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NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY HIV and Mycobacterium tuberculosis (Mtb) are among the world’s deadliest infections, and co-infection is particularly devastating because each pathogen accelerates the progression and severity of the other. Notably, for reasons that are not well understood, people living with HIV (PLWH) remain at elevated TB risk despite effective antiretroviral therapy (ART) and viral suppression. Our goal is to define how HIV-TB co-infection, even with virologic control, impairs Mtb immunity. Macrophages and CD4+ T cells are central to the pathogenesis of both diseases; Mtb infects lung macrophages and depends to CD4+ T cells to prevent disease progression, while HIV infects both macrophages and CD4+ T cells. Macrophages can harbor latent HIV proviruses, which persist despite treatment. Both pathogens reprogram macrophage metabolism, which is intimately linked to antimicrobial functions. However, the impact of co-infection on macrophage immunometabolism and Mtb control remains unclear. In addition, although antiretroviral treatment (ART) can restore CD4+ T cell counts to normal ranges, the T cells often remain dysfunctional and exhibit signs of exhaustion. We unite leading HIV and TB investigators and leverage unique cellular and animal models of HIV latency. We hypothesize that, despite ART and virologic suppression, PLWH experience macrophage immunometabolic reprogramming that enhances TB susceptibility and that ART-restored CD4+ T cells are dysfunctional and fail to enhance microbicidal properties of macrophages. Using dual-reporter human macrophage models and ex vivo studies of PLWH and controls, we will profile antimicrobial and immunometabolic responses of Mtb-infected macrophages, and we will test the contribution of exhausted CD4+ T cells to macrophage dysfunction. A long-standing obstacle to studying HIV- TB coinfection has been the absence of a small animal model. We will use a novel humanized mouse model that recapitulates human lung immune cell populations and HIV infection dynamics, including active viral replication, latency establishment, and viral suppression with ART. We will assess how untreated and treated HIV infection affects Mtb pathogenesis, assessing pathogen burden, immunometabolic responses, and cellular infection patterns, using spectral flow cytometry, scRNAseq and metabolic profiling. These studies will clarify the molecular basis of immune dysfunction during HIV-TB co-infection and inform on host-directed therapies to restore immune function and improve outcomes.

NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY / ABSTRACT Orofacial neuropathic pain, often stemming from somatosensory nervous system dysregulation, frequently manifests in conditions such as chemotherapy-induced neuropathy and trigeminal neuralgia. This pain commonly results in altered somatosensory experiences, including orofacial cold allodynia (pain from normally innocuous cool stimuli) and cold hyperalgesia (exaggerated pain in response to noxious cold). Current treatments often fail to alleviate these cold-sensation symptoms because the underlying cellular and molecular mechanisms for low temperature sensation are not well defined. Recent single-cell sequencing has revealed new layers of molecularly distinct somatosensory neuron populations, yet how the coding logic underlying low temperature sensation and cold-nociception is distributed across these neurons remains severely understudied. This proposal aims to delineate the neural and molecular logic underlying low temperature sensation, revealing fundamental principles essential for informing development of new strategies for cold allodynia and neuropathic pain. To accomplish this, we will apply an intersectional genetic strategy in mice, combining state-of-the-art thermoelectric cooling (TEC) probes, in vivo trigeminal (TG) functional imaging, multiplexed in situ hybridization, neural tracing, and advanced AI-based behavioral analyses. Preliminary data reveal Chrna7+ TG Aδ-nociceptors encode noxious cold sensation in teeth independent of the canonical cool receptor Trpm8, providing direct evidence that low temperature encoding is distributed across several TG classes. This proposal will 1) define molecular and neural mechanisms underlying orofacial low temperature sensation and 2) characterize behavioral outputs and central projections of low temperature encoding TG populations using optogenetics and AI-based machine learning, and mapping associated afferent brainstem nuclei.This research will launch the candidate’s independent research program aimed at elucidating low temperature encoding mechanisms throughout the periphery. This will set the stage for future directions examining higher-order circuit mechanisms of cold sensation versus pain, and how sensation is transformed in disease/pain models. This work will bring new perspectives and hypotheses towards the development of pain treatment strategies, including those for neuropathic cold allodynia and hyperalgesia. During the mentored stage, the candidate will gain valuable training in: 1) intersectional genetic techniques for neuroscience studies, 2) advanced computational analysis for calcium imaging and behavior, and 3) guidance from the formal advisory committee in lab leadership, grant writing, networking, and presentation skills. This award will set the candidate up for success in transitioning to independence and making significant discoveries towards understanding and treating pain.

National Park Service

A. Research: develop and implement new technologies for the preservation and conservation of cultural heritage. B. Training: adapt new and existing technologies to the field of art conservation. Offer training courses and convene experts on technical and scientific aspects of hands-on conservation. C. Information Management: serve as knowledge centers and clearinghouses for conservation and preservation information. D. Grants: serve the preservation and conservation community by offering professional development opportunities through internships, scholarships, and grants. E. Conference participation: to include holding sessions, participation in exhibits and sharing meeting facilities. RECIPIENT AGREES

NEI - National Eye Institute

Abstract: This project aims to establish distributed federated learning (FL) approaches for multi-task training of foundational machine learning (ML) models for diabetic retinopathy (DR), using multi-modal, real-world optical coherence tomography (OCT) data (OCT cross-section, OCT angiography (OCTA), and OCT enface). DR is one of the leading causes of severe vision loss. Early detection, prompt intervention, and reliable assessment of treatment outcomes are essential to prevent irreversible vision loss from DR. However, there are major challenges towards developing clinically relevant holistic algorithms that can perform multi-tasks, i.e., multi-class classification of disease stages (diagnosis), prediction of onset and progression of disease stages (prognosis), and assessment of treatment outcomes. They require large amounts of well curated and labelled datasets from a diverse sub-population for robust performance. Moreover, efforts towards large, centralized datasets for ML research are hindered by significant barriers to data sharing and privacy concerns. In this project, we propose to develop foundational ML models that allow efficient learning of feature representations from a large corpus of ophthalmic imaging data for various downstream tasks – breaking the task-specific paradigm of current ML models. We also establish novel federated ML approaches, where the model training is distributed across institutions instead of sharing patient data. Our first aim is to establish and validate a domain adaptive FL framework for DR diagnosis across four independent institutions. We propose a novel ophthalmic adaptive personalized FL (optho-APFL) technique to tackle domain shift caused by heterogeneous data distribution at different institutions (due to different sub-population density and OCT devices/imaging protocols). We will conduct experiments on the FL deployment in a clinical setting and integrate a granular differential privacy (DP) algorithm into our FL framework to provide ‘patient-level’ data privacy. Key success criterion is to deploy the FL framework and validate FL-trained ML models against state-of-the-art models for DR diagnosis. The second aim is to develop foundational ML models with self-supervised learning (SSL) to learn multiple tasks within the same framework from label invariant OCT/OCTA data, where different institutions don’t need to have labeled data for each of the tasks. We will train these foundational models in a centralized and FL framework for comparative analysis. Key success criterion is to i) validate foundational model performance for multi-task learning (MTL) (DR staging, prediction of NPDR to PDR progression, and prediction of DME treatment evaluation) on new clinical data (centralized and FL approach, and ii) identify task-specific quantitative OCT/OCTA (mean and artery-vein specific) features. As an alternative approach, we propose diffusion probabilistic modeling (DPM) for SSL to learn holistic representations from multi-modal OCT data for MTL, and to explore dynamic federated averaging approaches. Success of this project will establish OCT/OCTA based distributed foundational models for objective MTL in DR using label-invariant data across multi-institutions and standardize OCT/OCTA features for MTL.

NINDS - National Institute of Neurological Disorders and Stroke

ABSTRACT Alternative splicing vastly expands the functional repertoire of genes, and is especially important during human synapse development. Human synapses have unique structures and compositions, but the mechanisms involved in their development remains elusive. Investigations into human-specific aspects of synaptic machinery have revealed a critical role for Rho guanine nucleotide exchange factor (GEF) signaling. TRIO is a large multi-domain RhoGEF with essential roles in neuronal and synaptic development. TRIO is also a genome-wide significant risk factor for neurodevelopmental disorders and glutamatergic synapses have been implicated by genomic, neuropathological, and functional studies as key sites of pathogenesis. Individuals with pathogenic TRIO variants are characterized by intellectual disability, developmental delay, and seizures. The TRIO gene produces multiple distinct isoforms that differentially incorporate TRIO’s functional domains including two GEF domains that having opposing functions on the actin cytoskeleton. Thus, precise control of TRIO’s GEF domains through expression and localization of isoforms is paramount for its function. However, the diversity and expression patterns of TRIO isoforms are poorly understood, and their impact on human synapse development is unknown. A complete catalogue of isoform diversity is necessary for a holistic view of gene function, and is critical for gene therapy designs, interpreting clinical variants, and revealing novel biological mechanisms. Here, we will leverage state- of-the-art long-read sequencing, iPSC-models and fluorescence imaging to characterize human TRIO isoforms. Our central hypothesis is that TRIO produces an array of isoforms with distinct expression patterns and domain architectures that assist with the precise timing and spatial control of synaptic development. In Aim 1, we will combine exon capture and long-read sequencing technologies to systematically profile full-length TRIO transcripts in the human brain. We will create comprehensive isoform maps at three postnatal time points, and analyze novel isoforms for differential expression, presence of clinical variants, and protein motifs. In Aim 2, human iPSC-derived neuron models will be utilized to assess the localization and functional roles of individual isoforms in synaptic compartments. Together, this work will reveal a high-resolution map of the structure, expression and function of TRIO isoforms in the human brain, providing mechanistic insight into human synapse development and TRIO-related neurodevelopmental disorders.

Northwest Share

Northwest Share will be hosting the Diwali Lights of India Festival on November 2, 2024, located at the Armory at Seattle Center, 305, Harrison St from 12pm to 6pm. The festival showcases Arts and culture of India through live music, dance performances, workshops, and various arts and crafts. This family friendly event is free and open to the public.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY ADP-ribosylation is a modification used across domains of life to mediate biological conflicts. The covalent attachment of ADP-ribose to diverse substrates ranging from proteins and small molecules to nucleic acids can render the target inaccessible or inactive. DNA targeting ADP-ribosylation has received less attention than the modification of other substrates, but is increasingly thought to be a widespread strategy in both interbacterial conflicts and in anti-phage defense mechanisms. DNA ADP-ribosylation was discovered in bacteria less than ten years ago, and therefore despite the prevalence of this modification, little is known about its biological function. My postdoctoral research provided a major advance for the field by revealing that a widely distributed bacterial DNA targeting ADP-ribosyltransferase (ART) toxin is the effector of a family of phage defense systems, thus ascribing a clear biological function to these enzymes. DNA targeted ADP-ribosylation blocks DNA replication and is accordingly highly toxic in bacterial cells but also potently anti-viral. These bacterial DNA targeting ARTs, a family termed DarT, are normally kept inactive by a cognate, neutralizing antitoxin, DarG, which is a DNA targeting ADP-ribosylglycohydrolase (ARG). Many fundamental questions remain about the biology of DarTG systems, including how the DarT toxin becomes active after phage infection. Phages, a co-evolving biological entity, are also a rich source of anti-DNA ART mechanisms. We recently discovered that some phages have co-opted DarG-like proteins and related DNA ARGs on multiple occasions, and that these “orphan antitoxins” protect these phages from DarTG-mediated defense. Thus, as with DarT, we were able to ascribe a biological function to a widespread family of previously mysterious phage enzymes. The distribution of DNA ARGs across the tree of life further suggests that DNA ADP-ribosylation is almost certainly more widespread than currently appreciated. The major goals of this study are both to investigate the underlying biology of DarTG systems in their biologically relevant context of phage infection, as well as to develop and apply cutting edge bioinformatic approaches to identify novel DNA ART and ARG families. To this end, we will pursue the following aims: 1) elucidate the molecular mechanism by which phage infection activates DarTG1 using genome-wide, single-cell, and in vitro approaches; 2) investigate the specificity and diversity of phage- encoded DNA ARGs and other phage anti-DNA ART counter-defenses, and 3) mechanistically dissect a third, unstudied DarTG family and develop methods for discovery of additional DarT- and non-DarT-related DNA ARTs. The discoveries we make in this bacterial-phage system, with its powerful experimental and genetic tools, will reveal fundamental facets of DNA ART and ARG biology relevant to the bacterial immune system and lay the groundwork for future studies of anti-viral DNA ADP-ribosylation in eukaryotes.

Dept. of the Army -- USAMRAA

<p>The USAMRDC’s mission is to provide solutions to medical problems of importance to the American Service Member at home and abroad, as well as to the general public at large. The scope of this effort and the priorities attached to specific projects are influenced by changes in military and civilian medical science and technology (S&amp;T), operational requirements, military threat assessments, and national defense strategies. Extramural research and development programs play a vital role in the fulfillment of the objectives established by the USAMRDC. General information on the USAMRDC can be obtained at https://mrdc.health.mil/.</p><p>This BAA is intended to solicit extramural research and development ideas using the authority provided by 10 USC 4001. The BAA is issued under the provisions of the Competition in Contracting Act of 1984 (Public Law 98-369), as implemented in FAR 6.102(d)(2) and 35.016 and in Department of Defense Grant and Agreement Regulations (DoDGARs) 22.315. In accordance with FAR 35.016, projects funded under this BAA must be for basic and applied research to support scientific study and experimentation directed toward advancing the state-of-the-art or increasing knowledge or understanding rather than focusing on development of a specific system or hardware solution. Research and development funded through this BAA are intended and expected to benefit and inform both military and civilian medical practice and knowledge. This BAA utilizes competitive procedures in accordance with 10 USC 3012 for the selection for award of S&amp;T proposals/applications. For the purposes of this BAA, S&amp;T includes activities involving basic research, applied research, advanced technology development, and, under certain conditions, may include activities involving advanced component development and prototypes.</p><p>The selection process is highly competitive, and the quantity of meaningful submissions (both pre-proposals/pre-applications and full proposals/applications) received typically exceeds the number of awards that available funding can support.</p><p>This BAA provides a general description of USAMRDC’s research and development programs, including Research Areas of Interest, evaluation and selection criteria, pre-proposal/ pre-application and full proposal/application preparation instructions, and general administrative information. Specific submission information and additional administrative requirements can be found in the document titled, “General Submission Instructions,” which is available on Grants.gov along with this BAA.</p><p>The FY23-FY27 USAMRDC BAA is continuously open for a 5-year period, from October 1, 2022 through September 30, 2027, at 11:59 p.m. Eastern Time. Submission of a pre-proposal/pre-application is required and must be submitted through the electronic Biomedical Research Application Portal (eBRAP) (https://eBRAP.org/). Pre-proposals/pre-applications may be submitted at any time throughout the 5-year period. If the USAMRDC is interested in receiving a full proposal/application, the Principal Investigator will be sent an invitation to submit via eBRAP. A full proposal/application must be submitted through Grants.gov (http://www.grants.gov/). Invited full proposals/applications can be submitted under this FY23-FY27 BAA through September 30, 2027.</p>

Defense Health Agency Contracting Activity - DHACA

The USAMRDC s mission is to provide solutions to medical problems of importance to the American Service Member at home and abroad, as well as to the general public at large. The scope of this effort and the priorities attached to specific projects are influenced by changes in military and civilian medical science and technology (S&amp;T), operational requirements, military threat assessments, and national defense strategies. Extramural research and development programs play a vital role in the fulfillment of the objectives established by the USAMRDC. General information on the USAMRDC can be obtained at https://mrdc.health.mil/.This BAA is intended to solicit extramural research and development ideas using the authority provided by 10 USC 4001. The BAA is issued under the provisions of the Competition in Contracting Act of 1984 (Public Law 98-369), as implemented in FAR 6.102(d)(2) and 35.016 and in Department of Defense Grant and Agreement Regulations (DoDGARs) 22.315. In accordance with FAR 35.016, projects funded under this BAA must be for basic and applied research to support scientific study and experimentation directed toward advancing the state-of-the-art or increasing knowledge or understanding rather than focusing on development of a specific system or hardware solution. Research and development funded through this BAA are intended and expected to benefit and inform both military and civilian medical practice and knowledge. This BAA utilizes competitive procedures in accordance with 10 USC 3012 for the selection for award of S&amp;T proposals/applications. For the purposes of this BAA, S&amp;T includes activities involving basic research, applied research, advanced technology development, and, under certain conditions, may include activities involving advanced component development and prototypes.The selection process is highly competitive, and the quantity of meaningful submissions (both pre-proposals/pre-applications and full proposals/applications) received typically exceeds the number of awards that available funding can support.This BAA provides a general description of USAMRDC s research and development programs, including Research Areas of Interest, evaluation and selection criteria, pre-proposal/ pre-application and full proposal/application preparation instructions, and general administrative information. Specific submission information and additional administrative requirements can be found in the document titled, General Submission Instructions, which is available on Grants.gov along with this BAA.The FY23-FY27 USAMRDC BAA is continuously open for a 5-year period, from October 1, 2022 through September 30, 2027, at 11:59 p.m. Eastern Time. Submission of a pre-proposal/pre-application is required and must be submitted through the electronic Biomedical Research Application Portal (eBRAP) (https://eBRAP.org/). Pre-proposals/pre-applications may be submitted at any time throughout the 5-year period. If the USAMRDC is interested in receiving a full proposal/application, the Principal Investigator will be sent an invitation to submit via eBRAP. A full proposal/application must be submitted through Grants.gov (http://www.grants.gov/). Invited full proposals/applications can be submitted under this FY23-FY27 BAA through September 30, 2027.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Immune tolerance remains the goal of allogeneic human organ transplantation in order to achieve safe and long-term transplant function. If achieved, tolerance would reduce the need for retransplants by substantially prolonging the durability of organ transplants and preventing immunologic rejection. This elusive goal is the aim of this proposal, which is based on observations that T regulatory cells (Treg) are able to downregulate the peripheral immune response to organ transplants in animal models and humans. Harnessing such Tregs for the purposes of donor-specific tolerance may be possible using a combination of recently developed novel approaches. These approaches include administering an IL-2 mutein (mIL-2) to promote Tregs in combination with drugs such as rapamycin, anti-CD154 mAb, IL-6 receptor blockade (Tocilizumab) and complement blockade (anti-C3). The need for donor-specificity to tolerance can be substantially enhanced by the exposure of the organ transplant recipient to chemically treated (ECDI) donor B cells, as well as the administration of CAR-Tregs that confer regulation to a specific donor MHC antigen. Each of these technologies is available to us to apply to what is likely the most relevant and feasible animal model that accurately simulates human biology: namely, a rhesus monkey kidney allograft model. We have considerable experience using this model to develop novel immunotherapies that have been successfully introduced into the clinical transplant arena. Examples include T cell depleting therapy, co-stimulation blockade, and desensitization to MHC. We propose to use a combination of Treg promoting strategies in combination with ECDI-treated donor B cells and CAR- Tregs in controlled experiments and with state-of-the-art mechanistic support to define the immunologic impact of each therapy. These data would guide the rational development of a tolerance-inducing strategy and monitoring tools that would be feasible to apply to an initial human kidney transplant trial of Treg-based peripheral tolerance.

NIDA - National Institute on Drug Abuse

Neurologic complications remain prevalent in nearly 50% of people with HIV (PWH) and persist despite viral suppression with antiretroviral therapy (ART). Though the exact processes mediating HIV neuropathogenesis are not well understood, co-morbidities such as substance use disorders (SUD), which are higher in PWH compared to the general population, exacerbate neuropathogenesis of HIV and worsen outcomes. Multiple substances of misuse are reported to increase HIV replication, induce inflammatory signaling, and amplify neurodegenerative phenotypes. Thus, there is a significant need to understand the intersection between SUD and NeuroHIV to improve longitudinal care and inform the public. The overlapping effects of distinct substances of misuse on HIV pathogenesis in the CNS suggest that a common pathway may be involved through presently undefined mechanisms. All addictive substances increase extracellular dopamine in the central nervous system (CNS), which signals neurons and other nearby glial cells expressing dopamine receptors. Our lab has shown that myeloid cells such as macrophages and microglia, which are major HIV reservoirs in the brain, express dopamine receptors more D1-like receptors (D1 and D5) than D2-like receptors (D2, D3, D4). Treatment of macrophages and microglia with micromolar concentrations of dopamine increased pro-inflammatory signaling, increased viral entry, and potentiated viral secretion in vitro. We recently found that a higher D1-like to D2-like ratio is associated with a more pro-inflammatory response in microglia. Further, we showed that dopamine increases activation of nuclear factor-kappa B (NF-κB) in macrophages, and that inhibition of NF-κB can block the pro-inflammatory effects of dopamine. Together, these data suggest that dopamine-enriched brain regions, such as the cortex and striatum, may be especially vulnerable to HIV and neuroinflammation in PWH and co-morbid addiction through the action of dopamine on microglia. Therefore, the central hypothesis of this proposal is that dopamine D1-like receptor activation promotes HIV infection and NF-κB-mediated inflammation in microglia to worsen neurodegeneration. This hypothesis will be tested using human induced pluripotent stem cell (iPSC)-derived brain human cortical assembloids and several orthogonal assays to explore the dopamine-mediated pathways that modulate HIV neuroimmune pathogenesis. We will use pharmacologic activation of dopamine receptors in cortical assembloids to assess viral kinetics (Aim 1), neuroinflammation (Aim 2), and neuronal degeneration of synapses and dendrites (Aim 3). Together, these studies will significantly advance our understanding of dopamine as an immunomodulatory signaling molecule in the context of substance use and HIV, as well as expand the approaches to studying neuroimmune pharmacology using human micro-physiological systems.

Doris Duke Foundation

Multi-year grants for performing arts organizations building audiences and developing new work in contemporary dance, jazz, and theater.

Dozer Art

Dozer Art will organize a temporary art exhibit at 2507 Beacon Ave S featuring local muralists and painters. An opening event for the exhibit will be held on September 8, 2017 from 5 pm - 10 pm. The free all ages event will feature performance art, music, and food.

Bureau of Democracy Human Rights and Labor

This program will counter forced labor in seafood supply chains associated with countries that have signed Agreements on Reciprocal Trade (ART) in East Asia and the Pacific (excluding Indonesia and the Philippines) and the Western Hemisphere, as well as other strategically important countries and prospective ART partners where engagement advances U.S. economic, trade, and maritime interests.

Bureau of Democracy Human Rights and Labor

DRL solicits proposals of up to $1,973,359 that aim to strengthen the ability of the United States and partner countries with ARTs to detect and disrupt transshipment practices that evade U.S. laws that prohibit the importation of goods made with forced labor and/or other country s forced labor import prohibitions.

NEI - National Eye Institute

ABSTRACT Eye diseases can have a profound impact on an individual’s quality-of-life, overall health, and life expectancy, and impose a tremendous burden on society and public health. There have been many advances in vision research, but there is a need for physician scientists who are highly trained in contemporary multidisciplinary research and can bring cutting-edge expertise in clinical/translational/population-outcomes research to solve contemporary vision impairing challenges. The Duke Ophthalmology Mentored Physician Scientist Program will train the next generation of ophthalmology physician scientists by fostering their career development in state-of-the art multidisciplinary research emphasizing the importance of scientific rigor, innovative scientific methods, appreciation of team science, and translation to improve patient health. The program will provide two qualified early-career physician scientist scholars per year with cutting-edge research experiences in a robust, innovative, career development framework to develop the next generation of physician scientists in ophthalmology. The Program will address gaps in scientific knowledge related to ophthalmology by providing skills, support and resources needed for the physician scientist to innovate and build inter- and cross- disciplinary collaboration within ophthalmology research. In that way, this Program will prepare the Duke K12 Mentored Physician Scientist Scholars to lead their own multidisciplinary teams in clinical/translational and/or population heath eye research, advance the field and ocular health, and become mentors and leaders of tomorrow. Upon completing this program, these vision scientists will have both a fundamental understanding of the clinical impact and the ability to apply rigorous and innovative methods to enable discoveries and translate these into tangible interventions. The impact of the Program will be gauged by their development of a research program and its contribution to the improvement of eye health.

Duluth Superior Area Community Foundation

Duluth Superior Area Community Foundation ($150M in assets) supports nonprofits in MN through grants focused on education, environment, community development, arts. Awards range from $1,000 to $50,000.

NEI - National Eye Institute

PROJECT ABSTRACT Cataracts and glaucoma are the two leading causes of blindness worldwide. Crucial ophthalmic procedures to treat cataract, glaucoma, and other vision conditions require precise visualization of anatomy and microsurgical instruments. Visualization in such surgeries has been limited to stereo optical microscopes since the early 20th century. With advancements in optical coherence tomography (OCT), we can now obtain real-time 3D visualization within the eye. Over the past decade, intraoperative OCT (iOCT) systems have become widely researched and integrated into the latest ophthalmic microscopes built by companies such as Zeiss and Leica. These iOCT systems come with the potential to revolutionize ophthalmic surgery, with an unparalleled ability to resolve key anatomic features at micron-level precision. However, there is a crucial challenge that hampers the clinical utility of iOCT. This challenge stems from the fundamental tradeoff between OCT field-of-view and imaging speed. This tradeoff constrains state-of-the-art systems to operate with a relatively small (e.g. 5x5 mm) field of view to achieve the volume update speeds (~10-15 Hz) required for surgical visualization. Consequently, a trained operator on the surgical team must manually reposition the OCT scan throughout the surgery. The current implementation of iOCT results in a “point-and-shoot” approach to imaging, i.e. using OCT as an intermittent snapshot tool, rather than as a continuous surgical visualization technology. With even small movements of the surgical instruments, the OCT image can quickly lose sight of the surgical region of interest (ROI). Manual tracking of iOCT discards a key advantage of OCT, which is real-time 3D data collection. With advances in deep learning methods for image processing and object recognition, there are new opportunities to tackle this problem. The goal of this project is to engineer a novel computational system for automatic, real- time tracking of the surgical ROI in a clinical iOCT system. Our vision is to develop a system that can be readily applied to existing clinical microscopes, and adaptable to future robotic surgical systems. As part of our preliminary work, we have created a lateral tool tracking OCT system using deep learning models applied to the microscope feed. Our current system utilizes a novel synthetic data approach, making use of 3D-rendered models of eyes and tools to accelerate deep learning model development. In the proposed project, we expand on this preliminary work by developing a system for 3D multimodal surgical ROI tracking of iOCT that can be applied to many different types of ophthalmic surgeries. We will then evaluate our platform via ex-vivo porcine and human cadaver eye studies with wet-lab benchmarking and simulated surgeries with our clinical collaborators. Our immediate application is ophthalmic surgery, but the methodology has relevance to a wide range of 3D imaging systems for microsurgical procedures. By developing this system for dynamic OCT surgical tracking, we hope to improve ophthalmic visualization in both training and surgical practice.

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

PROJECT SUMMARY/ABSTRACT More than 17% of infants born in the United States have motor deficits which restrict their development, daily function, and quality of life. Early intervention can improve outcomes for these infants by effectively retraining the brain and body during a critical period of development. However, motor deficits are often not detected until 1-2 years of age or later, which can reduce the efficacy of interventions due to late initiation and lowered brain plasticity. Current evaluation methods, such as caregiver reports and observation-based clinical assessments, lack the accessibility, objectivity, and precision needed to evaluate early infant movement outside of a clinical setting and screen for atypical motor behaviors. The objective of the proposed study is to develop a fully automated wearable sensor toolkit to detect infant motor deficits within the first few months of life during free- living activities the home and community, and to surveil these deficits over the first year of life. Capturing free- living infant movements would provide a more comprehensive and representative picture of everyday infant behavior compared to current evaluation methods. We will develop the wearable sensor toolkit via the following Aims. In Aim 1, whole-body inertial sensor data will be recorded in the home and community from up to 60 newborn infants across the risk spectrum for motor deficits to curate a pediatric dataset of real-world, early motor development. In Aim 2, this dataset will be used along with state-of-the-art signal processing and machine learning techniques to develop a toolkit that collects and automatically analyzes wearable sensor data to evaluate motor development for infants less than 3 months of age during everyday activities and infant behaviors in the home and community. Finally, in Aim 3, the toolkit will be validated in a separate cohort of 30 newborn infants to evaluate its effectiveness in detecting and describing infant motor deficits over the first year of life compared to traditional clinical assessments. The primary outcomes will be a fully annotated, free-living dataset characterizing infant motor development between birth and 3 months of age, as well as the sensitivity and specificity of the wearable sensor toolkit to detect infant motor deficits during these early ages. Secondary outcomes will include surveillance curves of sensor-based metrics to track motor development over the first year of life, and clinical outcomes of infants tracked and not tracked by the toolkit. This study will revolutionize detection and surveillance of infant motor development and deficits by automatically evaluating early-life movement patterns in the home and community, alerting clinicians and caregivers when further examination is needed. Early, accurate, and accessible methods of identifying infant motor deficits would allow for more widespread developmental screening and earlier, targeted interventions to improve lifelong outcomes.

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is tofurther elucidate the mechanisms of early immune development in utero, during the early post-natal period and during early childhood in neonates, infants, and children and adolescents with or without in-utero exposure to HIV or Anti-Retroviral Therapeutics (ART).This initiative aims to understand intricate mechanisms of immune cells at the maternal-fetal interface, T and B cell development and maturation in offspring, and local immune responses and the role of systemic immunity.

National Institutes of Health

<p>The purpose of this Notice of Funding Opportunity (NOFO) is tofurther elucidate the mechanisms of early immune development in utero, during the early post-natal period and during early childhood in neonates, infants, and children and adolescents with or without in-utero exposure to HIV or Anti-Retroviral Therapeutics (ART).This initiative aims to understand intricate mechanisms of immune cells at the maternal-fetal interface, T and B cell development and maturation in offspring, and local immune responses and the role of systemic immunity.</p>

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY Early life stress (ELS), particularly during fetal development, is a critical risk factor for long-term health, including obesity and metabolic disorders. This project investigates how prenatal stress exposure is biologically embedded, leading to increased vulnerability to abdominal adiposity and metabolic dysfunction. Our long-term goal is to eluci- date cellular and molecular pathways that mediate the developmental origins of metabolic disease, supporting early identification and prevention strategies for at-risk children. Despite known associations between ELS and adult dis- ease, current research is limited by inconsistent findings in early life, inadequate biomarkers of fetal stress exposure, and poor measurement of adiposity in infants. Traditional reliance on weight-based metrics fails to capture fat dis- tribution, which is key to metabolic risk. Moreover, stress exposure during pregnancy is typically estimated from basal circulating biomarkers, neglecting dynamic physiological stress responses. To address these gaps, we employ a translational, multi-level design integrating basic science and clinical research. Using umbilical-derived mesenchy- mal stromal cells (MSCs) from human newborns, we will model individualized cellular vulnerability to ELS. In par- allel, we will track in vivo adipose development using serial MRI assessments and metabolic profiling in infants. Our specific aims are: Aim 1: Determine if biological stress during pregnancy predicts infant adiposity, distribution, and metabolic function using state-of-the-art MR imaging at birth and 5–6 months. Aim 2: Test whether MSCs from high-stress exposed infants exhibit greater cellular vulnerability under in vitro adi- pogenic challenge conditions. Stress exposure will be comprehensively quantified using ex vivo glucocorticoid-cytokine stimulation, diurnal sali- vary cortisol sampling, and maternal blood assays during early and late pregnancy. These data will be synthesized into a composite (PCA) biological stress exposure score. We hypothesize that dynamic, functionally derived measures of maternal stress will better predict infant abdominal adiposity and metabolic function than static bi- omarkers, and that stem cells from high-stress-exposed infants will exhibit greater vulnerability—reflected by in- creased lipid accumulation and hypertrophy—especially under in vitro challenge conditions. This integrated ap- proach will illuminate mechanisms of biological embedding and identify novel markers of metabolic risk. Findings will advance precision health by enabling targeted early-life interventions. This project will also establish a scalable human newborn stem cell biobank for future studies of stress-related disease pathways.

East Bay Community Foundation

East Bay Community Foundation ($800M in assets) supports nonprofits in CA through grants focused on racial equity, economic opportunity, arts, environment. Awards range from $5,000 to $200,000.

East Bay Performing Arts

Support of the vital programs conducted by each of its three divisions: Oakland East Bay Symphony, Oakland Youth Orchestra, and Oakland Symphony Chorus.