other diverse groups of bilinguals and readers for whom the exploitation of letter-sound correspondences is not beneficial. Results from this project will inform a later R01 proposal which will track the development of reading skill longitudinally and will include a more diverse group of DHH readers as well as hearing mono- and bilingual controls. This project assesses reading in DHH child signers from a strengths-based perspective, shifting focus from what these readers cannot do (e.g., hear speech sounds) to what they can do: Leverage the knowledge of their L1 to acquire an L2 via print. These results may help guide early linguistic and educational practices for DHH students to optimize literacy achievement.

City of Richmond

The Nail Pope

32nd Ave S Block Watch

Our project is to throw a block party for our neighbors to meet each other, share food, and have fun.

Deborah Hospital Foundation

Deborah Hospital Foundation is an active grantmaking foundation based in Browns Mills, NJ. Focus: health. Contact the foundation directly for current funding opportunities.

City of Oakland

ART is Education-Sequoia Elementary is ART is an artist residency which provides every student with weekly instruction in the visual arts, while tying this instruction to classroom curricula, professional development of teachers, and the creation of permanent artworks which are coming to define the visual and embodied character of the school.

City of Chiloquin

Debris Pile Cleanup Project

Queens Council of the Arts

DEC Program Development

Tri-County Arts Council

DEC Program in Allegany and Cattaraugus Counties

Schoharie County Arts Council, Inc.

DEC Program in Fulton, Montgomery and Schoharie Counties

North Country Library System

DEC Program in Jefferson, Lewis, and St. Lawrence Counties

Queens Council of the Arts

DEC Program in Queens County

Saratoga Arts Inc

DEC Program in Sarataga County

West Seattle Community Orchestras

We will provide free concerts for the West Seattle community in December 2024. The first concert will be held on December 9, 2024 at 6pm at Chief Sealth High School located at 2600 SW Thistle St, Seattle, WA 98126. This program promotes the arts in our community through supporting children's musical education as well as local artists conducting the ensembles.

The Arts Center of the Capital Region

Decentralization

Putnam Arts Council

Decentralization

Niagara Arts Council, Inc.

Decentralization Regrant

Niagara Arts Council, Inc.

Decentralization Regrant **RECONSIDERATION**

Wayne County Council for the Arts

Decentralization Regrant of NYS Funds

NEI - National Eye Institute

PROJECT SUMMARY Dry eye disease (DED) is one of the most common chronic eye diseases. Traditional randomized clinical trials for DED are challenged with sample sizes too small to demonstrate effect, lack of diversity among participants, and insufficient correlation between objective markers and patient-reported symptoms. This proposal outlines a novel approach to studying evaporative loss DED through a decentralized clinical trial design. This non- interventional planning and feasibility proposal shifts the focus of DED study away from doctors’ offices and into participants’ home environments. Subjective evaporative loss DED symptoms are collected remotely, electronically, and sequentially. Self-collected ocular surface samples are collected in two ways: with a self- collected Schirmer strip and with a self-collected conjunctival swab. All study material is mailed to participants’ homes. Self-collected ocular surface samples are placed in study vials and return mailed to a central location, UCSF Proctor Foundation laboratory, for RNA-deep sequence exploratory analysis of the transcriptome as a biomarker for DED. To mimic repeat ocular surface collection after a future DED intervention, Schirmer strips and conjunctiva self-swabbing will be repeated after 4 weeks. This decentralized approach to DED study promotes patient engagement, recruitment, communication, and participant diversity and also seeks to identify new objective markers of DED efficacy that can be collected remotely. Specific aims of this R34 are (1) To develop a remote trial design allowing for decentralized recruitment and study of DED, (2) To prepare an operations manual and statistical analysis plan allowing for execution and scalability of a decentralized DED study design, and (3) To determine feasibility and utility of obtaining transcriptomic analysis from remotely collected Schirmer strips and conjunctiva self-swab collection. This planning grant leverages the power of decentralized trials to efficiently, economically, and objectively study one of the most encountered eye diseases, evaporative loss dry eye. Ultimately, this decentralized study platform will provide a foundation for future DED trials, facilitating the comparative re-evaluation of existing therapeutics and a standardized platform for assessing the efficacy of new dry eye treatments.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

PROJECTS SUMMARY/ABSTRACT BACKGROUND: With 2.3 million new cases per year, breast cancer is among the most diagnosed cancers in women globally and is the leading cause of cancer mortality in low-and middle-income countries (LMICs), including Rwanda. Breast cancer outcomes in LMICs are far worse as 33-90% of women with breast cancer present with advanced-stage disease, due to delays in diagnosis exacerbated by the absence of decentralized biopsy services, forcing patients in rural areas to travel to tertiary centers for diagnosis. Centralization of breast biopsy creates bottlenecks and delays treatment initiation. The feasibility of implementing decentralized breast biopsy services at district (Level II) hospitals to facilitate early cancer treatment, save lives, and create sustainable improvements in breast cancer care across Rwanda has not yet been demonstrated. This research aligns with National Cancer Institute’s focus on implementation science and health systems research, cross disciplinary capacity development in research methods for LMICs, and technology for cancer control, in addition to Fogarty’s support for global health research, partnerships, and capacity building. CANDIDATE: This Emerging Global Leader (K43) Award will transition the clinician researcher and faculty general surgeon at the Center for Equity in Global Surgery, University of Global Health Equity to independence in strengthening breast cancer care in Rwanda through rigorously researched, locally relevant interventions that increase access to early cancer biopsy, and timely, high-quality care. He will gain additional training in advanced health services research, qualitative research and implementation research, and clinical epidemiology with process improvement. This K43 will support his long-term career goals by offering structured training in critical areas, guidance from leading global experts, and applied research experience to accomplish his scientific objectives. RESEARCH: The researcher will evaluate the capacity, determinants, and feasibility of integrating decentralized breast biopsy services into district (Level II) hospitals across Rwanda through the following AIMS: 1- Quantitatively evaluate the capacity and organizational readiness for decentralized breast biopsy services at district hospitals across Rwanda; 2- qualitatively assess the facilitators and barriers to implementing decentralized breast biopsy services at district hospitals across Rwanda; 3- To assess feasibility of implementation of decentralized breast biopsy services at five district hospitals. Innovation: Defining optimal means to reduce reliance on centralized systems, using innovative technology-driven training tools including gamification, simulation, and extended reality to train, pioneering use of organizational readiness tools in the global breast biopsy space are innovative. Few global surgeons are in the cancer implementation science space. DELIVERABLES AND FUTURE DIRECTIONS: The researcher will publish 8 relevant manuscripts and submit an R01 proposal to test the impact of implementing decentralized models of care across the region.

NIGMS - National Institute of General Medical Sciences

ABSTRACT Metabolic health depends on acquiring an appropriate amount of energy and allocating it efficiently across tissues. The human gut microbiome modulates energy acquisition and allocation and exhibits high sensitivity to modifiable lifestyle factors such as diet, exercise, and social contact, resulting in gut microbiome contributions to metabolic health that differ across individuals and within individuals over time. Ecological plasticity of the gut microbiome is a double-edged sword: it may increase disease risk if the microbiome departs from profiles to which the human body has adapted, but it may also confer protection by affording humans some capacity to adapt rapidly to changing ecological conditions. However, health outcomes of lifestyle-associated alterations in the gut microbiome remain untested. This situation complicates the interpretation of human gut microbiome variation, hinders efforts to develop equitable microbiome-targeted therapeutics, and obscures our view of features characterizing a ‘healthy’ human microbiome. In the coming five years, we will perform experiment-based, causally informative research toward three synergistic themes that elucidate when, why, and how lifestyle affects gut microbiome contributions to metabolic health. In Theme 1, we interrogate how ecological factors such as dietary digestibility, caloric intake, and exercise shape gut microbiome contributions to host metabolic health and the conditions favoring inflection points between beneficial and detrimental contributions. In Theme 2, we evaluate how ecological context shapes the metabolic health consequences of host-microbiome interactions and whether it may benefit health to restore putatively beneficial taxa depleted in industrialized or non-industrialized gut microbiomes. In Theme 3, we investigate how social microbial transmission may mediate metabolic disease risk and resilience, testing the idea that non-communicable conditions have a communicable component by virtue of the social exchange of risk-associated microbes. To address Themes 1 and 2, we will exploit natural variation in human microbiomes and controlled diet and exercise interventions in mice to foster conditioned gut microbiomes that can then be transplanted into germ-free animals to study the causal health impacts of a given microbiome profile. To address Theme 3, we will examine the transmissibility of microbes between focal individuals with metabolic disease and their social partners, varying focal and partner social networks to evaluate the risk landscape of social transmission in relation to social position and connectivity. Work toward Themes 1-3 will be enhanced by three overarching principles guiding our work: (1) consideration of both bacterial and non-bacterial constituents of the gut microbiome, (2) rigorous host and microbiome phenotyping enabling the elucidation of underlying mechanisms, and (3) development of machine learning models that identify metagenomic and metabolomic features predicting gut microbiome contributions to metabolic health. Collectively, our proposed research will enhance our understanding of human energy metabolism and help lay the groundwork for future health-directed manipulation of the gut microbiome.

NIAID - National Institute of Allergy and Infectious Diseases

Abstract Borrelia burgdorferi (Bb) is maintained in nature within an enzootic cycle involving a mammalian reservoir host and a tick vector. To sustain this dual-host lifestyle, Bb must remodel its transcriptome as it shuttles between these two host milieus. The RpoN/RpoS pathway is central to borrelial gene regulation. In addition to upregulating genes required for tick transmission and mammalian infection, this pathway represses tick-phase genes, hence its designation as the `gatekeeper'. Activation of the spirochete's other major pathway, Hk1/Rrp1, results in synthesis of the second messenger c-di-GMP, which is required for survival in ticks. c-di-GMP exerts its regulatory effect via the effector protein PlzA. Using a novel transcriptomic approach, TBDCapSeq, we compared the RpoS regulons during the nymphal blood meal and mammalian host-adaptation. These analyses established unequivocally that the contours of the RpoS regulon differ dramatically during the tick and mammalian phases and that RpoS-mediated repression occurs exclusively within mammals. Unexpectedly, we found that deletion of BosR in an IPTG-inducible rpoS strain diminished expression of RpoS-upregulated genes and abrogated RpoS-mediated repression. Thus, in addition to its well-recognized function as a cofactor for RpoN-dependent transcription of rpoS, BosR also plays an essential downstream role modulating promoter recognition by RNAP-RpoS. Using a Bb strain that synthesizes c-di-GMP constitutively, we made the intriguing observation that liganded-PlzA (PlzALig) exerts a `brake' effect on RNAP-RpoS, antagonizing RpoS-mediated repression and diminishing transcription of RpoS-upregulated genes. Remarkably, the effect of PlzALig on RNAP- RpoS mirrors BosR-deficiency. These findings lead to our central hypothesis that PlzALig and BosR determine the contours of the RpoS regulon by exerting reciprocal effects on RNAP-RpoS. In Aim 1, we will determine how DNA binding by BosR shapes the RpoS regulon and investigate the mechanism underlying RpoS-mediated repression. Experiments in Aim 2 will investigate two possible mechanisms to explain the PlzALig brake. Lastly, in Aim 3, we will assess the contributions of other regulatory factors to modulation of the tick- and mammalian-phase RpoS regulons. Our long-term objective is to develop a holistic understanding of how the RpoN/RpoS regulatory networks orchestrate gene expression to sustain Bb in nature.

NCI - National Cancer Institute

PROJECT SUMMARY/ABSTRACT DNA sequencing holds significant promise for precisely profiling individual tumors, which in turn can guide personalized cancer therapies and improve long-term patient outcomes. A key prognostic factor across tissue types is intra-tumor heterogeneity (ITH), resulting from somatic single-nucleotide variants and copy-number aberrations, that is highly predictive of patient survival and risks of metastasis and relapse. However, accurately estimating ITH and tumor growth from DNA data remains challenging, thereby impeding its broader adoption for clinical decision making. This proposed project will focus on developing DECODE (Deciphering Cancer Origin from DNA Evolution), a novel approach for reconstructing tumor evolution that can predict patient outcomes and facilitate risk stratification and treatment selection in clinical practice (Aim 1). DECODE will integrate the neutral tail in the site frequency spectrum (SFS), comprised of recent mutations that carry signals indicative of a tumor’s expansion mode. DECODE’s enhanced accuracy will be based on mathematical corrections for sample-specific coverage and effects of mutation filtering. This will reduce the risk of overfitting, enhance the detection of overlapping clusters, and render DECODE ideally suited for data generated by current DNA-seq technologies. In Aim 2, DECODE will be used to analyze the tumor heterogeneity and infer tumor evolution history in primary cancers from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For each sample, the SFS neutral tail will be characterized and the number of subclones and subclonal frequencies will be estimated. The tumor evolution timelines from these samples will then be inferred, using a novel mathematical framework to estimate the age of each tumor’s most recent common ancestor, subclonal arrival times and growth rates from DECODE’s parameters. Finally, the ITH estimates and tumor and subclonal growth rates will be examined for predictive power of patient outcome in specific cancer types, toward finding potential biomarkers. Relapsed and metastatic tumors from the Personalized OncoGenomics (POG) cohort will also be studied (Aim 3). For these samples, a multi-variate DECODE algorithm will be developed to consider mutations with distinct multiplicities occurring on different copy number backgrounds. The multi-variate DECODE will be able to analyze advanced cancers, which often exhibit variable copy numbers due to chromosomal instability. The comparison of ITH estimates and clonal evolutions inferred from DECODE between samples in POG and ICGC/TCGA will enable a deeper understanding into differences in selection forces driving relapses and metastases compared to de novo cancers. In summary, DECODE is a novel approach toward reliable tumor evolution reconstruction, enabled by advances in mathematical modeling and parameter inference. Its accuracy, notably for samples sequenced with currently available technologies, will enable deeper understanding of tumor adaptation, clinical patient stratification and outcome prediction, toward the goal of personalized therapy treatment.