University Of Iowa

NSF Awards · FY 2025 · 2025-07

The National Science Foundation (NSF) EPSCoR Graduate Fellowship Program (EGFP) supports EGFP designated institutions and programs in EPSCoR jurisdictions by providing funding for graduate fellowships for new or continuing EGFP-eligible applicants. EGFP awards provide funding for a total of three years of stipend and an associated cost-of-education (COE) allowance for each NSF EPSCoR Graduate Fellow. This award at the University of Iowa will support eight EPSCoR Graduate Fellows whose research will align with the unique goals and programs supported by the Directorate for Engineering (ENG), Directorate for Computer and Information Science and Engineering (CISE), Directorate for Biological Sciences (BIO), and Directorate for Technology, Innovation and Partnerships (TIP). The project aims to enhance Iowa’s and the nation’s manufacturing capacity by training graduate students to become future industry and academic leaders in advanced manufacturing. The project leverages recent advancements in AI, sensing, and robotics technologies to transform manufacturing systems into data-rich smart and connected systems. It aligns with Iowa’s Manufacturing 4.0 strategy and aims to boost the global competitiveness of Iowa's manufacturing sector. The project will focus on four key areas: Advanced Manufacturing Processes, Sensing and Robotics, Data Integration for Smart Manufacturing Systems, and Biomanufacturing and Biotechnology. Researchers at the University of Iowa’s College of Engineering will utilize additive manufacturing, laser materials processing, photonics/optical sensors, motion planning and control, data fusion, and transfer learning to develop next-generation manufacturing systems. The expected outcomes include the development of AI-enabled, data-driven technologies that reduce costs, boost productivity and innovation, shorten time to market, and improve the quality and scalability of complex manufacturing systems. The project will involve collaboration between various departments in the College of Engineering at the University of Iowa. The educational outcomes will focus on providing high-quality personalized graduate experiences, developing interdisciplinary technical skills and leadership abilities through an interdisciplinary curriculum, hands-on research experiences, professional development workshops, and mentorship programs to ensure the Fellows are well-prepared for successful careers in both academia and industry. Additionally, the program will include a structured mentoring and progress assessment plan, onboarding and orientation activities, professional skill development sessions, and engagement activities to foster a sense of community and collaboration. The researchers will integrate advanced technologies and bioscience expertise to drive economic development, train future manufacturing researchers and engineers, and strengthen the national talent pool in advanced manufacturing. 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 · 2025-07

PROJECT SUMMARY/ABSTRACT Noncarious cervical lesions (NCCLs) are a common dental condition that can result in significant loss of tooth structure and pain, affecting the individual throughout their lifetime. Available intervention options for this condition are limited and not effective long-term. This condition has high prevalence among adults (up to 85% in specific populations), however there is scarce information concerning mechanisms leading to the condition and its progression, especially for wedge-shaped NCCLs. The on-set of these lesions, which can affect different teeth in the individual cannot be explained based on current evidence. There is a significant gap in the understanding of mechanisms behind dentin breakdown during the establishment of wedge-shaped lesions, which may be linked to changes in the dentin organic matrix composition and morphology. Our preliminary data has shown compositional differences of NCCL-affected teeth when compared to sound teeth, indicating that there is a critical need to evaluate the specific roles that enamel and dentin may play in the development and progression of this prevalent condition. The goal of this R03 is to investigate the individual relative contributions leading to tooth breakdown, characterized by loss of mineral and organic components, largely affecting dentin within the cementoenamel junction. To achieve this goal we will investigate compositional, morphological, and histological changes in the affected dentin and enamel (aim 1); and the relationships between those and the biomechanical properties of NCCL-affected dental tissues that could impair the protective mechanisms of the tooth. Dentin and enamel biomechanical properties will be characterized at the nanoscale and relationships will be investigated between key components of the dentin extracellular matrix, including biodegradative mechanisms and the nanomechanical properties of the wedge-shaped NCCL-affected (bounding) tissue (aim 2). Our approach is innovative considering previously unknown factors related to this prevalent condition and providing data for future comprehensive funding mechanisms. Furthermore, these findings will be the key to our long-term translational goal, which is the establishment of targeted successful therapeutic approaches for the prevention and decrease in prevalence of this condition.

NSF Awards · FY 2025 · 2025-07

The radiation belts are a region of high-energy particles that orbit around the Earth. These energetic particles present a hazard to human exploration and technology in space, especially for satellites in geostationary orbit. Understanding the timing and dominant mechanism of radiation belt enhancement events (sudden, system-wide energization of radiation belt particles) is critical to nation security. This project will determine how the plasmapause (the outer boundary of a region of cold, dense plasma surrounding the Earth) controls radiation belt enhancements. One major acceleration mechanism of radiation belt particles (local acceleration) is driven by plasma waves that only occur outside the plasmapause, so we expect that the radiation belt enhancements that are driven by local acceleration would occur outside the plasmapause while other acceleration mechanisms may drive enhancements inside the plasmasphere. This study will systematically evaluate the long-term behavior of radiation belt enhancements and conduct in-depth case studies to evaluate how plasmapause controls radiation belt enhancement events. Radiation belt enhancement events occur when electrons in near-Earth space are accelerated close to the speed of light. Local acceleration is a major acceleration mechanism, which occurs when 10’s – 100’s keV electrons interact with chorus waves, resulting in particle energization to multiple MeV. Chorus waves can only happen outside the plasmapause, so radiation belt enhancements tend to occur outside the plasmasphere. This study will use multi-spacecraft observations provided by the Global Positioning System (GPS) constellation to study the control of the plasmapause on radiation belt enhancements on timescales over a solar cycle. We will study data from 2008 (when 8 GPS with combined X-ray dosimeters, CXDs, were active) until 2023 (25 active GPS with CXD) and combine these data with plasmapause models to statistically analyze the offset of enhancement locations from the plasmapause and energy-dependence of radiation belt enhancements. Case studies will then be performed to examine why the radiation belt enhancements tend to be offset from the plasmapause, determine the spatial extent of the region of electron energization, and evaluate why some radiation belt enhancements occur inside the plasmasphere. 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 · 2025-07

Abstract The lack of clear mechanisms by which host proteins regulate HIV-1 innate immunity in macrophages is a significant knowledge barrier to a functional cure for HIV-1 persistent infection. In this revised R01 proposal, we seek to investigate non-canonical functions of the cellular protein sterile alpha motif and HD domain-containing protein 1 (SAMHD1) in regulating innate immune responses during HIV-1 infection of primary macrophages. Since SAMHD1 was discovered as an HIV-1 restriction factor in 2011, extensive studies have revealed the mechanisms underlying SAMHD1-mediated restriction of HIV-1 replication in myeloid cells and resting CD4+ T cells. In 2018, we discovered a novel function of SAMHD1 in suppressing the innate immune response to viral infections and inflammation in macrophages. However, the underlying mechanisms of action remain unclear, representing a significant knowledge gap given the importance of macrophages in HIV-1 persistence. Our long-term goal is to define the functional roles and molecular mechanisms of cellular proteins, such as SAMHD1, in regulating innate immunity during persistent HIV-1 infection of macrophages. Our overall objective is to reveal how SAMHD1 inhibits the type I interferon (IFN-I) and NF-κB pathways in primary macrophages, acting as a multifaceted repressor of innate immune signaling induced by viral infection. IFN-I induction plays a key role in antiviral innate immunity; however, HIV-1 infection does not induce a strong IFN-I response. NF-κB is critical for HIV-1 gene transcription and immune activation, and transcriptional inhibition of viral gene expression is the main mechanism of HIV-1 latency. Thus, our central hypothesis is that SAMHD1 suppresses innate immunity to HIV-1 infection in primary macrophages by inhibiting IFN-I induction and NF-κB activation. Our three specific aims are: Aim 1. Define how SAMHD1 and IRF7 interaction inhibits IFN-I induction during HIV-1 infection; Aim 2. Examine SAMHD1 interaction with MAVS and effects on anti-HIV-1 innate immune responses; Aim 3. Investigate the mechanisms by which SAMHD1 inhibits NF-kB activation during HIV-1 infection. Our interdisciplinary studies will fill knowledge gaps to fundamentally enhance our mechanistic understanding of SAMHD1 and associated proteins in regulating HIV-1 infection, viral gene expression, immune activation, and anti-HIV-1 innate immune responses. Thus, our proposed studies of how SAMHD1 regulates immune activation and HIV-1 infection in macrophages will provide new knowledge studying viral persistence.

NIH Research Projects · FY 2025 · 2025-07

PROJECT SUMMARY Lithium, a small alkali metal, has unique and complex effects on the nervous system. Known for its protective and proliferative effects on neurons, lithium has long been the primary treatment for bipolar disorder and also shows potential for treating a variety of other nervous system disorders. However, the mechanisms behind its therapeutic benefits and side effects remain largely unknown. Gaining a comprehensive understanding of the molecular and cellular mechanisms that underlie lithium's biological actions is both neurobiologically significant and essential for maximizing its therapeutic potential while minimizing adverse effects. This project focuses on lithium's adverse effects, aiming to identify the underlying biological processes through Drosophila genetics and physiology. The central hypothesis is that the metabolism of amino acids, particularly proline metabolism, plays a crucial role in controlling susceptibility to lithium. Supporting this hypothesis, findings have shown that a putative proline transporter, known as the Lithium-inducible SLC6 transporter (List), is significantly upregulated following lithium treatment. Furthermore, loss-of-function mutations in List result in marked increase in sensitivity to lithium's adverse effects, along with reduced proline levels following lithium treatment. To test the hypothesis, the project will pursue three specific aims: (1) Elucidate the role of proline metabolism in lithium susceptibility. The mouse proline transporter, which is a putative ortholog of Drosophila List, will be assessed for its potential to reduce the mortality in List mutants exposed to lithium. Additionally, genetic variants involved in proline synthesis and degradation will be analyzed to understand the unique roles of proline metabolism in response to lithium. (2) Determine the effects of List and lithium on neural function. Semi-intact neuromuscular junction (NMJ) preparations will be used to examine how specific neurophysiological properties of nerves, synapses, and muscles are altered by List manipulations and lithium treatment. (3) Identify additional genes that influence lithium's adverse effects. Genome-wide association studies will be conducted to identify genes essential for the molecular and cellular processes involved in response to lithium treatment. This work will utilize the Drosophila Genetic Reference Panel, a very powerful collection of genetically and phenotypically diverse inbred fly strains with fully sequenced genomes, under both normal and lithium-sensitized conditions. Given the extensive conservation of fundamental biological processes between Drosophila and mammals, insights gained from this project are expected to illuminate mechanisms underlying lithium's effects in humans. This research will establish a strong foundation for future studies exploring the detailed mechanisms of lithium-responsive biological processes through Drosophila genetics and physiology. Furthermore, collaboration with experts in mammalian biology will support the investigation of these findings' relevance and applicability to mammalian systems. This comprehensive approach aims to significantly enhance our understanding of lithium's beneficial and adverse effects, ultimately contributing to improved treatment options for various nervous system dysfunctions. .

NIH Research Projects · FY 2025 · 2025-07

PROJECT ABSTRACT Potential for Epstein-Barr virus (EBV) involvement in multiple sclerosis (MS) etiology is increasingly recognized, but how infection could trigger or augment myelin autoreactivity is unclear. MS is an immune-mediated demyelinating disease of the central nervous system (CNS), and despite first line drugs that limit symptoms, disease remains incurable. Due to its early life onset and rise in prevalence for nearly 1 million Americans, MS imparts an immense health and economic burden on the United States. Adaptive immune cells, particularly CD4 T cells (CD4s), have long been considered integral players in neuroinflammation and demyelination in MS, and B cells have been appreciated as playing a pathobiological role, highlighted by the success of anti-CD20 B cell depletion therapy (BCDT). Mechanistically, B cells are thought to support autoreactive CD4s through antigen presentation. Given EBV is a gamma herpesvirus (gHV) that latently infects human B cells, it is postulated infection may influence disease-driving B:CD4 interactions by enhancing autoantigen presentation. Few MS animal models are well-equipped to dissect B:CD4 interactions in this viral context, as the vast majority of EAE (experimental autoimmune encephalomyelitis) studies feature B cell- independent disease. To circumvent this, we have developed a B cell-dependent, antibody- independent EAE model in WT B6 mice featuring CD4 T cell immunoreactivity to the extracellular domain sequences of the highly abundant and 100% conserved myelin proteolipid protein (PLPECD). Through rigorous experimentation, we have identified B cell-mediated antigen presentation to CD4s through MHC class II as the required pathogenic B cell mechanism in PLPECD-induced EAE, where B cells engage PLPECD through the B cell receptor and are more efficient than dendritic cells at processing and presenting immunodominant residues from within PLPECD to PLP178-191-reactive CD4 T cells. Further mimicking the sustained pathogenic B cell involvement seen in MS and unlike B cell-independent EAE driven by PLP178-191, BCDT robustly ameliorates established PLPECD disease. Thus, we have developed a novel and powerful tool to investigate how gHV infection impacts key pathogenic B:CD4 interactions during development of autoimmune demyelinating disease. We hypothesize that gHV infection of WT B6 mice exacerbates B cell-dependent but not B cell-independent EAE by enhancing B cells’ support of autoreactive CD4s. Specific Aim 1 will determine how gHV infection affects B cells’ support of disease-driving CD4 T cells. Specific Aim 2 will determine how gHV infection impacts B cell- dependent vs. B cell-independent EAE.

NSF Awards · FY 2025 · 2025-07

In the world of high-performance computing (HPC), the growing complexity and shrinking size of hardware components make systems more vulnerable to "soft errors"— temporary glitches that can disrupt calculations. Traditionally, these issues were managed through hardware-based solutions like redundancy, but these approaches consume significant energy, a major concern for modern processors. This project addresses the challenge of making HPC systems more resilient to soft errors without the high energy costs of traditional methods. It focuses on identifying and protecting the most vulnerable parts of a program — the specific states where errors are most likely to cause problems. By doing this efficiently, the project aims to ensure that programs can continue to function correctly even when errors occur. The broader benefits of this project include advancing the field of reliable computing, promoting energy-efficient technologies, and supporting education by making cutting-edge resilience techniques accessible to software developers and classrooms. Ultimately, this work contributes to the creation of more robust and efficient computing systems that can handle the increasing demands of modern technology, benefiting industries, education, and society as a whole. This project aims to address the increasing vulnerability of HPC systems to transient hardware faults, or soft errors, which are exacerbated by larger system scales, advanced technology scaling, and lower operating voltages. Traditional hardware-only solutions such as dual modular redundancy are becoming less viable due to their high energy consumption, making it essential for future HPC applications to tolerate such faults. The project focuses on developing a compiler-directed framework that rapidly and accurately models error propagation, identifying and protecting only the most vulnerable program states to minimize performance and energy overheads. The project involves integrating static program analysis, dynamic input fuzzing, program invariants, redundancy, and compiler code transformations to create an efficient protection strategy. By automating the process of hardening programs to meet specific reliability targets, the investigator aims to advance the field of reliable computing, reducing the barriers to implementing resilience techniques in HPC systems, and contributing to the development of energy-efficient, fault-tolerant software. This project is jointly funded by the Software and Hardware Foundations Program, the Office of Advanced Cyberinfrastructure, and the Established Program to Stimulate Competitive Research (EPSCoR) Program. 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 · 2025-07

ABSTRACT Allosterically active enzymes are flexible for a number of reasons. Understanding the changes in macromolecular dynamics due to small molecule complexation and the enzyme's catalytic power is often the key to unlocking better avenues for drug lead development, and can often yield insights into the raison d'être for such flexibility. Glutamate racemases (GR) and the executioner caspases-7 (C7) are two such systems, both coveted and validated drug targets, the former for antimicrobials and the latter for Parkinson's and inflammatory diseases. Interestingly, the similarities between the two are manifold. We have employed a range of experimental and computational approaches to elucidate their respective allosteric mechanisms and to discover novel drug lead compounds that exploit these requisite dynamics. GR is essential to a wide variety of microbes, and an excellent antimicrobial drug target: D-glutamate, an essential component of the peptidoglycan layer of bacterial cell walls is synthesized by bacterial GRs. A large body of biological and pharmacological studies have established GR's essentiality. A particularly attractive GR system for understanding long range allosteric mechanisms is the GR from H. pylori, (HpGR; a target for gastric cancer). Early allosteric hits against HpGR were not able to move beyond the laboratory for reasons related to the nature of the enzyme's allsoteric pockets. A compounding factor is that a mechanism of action, by which occupancy of the cryptic allosteric pocket remotely leads to inhibition, has heretofore remained elusive. This is a trend that has plagued allosteric drug discovery in general. Our research program has made progress in addressing these knowledge gaps by employing both experimental biophysical and computational approaches. Our simulations on HpGR and C7 complexes have found that key global motions are dampened when allosteric drugs are bound. Critical networks involving their catalytic Cys/His dyads remain non-productively trapped. In the case of C7 our group has developed the first drug-like allosteric inhibitors, and have determined high resolution structures of these complexes that show how the Cys/His catalytic dyads are distorted, including a disorientation of C7's oxyanion hole. In the case of HpGR, we have used these structural and computational insights to design a novel series of drug-like inhibitors that have excellent MIC values against clinically relevant drug-resistant H. pylori strains. Our goal is to elucidate the relationships between catalytic determinants and global enzyme dynamics driven by small molecule complexation. Understanding how catalytic potential and dynamics are being altered will clarify why allosteric drugs are inhibiting these pharmacologically important enzymes. This proposal will develop a new kind of metric, the Allosteric Structure Activity Relationship (ASAR), for which we have an excellent start on both HpGR and C7. Closing these gaps via development of ASARs, will be accomplished by linking experimental and computational horizons which are not often employed together.

NSF Awards · FY 2025 · 2025-07

This award is made in response to Dear Colleague Letter 24-130, as part of the ECosystem for Leading Innovation in Plasma Science and Engineering (ECLIPSE) interdisciplinary program. In semiconductor manufacturing, small solid particles, such as dust particles, are a source of contamination. Microchips made from silicon wafers are ruined when a particle lands on its surface during one of the manufacturing steps. Many of these steps involve a plasma to etch or deposit thin films. During these steps, small particles of nanometer or micron size can flake from chamber walls, or grow in the plasma itself, and then fall to the wafer and contaminate it. In this project, a recently invented method of mitigating this contamination is explored to gain an understanding of the physical processes involved towards developing even better mitigation methods. These methods involve applying an electric charge to the particles before they fall on the wafer, and using electric forces to lift and eliminate the particles before they contaminate the wafer. This project includes K12 outreach, course development, and training of both undergraduate and graduate students. This collaborative research effort by the University of Iowa and Appalachian State University focuses on the plasma afterglow, which is the condition lasting a few milliseconds after turning off the radio-frequency electrical power that had sustained the plasma. It is during an afterglow that particles can fall to a wafer and contaminate it. An afterglow occurs also during the off-time in modulated-power operation, which is commonly used in manufacturing. During the afterglow, the particle’s electric charge changes rapidly. It was recently discovered that the residual charge can be controlled by applying voltages to electrodes in the plasma chamber during the afterglow, thereby allowing an electric force to lift the particles and reduce the number that fall to the wafer. In this project, understanding of processes in the afterglow will be expanded by performing experiments and simulations. In the experiments, particle charge and movement during modulated plasma operation will be measured by video microscopy. 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 · 2025-07

This project is about using recent advances in mathematics to improve lattice based cryptography. Lattice based cryptography is a foundation for advanced cryptographic schemes that are resistant to attacks by quantum computers. Secure cryptography is essential for digital communication, for example for ensuring the safe transfer of sensitive financial data. The new mathematical advance behind this project is the efficient construction of lattices that have both addition and multiplication operations and that are more densely packed than the ones now typically used in cryptography. The central goals of the project are to improve these constructions, to develop faster algorithms to operate on these lattices, and to build more efficient cryptographic applications using them. The technical advances in this project concern number fields with small root discriminants. This project will study the computational complexity of constructing such number fields and of performing arithmetic operations in them. Prior work on infinite families of number fields with small root discriminants has focused on existence theorems. This project will build on work of two of the P.I.s on efficient explicit constructions of such families. The goal is to improve these constructions using a variety of mathematical techniques including Galois cohomology, explicit Chebotarev theorems and recent advances on Hilbert's 12th problem via p-adic methods and modular forms. Another goal is to develop fast Fourier methods for performing arithmetic operations of the kind needed in cryptography. The relevance of number fields with small root discriminants was noted by Peikert and Rosen in 2006. They showed that such fields lead to very small connection factors relating the difficulty of solving the worst case of the short vector problem to the difficulty of solving the average case of the short integer solution problem. The cryptographic protocols to be studied using the rings of integers of the above fields include collision resistant hash functions, homomorphic commitment schemes, streaming authenticated data structures, zero-knowledge proof systems, and some types of digital signature schemes. 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 · 2025-07

PROJECT ABSTRACT Cochlear implants (CI) provide an effective form of hearing rehabilitation for adult and pediatric patients with hearing loss. However, multiple factors, including neo-ossification, may negatively impact long term CI performance and hinder the consistency and durability of recipient benefit. Post-CI neo-ossification is ubiquitously seen in human cadaveric studies of CI recipients and has been associated with 1) worse speech recognition scores, 2) poor neural health and 3) delayed loss of residual acoustic hearing after cochlear implantation. Prior data shows a diverse pattern of post-CI neo-ossification within the cochlea, often forming both de-novo in the scala tympani, separate from direct from otic capsule endosteal extension. The factors which contribute to the cochlear pre-disposition to neo-ossification from varied insult (surgical trauma, infectious, autoimmune) remain unidentified. Objective CI measurements, including complex impedances measures (CIM) and electrically evoked compound actional potential (eCAP) derived measurements, are proposed as biomarkers sensitive to local changes in neural health and the electrode microenvironment (including neo-ossification). However, these biomarkers have not been validated with direct, in-vivo observations of the cochlear environment in humans. There is currently a lack of direct clinical assessments and basic mechanistic investigations of post- CI neo-ossification, creating a critical knowledge gap in understanding the clinical impact, time course and biologic mechanisms of post-CI neo-ossification. The goal of this proposal is to understand the time-course and clinical impact of post-CI neo-ossification in human CI recipients, validate proposed clinical biomarkers of post- CI neo-ossification and investigate the cellular mechanisms of post-CI neo-ossification in a mouse model. We hypothesize that post-CI neo-ossification negatively impacts clinical CI outcomes, is detectable through impedance and eCAP CI measures and that neo-ossification occurs through a process of endochondral ossification. To test this hypothesis, Aim 1 will leverage photon counting computed tomography and 3D X-ray microscopy imaging to obtain novel in-vivo, inner ear assessments of post-CI cochlear neo-ossification in human and mouse CI recipients to better understand the impact of neo-ossification on objective CI measures, neural health and clinical outcomes. Aim 2 will utilize a mouse model of cochlear implantation to define the pathophysiologic mechanisms of post-CI neo-ossification and identify relevant cellular populations and signaling pathways that contribute to the cochlear pre-disposition for neo-ossification. The expected results of this study will have high scientific and clinical relevance because they will 1) identify common mechanisms of post-CI neo- ossification relevant to both future studies of other causes of cochlear neo-ossification and the development of mitigative strategies to improve CI efficacy, 2) validate clinical biomarkers and radiologic protocols for assessing post-CI neo-ossification and 3) determine the effect of neo-ossification on CI outcomes.

NSF Awards · FY 2025 · 2025-07

This award will cover travel for fourteen early-career mathematicians to attend the International Workshop in Operator Theory and Applications (IWOTA), to be held at the University of Twente in the Netherlands, during July 14 - 18, 2025. The conference is not only the largest operator theory conference in the world, but it is also considered the premier event that connects operator theory to other disciplines that employ operator theoretic techniques and related mathematical results. IWOTA 2025 will be devoted to all aspects of operator theory and its applications and will feature top researchers from all around the world. Having such a major event organized in Twente will also provide a unique opportunity to reinforce research ties between some of the best experts in the field in the United States, the Netherlands, the United Kingdom, and Europe. Many problems in physics, mathematics, and engineering can be best described by representing complex physical entities as large arrays of numbers and mathematical symbols called matrices. Matrices help us visualize how linear transformations act on vector spaces; determining their structure reveals important properties of the transformations. Hilbert space operators are infinite-dimensional generalizations of matrices. The generalization of a vector is often a function, so operators are frequently modeled as multiplications on spaces of functions. IWOTA 2025 will consist of several plenary mathematics lectures describing the latest developments in the relevant workshop areas. These lectures will cover the latest developments in the connections of single and multivariable operator theory with such specific topics as mathematical foundations of artificial intelligence and machine learning, numerical linear algebra, mathematical system and control theory, harmonic analysis, and spectral theory of both random and non-selfadjoint operators. Based on attendance figures at past meetings, the local organizers expect approximately three-hundred participants, including about forty graduate students. The conference website is https://www.utwente.nl/en/iwota2025/. 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 · 2025-07

Michael Schnieders of the University of Iowa is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to develop new computational methods to simulate and predict the physical properties of complex organic crystals. These crystals play a vital role in daily life: from helping to transform promising pharmacueticals into bioavailable tablets to allowing scientists to explore how the building blocks of cells function using crystallography experiments. For small molecules with just a few dozen atoms, computational methods can predict packing into different crystalline structures called polymorphs—each with unique properties such as stability and water solubility. But for larger, more flexible molecules—like proteins or new drugs with hundreds or thousands of atoms—this prediction becomes far more difficult. Schnieders and his team will tackle this challenge in two key ways. First, they’ll create a method—up to 100 times faster—to determine which crystal polymorph is most stable by simulating how crystals shift from one form to another. Second, they’ll integrate acid/base chemistry into their models to better capture how molecular crystals are influenced by pH. These breakthroughs could speed up the design of new therapuetics and help uncover enzymatic mechanisms. Beyond the lab, Schnieders will spark interest in science through a high school internship program, train graduate students in cutting-edge computational skills, and share the software developed to support these efforts , Force Field X, freely with the scientific community. Organic crystals are essential for developing bioavailable pharmaceuticals and studying biomolecular structures via crystallography. Molecules within a crystal can form multiple polymorphs, each with distinct properties like stability and solubility, making accurate prediction of observed polymorphs critical. Current methods for estimating free energy differences between polymorphs rely on inefficient approaches, such as the Einstein crystal method, which involves summing large, opposing free energy terms. Schnieders will develop methods to overcome this by introducing a novel dual-topology approach for solid-solid phase transitions, enabling direct, efficient estimation of relative free energies between complex crystal polymorphs with equilibrium sampling methods. For protein crystals, Schnieders will advance molecular simulations by integrating charge penetration, charge transfer, and neural network terms into polarizable atomic multipole models, enhancing the treatment of (de)protonation via constant pH molecular dynamics (CpHMD). These innovations will improve the accuracy of crystal structure prediction and deepen insights into protein behavior. Broader impacts include mentoring high school students in STEM, integrating new methods into a Computational Biochemistry course for graduate training, and disseminating all algorithms via the open-source Force Field X software (http://ffx.biochem.uiowa.edu). 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 · 2025-07

With the support of the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Dr. Bowden and Dr. Leddy of the University of Iowa will synthesize polymers that have potential applications as flexible solar cells, supercapacitors, and wires for the next generation of electrical devices. The polymers to be synthesized are based on sulfur and nitrogen, inexpensive materials commonly found throughout nature. This project will result in the design and synthesis of numerous examples of these polymers, followed by an extensive investigation of their electrical and electrochemical properties, including how well the polymers conduct electricity. The electrical properties will identify their best technological and, potentially, practical applications. A key broader impact of this work is that it will result in the fabrication of polymers that are vastly underexplored and can yield new insights into how to make electronic devices from plastics. A further broader impact will be integration of graduate and undergraduate students throughout the research project to teach them advanced methods for the synthesis of polymers and measurement of their properties. Students will also investigate how these polymers can be used to remediate highly polluted Superfund sites by the removal of toxic heavy metal and lead contaminants from water. The proposed work will result in the synthesis and characterization of polymers with backbones that contain only sulfur and nitrogen. These polymers are rare in macromolecular science despite the potentially high electrical conductivity of the polymer backbones that may find applications in advanced technologies. Professor Bowden’s group will synthesize these polymers using carbamates, amides, and urethanes and some of these polymers will be further reacted to yield well-defined polymers that are greater than 98% by weight nitrogen and sulfur. The electrical and electrochemical properties of these polymers will be thoroughly investigated by Professor Leddy’s group to determine how polymer structures relate to electrical conductivities. The synergy of this collaboration will advance our fundamental understanding of sulfur and nitrogen rich polymers and the development of these novel materials as electroactive polymers. In addition, as these polymers possess both soft and hard atoms along their backbones, the polymers will be investigated for their efficiency to complex and remove heavy metals from Superfund sites. 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 · 2025-06

PROJECT SUMMARY/ABSTRACT Measles virus (MeV) is a leading cause of vaccine-preventable deaths worldwide. Measles outbreaks outnumber mumps, polio, rubella, and whooping cough combined. We reported that MeV rapidly spreads from cell-to-cell through intercellular pores within well-differentiated primary cultures of airway epithelial cells (HAE). This cell culture model is unpassaged and cultured directly from human donor lungs onto support filters at an air-liquid interface. Cell-to-cell spread of MeV in HAE gives rise to distinct foci termed infectious centers. Infectious centers in HAE are not observed with any other respiratory virus tested to date. Our research suggests that the formation of infectious centers, their subsequent release, and the resulting environmental contamination play a crucial role in the efficient host-to-host spread of MeV. In this R21 proposal, we investigate how MeV forms infectious centers and why other paramyxoviruses don’t. We postulate that MeV uses a shrewd strategy in which a membrane fusion apparatus (MFA), consisting of 3 viral proteins (i.e., matrix (M), fusion (F), and hemagglutinin (H)) opens intercellular pores. Following pore formation, the ribonucleoprotein (RNP) complex that minimally contains the viral RNA genome, nucleoprotein (N), phosphoprotein (P), and polymerase (L), passes through the pore. In this proposal, we term this process “MFA trailblazing.” Our long-term objective is to explain why MeV is more contagious than closely related respiratory viruses. The immediate objective of this proposal is to probe the mechanism of rapid infectious center formation in airway cells. In Aim 1, we propose to use live-cell imaging and two fluorescently tagged viruses to confirm our preliminary immunocytochemistry results that show MFAs precede RNPs in newly infected airway cells. MeV- RNPtracker expresses GFP-tagged P protein (in addition to endogenous P). Similarly, MeV-MFAtracker expresses mCherry-tagged H protein and can track the MFA in real-time. In Aim 2, we demonstrate that infectious center formation can be replicated by expression of only 3 MeV proteins that make up the MFA (i.e., M, F, and H). We use replication deficient adenoviral vectors for delivery. Modular expression of adenoviral expressed viral proteins allows numerous advantages including: 1) rapid generation of recombinant expression vectors; 2) low risk that genetic manipulations of transgenes will impact vector titer; and 3) many combinations of viral protein comparisons are possible. This novel tool will allow for the substitution of proteins with known mutations that will alter complex formation; as well as, substitution of orthologous proteins from other paramyxoviruses. MFA trailblazing is a novel mechanism to explain the rapid formation of infectious centers in HAE and has the potential to uncover crucial interactions between virus and host.

NIH Research Projects · FY 2026 · 2025-06

Project Summary Clostridioides difficile is an opportunistic pathogen and a leading cause of hospital-acquired infectious diarrhea. The Centers for Disease Control has declared C. difficile an urgent threat to public health. The frontline antibiotic against C. difficile is the broad-spectrum antibiotic vancomycin. Although vancomycin is highly effective against C. difficile, it also targets the healthy microbiota. C. difficile spores survive antibiotic treatment, leading to unacceptably high rates of relapse when the course of vancomycin comes to an end. An antibiotic that kills C. difficile more selectively would presumably improve outcomes, but developing such a drug requires identifying targets uniquely important to C. difficile. One potential target is the enzymes that crosslink the peptidoglycan (PG) cell wall that protects C. difficile from lysis due to internal osmotic pressure. The PG is a bag-like molecule composed of glycan strands stitched together with peptide crosslinks. In most bacteria, the crosslinks are classified as 4-3 crosslinks and are created by enzymes called PBPs. C. difficile is unusual in that most of its crosslinks are classified as 3- 3 crosslinks and are created by enzymes called LDTs. We recently discovered that 3-3 crosslinks and LDTs are essential for viability in C. difficile. That makes C. difficile the first organism known to require 3-3 crosslinks for survival. We also found that LDTs are important for cell division and sporulation. In the course of those studies, we identified a new family of LDTs whose hallmark is a catalytic VanW domain. We propose that a deeper understanding of VanW-type LDTs will advance basic science and might lead to the development of antibiotics that kill C. difficile without disrupting the healthy microbiota needed to keep C. difficile infections from recurring. The goals of this proposal are to: (i) determine the structure of a VanW domain and how it catalyzes transpeptidation; (ii) determine how VanW domain LDTs are recruited to the site of cell division; and (iii) determine the role of LDTs during sporulation. In summary, the work proposed here will provide insight into the function of a novel family of LDTs present in C. difficile and other Gram-positive bacteria and provide foundational knowledge to advance exploiting LDTs as drug targets.

NSF Awards · FY 2025 · 2025-06

This I-Corps project focuses on the development of a portable surgical simulation platform that enables structured training and objective assessment of orthopedic procedures. The project addresses a critical gap in surgical education by providing a reusable, radiation free, and cost-effective alternative to traditional education methods such as cadaver labs and live patient instruction. This simulator recreates common orthopedic trauma scenarios using anatomically accurate models and real surgical tools, allowing residents to develop technical skills in a low-risk and repeatable environment. A built-in three-dimensional tracking system enables precise simulated X-ray imaging, a core component of orthopedic procedures, while also providing automated performance assessments for objective feedback and skill benchmarking. This approach supports measurable learning outcomes and the establishment of national competency standards. The need for such technology is underscored by recent mandates for simulation-based training in residency programs and the growing emphasis on hands-on, data-driven education to improve patient safety and surgical outcomes. This project promotes the advancement of medical education across diverse training environments, particularly benefiting institutions with limited access to cadaveric or operating room-based instruction and ultimately contributes to national health and welfare by strengthening surgical training and preparing future surgeons for safe, effective clinical practice. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of a high-fidelity orthopedic simulation platform that integrates anatomically accurate surgical models and real surgical tools with an electromagnetic 3D tracking system. Together, this enables sub-millimeter tracking of surgical tools and anatomical models, provides radiation-free simulation of intraoperative imaging, and captures quantitative metrics such as procedural efficiency, accuracy, tool-to-bone interactions, and decision-making abilities. These data-driven insights enhance learning by providing objective feedback and performance benchmarking against other residents and expert surgeons. Unlike conventional training solutions, which lack objective assessment or real-world tool dynamics, this platform merges physical and digital components to create a scalable and modular training environment with high surgical accuracy. The approach builds on advancements in simulation, image-guided surgical navigation, and real-time tracking systems to produce a product with immediate applicability in residency programs. Its technical innovation and focus on measurable outcomes establish a new benchmark in surgical education, with potential to expand into other image-guided procedural specialties such as neurosurgery, interventional radiology, and general surgery. 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 · 2025-06

OVERALL ABSTRACT/PROJECT SUMMARY Mutations in more than 50 different genes cause Primary Ciliary Dyskinesia (PCD) by disrupting the activity of motile cilia that facilitate mucociliary transport. Knowledge of PCD has come from studies identifying disease- causing mutations, characterizing structural cilia abnormalities, finding genotype-phenotype relationships, and studying the cell biology of cilia. Despite these important findings, we still lack effective treatments and people with PCD have significant pulmonary impairment. As with nearly every other disease, a better understanding of pathogenic mechanisms can lead us to effective treatments. To overcome some of these limitations, we developed a PCD pig with DNAI1 disrupted. PCD pigs develop the hallmark sinonasal and pulmonary features of human PCD including neonatal respiratory distress in newborns and mucus obstruction, inflammation, infection, and bronchiectasis in older pigs. It is already providing exciting discoveries that provide some of the foundation for the central theme of this PPG. The overarching goal of this program is to understand better the pathophysiology of PCD airway disease to improve treatments and preventions that will change the lives of people who suffer from this debilitating disease. The Projects are closely interrelated. We will address 3 main questions: What is the early pathogenesis of PCD? What happens to mitochondrial-dependent metabolism when ciliary beating is impaired? Will DNAI1 gene addition to ciliated epithelial cells repair the outer dynein arm, restore cilia function, and impact disease development and progression? We hope to have an important positive impact on accelerating discovery of new disease mechanisms and therapeutic interventions for PCD.

NSF Awards · FY 2025 · 2025-06

Von Neumann algebras are collections of infinite matrices with complex entries and were initially developed to provide a rigorous mathematical framework for quantum mechanics. Early work by pioneers of the field during the 1930s and 1940s revealed that von Neumann algebras are highly complex objects exhibiting remarkably rich structural properties. Over time, their study evolved into an independent and vibrant area of mathematics, spurring the development of powerful mathematical theories and uncovering deep connections with other fields such as group theory, dynamical systems, topology, and more recently, model theory. Beyond mathematics, von Neumann algebras have also provided valuable insights in physics (notably statistical mechanics), biology (DNA molecular structure), engineering (cell phone network design), and computer science (including error-correcting codes, quantum information theory, and quantum computing). These algebras naturally arise from simpler mathematical concepts like groups (symmetries) and their actions on spaces, which are extensively studied in geometric group theory and ergodic theory. The project investigates a number of open problems, with the central goal of developing new methods at the intersection of these disciplines to advance the classification of von Neumann algebras arising from such structures. Additionally, the project offers extensive opportunities for graduate student training and career development. Building on the PI’s prior work, this project will investigate new research avenues in the classification of group and measure space von Neumann algebras, along with their broader applications. The PI will develop innovative techniques that lie at the crossroads of deformation/rigidity theory, group theory, ergodic theory, and continuous model theory to advance several fundamental open problems: (i) identifying new groups and algebraic group structures that are fully determined by the von Neumann and C*-algebraic frameworks, such as property (T) W*- and C*-superrigid groups, including those with infinite centers; (ii) calculating the endomorphism semigroup, the fundamental semigroup, and the Jones index set of property (T) group factors, as well as automorphism groups of reduced group C*-algebras; (iii) constructing new, naturally occurring examples of W*-superrigid actions—an area of mutual interest in orbit equivalence and von Neumann algebras; (iv) investigating tensor product decompositions for factors associated with negatively curved groups and existentially closed factors; and (v) developing new methodologies to distinguish ultrapowers of factors. This work is inherently interdisciplinary, promising significant synergies among geometric group theory, ergodic theory, C*-algebras, model theory, and von Neumann algebras. To foster the professional growth of the PI’s graduate students, the project will continue to support a visiting program that enables students to collaborate with peers at leading institutions, broadening their exposure to diverse research perspectives and expertise. In addition, the PI will continue to promote this field by teaching advanced graduate courses, organizing specialized seminars, and actively disseminating research outcomes through publications, invited talks, and presentations at national and international conferences and research seminars. 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 · 2025-06

PROJECT SUMMARY: Development of the mouth is complex, requiring the proper segmentation of epithelial domains along the dorsoventral axis into oral, dental, and skin lineages. Congenital defects impacting structures derived from these lineages are common and can be severely debilitating for those afflicted, thus necessitating a precise understanding of their underlying genetic control. Knockout (KO) mouse models have begun to identify genetic programs responsible for driving individual epithelial lineages. However, despite these efforts, if and how these programs (oral, dental, skin) intersect and their functional influence on one another remains poorly understood. We found that in the mandibular ectoderm SHH, Sox2, Pitx1 and Pitx2 are strongly expressed on the dorsal, oral/dental-fated side, while WNT, Tfap2a and Tfap2b are strongly expressed on the ventral, skin-fated side. While expression domains initially overlapped at E9.5, they formed complementary expression domains at E11.5, coincident with the specification of oral/dental or skin fates. Highlighting the functional significance of these partitioned networks, early ectodermal double KO of Tfap2a/Tfap2b (Tfap2- LOF) led to a ventral expansion of the oral/dental domain, including associated transcription factors, signaling pathways, and structures, such as an ectopic incisor. Conversely, KO of Pitx2, associated with arrest of the dental lineage, led to a dorsal expansion of the skin domain, including associated transcription factors and signaling pathways. Our overall objective with this proposal is to determine how interactions between different groups of transcription factors—namely, SOX2/PITX1/PITX2 and TFAP2A/TFAP2B—drive the specification of oral/dental or skin fates, respectively, within the mandibular ectoderm. In Aim 1, we will determine how these domain specific transcription factors, including SOX2, PITX1, and PITX2 in the dorsal oral/dental epithelium and TFAP2A and TFAP2B in the ventral, aboral, skin epithelium counteract one another, to both strengthen and refine these domains. In Aim 2, we will identify how TFAP2 programs a ventral/skin identity, including regulation of this program at a chromatin level. Finally, in Aim 3, we will identify the cellular and molecular underpinnings associated with the expanded dorsal domains, including communication between epithelium and underlying mesenchyme, and the involvement of SHH and WNT in defining odontogenic competence of the underlying mesenchyme, in Tfap2-LOF embryos. Collectively, using a strong set of in vivo animal models, explant, and genome wide assays, these studies will fill a critical knowledge-gap in our current understanding of epithelial patterning along the dorsal-ventral axis of the mandible. The Principal Investigators of this MPI study have complementary expertise in relevant areas for this proposal. They will collaborate with Dr. Kenny, an expert in gene regulatory networks and genome wide assays. Collectively, the experimental design and approach, the PIs, and the environment outlined provide the catalyst to improve oral and craniofacial health.

NIH Research Projects · FY 2025 · 2025-06

Project Summary Monoamine oxidase (MAO) is a mitochondria-localized enzyme that metabolizes catecholamines via oxidative deamination to produce H2O2, NH4+, and catecholaldehydes, each of which may individually induce toxicity and/or lead to secondary metabolic effects in the cell. Our lab and others have demonstrated the pathophysiological significance of MAO in heart with experimental and clinical models of pressure overload, arrhythmia, and diabetes. Obesity and insulin resistance are widespread and growing metabolic disorders known to be linked to cardiomyopathy, and previous work from our lab has shown that MAO activity increases while catecholaldehyde-detoxifying enzyme decreases in the heart with these disorders, leading to a buildup of reactive metabolites causing derangements in mitochondrial ATP production. We have also shown that catecholaldehydes stimulate pro-inflammatory and pro-fibrotic signaling in the heart, and that the histidyl dipeptide carnosine mitigates these effects by neutralizing these reactive molecules. Together, this suggests a significant role for MAO in obesity/insulin resistance-associated cardiomyopathy, although the targets and mechanisms driving the metabolite toxicity are unknown, largely due to the highly reactive nature of these molecules and difficulties associated with their detection. These knowledge gaps must be addressed in order for therapeutic development to proceed. In this project I will test the hypothesis that all 3 of MAO’s reactive metabolites (i.e., H2O2, NH4+, and catecholaldehydes) contribute individually to mitochondrial abnormalities and electromechanical dysfunction in heart with diet-induced obesity, and reducing their production in cardiomyocytes via genetic (i.e., cardiomyocyte-specific MAO-A deficiency, cMAO-Adef) and pharmacological approaches (i.e., oral carnosine therapy) will be cardioprotective. As part of my dissertation project I have recently developed a sensitive LC-MS/MS method to detect and quantify catecholaldehyde-carnosine adducts in biological material, which will be used as a quantitative biomarker to track effectiveness of MAO inhibition and carnosine efficacy in the mouse models employed. I will accomplish the goals of this research through three specific aims using wild-type and cMAO-Adef mice on normal chow and high fat, high sucrose diet. In Aim 1, I will determine the extent to which cardiomyocyte MAO-A deficiency mitigates derangements in myocardial structure, tissue composition and function with obesity/insulin-resistance. In Aim 2, I will determine the mechanisms by which MAO metabolites contributes to mitochondrial abnormalities in the heart with obesity/insulin-resistance. In Aim 3, I will interrogate molecular targets of catecholaldehydes and MAO- dependent oxidative damage in the hearts of obese/insulin-resistant mice. To accomplish these goals, I will work with an interdisciplinary team of toxicologists and cardiovascular physiologists and the core facilities at the University of Iowa. It is anticipated that my project will advance the fields of toxicology and molecular cardiology, and illustrate pathways by which MAO and its metabolites are viable drug targets in the heart with obesity.

NSF Awards · FY 2025 · 2025-06

Thousands of times a day, people hear speech and implicitly know whether what they heard was a consonant like “b” or a “p” or a vowel like “ee”. This act feels automatic and simple, but cognitive science suggests it is enormously challenging. Every talker says these same sounds a little differently, and they sound different in different contexts. Thus, the auditory system must do a lot of work just to identify these basic sounds. This is particularly important in the context of learning language and reading. Children can’t recognize a word like “beach” if they can’t identify the “b’s” and “ee’s” and “ch’s” that comprise it. More importantly, when learning to read, children must learn the complex mapping between letters and these auditory categories—that have to learn that a letter string like EE, EA or Y can make the “ee” sound. If the auditory process is not working effectively, learning these crucial phonics skills will be hard. Supporting these points, much prior research has linked differences in how listeners categorize speech to real-world concerns including development, language and reading disorders, second language learning, and aging. This project builds on previous work in significant and novel ways. The study team’s prior work has led to a simple new way to assess these skills in which people hear sounds that have been morphed from one to another and rate them on a continuous scale. This new task has revealed a surprising new dimension to the problem of speech perception which is, the degree to which a people’s percept is stable across multiple encounters with the same sound, or consistency. Consistency changes with development. It is linked to both reading and language disorders. It predicts 30% of the variance in overall language ability in adults. One part of the project investigates the nature of categorization consistency, by asking whether it reflects general cognitive tendencies, noise in the auditory system, or something specific to speech, looking at both children and adults and relating consistency to real-world variation in language and reading ability. Another part of the project develops a new eye-tracking paradigm and asks if the language system has “clean-up” mechanisms that leverage higher level knowledge to enhance consistency to cope with noise in the auditory system and asks whether variability in mechanisms explain differences in language and reading ability. The broader impacts of the project are to develop real-world interventions that apply this knowledge to reading disorders. As a first step towards this eventual translation, the project focuses on bridging the gap between cognitive science and the classroom, a key issue in the public discussion over the “Science of Reading”. The study team, which includes cognitive scientists and education researchers, are teaching a semester-long workshop intended for students from both disciplines. In this class, students design a new assessment of categorization consistency – consulting with private sector partners – and field-test it in local schools to gather real-world data, as well as teacher and student insights. This activity will pave the way for a potential real-world application of the basic research. This project is jointly funded by the Perception, Action and Cognition (PAC) Program and the Established Program to Stimulate Competitive Research (EPSCoR). 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 · 2025-05

This Partnerships for Innovation - Technology Translation (PFI-TT) project aims to improve how river flow is monitored. River flow is important for managing water supplies and reducing flood risks. Many organizations face challenges in measuring stream flow accurately due to increasing demand on water resources. This project introduces a new monitoring system designed to be safer, more efficient, and more precise than traditional methods. By using advanced instruments and modern communication technology, the solution will enhance understanding of river systems and provide data for decision-making in agriculture and infrastructure protection. The project outcomes have commercial potential, offering benefits to federal and local agencies, businesses, and other organizations involved in water management. This project seeks to improve stream flow monitoring by addressing the inaccuracies of current methods. Traditional monitoring systems often struggle to provide reliable data during rapidly changing flow conditions because they rely on simplistic empirical models. This technology takes a different approach, using physical principles and advanced technology to deliver more precise measurements. Unlike conventional methods that focus on a single section of a river, the solution employs a multivariate hybrid system, capturing a broader and more accurate picture of stream flow. This innovation is expected to enhance forecasting accuracy and hazard prediction, making it a valuable tool for improving water management and flood mitigation 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.

NIH Research Projects · FY 2025 · 2025-05

Project Summary Oral disease causes a significant burden on overall health and 3.9 billion people are affected worldwide. Oral diseases such as periodontitis, cancer, tooth loss, craniofacial birth defects and pain all affect growth and maintenance of the oral cavity and oral mucosa. Improving oral wound healing due to diseases, chronic wounding and scarring would greatly affect quality of life. The oral mucosa is primed with wound- activated gene signatures to facilitate the rapid and scarless wound healing. However, the genetic and molecular mechanism underlying this process is still largely unknown. We have found that Iroquois Homeobox 1 (IRX1/Irx1) is expressed in the basal layer of gingival epithelium and cell populations in the mesenchyme in both murine and human samples, which indicates its potential role in regulating gingival wound healing. Moreover, Irx1 expression may mark potential stem cell niches in the basal cell layer of the oral epithelium. We are investigating the role of Irx1 in epithelial basal cells during gingival wound healing utilizing our mouse gingival injury model. We have previously reported that Irx1 is expressed lung stem cells. By analyzing the wound healing progression and lineage tracing of basal cell activity during gingival wound healing, our preliminary data suggests that re-epithelialization is negatively affected during gingival wound healing in adult Irx1+/- (Het) mice, as indicated by delayed wound closure, delayed structural changes in regenerated epithelium and altered differentiation of keratinocytes. The transcriptomic analysis revealed a wound associated gene signature in the Irx1+/- epithelium. In preliminary studies, Irx1 was identified as a new gene that is primed at the base of the gingiva, which may facilitate rapid and scarless wound healing through the EGF signaling pathway. To determine if Irx1 regulates a progenitor cell niche in the oral cavity we propose three specific aims. 1) Determine the expression pattern of Irx1 during embryogenesis and homeostasis in potential progenitor cell niches in the oral cavity; 2) Identify the role of Irx1 in oral tissues using inducible Cre models for lineage tracing; 3) To analyze the effects of oral wound healing regulated by Irx1.

NIH Research Projects · FY 2026 · 2025-05

Lyme Arthritis is indicative of disseminated B. burgdorferi that has invaded the joint space to cause both acute infection and/or relapsing/remitting disease. Even if appropriately treated, Lyme Arthritis (LA) may transition to Antibiotic-Refractory Lyme Arthritis (ARLA), a condition with significant morbidity and long-term disability. The transition from LA to ARLA is not well understood, but understanding how an infectious arthritis becomes an inflammatory arthritis is essential to both treating and preventing this disease of growing prevalence. This is in line with NIAMS’ mission of supporting research into the causes, treatment, and prevention of arthritis. The central hypothesis of this proposal is that the joint space is immune-privileged and typically protected by anti-inflammatory/M2 resident synovial macrophages. In ARLA, however, these intimal-lining macrophages transition to an inflammatory M1 phenotype. Our rationale is that a similar mechanism has been observed in Rheumatoid Arthritis (RA), where these intimal lining RSMs dissociate tight junctions to allow circulating cells and/or pathogens to gain entry to the typically acellular synovial fluid (SF). The objective of this proposal is to determine the role of intimal and sub-intimal RSMs during B. burgdorferi infection and development of ARLA. We intend to evaluate this using 3 aims: 1) quantify the integrity of the RSM intimal lining during ex vivo infection using confocal microscopy and histomorphometry; 2) evaluate phagocytic and ROS capabilities of in situ RSMs exposed to B. burgdorferi using RNAscope and compare this to alterations in the immune transcriptome using spatial transcriptomics; 3) relate loss of barrier integrity to bone/cartilage damage based on SF and media transfer experiments. Our long-term goal is to prevent the transition of LA to ARLA and use the same principles to prevent the transition of any infectious arthritis to inflammatory arthritis. The significance of this proposal is in its focus on mechanisms of tick-borne disease, a growing public health concern; but also, in the likely universal mechanism of joint space inflammation, and how lessons learned through these experiments can be applied to other forms of infections and inflammatory arthritis. The innovation of this proposal is in the pioneering use of primary human synovial explants to truly evaluate human-relevant disease processes, in addition to the novel methodologies of RNAscope and spatial transcriptomics. The former will provide direct visualization of B. burgdorferi in relation to RSM tight junction integrity, ROS generation, and phagocytosis; the latter will provide functional immune information directly comparing differing layers of the synovium simultaneously. We expect these experiments to provide not only great insight into the initiation and propagation of the joint-specific immune response, but also provide new therapeutic targets for LA and ARLA treatment. This work will have a cross- specialty impact on mechanisms of infection, autoimmunity, synovial pathology, all of which will be applicable to patients suffering from a multitude of arthridities. This proposal is essential to the PI’s career goal of reaching independence, and has essential training provided by a panel of successful, multi-specialty mentors.