University Of Rochester

NSF Awards · FY 2026 · 2026-08

The Center for Matter at Atomic Pressures (CMAP) is an NSF Physics Frontiers Center that explores matter at pressures strong enough to change the nature of atoms themselves. Such conditions dominate the interiors of planets and stars, but only recently could such conditions be explored or exploited on Earth. To date, thousands of planets have been discovered, providing numerous possible platforms for life throughout the universe. To understand the origin, evolution, and nature of these planets, one has to understand properties of high energy density matter at and beyond atomic pressures. CMAP has pioneered the use of powerful lasers and pulsed-power facilities, facilities developed for exploring fusion, as well as x-ray beam facilities, to recreate and characterize matter under the extreme conditions of the deep interiors of planets and stars. CMAP brings together a diverse team, spanning disciplines from plasma physics, condensed matter, atomic physics, astrophysics and planetary science, to address gaps that limit our understanding of most of the atomic and chemical constituents of the Universe. CMAP aims to develop a new discipline of physics at extreme pressures, combined with the most advanced laboratory and theoretical capabilities available, to train tomorrow’s science leaders. CMAP’s research, education and outreach programs aim to bring a new understanding of the universe to the public and inspire and engage a new generation of scientists of all ages and backgrounds. The NSF Physics Frontiers Center for Matter at Atomic Pressures exploits a new generation of laboratory capabilities -- kilo-joule to Mega-Joule lasers, tens of Mega-Amp pulsed power, and advanced x-ray facilities -- first-principles theory -- artificial intelligence algorithms to explore the properties of matter under the high energy density conditions that exist in the deep interiors of planets and stars. CMAP will explore the nature and astrophysical implications of matter extending to and beyond the atomic unit of pressure, the pressure determined by the Hartree energy and Bohr radius, conditions that disrupt the electronic-shell structure of atoms, engage core electrons in bonding, and unlock a new quantum regime in which electron and ion quantum correlations can grow to macroscopic scales at high temperatures. Such extreme conditions are also implicit to intertial fusion experiments in effort to control and harness fusion energy, so CMAP also provides the foundational understanding for today’s and tomorrow’s fusion strategies. Atomic pressure is a fundamental physical unit that remains unexplored. CMAP will bring together experts in plasma, atomic, and condensed matter physics leading to new discoveries and breakthroughs in physics. To do so, the CMAP team has a particular focus on excellence and on convergence of research and a broad range of education efforts. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2026 · 2026-07

In this CAREER project, Professor Agnes Thorarinsdottir of the Department of Chemistry at the University of Rochester is developing transition metal coordination compounds with highly temperature-sensitive electrochemical properties. Thermoelectric devices are important for the advanced manufacturing of instruments for energy generation, cooling and heating, wearable electronics, and healthcare. The fundamental knowledge gained from this project will enable a transformative approach to the design of next-generation thermoelectric devices that can convert waste heat into electricity for immediate or later use and employ electricity for cooling applications, as well as electrochemical temperature sensors that can operate continuously in remote locations. The goal of this research is to exploit the well-defined structures and synthetic modularity of transition metal complexes to elucidate design principles for molecular compounds that display electrochemical properties that are highly sensitive to temperature changes. Beyond the technical contributions that lie at the interface of inorganic chemistry, materials chemistry, and electrochemistry, the project integrates an educational plan that seeks to educate students and the general public on topics in energy and electrochemistry pertinent to everyday activities and engage students across multiple training stages in hands-on scientific research. These educational efforts will be accomplished through a combination of in-person and online educational activities, including videos, forums, games, workshops, and research opportunities for students, thereby reaching a broad audience of scientists, non-scientists, and students at all levels. Gaining fundamental understanding of factors that govern the temperature sensitivity of the electrochemical potential of molecular compounds is critical to enable the realization of next-generation thermoelectric devices and electrochemical temperature sensors. This project will harness coordination chemistry to rationally design transition metal complexes with highly temperature-sensitive electrochemical potentials, with the goal of understanding how to maximize entropic changes during electron-transfer reactions through synthetic design. This work will establish the impact of chemical structure and physical properties on the temperature dependence of electrochemical behavior. Specifically, the influence of the type, coordination number, and coordination environment of the redox-active transition metal center, electronic metal–metal and metal–ligand interactions, and overall charge of the complex on the temperature sensitivity of electrochemical potential will be investigated. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-06

This IRSDA K-award will provide me with mentored research and career development training to build expertise in translating global health findings to benefit U.S. populations and underserved healthcare systems. I will learn to validate neurocognitive impairment (NI) screening tools and analyze inflammatory biomarkers that predict NI in meningitis patients with or without HIV in rural, northern Uganda, an area of high meningitis burden within Africa’s meningitis belt. Meningitis affects over 2.5 million people globally each year, and causes significant disability, with 20-32% of survivors experiencing long-term morbidity and 14-38% developing prolonged NI, yet data on NI burden in meningitis patients remain scarce. Despite evidence that inflammation in central nervous system infections is associated with NI, limited information is available about the biomarkers involved in NI development. This study seeks to fill the gaps in our understanding of the burden and pathogenesis of NI by identifying which brain injury biomarkers are expressed in patients with NI and can be used to predict NI development among meningitis patients with and without HIV. This study will be embedded within my primary mentor’s existing Meningitis Diagnosis and Treatment Program (MEN-DTP) at Lira Regional Referral Hospital in northern Uganda, which focuses on understanding mortality due to various meningitis etiologies in an area with high meningitis and HIV burden. Aim 1 is to validate neurocognitive assessment tools to determine the burden of NI among meningitis patients living with and without HIV, including follow-up for two years to assess long- and short-term NI burden. Aim 2 is to identify clinical parameters and immune/inflammatory biomarkers predictive of NI. Serum and CSF samples will be collected from meningitis patients who do or do not develop NI to identify biomarkers specifically associated with NI. Investigating immunologic and brain injury biomarkers will provide insights into inflammatory pathways activated by meningitis that lead to NI in those with or without HIV. Our neurocognitive assessments will help determine the true burden of NI and enable timely diagnoses and interventions. Our findings from this high-burden setting will inform neurocognitive assessment and early intervention strategies to improve care for meningitis patients that could be implemented in underserved U.S. populations and globally.

NSF Awards · FY 2026 · 2026-06

With support from the Chemical Synthesis Program in the Division of Chemistry, Laura Anderson of the University of Illinois at Chicago (UIC) is developing new reactions to rapidly assemble novel molecular scaffolds through unconventional strategies that use the reactivity of two underdeveloped reactive intermediates, N-alkenylnitrones and N,O-dialkenylhydroxylamines. Dr. Anderson and her team are determining modular ways to generate these chemical linchpins from accessible reagents and to control the selectivity of the rearrangement activity to form more stable compounds with defined three-dimensional structures. This work is targeting improved synthetic efficiency to expand chemical space. Improvements in this area are expected to contribute to the discovery, accessibility, and study of biologically active molecules, as well as the development of new materials. These activities will also provide training for a diverse group of graduate and undergraduate students. Dr. Anderson plans to publicize the benefits of undergraduate research opportunities by organizing undergraduate research presentations in introductory organic chemistry courses and promoting inclusivity by leading a committee to establish cohort-building opportunities for aspiring undergraduate chemists at UIC, which is a minority serving institution. Improving efficiency to enable rapid access to sought after molecular targets and expanding chemical space to include new molecular architectures remain two critical needs in organic synthesis to support demands for new compounds with novel properties. Professor Anderson’s group is focused on developing the unique reactivity of N-alkenylnitrones and N,O-dialkenylhydroxylamines to address synthetic challenges and improve fundamental understanding of the reactivity of these versatile and unusual synthons. Specifically, Dr. Anderson and her team are developing: (i) torquoselective reactions for the asymmetric synthesis of azetidine nitrones; (ii) diastereoselective functionalizations of azetidine nitrones, (iii) substituent effects to control the rearrangements of N-alkenylisoxazolines, and (iv) metal-catalyzed alkyne addition methods for the generation N,O-dialkenylhydroxylamines and their asymmetric rearrangement to 1,4-dicarbonyl compounds. The architecturally diverse products of these studies are being included in medicinal and agrichemical libraries for activity testing. The foundational reactivity being investigated are expected to expand the synthetic toolbox of pericyclic and cascade reactions. These activities will also train graduate and undergraduate students in chemical experimentation and design, as well as be used to engage students in the types of opportunities available in chemistry-related career paths. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-06

PROJECT SUMMARY Bone implant-associated infections remain a major challenge in orthopaedic surgery. Staphylococcus aureus, a significant human pathogen, continues to be the leading cause of persistent bone implant-associated infections. Reinfections rates following orthopaedic surgery have remained constant over the last half-century, which has led to the orthopaedic paradigm that S. aureus infection of bone is broadly incurable. However, it is also known that some patients can resolve acute infections and live a full life with asymptomatic S. aureus bone infections. Unfortunately, clinical diagnostics to guide conservative vs. aggressive surgical treatment of these patients are anecdotal, time-based, and not evidence-based. To the end of developing functional clinical biomarkers, we performed host studies in a humanized mouse model, and found that implant-associated osteomyelitis is characterized by increases in bacterial load and bone osteolysis, and large numbers of proliferating human T cells adjacent to purulent abscesses in the bone marrow. Subsequent multi-omic investigation of human T cells in an improved humanized NSG-SGM3 BLT mouse model revealed remarkable human T cell heterogeneity in gene expression and numbers, upregulation of immune checkpoint proteins (TIM- 3 and LAG3) in Th1 and Th17 cells, and diminished cytokine production in CD4+ T cells 2-weeks post-infection. Surprisingly, these immune checkpoint proteins were upregulated in the serum of patients with S. aureus osteomyelitis, and a preliminary multiparametric nomogram revealed that TIM-3, LAG3, and PD-1 levels are predictive of adverse outcomes (arthrodesis, reinfection, amputation, and septic death) in these patients. Thus, our results indicate that functional impairment of T cells could occur in chronic osteomyelitis. To unravel this and derive a prognostic to guild life-altering surgical decisions, we hypothesize that persistent S. aureus infections cause impairment of CD4+ Th1/Th17 cells in the form of immune checkpoint expression and functional exhaustion at the bone infection site, and can be leveraged as a functional biomarker of S. aureus implant- associated osteomyelitis disease outcome. To test this, we will characterize the kinetics of human Th1/Th17 dysfunction during S. aureus bone infections in humanized BLT mice as the disease progresses from the acute to the chronic phase (Aim 1), and elucidate the mechanistic link between CD4 T cell exhaustion and disease progression, which could potentially be overcome by immune checkpoint blockade adjuvant therapy (Aim 2). Finally, we will assess if a blood-based multiparametric nomogram examining checkpoint proteins and associated cytokines is predictive of disease outcomes in patients with clinically defined S. aureus “acute” and “chronic” implant-associated bone infections (Aim 3). Collectively, these studies will provide novel insights into mechanisms of musculoskeletal injuries such as S. aureus osteomyelitis and will derive an evidence-based functional biomarker of human disease outcomes that could guide life-changing clinical decisions in orthopaedic surgery.

NSF Awards · FY 2026 · 2026-06

This S-STEM Net project will contribute to the national need for well-educated scientists, mathematicians, engineers, and technicians by supporting the retention and graduation of high-achieving, low-income students with demonstrated financial need. The Advancing Understanding & Resilience Actions (AURA) Research Hub will investigate how whole-student, holistic project interventions for S-STEM computer science and engineering scholars impact their resilience. The AURA Hub will examine factors that facilitate or impede scholars’ development of resilience. The AURA Hub will also strengthen the broader network of S-STEM project teams through the creation of interdisciplinary Professional Learning Communities and Discipline-Based Education Research Fellowships. The Research Fellows will conduct educational research focused on growth and fixed mindset, self-determination, and professional identity development in the context of S-STEM engineering and computer science projects. The overall goal of this project is to increase STEM degree completion of low-income, high-achieving undergraduates with demonstrated financial need. The AURA Research Hub aims to generate new knowledge about programmatic interventions and conditions that foster resilience among academically talented, low-income students supported by S-STEM projects. The proposed mixed-methods, multi-institution AURA Hub investigates the interaction of individual, community and environment for college students’ development of resilience in computer science- and engineering-focused S-STEM projects. The AURA Hub examines institutional issues and structures that support or hinder ‘resilience development’ for students, focusing on STEM professional identity formation, persistence in the major, academic success, and STEM workforce entry. S-STEM project designs/interventions and institutional supports are investigated using a combination of mindset theory, self-determination theory and theories of professional identity development in concert with college student developmental theory, yielding a novel AURA Framework for advancing resilience that bridges the environment, the community and the individual through holistic interventions in STEM higher education. Dissemination activities will utilize a research-to-practice approach, accelerating the dissemination of new knowledge and tools as public goods, advancing the understandings of supporting resilience and success for computer science and engineering students and addressing the urgent need for developing a strong national workforce in these domains. This project is funded by NSF’s Scholarships in Science, Technology, Engineering, and Mathematics program, which seeks to increase the number of low-income academically talented students with demonstrated financial need who earn degrees in STEM fields. It also aims to improve the education of future STEM workers, and to generate knowledge about academic success, retention, transfer, graduation, and academic/career pathways of low-income students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-05

We request support for the acquisition of the Bruker SkyScan 1276 CMOS Edition High-Resolution In Vivo MicroCT System to serve a large, diverse, and NIH-funded research community at the University of Rochester School of Medicine and Dentistry (URSMD). The instrument will be housed in the Biomechanics and Multimodal Tissue Imaging (BMTI) Core of the Center for Musculoskeletal Research (CMSR), which supports over 60 NIH-funded investigators across 12 departments. The SkyScan 1276 will replace an obsolete 21-year- old scanner and expand our capabilities in longitudinal and cross-sectional imaging of murine and larger animal models. The SkyScan 1276 provides true spatial resolution down to 6 µm, with voxel sizes as low as 2.8 µm, and enables high-throughput imaging with helical scanning, slip-ring gantry, and physiological monitoring. It supports a large field of view (75 mm × 310 mm), allowing full-body imaging of small animals and complex 3D constructs in a single scan. The SkyScan’s robust software suite will ensure reproducible, high- quality data analysis in alignment with ASBMR standards. These capabilities are vital for a broad range of applications, including skeletal biology, tumor progression, vascular imaging, implant osseointegration, and regenerative medicine. This shared instrument will be accessible to NIH-funded investigators in the CMSR, Wilmot Cancer Institute, Aab Cardiovascular Research Institute, Department of Oral and Craniofacial Sciences, Allergy/Immunology and Rheumatology unit, and Environmental Health Sciences Center. Collectively, these groups have ongoing projects funded by P30, P50, R01, and U grants that require the SkyScan’s resolution, throughput, and physiological imaging features. Major users collectively project over 1,600 annual usage hours, representing 83% of estimated available time. The system will be operated by a dedicated and experienced technician and overseen by a seasoned core director and a previous S10 recipient. The core will be supervised by an internal Advisory Oversight Committee comprised of intuitional leaders and experts. Training plans include on-site and vendor-led education, annual workshops, and on-demand hands-on sessions. The acquisition of the SkyScan 1276 will transform imaging capabilities at URSMD by enabling precise, minimally invasive, and translational research. This investment will significantly enhance productivity, innovation, and impact across multiple NIH-funded programs and catalyze new discoveries at the interface of basic science and clinical translation.

NIH Research Projects · FY 2026 · 2026-05

Olfaction plays a critical role in animal survival, enabling the detection of food sources, dangers, and potential mates. The remarkable plasticity of the olfactory system allows for the modification of responses to cues based on various internal states. However, the precise mechanisms underlying olfactory plasticity, particularly at the level of peripheral sensory neuronal activity, remain poorly understood. In this research proposal, we aim to investigate the role of long non-coding (lnc)RNA-micropeptide systems in the functions of olfactory receptor neurons. LncRNAs are transcripts longer than 500 nucleotides that lack an open reading frame longer than 100 codons. Various lncRNAs have been implicated in neural development, function, and diseases. While lncRNAs are traditionally considered non-coding, certain lncRNAs encode micropeptides, which can contribute to diverse biological processes. Despite their potential importance, the functions of lncRNA-micropeptide systems in the nervous system, particularly in olfaction, remain largely unexplored. To address this knowledge gap, we will capitalize on the well-characterized olfactory system of the fruit fly. This system offers several advantages, including numerical simplicity, well-defined neurons that drive complex behaviors, and the availability of powerful genetic tools. We recently generated a comprehensive survey of lncRNAs in the main fly olfactory organ that demonstrated the diversity and expression patterns of lncRNAs in the olfactory system and set the stage for investigating their functional roles and their impact on sensory behaviors. Through a multidisciplinary approach that includes genetic, electrophysiological, behavioral, and molecular assays, we will test the hypothesis that lncRNA-micropeptide systems contribute to olfactory function. Our initial focus will be on the lncRNA AnRUS (Antennal RNA Upregulated by Starvation) and its micropeptide. We have recently shown AnRUS is modulated by nutrient availability and food odor, and acts in the modulation of the response of a pheromone-sensing neuron to odors. Here, we will investigate the mechanism by which AnRUS modulates neuronal responses and how its expression is regulated by nutrients and food odors. Finally, we will expand our investigation by characterizing the micropeptidome of the antenna, a first step toward exploring the regulatory roles of these micropeptides in olfaction.

NIH Research Projects · FY 2026 · 2026-05

Project Summary A fundamental challenge in neuroscience is to understand the functional architecture of brain circuits. Selective targeting of neural circuits has been possible in transgenic mouse Cre-lines, but in non-human primates (NHPs) comparable methods have been limited. While viral approaches in NHPs using AAV’s to deliver opsins reliably produce expression in cortex, targeting specific cell classes is challenging and when applied in awake animals can produce effects that are difficult to interpret or weak. Our preliminary data highlight that there is a unique opportunity in NHP models to achieve greater specificity in opto-genetic manipulations by targeting projection pathways. Specifically, highly efficient retrograde viral vectors have been recently developed to target specific populations of neurons based on their projection patterns. One way to label neurons is to use a viral vector that can travel retrogradely from axon terminals in the target area back to cell bodies in the source area. However, retrograde vectors, such as AAV2-retro, will also directly infect cell bodies in the target area resulting in the labeling of reciprocal projection pathway. This represents a major challenge as nearly all connection pathways in the primate cortex are reciprocally connected. To solve this problem, a two-vector Cre-intersectional labeling method can be adopted, which we have previously established in rodent studies and in our preliminary data have applied in a non-human primate model, the marmoset monkey. The goal of the current proposal is to test and validate this intersectional viral method for inactivating a specific pathway (V1 to MT) in the visual cortex of awake marmosets. Specifically, in Aim 1, we will develop a Cre-intersectional strategy that targets a projection pathway and apply it to the pathway from visual area V1 to MT. We will optogenetically inactivate this pathway, confirm the suppression of projection neurons in V1, and evaluate its impact on downstream visual processing in area MT. In Aim 2, we will target the same projection pathway but instead use a chemogenetic approach with hM4Di, which will suppress projection neuron activity and synaptic transmission through a non- invasive systemic administration of the DCZ ligand. Successful implementation of these methods will provide versatile tools for investigating the functional role of projection pathways between primate cortical or sub-cortical areas, while also enabling non-invasive modulation through DCZ administration. This approach could ultimately contribute towards studies in other NHP models and human gene therapies.

NIH Research Projects · FY 2026 · 2026-05

Abstract My goal is to head an independent research program studying dopaminergic system dysfunction in neurodevelopmental disorders. I have extensive in vivo two-photon microscopy, neural circuit dissection, microglial physiology, and behavioral assay experience. Under my proposed training plan, I will work closely with my co-mentors, Drs. Kuan Wang, Zhigang He, Yi Zuo, and Julie Fudge to broaden and strengthen my research expertise to prepare for full research independence. Dr. Wang is an expert in the developmental plasticity and function of dopaminergic projections to the frontal cortex and in vivo imaging. Dr. He is an expert in sequencing and bioinformatic analyses of transcriptomic changes in microglia in response to CNS milieu disruption. Dr. Zuo is an expert on behavioral assays and circuit plasticity. Dr. Fudge is an expert in the dopaminergic system and psychiatric conditions. Collectively, my mentorship team and experimental plans will provide me with the technical skills and conceptual expertise to become an independent researcher in the fields of dopaminergic development and neuroimmune interactions. The Del Monte Institute of Neuroscience will provide a rich and collaborative training environment with an extensive network of investigators working on neurodevelopmental disorders within the URMC UR-IDDRC. In the Wang Lab, I have explored the mechanisms which drive mesocortical plasticity. Previous published work in the Wang lab established that the mesocortical dopaminergic projections from the ventral tegmental area (VTA) to the frontal cortex undergo activity dependent axonal bouton formation in response to VTA stimulation in adolescents but not adults. However, dopamine receptor 2 (D2R) inhibition paired with stimulation reopens adult plasticity. Interestingly, chemogenetic stimulation of dopaminergic VTA projections during adolescence ameliorates circuit and behavioral deficits in mice with genetic mutations disrupting mesocortical circuit function. My postdoctoral work shows that activity-dependent changes in the adolescent mesocortical circuit increase microglial surveillance of the parenchyma and microglial contacts with axonal boutons and that DR manipulation disrupts these interactions. My immediate goals are to understand the signals which regulate mesocortical dopaminergic plasticity, and to evaluate the therapeutic potential of reopening plasticity after developmental insult. (Aim 1) I will evaluate if microglia are necessary for the reopening of mesocortical plasticity in adult animals. (Aim 2) I will determine if reopening plasticity in adult mice with circuit disruptions from juvenile Δ-9-tetrahydrocannabinol exposure is effective at rescuing both dopaminergic hypofrontality and behavioral deficits. (Aim 3) I will use single-cell sequencing to identify changes in dopaminergic receptor signaling pathways between adolescent and adult animals which close the window of mesocortical plasticity. These experiments will provide a mechanistic understanding of mesocortical plasticity regulation and they will evaluate the therapeutic potential of reopening plasticity in the adult mesocortical circuit.

NSF Awards · FY 2026 · 2026-05

Many factories in the United States use materials called catalysts to speed up chemical reactions to make fuels, plastics, and other everyday products. A major cost in these manufacturing processes is managing heat inside chemical reactors. Some reactions require heat to occur, but others release heat. The heat that is produced is often wasted instead of being reused. This project will study how heat moves inside chemical reactors so that heat produced by one reaction can be used to power another reaction, making the process more efficient and lowering costs. The project will use special nanoparticles to develop better ways to measure temperature inside reactors, which can vary greatly in large systems filled with catalysts. The project will also help train students in catalysis and energy science and will include a hands-on activity that teaches high school students how heat-producing and heat-absorbing reactions can work together. This project will establish a mechanistic understanding and transferable design principles for thermally coupling tandem catalytic reactions to reduce external heating requirements. To investigate thermal coupling at the micro- and nanoscale, the project will study the exothermic reaction of CO methanation as a localized heat source to drive the endothermic reverse water–gas shift (RWGS) reaction for CO₂ conversion to CO. The research will have three aims: (1) identifying catalysts that selectively promote RWGS and CO methanation on distinct active sites; (2) elucidating the mechanistic linkages that govern their thermal coupling; and (3) tuning reaction parameters, including catalyst intimacy, bed composition, and reactant partial pressures, to precisely control heat flow while minimizing undesired byproducts. A key innovation is the use of in situ microthermometry based on photoluminescent upconverting nanoparticles (UCNPs), which enable spatially resolved measurements of local thermal gradients within the catalyst bed and quantification of useful work under heat-transfer limitations. These temperature measurements will be integrated with kinetic studies and thermodynamic analysis using de Donder relations to directly correlate local temperature gradients with reaction rates. Together, these approaches will identify catalyst design heuristics and operating conditions that enable efficient thermal coupling while preventing thermal runaway and parasitic side reactions. The efficiency of thermal coupling will be quantified by comparing heater duty at equivalent conversions. Overall, the project will provide broadly applicable insights into thermal catalysis and inform the rational design of tandem catalysts and dual-functional materials that integrate coupled exothermic and endothermic reactions. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-05

Abstract Rheumatoid Arthritis (RA) is a prevalent autoimmune inflammatory disorder that arises through dysregulation of multiple mucosal endotypes via an array of pathways. Thus, effective treatment requires tailored therapies that target inflammation and adjuvants to ameliorate common physiologic maladies. To this end and based on our discoveries, we generated a transgenic mouse (Efhd1-CreERT2) and identified peri-popliteal lymphatic vessel (PLV) telocyte networks elaborated with mast cells, and synoviocytes phenotypic of telocytes. Of particular relevance is that telocytes regulate smooth muscle contractions through mast cell interactions, telocytes are greatly diminished in RA synovium, and their numbers increase following exercise. Based on the findings, we hypothesize that: 1) contiguous telocyte networks elaborated with mast cells extend from the synovium to their joint-draining collecting lymphatic vessels (cLV); 2) these telocyte networks fragment during chronic inflammatory arthritis; and 3) exercise preserves the telocyte network within the synovial lymphatic system (SLS). We also hypothesize that exercise maintains a stable synovial telocyte network, which results in improved lymphatic function and decreased arthritis-associated inflammation. To test these hypotheses, we propose two Specific Aims. In Aim 1 we will perform whole-mount immunofluorescent microscopy (WMIFM) and light-sheet microscopy (LSM) to formally examine the existence of contiguous mast cell elaborated telocyte networks adjacent to lymphatic capillaries in the synovium that extend to joint-draining cLV. We will also use these methods to examine telocyte network fragmentation in mice with lymphatic defects and advanced inflammatory arthritis. In Aim 2 we will investigate the effects of exercise on telocytes within the SLS in WT mice and its efficacy in preventing telocyte loss and lymphatic dysfunction in mice with inflammatory- erosive arthritis. Currently the mechanisms responsible for lymphatic dysfunction in RA are unknown, and there are no FDA-approved drugs that alter lymphatic function. Thus, it has been argued that addressing this therapeutic approach requires a deep characterization of lymphatic biology that is now a high priority area of research for the NIH. Thus, we developed a novel transgenic mouse for SLS telocyte genetic gain and loss of function studies, and a unifying hypothesis of SLS telocyte function, which begs testing in a R01 research program. To this end, we propose high risk-high-reward critical proof of concept studies that will provide sufficient scientific rigor of prior research to support an R01 application and provide a quantum leap in the field both in terms of understanding RA progression and the benefits of exercise.

NSF Awards · FY 2026 · 2026-05

Modern technologies depend on understanding how atoms are arranged inside materials. This atomic arrangement determines how materials conduct electricity, withstand extreme environments, store energy, and perform in applications ranging from microelectronics to national defense systems. X-ray diffraction (XRD) and related scattering techniques are powerful tools for revealing atomic structure, yet analyzing XRD data is a complex task, especially since it is usually large in volume. Although thousands of diffraction patterns are generated every year in laboratories and national facilities, the results remain scattered across publications or stored locally without standardized formats, limiting its reuse and slowing scientific progress. There is no public database of experimental powder diffraction data. This project addresses this need. This project will develop DiffAI, an open, community driven platform that will host public experimental powder diffraction data, associated metadata, and provide artificial intelligence (AI) tools for automated analysis. These will enable more accurate structure determination of materials with complicated atomic arrangements, such as quantum materials that may underlie future quantum information technology. By making high-quality diffraction data findable, accessible, and reusable, DiffAI will accelerate and lower barriers for materials discovery. By democratizing access to experimental data and machine learning models, DiffAI will enable efficient analysis of diffraction data and foster collaboration within the global research community. Through open-access tools, student training, and community workshops, DiffAI aims to establish a global standard for sharing and analyzing diffraction data, ultimately driving progress in materials characterization and discovery. This project advances the foundations of scientific cyberinfrastructure in three key ways: 1) A novel, extensible data architecture for experimental diffraction that will combine metadata schemas, JavaScript Object Notation (JSON) based data records, and a public data repository for experimental powder diffraction patterns that supports scalable, persistent storage of heterogeneous diffraction datasets. Persistent Digital Object Identifiers (DOIs), curated releases, and open APIs will facilitate reproducible workflows and long-term sustainability. 2) Automated agentic large language model (LLM) workflows for large-scale data extraction and digitization that identify relevant literature, detect and classify XRD figures, extract labels, and digitize plots into machine-readable formats. The team also plan to develop software tools for more automated data and metadata capture from laboratory instruments and synchrotron X-ray and neutron diffractometers at national laboratories, thereby creating a generalizable blueprint for automated experimental data recovery, an emerging need across multiple scientific domains. 3) Building on prior NSF work, DiffAI will implement domain-adapted AI models integrated into cyberinfrastructure that bridge synthetic training sets with real experimental data for automated XRD data and metadata validation tasks. These will enable more accurate structure determination for complex martials, such as quantum materials. Collectively, these advances will provide a scalable, community-driven cyberinfrastructure element that enables modern, AI-ready diffraction workflows. This award by the Office of Advanced Cyberinfrastructure is jointly supported by the Materials Research Section within the Directorate for Mathematical and Physical Sciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-05

ABSTRACT Bacterial keratitis (BK) (corneal infection) is an aggressive disease, responsible for over 2 million cases of blindness annually. Healthcare concern is further exacerbated due to rising antibiotic resistance. Indeed, the 2023 US outbreak of extensively drug-resistant Pseudomonas aeruginosa from contaminated artificial tears was a stark reminder of the devastating consequences of drug-resistant corneal infections; out of 81 reported keratitis cases, 14 patients suffered permanent vision loss, 4 resulted in loss of the eye, and 4 patients died. Unfortunately, most large pharmaceutical companies have abandoned their antimicrobial drug discovery efforts in lieu of pursuing more lucrative, long-term medications. Moreover, the few entities developing antimicrobials are focused on systemic applications as opposed to alternative, ophthalmic formulations. As such there is a void in the ophthalmic antimicrobial pipeline, with no new classes of antimicrobials to market in nearly 15 years. To answer the critical need for new BK therapeutics, the central goal of this proposal is to advance the development of a novel, topical, ophthalmic antibiotic combination, polymyxin B/trimethoprim (PT) + rifampin. Through extensive screening of thousands of FDA-approved drug combinations we have identified PT + rifampin as a powerful, synergistic, broad-spectrum drug combination superior to currently available therapeutics. PT + rifampin displays rapid bacterial killing, potent anti-biofilm activity, and the ability to completely eradicate Staphylococcus aureus and P. aeruginosa infections in a murine model of keratitis, two of the most common causes of BK. Importantly, this drug combination has also been shown to completely eradicate contemporary, multi-drug resistant ocular clinical isolates. Of note, an ophthalmic formulation of polymyxin B/trimethoprim was approved by the FDA in 1988 for the treatment of conjunctivitis and rifampin is an FDA-approved systemic antibiotic that has been used for over 40 years in the treatment of tuberculosis. As such, all three components have decades-long established safety and efficacy in humans. Importantly, we have already achieved the key milestone of a pre-IND meeting with the FDA, during which a clear road map for further studies was established. Given the promise of PT + rifampin as a novel treatment for BK, we propose to pursue advance formulations with corresponding safety and efficacy studies during the R61 phase. Next, we propose to transition to the R33 phase to conduct IND-enabling studies in toxicology, pharmacokinetics, and define appropriate chemistry, manufacturing and controls (CMC). The development of new therapies for BK is well aligned to the NEI’s goals of supporting research to reduce visual impairment and the development of sight-saving treatments. We have compiled the necessary multi-disciplinary team of experts to support formulation development, perform necessary efficacy and safety studies, and guide regulatory and intellectual property strategies. As such this proposal is well poised for success to bring this exciting new technology from bench to bedside to treat this blinding disease.

NIH Research Projects · FY 2026 · 2026-05

Project Summary Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disorder caused by an expanded CTG repeat tract in the DMPK gene, leading to RNA toxicity and widespread tissue dysfunction. Germline and somatic repeat instability are key contributors to disease onset and progression, yet the molecular mechanisms driving these processes remain poorly understood. To investigate drivers of germline and somatic instability, this project leverages a novel CRISPR-Cas9 knock-in allelic series of mice (Dmpk-KI) which contain 400-5000 CTG repeats in the endogenous mouse locus. These mice faithfully recapitulate human DM1 genetics and demonstrate many features consistent with DM1 symptoms in human patients. Leveraging modern-day long-read sequencing (LRS) technologies, we can systematically investigate factors influencing repeat instability. Specific Aim 1 will determine how parental sex and age impact germline instability, and also look at methylation signatures around the CTG repeat. Each of these focus areas has implications for congenital DM1, the most severe form of the disease. Specific Aim 2 will evaluate somatic expansion across multiple tissues, with a focus on R-loop formation as a potential driver of instability in post-mitotic cells. All work will be conducted in a highly collaborative environment, under the primary mentorship of Dr. Charles Thornton, a renowned expert in the field with over 30 years of working on DM1. By integrating cutting-edge sequencing and molecular biology techniques, this work will provide critical insights into mechanisms of DM1 and inform therapeutic strategies aimed at stabilizing expanded repeats. In parallel, this project serves as a career development platform, fostering expertise in animal models of neuromuscular disease, LRS, molecular genetics, and bioinformatics, all of which are critical skill gaps. This will be accomplished through formal and informal coursework at the University of Rochester, attending targeted symposia focused on LRS, and close relationships with my mentors and advisors. The proposed research and training will prepare me to lead larger studies on DM1 instability, and independently investigate mechanisms and treatments for other pediatric neuromuscular and repeat expansion disorders.

NIH Research Projects · FY 2026 · 2026-04

ABSTRACT The Measuring Micro- and Nanoplastics in Environmental Samples Workshop (“the Workshop”) will be held as part of a Great Lakes Microplastic and Health Symposium (June 17-18, 2026) in Rochester, New York. This Workshop aims to pool existing expertise, establish new collaborations, and prioritize future needs for characterizing micro- and nanoplastics (MNP) in complex environmental matrices relevant to health research in the Great Lakes ecosystem. This Workshop will bring together national experts on MNP analysis with researchers studying the interactions between Great Lakes ecosystems (particularly water and air) and health. The Workshop will be hosted by two multidisciplinary centers that are part of the NIH/NSF Centers for Oceans and Human Health program. The University of Rochester and Rochester Institute of Technology co-host the Lake Ontario MicroPlastics (LOMP) Center, a transdisciplinary hub for research, translation and engagement on how MNPs affect human health and the Great Lakes environment (particularly water and near shore air). The Great Lakes Center for Fresh Water and Human Health is based at the University of Michigan (the Great Lakes Center). Its central goal is to better understand the increasing risks that cyanobacterial harmful algal blooms (cHAB) pose to freshwater ecosystems and human health. One aspect of the Great Lakes Center’s research is to explore the association of aerosolized microplastics and cHABs. Fostering collaboration and scientific exchange between the Great Lakes Center, LOMP, and national experts studying MNPs is one example of how this workshop may have long-term impacts on regional MNP research collaborations that may yield results of global significance. The Workshop has three objectives: 1) Bring together scientists from multiple laboratories and institutions to present new findings, identify methodological challenges, and share analytical approaches to better understand environmental exposures to MNPs and their potential impact on human and environmental health; 2) Develop new collaborations between researchers and trainees across institutions, both regionally and nationally; and 3) Identify priorities and opportunities for analytical advances to support this rapidly growing field. The objectives will be met through a Workshop format with a limited number of participants (30-40) to encourage close interaction. The requested R13 conference funds will be used to pay for expenses for the June 17 Workshop, including travel expenses for trainees, invited experts, and researchers from other institutions. R-13 support will also enable these attendees to participate in the full Great Lakes Microplastic and Health Symposium, to be held on June 18 at the University of Rochester’s Memorial Art Gallery, that will include a larger number of researchers, trainees, and community partners (120-150) on a broad range of topics related to Microplastics and Health with a focus on the Great Lakes region.

NIH Research Projects · FY 2026 · 2026-04

Project Summary Improved treatments for chronic neuropathic pain are needed but hindered by an incomplete understanding of the biological mechanisms of pain development. Sleep disruptions are associated with increased chronic neuropathic pain. Thus, understanding processes critical to sleep may be the key to understanding chronic pain. The glymphatic system is a network of perivascular spaces alongside blood vessels, which facilitates cerebrospinal fluid (CSF) movement into, and interstitial fluid through the brain, ultimately draining into the meningeal lymphatic system. CSF movement between the glymphatic system and the cervical lymphatic system follows circadian (~24h) timing. During sleep, CSF influx and brain solute clearance increase, while direct CSF drainage to peripheral lymphatics predominates during the active phase. The glymphatic system presents a novel therapeutic target for neuropathic pain. This proposal introduces the hypothesis that circadian timing governs CSF movement between the glymphatic and lymphatic systems, driving cytokine redistribution across neuroimmune tissues, regulating nociception and the development of chronic pain. Aim 1 will test whether the daily glymphatic/lymphatic CSF switch deteriorates during the development of chronic pain, altering cytokine distribution across neuroimmune tissues and increasing nociception and hyperalgesia. Aim 2 will test whether the molecular clock controls daily glymphatic/lymphatic CSF distribution and cytokine distribution across neuroimmune tissue, influencing nociception across the day. Aim 3 will assess whether reinforcing circadian timing through food restriction attenuates chronic pain. Aligning peripheral rhythms with central timing provides a non-invasive therapy for chronic pain. These experiments will reveal new insights into chronic pain pathology and explore non-pharmacological interventions for a critical unmet need.

NSF Awards · FY 2026 · 2026-04

Pengfei Huo of the University of Rochester is supported by an award from the Chemical Theory, Models, and Computational Methods program to explore how collective coupling between molecules and a quantized cavity radiation field influences photochemistry. Coupling molecules to an optical cavity generates new photon-matter hybrid states, known as polaritons, which feature delocalized excitations across molecules and cavity modes. These states have been shown to enable novel chemical reactivities and offer a promising strategy for controlling reactions by tuning fundamental photon properties. Such control could open a new paradigm for chemical transformations with significant implications for catalysis, energy production, and the broader field of chemistry. Dr. Huo and his group are developing advanced theoretical and computational tools to simulate polariton dynamics in the collective coupling regime. Using these approaches, they aim to uncover how light-matter interactions at this scale affect photochemical processes. Beyond research, Dr. Huo continues to inspire the next generation through his Journey to the Molecular World summer school for high school students in the Rochester City School District, fostering curiosity and enthusiasm for molecular science. He also collaborates with colleagues to organize the Telluride Workshop on Polariton Chemistry, which brings together experimentalists and theorists to share the latest discoveries in this emerging field. Dr. Huo and his group will develop a set of general and powerful theoretical and computational tools that enable direct ab initio on-the-fly simulations of polariton quantum dynamics under the collective coupling regime. These theoretical efforts include (1) developing approaches that enable direct simulations of polariton quantum dynamics under the collective coupling regime, (2) investigating the fundamental mechanisms of collective polariton photochemistry, and (3) developing on-the-fly computational techniques and machine learning models to simulate ab initio polariton dynamics under the collective regime. The proposed work will provide the emerging molecular polariton field with a set of general and powerful tools to simulate collective polariton photochemistry, as well as new mechanistic insights into polariton photochemistry. The proposed theoretical development will enable a full spatial-temporal description of polariton dynamics, going beyond typical single cavity mode approximation and long-wavelength approximations. The investigations will likely yield new mechanistic insights into the collective polariton photochemistry and help answer several conceptual questions, including how collective quantities (such as Rabi splitting of polaritons) impact chemical kinetics, and provide valuable theoretical guidance for future experimental works. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-04

PROJECT SUMMARY Pathophysiological studies in first episode psychosis (FEP) have been inconsistent due to the heterogeneity in age of onset, clinical presentation, and neurobiology in schizophrenia spectrum disorders (SSD). Neuroimaging studies, postmortem investigations, and blood-based biomarker experiments provide intriguing insights into potential abnormalities related to the barriers of the brain of individuals with SSD, but only 1% of existing studies have focused on mid- to late-life FEP. Clinical and biomarker studies in SSD have repeatedly shown three phenomena: First, is blood brain barrier (BBB) dysfunction in neuroimaging, postmortem, blood- and CSF-based studies in individuals with SSD. Second, is the involvement of the blood cerebral spinal fluid barrier (BCSFB) as evidenced by enlargement of the choroid plexus (ChP) in SSD, FEP and in individuals at high risk for psychosis. Third, there is a nascent but growing research area related to the disruption of the glymphatic system (GS) in SSD. Moreover, there is a growing body of evidence in aging, sleep, and neurodegenerative studies suggesting a link between disruptions in the BBB, BCSFB, and GS to clinical outcomes. These barrier systems, regulate trafficking between the blood and the brain through physical, enzymatic, transport, and immunological processes, and they have tightly regulated interrelationships between them to ensure a healthy brain environment. However, despite the complementary roles between the BBB, BCSFB, and GS, the interaction between these systems in mid- to late-life FEP has not been explored. Advances in neuromaging and blood-based techniques have improved upon existing tools to assess BBB, BCSFB, and GS function and they include gadolinium-enhanced MRI methods like dynamic contrast enhanced-MRI (DCE-MRI) and the isolation of circulating brain microvascular endothelial cells (cBMECs) in the blood. Therefore, the critical need and overall objectives for this study are to unite neuroimaging, cBMEC, and clinical phenotypes in the same individuals to mechanistically link barrier disruptions to clinical outcomes in mid- to late-life FEP. Our central hypothesis is that biomarkers of BBB, BSCFB, and GS dysfunction are associated with poorer clinical outcomes in mid- to late-life FEP. Here, we aim to test the hypothesis that: 1) barrier/GS disruptions are associated with mid- to late-life FEP, 2) cBMECs are a proxy of BBB deficits in mid- to late-life FEP, and 3) barrier/GS deficits are associated with worse symptoms, cognition, and functioning in mid- to late-life FEP. Lastly, we will determine the interrelationship between barrier and GS deficits in mid- to late-life FEP. The proposed research is innovative in combining in vivo imaging of the BBB, BCSFB, and GS with clinical measures in the same individuals to better understand the barrier/GS deficits associated with clinical outcomes in mid- to late-life FEP. The proposed research is significant because it will lay the groundwork for a robust non-invasive platform to screen for cBMECs to pathophysiologically stratify patients, a first for SSD, that may lead to the prioritization of novel therapeutic approaches to regulate barrier dysfunction in SSD.

NIH Research Projects · FY 2026 · 2026-04

ABSTRACT Children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often struggle to understand speech in noisy environments, impairing community participation. Despite the high prevalence of these auditory processing disorders, evidence-based interventions remain limited due to gaps in understanding neural mechanisms and the impact of clinical heterogeneity. This project addresses these gaps through a series of translational aims that combine electrophysiology (EEG), virtual reality (VR), neuropsychological phenotyping, and community-engaged research to inform the development of targeted interventions. Prior work has implicated audiovisual integration of lip movements with speech sounds as a contributing mechanism to auditory processing disorders but has largely overlooked the confounding role of spatial attention deficits. Disambiguating their contributions is critical for designing mechanism-targeted interventions. This project tests the hypothesis that disrupted visual and/or auditory spatial attention mechanisms negatively impact audiovisual speech-in-noise perception in specific subpopulations of children with neurodevelopmental disorders and serve as a promising target for mechanism-informed VR interventions. In Aim 1, we will use EEG to compare neural signatures of audiovisual integration and spatial attention in school-age children with TD, ADHD-only, ASD-only, and ASD+ADHD, clarifying mechanisms driving auditory processing challenges. In Aim 2, we will conduct deep phenotyping across cognitive, attentional, and sensory domains and perform neural-phenotypic correlations to examine how the neural differences from Aim 1 relate to heterogeneity in clinical presentation. In Aim 3, we will leverage an existing ADHD cohort for whom we have already demonstrated spatial attention deficits to develop a prototype VR-based spatial attention training via a user-centered design process. This work will improve precision in identifying subgroups of children with ASD and ADHD who may benefit from targeted interventions, bridging the gap between neuroscience and clinical application. It also centers family and stakeholder perspectives, ensuring real-world feasibility. As an early-stage investigator trained in developmental-behavioral pediatrics and neuroscience, the PI is well-positioned to benefit from leading this translational work. The PI has strong mentorship at the University of Rochester Medical Center across neuroscience and pediatrics departments and external collaborators in VR design at the nearby Rochester Institute of Technology. The training plan will develop the PI’s skills in qualitative research and clinical trial design, fostering a research program focused on the translation of mechanistic understanding into evidence-based intervention.

NSF Awards · FY 2026 · 2026-04

This award supports participation in a symposium focused on microplastics in aquatic environments. Concerns about global microplastic contamination and the potential human and ecological health risks have grown in recent years. The symposium will bring together researchers from multiple disciplines to share findings and identify priorities for understanding microplastic contamination in freshwater systems, with particular attention to environmental samples from the Great Lakes. These efforts will advance understanding of emerging environmental contaminants affecting aquatic ecosystems and water resources while supporting the participation and training of students and early-career researchers. The Great Lakes Microplastics Research Symposium: Integrating Environment and Health is being organized by the University of Rochester in partnership with the Lake Ontario MicroPlastics Center (University of Rochester and Rochester Institute of Technology) and the Great Lakes Center for Fresh Waters and Human Health both of which are supported through the Centers for Oceans and Human Health program, a partnership between NSF and the National Institute of Environmental Health Sciences. The primary focus of the symposium is on fresh surface water, but sessions will also address microplastics in other media (such as nearshore air, wastewater, soil, plant material, fish and other aquatic organisms) relevant to the Great Lakes region. This interdisciplinary event will bring together experts and trainees in microplastics toxicology, analytical chemistry, aquatic ecology, and environmental science, as well as private sector, government, and community partners, to discuss emerging findings and prioritize needs for future work. Key outcomes will include 1) broad sharing of findings from multiple labs on approaches to all aspects of microplastic and nanoplastic analysis, 2) development of new collaborative efforts, and 3) collaboration and career pathways for students and postdoctoral researchers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-04

PROJECT SUMMARY/ABSTRACT Dendritic cells are immune sentinels capable of sensing pathogen-derived products and initiating an adaptive immune response. Type 1 conventional DCs (cDC1s) are a specialized subset of DCs that excel in cross- presenting exogenous antigens to CD8+ T cells and secreting interleukin-12, making them an attractive target in evolving therapies for many diseases. Despite the identification of several transcription factors that govern cDC1 biology, little is known about how these transcriptional events are controlled epigenetically to facilitate cDC1 development. In my current research, which serves as preliminary data for this proposal, we determined that optimal cDC1 differentiation, in particular cDC1 terminal maturation and lineage identity, requires cohesin, a complex responsible for establishing the 3D organization of the genome. Thus, the proposed studies to be continued in the independent phase aim to elucidate the chromatin-level control of cDC1 differentiation by cohesin, both globally and at the locus encoding Id2. We will first use scRNA-seq and scATAC-seq in our developed system of cohesin-deficient DC differentiation to precisely define the aberrant differentiation trajectory of cohesin-deficient cDC1s at single-cell resolution and understand the cohesin-dependent transcriptional and chromatin accessibility changes associated with this incomplete and/or divergent trajectory. By integrating these with complementary chromatin conformation capture by Hi-C and CUT&RUN of histone post-translational modifications in cohesin-deficient cDC1s, we will directly test the hypothesis that cohesin- mediated chromatin remodeling is required for the appropriate gene expression program of differentiating cDC1s (Aim 1). We will in parallel investigate the chromatin-level control of the locus encoding Id2, a transcription factor required for cDC1 development (Aim 2). Using CRISPR/Cas9 to engineer mice lacking an architectural element near the Id2 locus, we will evaluate the role of this regulatory region for Id2 locus organization, Id2 expression in cDC1s, and cDC1 differentiation. Findings from these studies are expected to provide a fundamental understanding of the molecular regulation of cDC1 differentiation and to integrate existing knowledge about the transcriptional regulation of cDC1 differentiation into a unified model. These studies align well with NIAID’s mission: by advancing basic knowledge of the mechanisms governing cDC1 differentiation and subsequently cDC1 function, the proposed research may inform strategies to optimize the development or efficacy of cDC1-based therapies. In addition to these proposed studies, I have planned career development activities to hone my toolkit of research, mentoring, lab management, presentation and writing skills that will equip me for success as an independent investigator. This project and career development plan, to be initiated at NYU and continued at a sponsoring institution, will promote my professional development as a scientist, communicator, and mentor, and form the basis of my research program as an independent investigator studying the molecular regulation of innate immune cells in health and disease.

NIH Research Projects · FY 2026 · 2026-03

Abstract Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are leading causes of adult blindness with limited treatment options. AMD/MDs can present in two forms, geographic atrophy/GA (dry form) and choroidal neovascularization/CNV (wet form). There is strong evidence linking sterile inflammation to AMD/MD pathogenesis and two complement pathway inhibitors are already approved by FDA for treating GA in the dry form of AMD. However, due to limited therapeutic impact and adverse effects of complement inhibitors and other approved drugs for both dry AMD and wet AMD, there is a significant need for novel therapies for AMD/MDs. Our recently published data and preliminary studies identified secretory phospholipase A2-IIA (sPLA2-IIA), a pro-inflammatory enzyme, as a key molecular player in AMD/MD pathogenesis. AMD/MD primarily affect the retinal pigment epithelium (RPE) cells in the eye and patient-derived induced pluripotent stem cell- RPE (iRPE) from AMD and 2 distinct MDs showed elevated levels of sPLA2-IIA. Furthermore, AMD/MD iRPE cultures and AMD donor eyes showed elevated sPLA2-IIA levels in drusen, a pathological hallmark of early AMD/MD that is the key driver of later stage pathologies in AMD/MDs. Notably, pharmacological modulation of sPLA2-IIA activity in AMD and MD iRPE cultures led to reduced drusen. In addition, directly linking elevated sPLA2-IIA activity to AMD/MD pathology, sPLA2-IIA overexpression led to AMD-associated pathological alterations (drusen, Bruch’s membrane thickening, RPE thinning, CNV and visual deficits) in C57BL/6J mice. Altogether, these studies provide a strong rationale for targeting sPLA2-IIA activity in AMD/MDs. Toward this goal, we propose to develop proteolysis-targeting chimeras (PROTAC) compounds for specific inhibition of sPLA2-IIA in AMD/MDs. In initial experiments, we have synthesized a ‘lead‘ PROTAC (UR-00059) that can induce degradation of sPLA2-IIA in iRPE cells with half-maximal degradation concentration DC50 of 295.5 nM. The following milestone-driven aims will allow us to develop an effective PROTAC-based therapy targeting sPLA2-IIA for AMD/MDs. Aim 1: Optimize UR-00059 structure and activity and characterize the target engagement in vivo; Aim 2: Conduct in vivo efficacy studies and non-GLP absorption, distribution, metabolism, and toxicology of UR-00059; Aim 3: Perform IND enabling studies and obtain FDA approval for human testing. Ultimately, the proposed studies will develop a novel PROTAC-based therapy for targeting inflammation, drusen and consequently late stage pathologies of AMD and related MDs.

NIH Research Projects · FY 2026 · 2026-03

PROJECT SUMMARY Drug use disorders (DUDs), a subclassification of substance use disorders (SUDs) involving the misuse of non-alcohol illicit drugs, remain a major public health crisis in the U.S., affecting 27 million persons and contributing to over 100,000 overdose deaths annually. Among those with DUDs, 30% to 50% have a primary sexual partner who also has a DUD—dual-DUD couples. These couples experience significantly poorer treatment outcomes, including higher relapse rates and lower treatment engagement, compared to individuals without a drug-using partner. Despite the well-documented reciprocal influence of partners on each other’s substance use, current treatment paradigms remain predominantly individual-focused, overlooking the relational context in which substance use and recovery occur. The absence of couples-based treatment models designed specifically for dual-DUD couples represents a critical gap in the addiction treatment landscape. This study aims to address this gap by developing and piloting a novel couples-based intervention tailored to the needs of dual-DUD couples who use opioids and/or stimulants. Grounded in the Recovery Capital framework and the SUD Couple System model, this study will incorporate a Co-Creation approach to intervention development, ensuring meaningful engagement from stakeholders, including affected couples, treatment providers, and administrators. The research design follows an R61/R33 phased structure, integrating the Intervention Mapping + Adapt (IMA) framework for intervention development with the Consolidated Framework for Implementation Research (CFIR) to guide and evaluate implementation strategies. In the R61 phase, formative mixed-methods research will be conducted to identify key determinants and recovery assets influencing drug use behavior and treatment outcomes among dual-DUD couples (Aim 1). These findings will inform the development and adaptation of a couples-based treatment program using an intervention mapping approach (Aim 2). The R33 phase will involve finalizing intervention materials and implementation strategies (Aim 3), conducting a dual-site pilot randomized controlled trial (RCT) at SUD treatment centers in Rochester, NY, and Newark, NJ (Aim 4), and evaluating post-pilot data to refine the intervention and assess readiness for a confirmatory Hybrid Type 2 effectiveness trial (Aim 5). This project aligns with the objectives of RFA DA-26-024 (R61/R33 Exploratory/Developmental Phased Award), which seeks to engage loved ones in the recovery process and enhance access to evidence-based care for those affected by DUDs. develop and test dyadic approaches to support engagement in evidence-based care for individuals in DUD-affected relationships. By addressing a longstanding treatment gap, this study aims to contribute to the broader goal of reducing substance use-related harm and improving public health through innovative, relationship-centered care models.

NIH Research Projects · FY 2026 · 2026-03

PROJECT SUMMARY Pathogenic variants in tRNA modification enzymes are the cause of numerous diseases and disorders in the human population. However, the molecular basis of these pathologies are unknown due to major knowledge gaps that prevent our complete understanding of tRNA modification enzymes such as: How do modifications impact tRNA structure and function? What are the functions of vertebrate-specific tRNA modification enzymes? How do tRNA modification enzymes regulate cellular and developmental pathways? To resolve these knowledge gaps, our lab aims to elucidate the biological roles of tRNA modification enzymes. We will use an integrated approach combining biochemistry, molecular biology, and genetics with the development of new disease models and tools for detecting RNA modifications. We plan to decipher how modifications impact the global tRNA transcriptome to reveal conserved and novel roles for tRNA modification enzymes. Our studies will resolve the enigmatic functions of tRNA modifications and unravel the tissue- and cell-specific roles of tRNA modification enzymes linked to human disease. Importantly, elucidation of these mechanisms could reveal new modes of gene regulation that would inform strategies to understand and treat human pathologies linked to tRNA modification.