University Of Arizona

NIH Research Projects · FY 2025 · 2025-09

Project Summary/Abstract Over 17,000 new cases of spinal cord injuries (SCIs) are experienced annually in the U.S. due to motor vehicle collisions, sports injuries, and other traumatic events. In addition to the loss of mobility, numerous complications including urinary tract infections, pressure sores, and chronic central neuropathic pain (CNP) significantly impact the quality of life and contribute to morbidity and mortality. However, no effective treatments exist for individuals with SCIs. A mechanism- based approach that based on individual spinal learning to promote motor recovery and re- balance the pain circuitry would be the key to developing personalized SCI treatment. In the New Innovator Award program, our team will develop novel response-contingent neuromodulation devices to electrically modulate neural circuit plasticity. This individualized treatment strategy will be based on establishing a close-loop electrical stimulation paradigm via novel design of neuromodulation to self-train spinal circuitry. Our team will assess if the motor- contingent electrical stimulation can promote motor recovery and pain sensitization and investigate the underlying molecular mechanisms associated with spinal plasticity using the rat SCI model. The proposed work will determine the biology behind adaptive plasticity associated with NP and lay down the foundation to develop a close-loop electrical modulation technology for individualized neurotrauma treatment in the future.

NSF Awards · FY 2025 · 2025-09

Defining a design problem is the catalyst for the engineering design process itself. Problem statements create a shared mental model for engineers and stakeholders, shaping the trajectory of subsequent design decisions. This critical framing of the problem to be solved is often established during the fuzzy front end of design, when project expectations and team understanding are still evolving. Problem formulations can exist in many different forms — such as lists of goals, value models, constraints, or requirements — and each form can introduce biases that predispose engineers towards certain decisions, potentially limiting creativity. However, isolating the effect of design problem formulation is challenging due to moderating variables like problem domain and complexity. This research seeks to use controlled experiments with engineering students and practitioners to investigate how problem formulation influences design exploration and decision-making. Findings looks to inform the development of evidence-based guidance to improve problem formulation practices, with the potential to reduce design cycle times in both educational and industrial settings, ultimately enhancing U.S. economic competitiveness. The project also seeks to promote industry adoption through practitioner workshops and close collaboration. This project looks to advance our understanding by addressing three critical research questions: In what ways do problem formulation styles affect exploration in the design process and creativity of design outcomes? In what ways does problem complexity affect the use of problem formulation styles? In what ways do designer attributes affect the use of problem formulation styles? The research centers on controlled experimentation, placing the designer at the core of analysis. To capture a comprehensive view of the design process, both process and outcome metrics will be assessed, including design time, idea generation, design space exploration, and creativity of outcomes. By quantifying how formulation styles impact creativity and exploration—and how designer experience moderates these effects—this project intends to generate actionable insights to guide effective design practices across academia and industry. 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 2025 · 2025-09

This program builds a visible-light extension for interferometric imaging (LIVE) on the Large Binocular Telescope (LBT). The LBT, featuring two 8.4-m mirrors on a common mount that form a 22.8-m effective aperture, can be considered the first of the Extremely Large Telescopes (ELTs). LIVE leverages existing LBT infrastructure with targeted, low-risk upgrades to improve its visible-light performance, and adds a fast, sensitive, visible-light camera. This project will enable groundbreaking science at unprecedented resolution, probing structures and planet formation in protoplanetary disks, mapping Solar system moons, imaging dynamical processes and feedback in active galactic nuclei, and imaging the outflows and binary interaction of massive and evolved stars. Early-stage researchers and students will benefit from access to instrument development and deployment for hands-on research experience. As a pathfinder, LIVE generates valuable optical design expertise and trains the next generation of scientists in Adaptive Optics techniques for interferometry and fringe tracking. The LBT Interferometer Visible Extension (LIVE) is a pioneering instrument for ELT-scale visible imaging. LIVE enables imaging at the 4-5 mas scale. The unprecedented high resolution will drive advances in both engineering and imaging, serving as a science and instrumentation pathfinder for the US-ELT program. As such, LIVE addresses numerous open questions in astronomy across an enormous range in physical scales by imaging (i) the surfaces of stars to measure their activity and evolution; (ii) Solar System bodies, such Io and Europa, to monitor surface changes; (iii) emission from highly ionized, outflowing material which traces the impact of the supermassive black hole on the host galaxy; and (iv) star-formation sites in external galaxies to pinpoint the driving processes. LIVE also supports the search for habitable exoplanets and our understanding of how planets form. 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 2025 · 2025-09

Although gravitational wave (GW) instruments have been detecting the mergers of two compact objects (either black holes or neutron stars) for nearly a decade, there is still uncertainty about how these binary systems form and develop over time. A research collaboration between Carnegie Mellon University (CMU) and the University of Arizona (UA) will investigate the formation of merging double compact objects by combining state-of-the-art population synthesis tools, used to model large populations of stellar objects, with detailed modelling of binary system development. The project will also support science teacher training programs at both universities: the Physics Teacher Program to connect high school physics teachers with CMU researchers, and the UA University Borderlands Education Center to create workshops that empower high school teachers to use research products in their classrooms. The use of binary population synthesis and detailed binary development modeling has been widely applied to understanding how isolated binary star populations can produce merging double compact objects. However, the assumptions usually made in population synthesis are unable to resolve the effects of the interior structural development of each stellar component in a given binary. This project will unite these previously disparate efforts through a new technique, BackPop, which simulates joint posterior distributions for uncertain binary interaction parameters that reproduce the observed properties of individual binary systems. These joint distributions can then be used to initialize detailed binary development models, which capture the effects of binary mass exchange on the interior structure of each star, thus testing the interaction parameters. The research will focus on three key populations: the binary black holes that make up the global merger rate maximum, the asymmetric mass ratio mergers that are treated as outliers in GW population analysis, and finally, the remaining population consisting of more massive black holes. 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 2025 · 2025-09

ABSTRACT This revised application is for a new Diabetes Research Training Program (DRTP) at the University of Arizona (UA). We expanded the scope to include UA College of Medicine Phoenix, ASU, and the NIDDK Epidemiology and Clinical Research Branch.UA is in the top 20 of Research I institutions with a proven record of interdisciplinary mentoring and research. UA has taken a path to broadening and improving faculty and research resources over the past 7 years, bringing new, well-funded faculty, committed to mentorship, to this application. Improvements in infrastructure will enable our trainees to gain true translational experiences across the spectrum of diabetes research. The DRTP is organized into 4 synergistic research themes: 1) Molecular Basis of Disease and Model Systems, 2) Mechanisms of pathogenesis of diabetes in humans, 3) Sequelae and Complications of Diabetes, and 4) Community-Engaged Research. This organizational structure creates a pipeline of integrative mentoring teams engaged in foundational physiological DRTP research, with modern and relevant research proficiencies, with verbal and written communication, mentorship, collaborative and networking competencies. The DRTP will meet the need for a diverse workforce in health-related careers by delivering a contemporary didactic experience in physiological DRTP research, applied research skills, community engagement, and career development. This program will include research related to type 1 and type 2 diabetes. Because type 2 diabetes is one of the major health concern among all communities in Arizona, trainees will have research opportunities in community-engaged research via our Community Diabetes Biobank, El Banco Community Biobank. All Trainees will receive instruction in community-engaged research. Trainees will benefit from state-of-the-art Core facilities, DRTP disease-focused Research Centers, and Institutional resources. The training plan aligns with the NIH mission of translational research training where predoctoral and postdoctoral trainees receive a background in interdisciplinary research, experimental approaches, and practical/ethical aspects of careers in science. Trainees will develop presentation and intrapersonal skills through journal clubs, colloquia, seminars and attending institutional, national/international diabetes and diabetes-related conferences. Career development training will be conducted in the Graduate Center. The postdoctoral training plan will foster a path towards independence by expanding research focus, learning state-of-the-art techniques, and honing scientific writing skills. Training in building translational teams via the Eureka International Institute is available. >90% of trainees supported by this program remain in research-positions.

NSF Awards · FY 2025 · 2025-09

The strength of solder joints can be reduced by pores caused by bubbles trapped during the soldering process. Small bubbles are especially likely to be trapped because their buoyancy is relatively weak, especially in reduced-gravity environments; hence, they do not quickly rise to the surface. This research project will explore acoustic waves as a means of quickly expelling small bubbles from molten solder. Acoustic methods have been used successfully in other situations, e.g. to remove bubbles from cell culture media. This project will transplant those methods to molten solder. Experiments in microgravity will allow acoustically driven bubble motion to be isolated from the effects of buoyancy-driven motion. These data will be used to validate simulations of bubble motion and improve future predictions of the same. The results look to speed up soldering operations and reduce the heat energy needed to keep the solder molten. Additional benefits will come from training next-generation aerospace and mechanical engineers. Experiments in space research provide excellent outreach opportunities targeting high-school students. This project aims to develop an acoustics-assisted soldering technique and identify the optimal acoustic parameters (e.g., power, frequency, and activation duration) for effective bubble removal. An acoustic transducer will be used to generate waves within molten solder, actively displacing bubbles. This looks to significantly improve the mechanical strength and thermal/electrical conductivity of soldered joints. Experiments in microgravity aboard the International Space Station (ISS) will eliminate the effects of buoyancy and natural convection. These results will be compared against ground-based experiments, thus decoupling the effects of buoyancy vs. acoustically-driven bubble dynamics. All experiments will be guided by thermal-acoustofluidics simulations, and experimental results will, in turn, be used to validate simulations. This project seeks to expand the application of acoustic manipulation of matter from traditional gels and colloidal materials to molten metals. The knowledge gained from this project intends to benefit manufacturing industries such as automotive, aerospace, and semiconductors, where defects in soldering processes have impeded device performance and jeopardized the longevity of mechanical structures. Beyond benefits on Earth, the microgravity experiments look to also help soldering operations in space, which are important for the emerging industry of space-based manufacturing. Beyond technological benefits, the project will also train students in advanced manufacturing methods and conduct outreach from pre-college to graduate levels. Experiments on the ISS provide an attractive vehicle to communicate the excitement of research, especially to younger 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 2025 · 2025-09

Dementia affects millions worldwide, yet remains without a cure, highlighting the urgent need for research into its causes. Frontotemporal lobar degeneration (FTLD) is a significant contributor to middle-age-onset dementias, accounting for up to 10% of cases and adding to the challenges faced by patients and caregivers. Genetic variation at the TMEM106B locus has been identified as a risk factor for FTLD and other dementias, like Alzheimer’s disease (AD). However, the specific mechanisms by which TMEM106B variants increase the risk of developing these diseases remain unclear. The extensive documentation of mitochondrial dysfunction as a feature of neurodegenerative diseases underscores its critical role in neuropathogenesis. Dysregulation of mitochondria-associated endoplasmic reticulum membranes (MAMs), which play an important role in regulating mitochondrial function, has been implicated in various neurodegenerative disorders. This dysregulation can lead to impaired calcium signaling, disrupted lipid metabolism, and altered mitochondrial dynamics, ultimately resulting in neuronal loss. Our ongoing research has uncovered a potential link between TMEM106B and mitochondrial dysfunction. We have observed that elevated levels of TMEM106B are associated with changes in mitochondrial morphology, reduced mitochondrial membrane potential, and impaired mitochondrial respiration in HEK293 cells. Furthermore, we have found that TMEM106B is enriched in MAMs and interacts with Sigma 1 receptor (SigR1), a key protein involved in regulating MAM function. To further investigate the role of TMEM106B in mitochondrial dysfunction and neuronal damage, we aim to determine if increased TMEM106B expression leads to these outcomes in cultured cortical neurons. Additionally, we will explore the mechanisms underlying TMEM106B-mediated mitochondrial dysfunction, focusing on its interaction with SigR1 and its impact on MAM function. Understanding the relationship between TMEM106B and mitochondrial dysfunction could provide valuable insights into the pathogenesis of FTLD and other related dementias. This knowledge could pave the way for new therapeutic approaches aimed at addressing mitochondrial dysfunction in these debilitating conditions.

NSF Awards · FY 2025 · 2025-09

The manufacturing industry has recently transformed into an intelligent and interconnected ecosystem, fueling many emerging services - such as connected healthcare, smart transportation, and modern manufacturing - to benefit people's daily life. As a key enabler to this new paradigm, smart computing devices (e.g., Industrial Internet of Things) leverage their computing capability and wireless connectivity to form a hierarchical service functionality, providing the ability to perform real-time data analytics, to detect anomalies, and to make predictions to improve the efficiency and quality of manufacturing. Although this paradigm is promising, environmental sustainability issues are becoming increasingly urgent, especially during industry expansion. The substantial increase of new device production and adoption inevitably leads to higher greenhouse-gas emissions, contributing to global warming, which in turn results in economic losses for industries. This project develops a framework, termed sustainable revitalization, to reduce the greenhouse-gas emissions by migrating current devices to their most suitable locations in the service hierarchy for continuing service. As such, computing devices maximize their lifespan by moving around inside a system at each device-updating stage while minimizing their environmental impact through greenhouse-gas emissions by avoiding frequent production and disposal processes during industry expansion. This project also seeks to improve the scientific training of undergraduates and students in the field of environmental science and engineering, computation optimization, and communication, preparing them with the cross-disciplinary skills needed to succeed in the modern workforce. This project introduces lifecycle sustainability into computing-system design and maintenance. By adopting an adapted approach to life-cycle assessment and by constructing new metrics for environmental sustainability as an optimization objective, this project addresses greenhouse-gas emissions during industry expansion. Specifically, this project lays a foundation by establishing a robust system boundary to comprehend the greenhouse-gas emissions of computing devices across various lifecycle stages, thus informing subsequent sustainable-revitalization efforts. To find optimal pathways for device migration, this project pioneers inventory analysis by integrating demand-based migration and compatibility-optimized computation strategies. From a system-design perspective, having these strategies within the system boundary facilitates examining the strategies' effectiveness. Based on the optimization strategies of migrated devices, this project introduces collaborative on-device learning that dynamically adapts smart devices to new scenarios while upholding environmental sustainability and addressing communication challenges through a novel physical-level parallel inclusive communication. This new methodology will help fully utilize obsolete computing and communication devices to meet environmental-sustainability demands. 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 2025 · 2025-09

PROJECT SUMMARY. Endothelial cell (EC) dysfunction occurs in a variety of acute and chronic pulmonary diseases. To correct EC dysfunction, there is an unmet need for development of nanoparticle systems that can deliver drugs and nucleic acids into pulmonary ECs in vivo with high efficiency and precision. While several nanoparticle delivery systems targeting ECs have been recently developed, none of these systems are specific to lung ECs without targeting ECs in other organs of the body. Bronchopulmonary dysplasia (BPD) is a severe complication of prematurity in newborns and infants, especially those born prior to 28 weeks of gestation. BPD is associated with significant mortality and morbidity, and it causes an increased susceptibility to chronic pulmonary diseases later in life. The most severe BPD cases (BPD-PH) are accompanied by irreversible vascular remodeling and pulmonary hypertension (PH) after exposure of preterm infants to supplemental oxygen. There is an urgent need for innovative therapeutic approaches to prevent vascular remodeling and stimulate endothelial regeneration in BPD-PH infants. FOXM1 is a well-known pro-proliferative transcription factor which is required for EC proliferation during lung regeneration after injury that is caused by various insults. We propose to test the hypothesis that newly developed and lung capillary endothelial-specific nanoparticles complexed with the FOXM1 minicircle DNA plasmid will stimulate lung regeneration and decrease PH in mouse and rat BPD-PH models. In Aim 1, we created a novel class of hybrid polyplex nanoparticles (P22-F1 PBAE/PEI/PEG) and demonstrated that after systemic (intravenous) injection these nanoparticles are non-toxic and effectively deliver non-integrating DNA plasmids to capillary ECs in the lung-specific manner. We propose to determine molecular mechanisms through which the P22-F1 PBAE/PEI/PEG nanoparticles specifically target lung capillary ECs without targeting other cells and organs in the body. Specifically, we will examine the cell surface binding of the nanoparticles, their endocytosis, endosomal/lysosomal escaping, and the cargo release, all of which are important mechanisms for successful delivery of DNA plasmids to develop nanoparticle therapeutics. In Aim 2, we will determine whether the P22-F1 PBAE/PEI/PEG nanoparticle delivery of the FOXM1 minicircle DNA vector into pulmonary capillaries will stimulate EC regeneration, prevent PH, and improve lung function in mouse and rat BPD-PH models. Conditional knockout mice will be used to perform the inactivation of Foxm1-floxed alleles in general capillary cells (gCAPs) or aerocytes (aCAPs) to determine differential requirements for FOXM1 in gCAPs and aCAPs during lung regeneration in a mouse BPD-PH model. We will also use mouse and human BPD-PH lung tissues to perform omics studies and identify novel downstream targets of FOXM1 in regenerating gCAPs and aCAPs. Altogether, the proposed preclinical studies will directly test whether lung capillary endothelial-specific delivery of the FOXM1 minicircle vector has therapeutic potential in BPD-PH.

NIH Research Projects · FY 2025 · 2025-09

Abstract: The University of Arizona Cancer Center (UACC) is the only NCI-designated comprehensive cancer center headquartered in the state of Arizona. The catchment population covers the five southern counties of Arizona and is close to 40% Hispanic while also including representation from many of the 22 federally recognized Native American tribes in the state. This R50 proposal focuses on growing the clinical research enterprise at UACC, specifically in NCI-funded research and through development of a clinical trials navigation program. The plan for growth over the next five year includes growing the breadth of the clinical trial portfolio to be accessible to the diverse populations seen at UACC while also increasing accruals to interventional treatment trials, especially in NCI-sponsored trials and investigator-initiated trials (IITs). The clinical trial navigators will work to increase clinical trial literacy and decrease barriers to participation. Part of this R50 effort is also focused on growing the Arizona Clinical Trials Network (ACTN), which will bring novel therapeutic trials to the underserved and underrepresented populations across the state, not just within our catchment. The ACTN will increase diversity and representation in NCI-funded clinical trials in particular since this will be the initial set of studies that we plan to open at pilot sites. UACC is uniquely positioned to increase its impactful reach by leveraging the ACTN and providing comprehensive cancer care to rural and underserved areas in Arizona. This proposal will provide time and effort to support my roles as UACC Site Principal Investigator (PI) for the Southwest Oncology Group (SWOG) and as Associate Director of Clinical Investigations at UACC so that we can increase the impact of our clinical research program and support the NCI’s interest in enhancing diversity and inclusion in their research efforts.

NSF Awards · FY 2025 · 2025-09

The last deglaciation occurred from approximately 20,000 to 11,700 years ago when rising atmospheric temperatures caused Earth’s main ice sheets to melt. Vast amounts of water from the vanishing Laurentide Ice Sheet flowed through the Mississippi River system into the marine environment. The mixing of fresh meltwater with saline ocean water on such a mass scale triggered abrupt changes in regional climate, ocean circulation, and ecosystems. This project seeks to understand how environmental systems responded to these freshwater inputs on seasonal and century timescales. By improving our understanding of the short- and long-term effects of past ice sheet melt, the research will help scientists and the public anticipate the potential consequences of modern ice sheet melting and freshwater input on marine ecosystems. The project will support student research and training and engage broad audiences through public-facing data visualizations and educational outreach. This research will develop a refined and detailed understanding of climatic and oceanographic changes across Earth’s last deglaciation due to the meltwater released from the Laurentide Ice Sheet. The project will generate new high-resolution reconstructions of ocean-atmospheric and biogeochemical variability from strategically located marine sediment cores (already collected) and integrate these with existing paleoclimate data. The cores derive from the Garrison Basin offshore Texas, where deposited sediment captures meltwater pulses with minimal influence from the Loop Current. The team will focus on characterizing the spatial extent, timing, and frequency of freshwater intrusions into the marine environment via the Mississippi River outflow and evaluate their influence on ocean stratification and regional climate. Specific emphasis will be placed on resolving both seasonal and century-scale dynamics by combining stable isotope, trace metal, and microfossil analyses with climate model simulations of the last deglaciation. The results will clarify critical feedbacks between freshwater forcing, ocean circulation, and marine ecosystem structure during periods of rapid ice sheet retreat, offering valuable analogs for ongoing and future global shifts. 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 2025 · 2025-09

Many naturally occurring microorganisms can produce soap-like substances, called biosurfactants, that alter how fluids and other substances in the liquids move through porous spaces such as soils and biological tissues. However, scientists still do not know how far and how fast these biosurfactants spread or how they redirect substances ranging from nutrients and pollutants to disease-causing bacteria. Yet, these microbial agents play important roles in the health of soils, plant roots, and even human lungs. This project tackles this knowledge gap by using laboratory models that mimic real soils to observe the microbes and biosurfactants in action and quantify their influence on the transport of fluids and dissolved chemicals. Outcomes from the project could support improved soil remediation strategies, more sustainable agricultural practices, and new methods to manage the spread of harmful bacteria. The project also promotes national goals in science and education by training undergraduate and graduate students, supporting interdisciplinary collaboration, and conducting outreach activities to help K-12 students appreciate fluid mechanics and microbiology and their relevance to daily life. This project integrates multiscale experiments and physics-based modeling to investigate how biosurfactants and the microbes that secrete them alter mass transport in unsaturated porous media. The goals are to: (1) quantify how time-dependent biosurfactant production alters transport behavior in two-dimensional porous systems; (2) characterize feedback loops between biosurfactant-induced flow, solute transport, and bacterial migration; and (3) measure and model biosurfactant-driven transport processes in three-dimensional porous media. Innovative visualization experiments paired with advanced multiscale models will reveal the intertwined dynamics of bacteria, biosurfactants, and transported substances. Model-data comparisons will guide the development of predictive tools that can be applied to environmental systems ranging from contaminated soils to biological tissues. The findings will provide a mechanistic framework for understanding biosurfactant-mediated mass transport, improving our ability to forecast chemical and microbial movement in complex, unsaturated porous media. 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 2025 · 2025-09

This project aims to improve understanding of the removal of atmospheric hydrogen due to microbe-mediated soil uptake. The central question addressed by the project is whether microbial adaptation to elevated hydrogen is sufficient to mitigate leaks from the hydrogen energy sector. Soil uptake is currently the largest source of uncertainty in the budget, lifetime, and distribution of hydrogen. The project evaluates microbial adaptation to two key forces: moisture regulation of soil hydrogen uptake and micrometeorological regulation of hydrogen plume-surface interactions. The research consists of field measurements in two natural systems differing in moisture and temperature regimes, computational modeling analyses, and measurements using a state-of-the-art mobile laboratory in the vicinity of real hydrogen energy installation sites and from controlled-release experiments. Advancing understanding of the hydrogen soil sink addresses societally important issues of air quality, radiative balance, and UV levels. The project includes research, education, and mentoring opportunities for young scientists and students. The proposal team will leverage their expertise in soil microbial hydrogen uptake, modeling, and novel in situ ecological and mobile lab measurements to generate data and improve models with the following specific project activities planned: (1) generate continuous in situ measurements of hydrogen fluxes under ambient and elevated hydrogen conditions at two sites with contrasting moisture regimes, (2) build a 1-D diffusion-consumption model and improve the hydrogen deposition scheme in a global community model, (3) characterize hydrogen releases from real and simulated hydrogen energy infrastructure using a mobile lab, and (4) quantify the proportion of hydrogen plumes intercepted by soil. Overall, this project will set expectations for the atmospheric and ecological impacts of growth in the hydrogen energy sector while also generating knowledge and tools to project changes to the atmospheric hydrogen budget. 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 2025 · 2025-09

This project examines legal actions involving insurance companies that have denied claims following natural disasters, because geographical variation in litigation may help to explain why communities vary in their pace of recovery. The research examines demographic and economic factors that potentially underlie variation in litigation rates and the legal outcomes. The study also investigates correlations between litigation and recovery rates as indicated by construction that is evident over time in satellite images, which are processed with deep-learning algorithms. The findings and recommendations are made available to a broad range of stakeholders, including regional planners. The project also provides opportunities for the training and education of multiple students. As a contribution to the geographical sciences, this study examines the dynamic processes that lead to spatial variation in recovery rates after natural disasters. Communities may vary in their litigiousness, and this study uses qualitative methods to elucidate the reasons for considering legal recourse among a sample of impacted residents. Complementary methods are used to construct a quantitative parcel-level dataset in communities that have been negatively impacted by recent disasters. This dataset combines property records, court records, and satellite images of the study area. Deep learning algorithms are used with the satellite images to detect evidence of damaged homes and subsequent recovery. The dataset facilitates multilevel hazard modeling of parcels’ time to recovery as a function of litigation participation and related outcomes. The study refines understandings of the role of litigation as an adaptive strategy for homeowners who have been affected by natural disasters. 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 2025 · 2025-09

Drought conditions in the Colorado River basin have persisted since the year 2000, and this has resulted in decreased Colorado River streamflow, challenging water management for communities, agriculture and ecosystems. According to existing tree-ring based drought reconstructions, this current drought is comparable to the most severe drought of the last 1200 years, which occurred in the twelfth century. However, there is limited evidence that suggests a more severe and sustained drought occurred in the 2nd century, which if it happened today would have severe impacts. This project will extend tree ring reconstruction of drought back to 2000 years ago and characterize the 2nd century drought. These data will be combined with other geological records of drought in order to assess how drought severity and duration has changed through time, the contributions of changes in rainfall and temperature on droughts and the streamflow of the Colorado River, and inform understanding of drought risk in the future. The project includes development of K-12 homeschool educational materials, and opportunities for a postdoc and undergraduate students to participate in the research. The goal of this project is to use existing and new tree ring samples to reconstruct drought in the Colorado River basin during the past 2000 years. The tree-ring data will be combined with other proxy records and hydrological modeling to investigate the intensity and persistence of the second century drought in this basin, determine how long-term trends may have amplified droughts through time, and evaluate the impacts of warming versus drying on streamflow. The project includes collaboration with water resource managers to explore how to apply these data to management, development of K-12 homeschool educational materials, and opportunities for a postdoc and undergraduate students to participate in the research. 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 2025 · 2025-09

Dendrochronology is the most precise archaeological dating method available to researchers interested in the last several thousands years. Tree-rings are accurate at the annual, and often seasonal, level of resolution and many other dating techniques are calibrated using tree-rings. Such resolution is critical when assessing hypotheses about settlement and subsistence change, and human/environment interaction. Societal benefits of this project include increasing understanding of long-term human adaptation to sociocultural and environmental variation and of increasing knowledge of past environmental variability, both of which are important for developing environmental and social policy. The Laboratory of Tree-Ring Research (LTRR) at the University of Arizona is the only institution active in all aspects of dendrochronological research. A major component of the Laboratory's research program is the analysis and dating of wood and charcoal from prehistoric and historic archaeological contexts. Thus, the LTRR has become the leading processor of archaeological tree-ring materials, the primary source of tree-ring dates in western North America and the eastern Mediterranean, and the largest repository of archaeological tree-ring samples in the world. The integration of the tree-ring dating program into the full range of dendrochronological research, teaching, and outreach activities at the Laboratory creates a unique interdisciplinary context that maximizes the scientific value of archaeological tree-ring samples and chronologies, and provides a variety of ways for different public to explore the research. The findings of the project are almost immediately integrated into University of Arizona classes. The project directly contributes to PhD dissertation and MA thesis research by students at the University of Arizona, Northern Arizona University, Washington State University, and other colleges and universities. The project contributes directly to extensive outreach activities that have reached more than 12,000 people in the last year. The LTRR tree-ring sample collections and data archives are unparalleled, easily accessed resources for archaeological, historical, and environmental research. Project results are distributed to the public through lectures, newspapers, radio, television, and the internet, improving the public's understanding of archaeological science and the scientific method. The project's primary contribution to archaeological research involves exact dating and chronology building, topics crucial to understanding past human behavior, human-environment interactions, and processes of sociocultural stability, variation, change, and evolution. The project contributes to understanding past human activities that remain outside written history, either because they occurred prior to written records or were in areas that were not recorded. Using traditional and new innovative techniques, the laboratory offers stakeholders a long-term perspective in which to understand past human land and resource use. 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 2025 · 2025-09

This project will develop innovative and sustainable technology for complete recycling of concrete waste, including recycled concrete aggregates and recycled concrete fines, to produce carbon-negative geopolymer concrete. The successful completion of this project will promote complete recycling of concrete waste in an environmentally friendly and sustainable way to avoid the use of energy-intensive and high-carbon-footprint. It will also save on monetary and environmental costs related to transportation and disposal of concrete waste, reduce the demand for using natural sand and aggregate, and sequester carbon dioxide. Additional societal benefits will be realized through outreach and educational activities including Summer Engineering Academy and K-12 mentoring programs, development and display of educational exhibits at Biosphere 2, and mentorship of undergraduate and graduate students. The approach of this project is based on the innovative integration of carbonation and geopolymerization, which could fundamentally revolutionize the conventional concept for recycling concrete waste. The research is guided by four hypotheses. These hypotheses address the fundamental mechanisms for complete recycling concrete waste to produce carbon-negative geopolymer concrete. To test them, the project will pursue four research objectives. They include elucidating how the carbonation of recycled concrete fines affects the geopolymerization process and enhance the geopolymer properties, obtaining a fundamental understanding of the interaction between the carbonated recycled concrete aggregates and the geopolymer, studying the performance of geopolymer concrete produced from fully recycled concrete waste through carbonation and geopolymerization, and evaluating the environmental impact and techno-economic feasibility of producing geopolymer concrete from fully recycled concrete waste through carbonation and geopolymerization. The research will not only evaluate macroscale behavior, but also investigate micro/nanoscale morphology, composition, and properties. Evaluation of the environmental impact and techno-economic feasibility will also be performed. Successful completion of the project will advance knowledge in mineral carbonation, geopolymerization, and concrete waste recycling. 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 2025 · 2025-09

The Paleobiology Database (PBDB) is one of the most impactful and widely used digital representations of the fossil record, capturing our best understanding of the age, location, identity, and geological context of fossils. Data held in the PBDB have been used in over 2,000 scientific publications and in a wide range of educational and public outreach materials. The PBDB is an essential resource for geoscientists, biologists, students, educators, and the public. Although the research and educational impact of the PBDB is tremendous, there are key issues with its current computer infrastructure, which was designed in the late 1990s and early 2000s. This project will combine PBDB with the Integrative Paleobotany Portal (PBot) to create a more modern and flexible digital system: the PBDB 2.0. Planned project activities will transform the PBDB to be more useful to a broad community of researchers, educators, and students in the Earth and life sciences, as well as the general public. In particular, the PBDB will adopt features from PBot that will allow users to easily contribute and interact with fossil identifications tied to specimen images, and outreach activities will further motivate community participation with PBDB. This project undertakes a complete technological overhaul of the PBDB, one of the most prominent and widely used fossil databases. Technical improvements include coupling the PBDB with the PBot, whose cutting-edge conceptual framework provides innovative user-centric capabilities. Specifically, development of the PBDB 2.0 will: 1) overhaul the PBDB's data model, database, and application logic to integrate PBot functions, streamline data entry, and improve technical sustainability; 2) create a more capable application programming interface; 3) construct a new web application to leverage back-end upgrades and facilitate new science; and 4) host community events and activities to assess progress, train new members, mobilize data, and produce new educational/outreach materials. Long-term costs of paleobiological cyberinfrastructure will be substantially reduced by consolidating development effort, expanding the PBDB's current functionality to better serve a large community, enhancing overall user experiences, mobilizing new science-critical data, and improving alignments with other data systems. Upgrades will provide explicit support for uncertain taxonomic classification, introduce a more specimen-forward approach to organizing fossil data, make high quality specimen images available alongside data, and add workbench capabilities. Researchers from around the world will utilize the PBDB 2.0 to understand Earth history and Earth systems processes, conduct Rules of Life research, and interpret ecological and evolutionary change across all taxonomic groups, continents, and time periods. The refreshed PBDB 2.0 will make it easier for anyone in the broader community, from professional Earth and life scientists to children, to engage with fossil science. This award by the Geoinformatics program within the Division of Earth Sciences is jointly supported by the Infrastructure Capacity for Biological Research program within the Division of Biological Infrastructure. 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 2025 · 2025-09

With the support of the Chemical Synthesis Program of the Division of Chemistry, Professor Jon Njardarson of the University of Arizona is developing new chemical reaction cascades in that leverage readily available feedstock materials in concert with negatively charged reaction partners to trigger sequences of reactions that produce higher-value fine chemical products. These new reaction processes will have broader scientific impacts by enabling researchers in industry and academia to construct and manufacture target architectures more efficiently, and the fundamental studies of reaction mechanisms will support the design of other new reactions. Broader impacts of this project also include workforce development and the continued dissemination of publicly available and popular educational work products from the PI and team. This project is focused on making significant advances on the asymmetric dienolate cascade reaction platform that the PI’s lab has been developing. Specific advances include in situ trapping of lithium enamides at carbon or nitrogen to expand the type of products that can be assembled in one pot, and realizing the formation of products containing all carbon quaternary centers. Detailed mechanistic investigations have opened and will continue to open new directions of reaction development, including the proposed routes to chiral lactams and atropisomers. This project is also focused on efficient assembly of chiral complex aromatic nitrogen heterocycles and fused ring structures via pericyclic and radical-metal-mediated cascades respectively, with the goal of increasing the impact of the chiral auxiliary. The suite of reactions being developed is expected to impact chemical synthesis and its applications in medicine, materials, and other areas. 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 2025 · 2025-08

Abstract Skeletal muscle plasticity is highly dependent on load, and muscles quickly atrophy under many conditions including disuse, systemic disease, aging, etc., causing drastic consequences for quality of life. Muscle wasting and weakness is caused by disassembly of the sarcomere, the basic contractile structure of muscle. The myofilament titin contains spring-like regions and multiple sites for signaling protein binding, making it a sentinel for changes in muscle load. Titin’s A-band to M-line transition contains an E3 ligase binding site (domains A168-170) adjacent to its mechanosensitive pseudokinase domain (TK). E3 ligases ubiquitinate proteins to target them for degradation, making them important members of the muscle atrophy program. The E3 ligase MuRF1 (TRIM63) is termed an “atrogene” for its propensity to be upregulated in the early stages of muscle atrophy. In vivo overexpression of MuRF1 in the absence of unloading causes muscle wasting at the muscle weight and fiber CSA levels. In vitro experiments have shown that overexpressed MuRF1 colocalizes with the A168-TK segment and causes loss of M-line and thick filament structure. Furthermore, in vitro and in vivo studies show that MuRF1 heavily ubiquitinates titin during atrophy, such that titin is MuRF1’s most highly ubiquitinated substrate. Myomesin and myosin heavy chain are also ubiquitinated by MuRF1, and several thick filament protein components are degraded in a MuRF1-dependent manner during atrophy. The overall goal of this proposal is to decipher the role of titin segment A168-170 and MuRF1 during muscle atrophy, and my overarching hypothesis is that the interaction of MuRF1 and titin A168-170 is important for initiating atrophy by promoting M-line and thick filament disassembly. Toward this end, I generated a mouse model, TtnA168-170→I104-106, in which titin’s E3-binding domains A168-170 are “substituted” with three titin domains lacking an E3 binding site, I104-106. I opted for this novel “substitution” model to preserve general titin structure while preventing MuRF1 (and other E3s) from binding. My preliminary data indicates that titin incorporation and expression are preserved in this mouse model, but that localization of overexpressed MuRF1 at the M-line is lost. To test my hypothesis, I will subject control (WT) and TtnA168-170→I104-106 “substitution” mice to two atrophy models: 1) MuRF1 overexpression via AAV9: CMV-MuRF1-Spot tag, and 2) sciatic nerve transection. I will critically analyze the response of both genotypes based on ubiquitin remnant-enriched quantitative proteomics, muscle structural features, and levels of autophagy- and proteasome-linked proteins and myofilament proteins in fractionated (sarcoplasmic vs. myofibrillar) muscle. Upon completion of this project, I will have established the role of the interaction between titin A168-170 and MuRF1 in initiating sarcomere disassembly during atrophy states, which will indicate if the titin-MuRF1 interaction is a viable therapeutic target.

NIH Research Projects · FY 2026 · 2025-08

SUMMARY The overall objective of this study is to advance our understanding of the role motile cilia play in the fallopian tubes (FTs) and to develop an endoscopic imaging system for in vivo clinical investigation of motile cilia function in FT pathologies. The FTs transport oocytes, sperm, embryos, and provide the environment for the complex and highly regulated process of fertilization and preimplantation development. Motile cilia, dynamic hair-like structures that cover the luminal epithelium of the FTs, are known to play an essential role in reproduction, and impaired cilia motility is associated with fertility disorders in women and reproductive pathologies, including endometriosis. However, because the cilia are microscopic structures and the FTs are positioned deep inside the female body, direct non-surgical imaging investigation has not previously been possible. Additionally, the female reproductive tract is significantly understudied compared to other organ systems. Despite the recognized and critical role of the motile cilia in the fallopian tubes, our understanding of their physiological function and dysfunction is extremely poor, limiting female reproductive disease management and development of infertility treatments. Through our unique integration of expertise in female fertility, endometriosis, imaging hardware and software, we will address this sore problem through three specific aims: Specific Aim 1: Define coordinated cilia function in healthy FTs and impairments in endometriosis. We will investigate cilia dynamics in freshly excised FT segments from premenopausal patients with and without endometriosis, using OCT, bright-field microscopy, and a miniature fiber bundle imager. This fundamental aim will reveal normal and altered FT cilia function and establish optimum imaging parameters. Specific Aim 2: Develop FT endoscopes with OCT and fiber bundle imaging, and test with intact specimens. Sub-mm diameter endoscopes that are clinically capable will be designed, built, and tested on intact reproductive tracts (uterus and FT). Algorithms for disentangling ciliary from probe and sample movement will be implemented, and the system readied for in vivo pilot studies. Specific Aim 3: Perform a pilot in vivo study to visualize cilia movement. Ten pre-menopausal patients undergoing hysterosalpingectomy will be recruited for endoscopic imaging of their FTs during a break in their standard of care surgery. The optimized endoscopes will be tested for their ability to enter the FT in vivo and quantify cilia movement in this challenging environment. Overall, we will advance the current understanding of normal FT cilia dynamics over the menstrual cycle, as well as alterations in the setting of endometriosis, and develop clinically-relevant imaging methods with promise for utility in diagnosing and monitoring FT dysfunction.

NSF Awards · FY 2025 · 2025-08

Distinct from conventional learning paradigms, interactive machine learning captures many real-world settings where learning agents adaptively acquire information and learn to make decisions or gain insights. This paradigm is beneficial in domains where experiments are expensive (e.g., biological imaging and material discovery), as well as in human-safeguarded artificial intelligence (AI) systems (e.g., autonomous driving and chatbots). Despite impressive successes, many critical challenges remain in deploying responsible and resource-efficient interactive learning agents, including a lack of data efficiency, safety, and reusability. The overarching goal of this project is to design principled and practical interactive machine learning algorithms with various feedback modalities that address these challenges, focusing on both single-step and sequential decision-making settings. To this end, the research team will establish theoretical guarantees for the algorithms and release their practical implementations. Integrated with this research project is an education plan that includes an intramural lecture series with the University of Arizona DataLab, a middle school outreach event series in collaboration with the University of Arizona Computer Science Ambassadors Program, as well as undergraduate research projects and curriculum development. The project consists of three interrelated research thrusts. The first thrust studies interactive learning for supervised learning, a single-step decision-making setting. Specifically, the project will focus on designing label-efficient active learning algorithms for nonlinear model classes, including moderately parameterized classes and overparameterized neural networks. The second thrust explores interactive learning for sequential decision-making. It focuses on safe imitation learning from interactive expert demonstrations and interventions, as well as robust reward inference from expert demonstrations. The third thrust aims to address the data reusability challenge in current interactive learning systems by bridging interactive learning and conventional offline learning. Specifically, this thrust will tackle two research questions: first, how to warm-start interactive learners using offline data, and second, how to design interactive learners that collect data amenable to future reuse. 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 2025 · 2025-08

Project Summary/Abstract Proteins carry out the majority of cellular functions and are essential for cellular activities. Most proteins must fold into the correct shape to fulfill their functions and need to endure constantly changing conditions within the cell. However, proteins cannot accomplish this on their own; they rely heavily on chaperones. Different chaperones fulfill various functions to ensure proteostasis. Here, we focus on Hsp60 and Hsp10, which assist in protein folding and prevent protein aggregation. Protein misfolding is implicated in many severe diseases such as Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, cystic fibrosis, and Huntington's disease. Despite decades of research, there is a fundamental gap in understanding the molecular mechanisms underlying the protective role of chaperones. This proposal will address four key questions: 1. How does ATP induce a simultaneous conformational change in all subunits of Hsp60? ATP can bind to each subunit of the heptameric or tetradecameric Hsp60 inducing an enormous conformational change. It is a cooperative process, but how the different subunits communicate with each other remains unknown. Understanding this allosteric mechanism is key to comprehending the kinetic cycle of Hsp60, which involves native substrate binding, encapsulation, and release of the folded substrate. 2. How do substrates interact with a chaperone? Is there a common binding motif? What is the timescale? A given chaperone can interact with many different client proteins. This study aims to determine if there is a common binding motif for substrates when interacting with the chaperone. This will provide detailed molecular principles of how substrates interact with chaperones, and this knowledge is valuable to provide insights into the chaperone's selectivity and its ability to handle various types of substrates. 3. What is the purpose of the tails of Hsp60? Several chaperones have unstructured flanking regions that are essential for their function. However, due to their flexible nature, these regions are not easily accessible to most biochemical methods. Solution-state NMR can provide visualization of how these regions interact with substrates, unraveling their contribution to substrate binding and encapsulation. 4. What is the role of the co-chaperone, Hsp10? Hsp10 has been overlooked for many decades, thought to be merely the helper of Hsp60. Recent studies reveal that Hsp10, in the absence of Hsp60, assists in protein folding and inhibits protein aggregation. Studies, how Hsp10 in the absence of Hsp60 interacts with substrates will help understand how Hsp10 contributes to proteostasis. The combination of all these studies will shed light on fundamental questions about the mechanisms that chaperones and co-chaperones use to efficiently fold proteins into their functional forms and prevent aggregation. A process which crucial to maintaining protein homeostasis, which is vital for life.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY TElomerase Reverse Transcriptase (TERT) is rate limiting in maintenance of telomere length by telomerase and also has telomere independent functions such as regulating cell growth. We showed TERT promoter mutations (mutTERT) occur in ~70% of Bladder Cancers (BC), most commonly at -146bp and −124bp which generate an identical 11 bp sequence that is recognized by a common upstream signaling mechanism. These mutations drive TERT overexpression, maintain BC growth and are associated with poor BC patient prognosis. These data led us to develop a panel of innovative assays specifically designed to identify, through a chemical library screening approach, small molecules that reduce TERT expression from mutTERT but not wtTERT. Discovery of such compounds is a first step in attaining our overall goal of developing a drug that is selectively toxic for BC cells, while having minimal toxicity on normal stem cells, which require TERT for self-renewal. Preliminary Data: Using CRISPR, we constructed BC cells expressing HiBiT or EGFP reporters downstream of mutant or wt TERT promoters. We validated these assays by showing that siRNA-mediated depletion of GABPA, a regulator of mutant promoter expression, selectively reduced mutTERT as monitored by HiBiT or EGFP. We deployed our mutTERT-HiBiT assay in an High-Throughput Screen (HTS) pilot screen of 605 kinase inhibitors and found 23 hits that reduced mutTERT-HiBiT. Among these were inhibitors to known drivers of TERT expression such as Aurora Kinase A, as well as inhibitors that were mutTERT selective, all of which targeted mTOR. This data leads us to the Hypothesis that small molecules that specifically suppress TERT expression driven by a mutant promoter can be identified by a phenotypic screen. Three Specific Aims test this hypothesis. In Aim 1, an HTS screen of a 350K chemical library will be conducted using a mutTERT-HiBiT reporter assay to identify compounds that decrease TERT expression driven off the mutant promoter at 16hrs. Hits will then be confirmed, and counter screened to remove those with unwanted activities. In Aim 2, priority hits will be purchased, reconfirmed in the primary assay and their selectivity to effect mutant over wt TERT evaluated head to head deploying EGFP reporter assays in BC cells and by allele-specific qPCR. An iterative analog-by-catalog (ABC) approach will be used to establish nascent structure-activity relationship of hit scaffolds and improve potency and selectivity. In Aim 3, the best hit from each scaffold that meet a set of rigorous potency and selectivity criteria will be selected as a probe and characterized in multiple assays to map their activity on downstream effects of TERT. These assays use a panel of BC and non-BC cell lines with and w/o TERT promoter mutations to determine the probes’ effects on: 1) downstream TERT-related gene transcription via evaluation of our TERT Expression Signature (TES); 2) telomere length quantitation; 3) Telomerase-dependent and independent TERT functions including cell growth. Future Directions: We set the stage for novel drugs targeting cancer specific, mutTERT driven, telomerase activity in patients with BC or other TERT-driven malignancies.

NSF Awards · FY 2025 · 2025-08

This program will support the manufacturing of a new set of optical filters to be installed in the Hyper Suprime-Cam of the Subaru telescope located in Hawaii. The set of filters built with the support of this program will allow the detailed study of the most distant galaxies in the Universe. The proposed work uses an instrumental design that is innovative and allows the filter set to be easily installed on the telescope. The proposed work uses an innovative design to divide one filter slot into four colors, allowing 16 filters to be installed in just 4 filter slots. This project will train the next generation of scientists in astronomical instrumentation. The PI of this program will partner with the public outreach offices of the Subaru Telescope and the University of Arizona to create science projects accessible to everyone in the states of Arizona and Hawaii. The additional filters to be built under this program, the four reddest bands covering 800-1000 nm, will significantly enhance the science outputs of the Subaru HSC MB survey, especially by extending the redshift baseline. This survey plans to use 56 nights in the Subaru telescope. This new filter set will provide crucial complementary data for the study of high-redshift galaxies. Additional Medium Band filters will improve the sampling of the Spectral Energy Distribution (SED) of distant galaxies, increasing accuracy in the measurements of their physical properties and their photometric redshifts. The new set of filters will contribute high-quality data to the study of galaxy-galaxy lensing, galaxy clustering, large-scale structure, and dark matter. This program will benefit the entire US astronomical community as US researchers will have access to Subaru observing time through time exchange programs such as the one run by the NSF/NOIRLab. Moreover, the NSF/DOE/Rubin Observatory will receive 50 Subaru nights as an in-kind contribution from Japan. 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.