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NIAID - National Institute of Allergy and Infectious Diseases

Abstract Cryptococcus remains the leading cause of HIV-related meningitis. Cryptococcal antigenemia (CrAg) is detectable weeks before onset of meningitis, offering a critical window for intervention. Conflicting guidelines on the timing of antiretroviral therapy (ART) initiation among asymptomatic CrAg+ persons result in potentially harmful delays for those with advanced HIV disease. Additionally, 10 weeks of preemptive fluconazole therapy for CrAg+ persons has demonstrated a 28% survival benefit in trials, yet current WHO guidelines—based on expert opinion alone—recommend an extended 6-month fluconazole treatment course. These inefficiencies drive unnecessary costs, excessive antifungal exposure, and missed opportunities for streamlined care. Objective: To inform international guidelines by rigorously evaluating: 1. The safest and most effective timing for ART initiation to maximize survival; 2. The optimal duration of fluconazole therapy for asymptomatic CrAg+ persons with low titers (<1:80). Methods: We propose a highly innovative sequential randomized clinical trial (RCT) in Uganda involving 505 CrAg+ persons with low plasma titers (<1:80): Aim 1: Determine whether immediate ART initiation yields non-inferior 10-week hospitalization-free survival compared to the current standard-of-care 2-week delay. Hypothesis: If immediate ART is safe and effective, this could eliminate unnecessary delays in lifesaving HIV care and streamline HIV care pathways globally. Aim 2: Determine whether a short 10-week course of fluconazole achieves non-inferior 24-week meningitis- free survival compared to the WHO-recommended 24-week regimen. Hypothesis: If 10 weeks of fluconazole preemptive therapy is non-inferior, this will reduce unnecessary antifungal exposure, drug toxicity, and costs. Innovation: This trial challenges the outdated one-size-fits-all approach by introducing treatment stratification based on CrAg titer levels, a biomarker for cryptococcal burden. Our results will directly address current gaps in treatment for CrAg+ persons, aligning guidelines with evidence-based care to improve survival, potentially reduce unnecessary antifungal exposure, and optimize resource use. Impact: This trial has the potential to redefine global HIV and cryptococcal care by: 1. Resolving uncertainty around ART timing to prevent harmful delays and reduce mortality, 2. Establishing the optimal duration of fluconazole therapy for people with low CrAg titers, 3. Informing and harmonizing WHO, U.S., and national treatment guidelines for cryptococcal prevention. We will generate evidence to maximize survival, streamline ART initiation, and optimize antifungal treatment for people with advanced HIV disease globally. This evidence-based approach will empower policymakers to optimize care for millions of people with advanced HIV disease and reduce AIDS-related deaths.

NIAID - National Institute of Allergy and Infectious Diseases

Abstract Cryptococcus remains the leading cause of HIV-related meningitis. Cryptococcal antigenemia (CrAg) is detectable weeks before onset of meningitis, offering a critical window for intervention. Conflicting guidelines on the timing of antiretroviral therapy (ART) initiation among asymptomatic CrAg+ persons result in potentially harmful delays for those with advanced HIV disease. Additionally, 10 weeks of preemptive fluconazole therapy for CrAg+ persons has demonstrated a 28% survival benefit in trials, yet current WHO guidelines—based on expert opinion alone—recommend an extended 6-month fluconazole treatment course. These inefficiencies drive unnecessary costs, excessive antifungal exposure, and missed opportunities for streamlined care. Objective: To inform international guidelines by rigorously evaluating: 1. The safest and most effective timing for ART initiation to maximize survival; 2. The optimal duration of fluconazole therapy for asymptomatic CrAg+ persons with low titers (<1:80). Methods: We propose a highly innovative sequential randomized clinical trial (RCT) in Uganda involving 505 CrAg+ persons with low plasma titers (<1:80): Aim 1: Determine whether immediate ART initiation yields non-inferior 10-week hospitalization-free survival compared to the current standard-of-care 2-week delay. Hypothesis: If immediate ART is safe and effective, this could eliminate unnecessary delays in lifesaving HIV care and streamline HIV care pathways globally. Aim 2: Determine whether a short 10-week course of fluconazole achieves non-inferior 24-week meningitis- free survival compared to the WHO-recommended 24-week regimen. Hypothesis: If 10 weeks of fluconazole preemptive therapy is non-inferior, this will reduce unnecessary antifungal exposure, drug toxicity, and costs. Innovation: This trial challenges the outdated one-size-fits-all approach by introducing treatment stratification based on CrAg titer levels, a biomarker for cryptococcal burden. Our results will directly address current gaps in treatment for CrAg+ persons, aligning guidelines with evidence-based care to improve survival, potentially reduce unnecessary antifungal exposure, and optimize resource use. Impact: This trial has the potential to redefine global HIV and cryptococcal care by: 1. Resolving uncertainty around ART timing to prevent harmful delays and reduce mortality, 2. Establishing the optimal duration of fluconazole therapy for people with low CrAg titers, 3. Informing and harmonizing WHO, U.S., and national treatment guidelines for cryptococcal prevention. We will generate evidence to maximize survival, streamline ART initiation, and optimize antifungal treatment for people with advanced HIV disease globally. This evidence-based approach will empower policymakers to optimize care for millions of people with advanced HIV disease and reduce AIDS-related deaths.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY HIV-1 establishes life-long infection that requires continual antiretroviral therapy (ART) to suppress virus replication. Although long-acting ART promises to improve treatment adherence, a therapeutic countermeasure for suppressing HIV-1 infection without lifelong treatment is needed. This type of HIV cure strategy is called a functional cure. In preliminary studies, we designed a series of immunogens that elicit serum nAbs against heterologous viruses in macaques. The nAbs target the second variable region (V2) Apex on HIV-1 envelope, with binding orientations similar to known human V2 Apex broadly nAbs (bnAbs). This B cell targeting countermeasure is the main innovation of our study. Furthermore, we developed an integrase-deficient lentiviral vector (IDLV) that delivers the viral gag gene to elicit specific CD8 T cells. Induction of these CD8 T cells suppressed viremia to undetectable levels in macaques. Our conceptual innovation is to combine both successful countermeasures together to potently and durably control viremia. The objective of this study is to sustainably suppress HIV viremia by combining a CD8 T cell countermeasure that controls viremia with a B cell countermeasure that elicits neutralizing antibodies (nAb) that are active against many heterologous viruses. The proposal has three specific aims. First, to determine the immunogenicity of the combination T cell and V2 Apex nAb-inducing countermeasure in ART-suppressed, SHIV-infected macaques by comparing the neutralization breadth of serum and monoclonal Abs, as well as CD8 T cell cytokine production and inhibition of virus-infected cells among a mock-treated group, the countermeasure treated group, and previous groups of uninfected macaques. Second, to demonstrate sustained viral suppression without ART by the administration of the therapeutic countermeasure in chronically SHIV-infected macaques by assessing changes in CD4 T cells and virus nucleic acid over time following ART cessation. Mechanistic studies will be done in macaques to show CD8 T cell and V2 apex nAb contributions to viral suppression. Third, to determine the impact of ART on the frequency of V2 Apex-specific B cells in people living with HIV-1 (PLWH) using a 10X Genomics BEAM-seq sequencing and AI/ML approach to identify V2 Apex B cells in PLWH before and during ART. The impact of this study is that it will define a therapeutic countermeasure that can permanently suppress viremia, taking the first steps toward a functional cure for the nearly 40 million people currently living with HIV-1.

NIAID - National Institute of Allergy and Infectious Diseases

Project summary Herpes simplex virus (HSV) establishes latency in ganglionic neurons of the peripheral nervous system. Latent HSV can later reactivate, causing recurrent disease and possible transmission to new hosts. Current anti-HSV therapy is inadequate, in that it does not eliminate latent HSV, and thus is only suppressive rather than curative. We developed a therapeutic approach based on gene editing using HSV-specific meganucleases. We showed that intravenous (IV) administration of adeno-associated virus (AAV) encoding anti-HSV-1 meganucleases can eliminate up to 97% of latent HSV DNA from dorsal root ganglia in mouse models of latent HSV-1 genital infection. We also demonstrated that this reduction in ganglionic viral load led to a corresponding reduction of viral shedding from treated vs. control mice. This approach offers the potential for a durable means of controlling latent HSV infection and subsequent reactivations, or even achieving a functional cure. In the R21 phase, we propose to extend our work to target HSV-2, and to determine whether IV or localized intrathecal (IT) administration is the optimal route. In the specific aims of the R33 phase we plan to address simultaneously several outstanding issues regarding both HSV biology and the safety and efficacy of in vivo gene therapy that are critical for clinical translation of our work. R21 Phase: Specific Aim 1. Evaluate IT vs. IV delivery of AAV/meganuclease therapy as a means to reduce AAV dose, minimize systemic exposure, and avoid pre-existing/induced anti-AAV immunity. We will evaluate the AAV biodistribution, antiviral efficacy, and dose response after IT vs. IV administration, and the doses at which toxicity occurs. We will also evaluate the ability of IT-delivered AAV to avoid neutralizing antibody present in serum, and whether IT administration will allow re-dosing of AAV. R33 Phase: Specific Aim 2. Compare the natural history of ganglionic HSV load and peripheral viral shedding in latently infected mice after IT or IV meganuclease therapy vs. untreated control animals. We will perform long-term studies of the ganglionic viral load and the frequency and quantity of peripheral shedding in control vs. AAV-meganuclease treated animals. These studies will shed light on the stability of reservoirs, the relationship of ganglionic viral load reductions with the frequency and quantity of viral shedding, and provide new insights into possible HSV re-seeding of ganglionic reservoirs after viral reactivations. R33 Phase: Specific Aim 3. Determine the host genomic consequences of AAV/meganuclease therapy, and compare to the effects after CRISPR/Cas9 exposure. We will perform an unbiased evaluation of genomic disruptions after our meganuclease therapy, and directly compare with CRISPR/Cas9 approaches, using the state-of-the-art techniques for the detection of off-target events, including GUIDE-seq, improved DISCOVER-Seq+, and analyses for the insertion of AAV vector (ITR-Seq) and HSV DNA (hybridization capture coupled with next generation sequencing) into the host genome.

OD - NIH Office of the Director

Project Summary/Abstract Nine NIH-funded investigators with similar but independent super-resolution microscopy needs are requesting funding to acquire an Abberior Mirava 3D STED microscope to enable imaging of molecular topographies in fixed or live tissues and cells at unprecedented resolution at the scale of tens of nanometers with fluorescent probes. This platform will be maintained in the Washington University Center for Cellular Imaging (WUCCI), an institution-wide shared technology resource. There is no instrument like this at WUCCI or anywhere else on campus. One huge advantage of this system is that it works just like a confocal microscope in terms of the field of view, imaging depth, and data acquisition interface. As such, many investigators will be ready to utilize it immediately. Sample preparation is nearly identical to conventional confocal microscopy, except for the use of specific fluorescent probes, and care taken to use mounting or immersion media and cover slips with matching refractive indexes to enable maximum resolution. STED technology breaks the traditional barrier of optical microscopy set by the diffraction-limited point spread function (PSF) by PSF engineering, achieving 40 nm resolution, exceeding the resolution of the already heavily subscribed Nikon NSPARC and Zeiss Airyscan. The major user group comprises nine investigators from 6 departments who will utilize this microscope to enable a wide range of basic and translational research studies. Scientific goals include understanding primary cilia, the role of actin cytoskeleton dynamics in intracellular networks, energy and lipid storage and lipid droplet or to resupply membranes with lipids, mechanobiological mechanisms underlying kidney glomerular filtration, glutamate receptor geography at cochlear synapses, receptor dynamics in pancreatic islet hormone secretion and neuroinflammation biomarkers for biological imaging and chemotherapeutics. Given its location in a busy core facility, we expect this microscope to be impactful to many research programs beyond the initial major user groups. The expertise and institutional support for this instrument are excellent. Dr. Mark Rutherford, Associate Professor of Otolaryngology, used STED microscopy extensively during the historical development of this technology. Dr. Rosa-Molinar and the WUCCI staff have a long-standing track record of training NIH- funded researchers to optimize their use of state-of-the-art microscopy methods. In support of this S10 grant application, the Washington University School of Medicine will commit $176,647 of matching funds for the acquisition of the instrumentation plus an additional $125,000 operational support ($25,000 per year for five years) to ensure the long-term success of this equipment.

NIA - National Institute on Aging

PROJECT SUMMARY ABSTRACT HIV infection results in numerous complications across multiple organ systems, with over 75% of patients with chronic HIV disease showing clinical manifestations, even when on long-term successful combination antiretro- viral therapy (ART). Additional inflammatory sequelae have patients on long-term successful ART therapy who suffer from residual and end organ diseases of HIV infection. We posit that astrocyte dysfunction in key brain regions is central to HIV-associated accelerated aging. Activated astrocytes are associated with increased leu- kocyte transmigration, HIV infection, and the establishment of a highly inflammatory environment, which further aggravates HIV-associated disease, including accelerated aging and associated cognitive decline. Thus, as glia are present in all brain regions, and can be exposed to virus and viral proteins during acute infection, glia will be activated before treatment can be administered. Chronic activation of glia are known to impact the blood-brain barrier and can be an underlying cause of fronto-temporal and vascular dementias. Numerous studies are show- ing that the chronic activation of glia following SIV infection leads to an accelerated aging phenotype, including cognitive decline. Long-term ART may diminish the neurodegeneration observed in chronic SIV infection but have minimal impact on accelerated aging in glial cells observed in multiple brain regions. Due to the protean nature of early HIV infection, it is likely that, even under the best of care, ART is administered only after several weeks of infection. However, ART is administered early after exposure in the case of post- exposure prophylaxis (PEP). To date, there are very few studies examining glial activation during PEP. Before attempting a targeted treatment strategy, it will be necessary to tease out the underlying pathways of activation and determine if it is even possible to prevent the aging from happening in the first place. To this end, we are proposing a group of animals that will begin treatment at the very earliest stage of infection. Dysregulation of glial function and associated accelerated aging, especially in the context of successful ART suppression of SIV infection, represents a significant gap in our knowledge. Therefore, there is a critical need to understand the mechanisms of SIV-induced inflammaging and the influence of very early versus ART administration after viral setpoint, including downstream cognitive function. This multidisciplinary R01 application, which piggy-backs on several NIH-funded projects, seeks to address how long-term successful ART influences the activation of astro- cytes, focusing on mechanisms of inflammaging and neurodegeneration in multiple brain regions.

Seniors Creating Art

Access to Art Expansion- West Seattle is a free weekly art workshops for one-year for the residents living in four Seattle Housing Authority (SHA) Senior Living Buildings in the West Seattle/High Point Neighborhoods. As well as weekly art programming, there will be monthly Intergenerational Creative Nights held at a selected SHA building and a Summer Community-wide ArtWalk taking place in High Point. The purpose of this project is to improve the physical and mental health of participants and provide jobs for artists within the Seattle region.

Shunpike

ACES is a BIPOC-led arts conference that fosters community, showcases talent, and facilitates professional development for BIPOC artists. It features performances, exhibits, workshops, films, presentations, artist talks, and info sessions. The conference will take place on April 2 & 3, 2022, at Langston Hughes Performing Arts Institute, located at 104 17th Ave S Seattle WA.

Shunpike Arts Collective

ACES, Artists of Color Expo & Symposium, is a BIPOC-led, community-curated program produced by Shunpike that uplifts and centers BIPOC artists. Located at The Studio 2+U and other locations in Seattle TBD. ACES provides space for artists of color to tell their stories through various mediums while leaning into the resources from community members provided at the event. In 2026, ACES will mark its 9th year of cultivating visibility, equity, and community through the arts. Building on its history of partnerships and collective leadership, ACES will continue to evolve as a dynamic platform for artists of color, celebrating their impact on Washington’s cultural and creative ecosystem. The events will be free and open to the public. The project will be completed in the summer of 2026.

Shunpike

Shunpike will organize ACES: Artists of Color Expo and Symposium, a POC-centered and led art conference that fosters community, showcases talent, facilitates professional development, and provides resources, will be held on February 28th-29th, 2020 at Seattle Center, 305 Harrison Street.

OD - NIH Office of the Director

Project Summary/Abstract The Simons Electron Microscopy Center (SEMC) is requesting funds to purchase Gatan BioContinuum energy filters to extend the capability of our TFS Titan Krios G2 300-keV cryo- transmission electron microscopes (Krios#1, Krios#2 and Krios#3) for high resolution data collection supporting both single particle and tomography experiments. SEMC is housed at the New York Structural Biology Center, a consortium of nine (9) research institutions in New York State, and is one of the largest cryoEM facilities in the world that provides access to state-of-the-art equipment, including nine (9) 300-keV TFS Krios microscopes and four (4) 200-keV TFS Glacios microscopes with direct detectors, and all other ancillary equipment required to solve structures to the highest possible resolution using cryoEM. A highly qualified technical team provides direct support, guidance, and assistance, ensuring the highest quality structures are resolved quickly and efficiently. The long- term objectives of this application are: 1) to ensure access to state-of-the-art cryoEM instrumentation and expertise in cryoEM technologies for NIH funded researchers, in the region and nation, for the structural analysis of biological macromolecules and their interactions; and 2) to provide training in the most modern techniques of cryoEM approaches for the current and next generation of biomedical researchers. The requested instrumentation is essential to the core purpose of the Center to ensure continued access for NIH funded researchers to the instrumentation required for their research projects. All major and minor users have active research projects that would immediately benefit from the proposed equipment. The impact of this funding will extend beyond the projects of the major and minor users, since the microscopes will also be made available to the broader scientific community. To highlight the past 5 years, the center has provided cryoEM access to 36 states across the nation and directly supported over 750 active researchers. Taken together, this instrumentation will benefit all users of Center by increasing the capability and capacity of these instruments and provide outstanding training opportunities to the next generation of biomedical scientists. SEMC has a proven track record of maintaining various high-end imaging systems, strong institutional support and a large userbase, which guarantees that the instrumentation will be used to its maximum potential for years to come.

OD - NIH Office of the Director

PROJECT SUMMARY This proposal seeks to acquire a RH96 Octet – a next-generation, high-throughput bio-layer interferometer (BLI HTS) for biomolecular interaction studies. BLI HTS is a “96-channel” instrument that allows quantitative measurements of protein-protein and protein-small molecule interactions of up to 96 samples simultaneously. It uses small sample volumes, and the ease of use allows researchers with broad scientific expertise to use the instrument for high-throughput screening of interactors such as proteins, antibodies, and small molecules. There is an urgent unmet need for this instrument, as there is no high-throughput BLI instrument in the entire Midwest region. We have identified 14 NIH-funded researchers whose work and progress is severely limited due to the absence of this instrument. They often travel to out-of-state institutions or use the 2-channel BLI instrument currently available at Northwestern; clearly, neither option is a long term solution. The 2-channel instrument is not amenable to high-throughput data collection and requires large sample volumes, impeding drug discovery and screening efforts. Moreover, the data collection on the 2-channel is tedious even for single protein-protein interaction studies when testing multiple concentrations. The proposed instrument will address a significant gap in the instrumentation available at Northwestern University and will be beneficial not just to the Northwestern community but the entire Midwest area. We propose to add the BLI HTS to the Northwestern High-throughput Analysis Laboratory, which houses several instruments for high-throughput screening and has full-time staff with the technical expertise to manage and operate the instrument. We anticipate that at least 14 research groups from 6 departments across the College of Arts and Sciences, the Feinberg School of Medicine and the McCormik School of Engineering will utilize this equipment. The availability of this state-of-the-art instrument at Northwestern will be particularly important for drug development efforts and will advance a range of studies aimed at creating therapeutic and diagnostic tools for various human diseases, including cancer, metabolic disorders and neurodegeneration.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary/Abstract Dr. Sumit Saurabh, a new tenure-track Assistant Professor of Cell Biology at Chicago State University (CSU), seeks support through the NIH Instrumentation Grant for Resource-Limited Institutions to acquire the first confocal microscope - Evident Scientific FLUOVIEW FV4000 Inverted Confocal Laser Scanning Microscope. CSU is a resource-limited Carnegie-designated Research University committed to STEM education and research training for undergraduate and master’s students. The FLUOVIEW FV4000 is a state-of-the-art confocal microscope that combines high sensitivity, rapid image acquisition, and automated capture with minimal user supervision, making it ideal for both research and training environments. This instrument is widely used at the University of Chicago and Northwestern thus validating imaging capabilities across multiple fields, including neuroscience and cell biology. It supports imaging of fixed and live brain tissues up to 200 µm in depth, and its fast resonance scanner enables the capture of real-time neural activity, further enhancing its functionality. Our current fluorescent microscopes, though well maintained, are old and offer limited functionality, severely restricting our ability to improve the quality of research and training. We propose to install this instrument in the shared imaging facility at CSU, where it will support a broad user base across multiple departments, advancing both research and education. This instrument will be critical for generating preliminary data for grants, particularly for new hires Dr. Saurabh and Dr. Carroll. Dr. Saurabh is establishing his laboratory focused on neurodegenerative disorders and the effects of environmental toxicants (e.g., PFAS). Dr. Carroll, starting in Fall 2025, will study the firing potentials of neurons. Dr. Maselli is investigating neural connectomics, and Dr. Richter from the Department of Chemistry is collaborating with Dr. Saurabh on PFAS detection and removal strategies. Together, these faculty members will engage students in experiential learning through research projects spanning multiple areas of public health significance. In addition to advancing faculty research, the microscope will enhance the quality and content of courses such as Advanced Cell Biology, Capstone, and Independent Study, while expanding STEM engagement through initiatives like the Neuroscience Bootcamp and the CSU–Purdue University Mentoring Program (SLOAN, MSEIP). By providing hands-on experience with cutting-edge technology, it will deepen student engagement, build confidence in experimental techniques, and better prepare them for careers in biomedical research and related fields. Furthermore, its modular design allows for future upgrades, enhances its functionality, and enables the adoption of emerging imaging techniques e.g. expansion microscopy.

NIGMS - National Institute of General Medical Sciences

Project Summary/Abstract This grant application requests funding to acquire an Agilent Seahorse XF Pro Analyzer, a state-of-the-art instrument for real-time assessment of mitochondrial respiration and cellular bioenergetics. The instrument is needed to expand and enhance the biomedical research and education capabilities of the University of Puerto Rico Medical Sciences Campus (UPRMSC). The Seahorse Analyzer will enable high-throughput, sensitive metabolic profiling of cells and isolated mitochondria, supporting multiple NIH- and NSF-funded projects investigating mitochondrial dysfunction in cardiovascular disease, neurodegeneration, and cancer. Three Major users and two Minor Users are listed in the grant application. In addition, an educational component is included in which the new instrument will replace the existing system currently used in an Instrumentation course offered as part of the Department of Physiology Ph.D. program, and will also be incorporated into a future interdepartmental MS program. By replacing an aging XFe24 model and providing improved sensitivity beyond the existing XF96 capacity, the requested instrument will overcome critical limitations in experimental efficiency, reproducibility, and sample throughput, thereby enhancing research productivity and educational activities at UPRMSC.

OD - NIH Office of the Director

Advanced mass spectrometry (MS) technologies unlock exceptional opportunities towards transformative applications and groundbreaking discoveries for life science research. We are requesting funding to purchase the latest Orbitrap Astral mass spectrometer interfaced with a Vanquish Neo ultra-high-performance liquid chromatography system from Thermo Fisher Scientific. This state-of-the-art system will be housed, operated and maintained in the Proteomics and Metabolomics Facility (PMF) at the Cornell University Biotechnology Resource Center (BRC). The BRC will provide administrative support to the PMF team with a proven track-record in managing shared resources for the biomedical and life science research community. Implementation of the instrument in the BRC as a university-wide shared research resource will enable cost-effective and flexible access to this vital technology for a broad range of NIH-funded research. There is a growing demand for proteomics and metabolomics applications at Cornell, as observed by the continuous growth in the number of facility users and processed samples by the facility over the past decade, and evidenced by the recently founded Center for Innovative Proteomics (CIP), which promotes campus-wide collaboration to develop cutting-edge proteomics methodologies for research. The proposed Orbitrap Astral system will replace the aging Orbitrap Fusion instrument, offering new capabilities as no such instrument is available across all Cornell campuses. It will also expand the capacity and capabilities of the facility on the existing instrumentation, which is currently utilized at near full capacity. The need for the increased performance and capacity is particularly critical with respect to applications involving analysis of complex samples with limited sample input (e.g. single-cell proteomics and affinity-enriched samples) for many NIH-funded projects, which require fast scan speed, ultra-high sensitivity and resolution, and highly accurate mass measurements. The requested instrument provides >5 orders of magnitude dynamic range, enabling confident identification of peptides from low abundance proteins and low stoichiometry modifications in complex samples. It will uniquely leverage the PMF’s and CIP’s expertise to support proteomics discovery studies at the single-cell level by developing and implementing high-throughput single-cell and spatial proteomics technologies, enabling Cornell PIs to propose and competitively undertake new research projects that are currently not feasible with our existing instrumentation. The BRC PMF has extensive experience in running LC-MS instruments and providing MS solutions to effectively advance research. The proposed instrument will be readily integrated into the facility’s established proteomics pipelines. Placement of the proposed system in the BRC will enable a large group of NIH-funded investigators to undertake research projects that would not otherwise be economically or technically feasible. This proposal describes 31 projects from 15 NIH-funded investigator groups that will utilize the proposed system. The requested instrument will benefit a wide range of current and future NIH-funded projects and other projects.

Community Dance Program

The Community Dance group will be hosting various " Fair Days" at the Centilia Cultural Center located at El Centro de la Raza 2524 16th Ave South. The Fair days will happen August 9 and September 13. The purpose of this project is to celebrate the rich diversity of the Beacon Hill neighborhood by highlighting various cultural activities and dance that reflect ethnic groups such as Latino, Asian, East African etc. The event is free and open to the public.

NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary Living materials—biohybrids combining both biological and synthetic components—exhibit dynamic responses to environmental stimuli and closely resemble native biological tissues, positioning them for transformative biomedical applications. This proposal introduces the second-generation Active Biointegrated Living Electronics (ABLE) system, designed specifically to manage and treat psoriasis through the integration of living materials and state-of-the-art bioelectronic technologies. The ABLE system consists of biocompatible hydrogel composites enriched with the commensal bacterium Staphylococcus epidermidis, coupled with a flexible, wireless bioelectronic device. This integrated platform continuously monitors critical skin parameters, including pH, temperature, inflammatory biomarkers, and tissue impedance, and delivers precise, adaptive electrical stimulation for effective inflammation management. In Aim 1, we will engineer and thoroughly characterize foundational living bioelectronic components by creating hydrogel matrices that mimic the extracellular matrix, supporting robust bacterial viability and metabolic function. Concurrently, we will develop flexible printed circuit boards (FPCB) equipped with energy-harvesting antennas, microcontrollers, multimodal sensors, and stimulation electrodes. These integrated systems will facilitate seamless bioelectronic interfacing, enabling real-time data acquisition and precise control of biological responses. Aim 2 focuses on systematically mapping and optimizing device parameters through detailed in vitro studies. We will elucidate how electrical modulation influences microbial physiology, including membrane potentials, ion fluxes, metabolic activities, and extracellular vesicle production. These studies will provide critical insights into microbial function and biofilm dynamics, guiding the identification of optimal electrical stimulation parameters necessary for therapeutic applications. Aim 3 will rigorously validate the therapeutic efficacy of the ABLE platform in vivo using a clinically relevant animal model of psoriasis. By combining advanced bioelectronics with commensal bacteria-based hydrogels, we will comprehensively assess therapeutic outcomes through histological analyses, cytokine profiling, transcriptomics, microbiome analysis, and detailed characterization of T-cell subsets. This multifaceted evaluation aims to establish a clear mechanistic understanding of the microbial- electrical interactions and demonstrate the potential clinical relevance of the ABLE platform. Our integrative approach not only offers fundamental insights into bioelectronic modulation of skin microbiota and immune responses but also sets the stage for groundbreaking translational applications, revolutionizing inflammation management and treatment paradigms in personalized medicine. The proposed ABLE system is poised to significantly advance healthcare innovation by enabling precise, minimally invasive, and adaptive therapeutic strategies for chronic inflammatory skin conditions.

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

In Vietnam, adolescent and young men vulnerable to HIV through sexual behaviors are among those most affected by the infection, with an HIV prevalence that quadrupled from 3% in 2011 to 13% in 2020. More than 20% of Vietnamese young men living with HIV had moderate-to-severe depression and anxiety symptoms. These youths experienced extensive stigma related to their HIV status and sexual behaviors. There is a dearth of youth-friendly mental health services in Vietnam where there is less than one psychiatrist per 100,000 people. Project YES+ is an intervention integrating two evidence-based interventions, Project YES! and Self-Help+ to improve mental health, stigma, and HIV outcomes among youth living with HIV in Zambia (5R01TW012411). Youth Engaging for Success (Project YES!) is an HIV clinic-based peer mentoring CDC-designated intervention that successfully decreased HIV self-stigma and increased viral suppression. Self-Help+ is a group-based lay-delivered program endorsed by WHO that effectively prevents the onset of mental disorders and reduces mental health symptoms in different cultures. We propose to adapt Project YES+ for adolescent and young men living with HIV in Vietnam to create To Hieu (I Understand) and to pilot test the adapted intervention. The specific aims are to (1) Adapt Project YES+ to create To Hieu to improve mental health and reduce internalized HIV stigma for adolescent and young men living with HIV in Vietnam and (2) Examine acceptability and feasibility of To Hieu among adolescent and young men living with HIV through a pilot randomized controlled trial. In Aim 1, the adaption will follow the 8-step ADAPT-ITT framework.38 We will conduct in-depth interviews with adolescent and young men living with HIV (N=20) to explore preferences for the core components and formats of To Hieu. We will hold a human-centered design workshop to engage adolescent and young men living with HIV in co-design activities to refine To Hieu. In Aim 2, we will recruit 80 adolescent and young men living with HIV with depression or anxiety symptoms at two HIV clinics in Hanoi, Vietnam and randomize them 1:1 into two arms. The intervention arm will receive To Hieu in 4 months, while the control arm will receive standard of care at the clinics. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework will guide the measurement of the outcomes. We will calculate participation rates of participants (Reach) at baseline. We will assess acceptability through the Client Satisfaction Questionnaire and feasibility through intervention attendance (Adoption) at 4 months. Depression, anxiety symptoms, internalized HIV and sexual stigma, ART adherence and viral suppression of participants will be evaluated at baseline, 4 months and compared between groups (preliminary Effectiveness). We will conduct exit interviews with participants, youth peer mentors and HIV providers (N=30) to explore acceptability, feasibility (Implementation) and sustainability (Maintenance) of To Hieu. This research will build local capacity and develop networks for collaborative research on mental health and stigma among adolescent and young men living with HIV between Vietnam and the US.

NIMH - National Institute of Mental Health

PROJECT SUMMARY This ambitious research project will test the effectiveness and dissemination of a digital intervention to promote home HIV testing and linkage to PrEP (Pre-Exposure Prophylaxis) among Men who have Sex with Men (MSM) in Philadelphia. In alignment with the strategic priorities of the Office of HIV Health in the Philadelphia Department of Public Health (PDPH), the experimental arm will deliver tailored social-media and SMS messages and nudges generated by a local Community Advisory Board (CAB) and Al-driven algorithms. We will randomize MSM participants (N = 1,000) to one of two conditions. The standard of care arm will involve the PhillyKeepOnLoving social marketing campaign that the PDPH is currently implementing and future city campaigns. The primary effectiveness outcome is annual routine HIV testing and PrEP (2 HIV tests at least 4 months apart from one another for HIV-negative participants and PrEP), and secondary effectiveness outcomes are ART uptake and retention, as well as sexual risk behavior. Implementation outcomes include reach, adoption, implementation, and maintenance, and dissemination outcomes include the number of shares and likes of the messages from the campaign. We will also evaluate mediators, including the personal relevance and trustworthiness of the messages, as well as motivation, information, and behavioral skills to seek services. This trial, led by an outstanding team and involving institutions committed to successful HIV prevention, will help to advance the Respond pillar of the Ending the HIV Epidemic (EHE) initiative. Through a novel synergy, the proposed research may transform how future campaigns are conducted to engage participants in HIV prevention leveraging LLMs (Large Language Models) and community engagement.

NINDS - National Institute of Neurological Disorders and Stroke

Spinal cord injury (SCI) affects over 300,000 patients in the US, often leading to severe complications. For example, more than 80% of these patients experience urinary dysfunctions, significantly diminishing their quality of life and sense of dignity. No effective treatment exists for these patients, as SCI frequently results in significant and permanent loss of neurons essential for normal functions. Progenitor cell transplantation is currently the most prevalent approach for replacing lost neurons following SCI. While progenitor cell transplantation has advanced to clinical trials, it presents several risks, including immunoreactions, uncertainty regarding the timeframe for transplantation following injury, and ethical considerations. Tumorigenesis is also a major concern with transplantation of cells derived from induced pluripotent stem cells. As an alternative, this project focuses on adult neurogenesis from resident glial cells in the adult spinal cord. This strategy not only generates neurons immune-compatible with the host but also ameliorates the pathological lesion microenvironment. Excitingly, our preliminary results demonstrate that adult neurogenesis promotes bladder function recovery following contusive SCI. Given that clinically relevant contusion SCI often leads to significant neuronal loss, generating a large number of new neurons may be particularly beneficial. Through recent in vivo screens, we identified a combination of transcription factors capable of rapidly inducing substantial neurogenesis from resident glial cells in the adult spinal cord. In this collaborative project, we will first systematically investigate the molecular and cellular mechanisms underlying induced adult neurogenesis after contusive SCI. Next, we will examine the maturation and synaptic integration of these newly generated neurons. Finally, we will assess their role in restoring bladder function post-SCI. Utilizing state-of-the-art technologies, this study has the potential to introduce a paradigm-shifting therapeutic strategy for treating autonomic dysfunction in SCI patients.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY This application describes the Columbia University Molecular Biophysics and Structural Biology (MBSB) Training Program, a cross-campus PhD training program designed to prepare graduate students for careers at the interface of biology, chemistry, physics, computation, and medicine. The program equips trainees with the theoretical, computational, and experimental skills needed to investigate the molecular mechanisms that govern biological function and disease. Molecular biophysics and structural biology have become central to modern biomedical research, driving advances ranging from fundamental studies of macromolecular structure and function to the development of new therapeutic strategies. As these fields continue to evolve rapidly, there is a growing need for scientists who can integrate quantitative approaches with state-of-the-art experimental technologies. A distinctive strength of the MBSB Training Program is its close integration with the Vagelos Institute for Research in Biomedical Education (VIBRE), which provides administrative support, trainee progress monitoring, and program evaluation. VIBRE supports Individual Development Plans, regular faculty-student reviews, and structured mentoring activities that strengthen trainee development and program effectiveness. Trainees receive advanced instruction in thermodynamics, kinetics, macromolecular structure, and quantitative methods, complemented by professional development activities that enhance scientific communication, leadership, and career readiness. Additional activities, including annual retreats, cross-campus seminars, and focused nanocourses, which help foster collaboration and intellectual exchange among trainees and faculty. The overall goal of the MBSB Training Program is to develop highly skilled biomedical scientists prepared for careers in academia, industry, government, and related scientific professions. By combining Columbia University's extensive research strengths with the resources of VIBRE and the New York Structural Biology Center, the program provides a comprehensive and integrated training environment that prepares trainees to address important challenges in biomedical research and contribute to future advances in human health.

NIMH - National Institute of Mental Health

PROJECT ABSTRACT/SUMMARY HIV-associated hospitalizations remain high and Advanced HIV Disease (AHD) remain a persistent global problem despite widespread availability of antiretroviral therapy (ART). People with HIV (PWH) are more likely to be hospitalized, in the U.S. and globally, and at the time of hospitalization, gaps in the HIV care continuum (retention, adherence to ART, and viral suppression) are more widespread than seen in clinic or population-level data. After the end of a hospitalization (i.e., after discharge), PWH, particularly those with AHD, continue to face adverse events, including mortality and readmission. Unfortunately, poor outcomes during the hospital to home transition of care can occur in a blind spot in the health system as most HIV programs are anchored in outpatient/community settings and are unable to ascertain or intervene on inpatient and post-discharge deaths/disengagement in care among their clients. In this project, we will conduct a randomized clinical trial in Zambia to evaluate a novel intervention package called Advanced HIV Re-engagement in Care (ARC) to improve post-discharge outcomes of AHD. ARC entails a package of evidence-based and theory-informed elements that are delivered by supervised community health workers (CHWs) during hospitalization and in the post-discharge period. In Aim 1, we will evaluate the effect of ARC, compared to standard of care, on post-discharge mortality and other HIV and comorbidity outcomes. In Aim 2, effect mechanisms will be identified to inform future refinements to the intervention package. In Aim 3, we will investigate early implementation factors, and cost and cost effectiveness, that are expected to influence future uptake and sustainability of ARC and other interventions to improve HIV outcomes after discharge. Having U.S. researchers and U.S. universities conduct this project in Zambia provides multiple advantages to the U.S. First, because HIV is 20-50 times more common in Zambia than in the U.S., and outcomes of AHD are often suboptimal, conducting the study in Zambia allows researchers to have statistical power to evaluate effects of ARC on mortality, not just the HIV care cascade. In addition, while being evaluated in Zambia, ARC has potential application in the U.S., where CHW delivered interventions have become increasingly common as they provide cost and implementation advantages. Finally, the study aligns with NIH-supported ‘global health reciprocal innovation’ where partnerships between U.S. and low and middle-income country research teams ensure that the U.S. also benefits from international research. Study leaders are practicing HIV clinicians in the U.S., which positions then to introduce the ARC intervention package in U.S. healthcare settings should it be found effective.

NIMH - National Institute of Mental Health

PROJECT ABSTRACT/SUMMARY HIV-associated hospitalizations remain high and Advanced HIV Disease (AHD) remain a persistent global problem despite widespread availability of antiretroviral therapy (ART). People with HIV (PWH) are more likely to be hospitalized, in the U.S. and globally, and at the time of hospitalization, gaps in the HIV care continuum (retention, adherence to ART, and viral suppression) are more widespread than seen in clinic or population-level data. After the end of a hospitalization (i.e., after discharge), PWH, particularly those with AHD, continue to face adverse events, including mortality and readmission. Unfortunately, poor outcomes during the hospital to home transition of care can occur in a blind spot in the health system as most HIV programs are anchored in outpatient/community settings and are unable to ascertain or intervene on inpatient and post-discharge deaths/disengagement in care among their clients. In this project, we will conduct a randomized clinical trial in Zambia to evaluate a novel intervention package called Advanced HIV Re-engagement in Care (ARC) to improve post-discharge outcomes of AHD. ARC entails a package of evidence-based and theory-informed elements that are delivered by supervised community health workers (CHWs) during hospitalization and in the post-discharge period. In Aim 1, we will evaluate the effect of ARC, compared to standard of care, on post-discharge mortality and other HIV and comorbidity outcomes. In Aim 2, effect mechanisms will be identified to inform future refinements to the intervention package. In Aim 3, we will investigate early implementation factors, and cost and cost effectiveness, that are expected to influence future uptake and sustainability of ARC and other interventions to improve HIV outcomes after discharge. Having U.S. researchers and U.S. universities conduct this project in Zambia provides multiple advantages to the U.S. First, because HIV is 20-50 times more common in Zambia than in the U.S., and outcomes of AHD are often suboptimal, conducting the study in Zambia allows researchers to have statistical power to evaluate effects of ARC on mortality, not just the HIV care cascade. In addition, while being evaluated in Zambia, ARC has potential application in the U.S., where CHW delivered interventions have become increasingly common as they provide cost and implementation advantages. Finally, the study aligns with NIH-supported ‘global health reciprocal innovation’ where partnerships between U.S. and low and middle-income country research teams ensure that the U.S. also benefits from international research. Study leaders are practicing HIV clinicians in the U.S., which positions then to introduce the ARC intervention package in U.S. healthcare settings should it be found effective.

OD - NIH Office of the Director

The Northwest Metabolomics Research Center (NW-MRC) at the University of Washington in Seattle is the largest comprehensive metabolic profiling laboratory in the Pacific Northwest Region. We have developed a robust and reproducible targeted mass spectrometry platform that measures more than 370 aqueous metabolites and is in very high demand. This platform is based on an AB-Sciex API 6500+ mass spectrometer coupled to Shimadzu NexeraXR LC-20 dual liquid chromatography pumps that separate aqueous metabolites using HILIC columns under two identical conditions for both positive and negative ionization. Due to its excellent measurement reproducibility and robustness, this assay has attracted a very high interest from basic and clinical researchers. For example, over the past 3 years, we have analyzed over 14,000 biological samples from more than 60 collaborators on this system. Since we installed this system in 2017, which was funded by a successful S10 grant application, the results have been reported in 37 peer-reviewed articles. At this point, demand for the system exceeds our capacity, and with the strong growth we have experienced, we anticipate longer and longer delays in running samples. In addition, we would like to add reversed phase chromatography to our assay in order to increase metabolite coverage, but we do not have the capacity to increase our overall analysis time given the large number of samples we currently run. Our AB-Sciex 6500+ system is the only one we have that can perform targeted measurements of over 370 aqueous molecules with high sensitivity and good long-term stability. While we have a Sciex 5500 system, it is dedicated to performing targeted lipidomics and oxylipin analysis. Given the high demand for our 6500 system and its targeted aqueous assay, we greatly need the addition of a more versatile and sensitive LC-MS/MS system for advanced targeted metabolomics. To further enhance targeted metabolomics capabilities, we propose to install a state-of-the-art multiplexed UPLC-MS/MS system capable of performing simultaneous separations on four analytical columns followed by highly sensitive targeted MS acquisition. Each column will be independently connected to a 4-port injection auto- sampler, which in turn will allow separations under four different chromatography conditions. The major benefits of this platform will be: (i) much broader coverage of measured metabolites since the higher sensitivity and 4 chromatography columns will allow us to add hundreds of additional metabolites to our targeted assay; (ii) significant enhancement in the throughput capabilities, which in turn will eliminate delays in analysis turnaround time; (iii) additional time available for method development. The proposed system will be available for collaborative research projects at least 75% of the run time, and its extensive utilization will lead to a better understanding of metabolic processes associated with disease development, biomarker discovery, and systems biology research.