University Of Iowa

NIH Research Projects · FY 2025 · 2025-09

RESEARCH SUMMARY Pulmonary lymphangioleiomyomatosis (LAM) is a rare, female-predominant lung disease that is caused by inactivating mutations in the tuberous sclerosis complex (TSC1/2) tumor suppressor genes and consequent downstream hyperactivation of the mammalian target of rapamycin (mTOR) pathway. TSC1/2 mutations in LAM- initiating cells are central to disease pathogenesis, in collaboration with non-mutated native lung cells, including fibroblasts, endothelial, and alveolar epithelial cells. Rapamycin, the only FDA-approved treatment for LAM is cytostatic rather than cytotoxic and is associated with acquired resistance and adverse effects resulting its discontinuation. My proposal addresses a critical need to identify new therapeutic targets in LAM, and this will require the development of tissue-level in vitro LAM models that represent the cellular complexity of the disease. Lung cells within and surrounding clusters of LAM cells exhibit notable changes, particularly in fibroblasts, where markers of activation are significantly upregulated. Additionally, in alveolar epithelial cells the number of KRT8+ transitional-state cells is abnormally high. Using TSC2-/- renal angiomyolipoma cells (TSC2-/-AML) as a surrogate for LAM cells, my preliminary data demonstrates that secreted levels of several growth factors, including TGF- β1 and TGF-β2 are upregulated. These growth factors are known to promote fibroblast activation and influence alveolar differentiation, however they have yet to be evaluated in the context of LAM pathogenesis. The objective of my study is, therefore, to elucidate the role of TGF-β signaling in LAM pathogenesis. My central hypothesis is that TGF-β acts as a critical regulator of intercellular signaling, and its upregulation drives LAM progression by promoting fibroblast activation and alveolar simplification. To test this hypothesis, in Aim 1, I will determine the extent to which TSC2 inactivation and subsequent mTOR hyperactivation, using TSC2-/-AML cells, influence intra- and intercellular TGF-β signaling. I will use 2D and 3D co-culture models seeded with TSC2-/- or TSC2+ AML cells and non-diseased fibroblasts to determine how TSC2 inactivation affects TGF-β signaling activation and fibroblast phenotypes. Quantitative methods including live cell imaging, protein and RNA quantification will be used to measure changes in TGF-β signaling and fibroblast activation. Functional assays, such as wound healing assays and electrical cell impedance sensing (ECIS), will quantify the impact of TSC2-/- cells on fibroblast function. In Aim 2, I will develop a trans-well model of co-cultured TSC2-/- cells and primary AT2 cells and a LAM- on-chip model, to recapitulate interactions among TSC2-/- cells, fibroblasts, and AT2 cells; and use this model in conjunction with genetic and pharmacologic manipulation of mTOR and TGF-β signaling to both determine the extent to which TSC2-dependent TGF-β signaling influences differentiation of the alveolar epithelium and identify mechanisms by which LAM causes alveolar dysfunction. The proposed study is expected to provide mechanistic insights into the role of TGF-β signaling in LAM and its impact on various cell types within the disease microenvironment, identifying new therapeutic targets.

NSF Awards · FY 2025 · 2025-09

Batteries play a tremendous role in our society and economy. From portable electronics and sensors to hybrid and electric transportation to our nation’s electrical grid, batteries provide an important way to store energy across large differences in scale. However, there is continued need to build better, safer batteries so that they can store more energy, be charged and discharged more times, and be assembled with less expensive and more readily available components. Addressing these challenges starts with the materials inside of the battery. This project will design new battery components that are made from earth abundant materials dissolved in water. These materials can be less expensive and safer than those found in conventional lithium-ion batteries, but they are not currently as powerful. Moreover, as these materials are made from mixtures of different chemicals at different concentrations, the space for design is expansive. To aid in the search through this complex chemical space, this project will develop and deploy robotic experiments and machine learning models to rapidly vary component combinations, record their properties, and make predictions as to new systems to explore. Promising materials will be tested in batteries to evaluate how they perform. Researchers will be trained as new battery scientists who understand both the chemistry and engineering of emerging battery science, and they will learn how to develop and use artificial intelligence to expedite discovery. The results of this investigation will help guide efforts to enhance our nation’s energy economy and support energy security. Water-based battery chemistries offer abundant, non-toxic, and non-flammable solutions to energy storage challenges. The goal of this project is to design and analyze redox electrolytes with large concentrations of redox-active, earth-abundant, ligand-metal coordination complexes capable of storing multiple electron equivalents in the metal and surrounding ligand framework. The hypothesis is that a framework for the co-design of redox electrolytes can be derived from systematic and concerted molecular synthesis and experimental characterization coupled with autonomous materials formulation, electrochemical characterization experiments, and development of aligned machine learning (ML) models. Solubility and stability will be regulated by the chemistry imbued to the metal complexes by sulfonation of the redox-active ligands and through judicious formulation of the aqueous electrolyte. Coupled with the human-centered electrolyte formulation and electrochemical characterization, autonomous formulation and electrochemical experiments and high-throughput computations will be implemented to expand the redox electrolyte chemical space being explored. A publicly accessible data infrastructure will be developed and released, and the data will be used to develop ML models to identify and optimize co-design principles for redox electrolytes. This project will also train professional scientists in a multidisciplinary project combining experimentation, computation, automation, data infrastructures, and artificial intelligence (AI), guiding the nation’s energy economy and supporting energy security. 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 Platelets and leukocytes play a crucial role in thrombotic cardiovascular disease (CVD) pathophysiology. While conventional antiplatelet therapies effectively reduce mortality and nonfatal events in over 50% of high-risk patients, they also increase the risk of bleeding, a significant concern in modern CVD treatment. Given that the interplay between platelets and leukocytes contributes to thrombotic vascular occlusion, an ideal therapeutic approach would be the one that inhibits thrombo-inflammatory responses without increasing bleeding risk. We propose to test an innovative concept that metabolic reprogramming through cytosolic malic enzyme 1 (ME1) inhibition in platelets and leukocytes will inhibit their hyperactivation and decrease susceptibility to arterial thrombosis while minimal bleeding risk. The premise is that ME1, a nicotinamide adenine dinucleotide phosphate (NADP+)-dependent enzyme, plays a crucial role in energy metabolism by facilitating the conversion of malate to pyruvate. This process links glycolysis to the tricarboxylic acid cycle, with the resulting pyruvate transported to the mitochondria. The NADP(H) generated is utilized by NADP(H)-oxidases, leading to increased reactive oxygen species that drive platelet and leukocyte activation. Pilot studies have demonstrated that reducing ME1 activity in human platelets or genetically ablating ME1 in mouse platelets inhibits agonist- induced platelet aggregation, total ATP production, and NADP(H) generation. Platelet-specific ME1-deficient mice exhibited reduced susceptibility to arterial thrombosis without compromising hemostasis. Additionally, inhibition of ME1 in human neutrophils or deficiency of ME1 in mouse neutrophils inhibited neutrophil extracellular trap formation. To pursue this research, we will utilize human samples, novel cell-specific mutant mice, experimental thrombosis models, and a range of molecular and immunological assays alongside metabolomics. Our specific aims include 1) assessing the regulatory role of ME1 in platelet and leukocyte function, 2) evaluating the regulatory role of ME1 in in vivo thrombosis and hemostasis models, and 3) determining if pharmacological inhibition of ME1 activity can reduce platelet hyperactivation and thrombosis in models with preexisting comorbidities. Our team possesses extensive expertise, enhancing this project's feasibility and potential success. The proposed research is significant because existing antiplatelet drugs carry bleeding risks and simultaneously do not target both platelets and leukocytes, which play a crucial role in triggering a thrombotic event. Reprogramming metabolic and energy pathways in platelets and leukocytes through a single target to inhibit arterial thrombosis represents a novel strategy that could be investigated for efficacy and safety in future studies.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY Heart failure with preserved ejection fraction (HFpEF) accounts for half of the heart failure hospitalizations in the US thus representing a major public health priority. However, currently, there are limited effective approaches to preventing and managing this complex syndrome. Systemically, obesity-associated hyperlipidemia, hyperglycemia, and chronic inflammation have been considered as the major factors for the pathogenesis of HFpEF. In the heart, maladaptive cardiac immuno-metabolic reprogramming is a hallmark of HFpEF. In cells, nutrient sensing, macromolecule catabolism, and inflammatory regulation are fine-tuned by the lysosome. However, the extent and mechanisms by which lysosomal dysfunction contributes to the pathogenesis of HEpEF are poorly defined. The objective of this proposal is to determine the pathophysiological impact of cardiac lysosomal dysfunction in the setting of HFpEF. The lysosome contains more than 70 enzymes. As such, murine studies of individual lysosomal enzymes have contradicting observations regarding cardiac pathophysiology. Lysosomal reductase Gamma Interferon-Inducible Thiol Reductase (GILT) is the only identified lysosomal reductase that controls diverse sets of lysosomal enzymes and cargoes. We found that GILT is reduced in the hearts of humans with HFpEF and obese mice, respectively. Notably, both lean and obese mice with a human GILT SNP for CVD risk displayed a significantly reduced diastolic function without other interventions. Furthermore, loss of GILT in cardiomyocytes accelerates the HFpEF-related cardiac decline. Transcriptomic and metabolic analyses further revealed that cardiac GILT deficiency disrupted the immuno-metabolic homeostasis in the heart. Therefore, we hypothesize that GILT protects against cardiac immuno-metabolic imbalance in obesity-associated HFpEF. We will pursue two specific aims to test this hypothesis. In Aim 1, we will investigate the pathological significance of cardiac GILT in the context of HFpEF by using novel gain- or loss-function of GILT mouse lines. In Aim 2, we will elucidate molecular mechanisms for cardiomyocyte GILT-regulated mitochondrial function, glucose homeostasis, and inflammasome activation. To answer these challenging questions, we have assembled a strong collaborative team. Each co-PI is a recognized expert in her/his respective field (organelle functions in obesity, cardiac pathophysiology, and cardiac metabolism). This collaborative research proposal is innovative, combining the use of cellular and molecular approaches, metabolomic analyses, as well as in vivo mouse metabolic and cardiac profiling. Findings from this study will provide insights into interplays between cardiac lysosomes, inflammatory responses, and metabolic homeostasis and should speed the development of novel therapies for improving cardiovascular health.

NSF Awards · FY 2025 · 2025-09

An award is made to the University of Iowa Museum of Natural History for a collections curation and access initiative to preserve, digitize, and increase research capacity for more than 140,000 invertebrate specimens. These collections span over 150 years of biodiversity records from Iowa, the Midwest, and beyond, and provide essential data for comparative analysis on environmental change, land use, and species distribution. A centerpiece of the project is the integration of the Iowa Insect Survey collection—approximately 50,000 specimens collected from all 99 Iowa counties between the 1920s and 1960s—rescued from the former Iowa Wesleyan University. To secure these irreplaceable and viable research specimens, the project will consolidate specimens and replace hazardous wooden cabinets and failing drawers with modern, sealed steel cabinetry mounted on compactor carriages in an environmentally controlled facility. During the rehousing process, specimens will be cataloged, photographed, and made digitally accessible through biodiversity data portals. The project will provide paid internships and hands-on training for undergraduate students. Other broader public impacts include the development of a new educational exhibition and outreach programming focused on the ecological roles of insects in Iowa, engaging visitors of all ages. This effort secures and activates one of the Midwest’s most comprehensive historical invertebrate collections for ongoing and future research. By addressing serious storage hazards and consolidating materials in a centralized location, the project supports studies on invasive species, habitat and climate impacts, water quality, and regional biodiversity trends. Digitization of specimen records and images will support both local and international scientific access, while new storage infrastructure will allow for the sustainable growth of the collections as a state repository. The project strengthens biodiversity literacy, provides applied training in museum careers, and preserves Iowa’s natural heritage for scientific and public benefit. 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

Overall – Summary Neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are orphan cancers whose incidence and prevalence are increasing in the US. NETs are slow-growing, yet relentlessly progressive and are notoriously resistant to chemotherapy. The University of Iowa is one of only a handful of institutions where patients with NETs and NECs are diagnosed, treated, and followed comprehensively over time by an interdisciplinary team that includes both clinical and laboratory-based investigators with a focused interest in these tumors. This SPORE will support innovative translational NET research through three projects: 1. Project 1 is a multi-institutional investigation of a new strategy to sensitize pNETs to immune checkpoint inhibitor (ICI) therapy culminating in a Phase 1b window of opportunity trial combining CDK4/6 inhibitor therapy with ICI therapy in pNET patients. 2. Project 2 combines pre-clinical metabolic studies of radiation-induced lipid peroxidation with a Phase 1 alpha-emitter radiation therapy trial using 212Pb Pentixather targeting C-X-C Receptor 4 (CXCR4) in lung NETs and NECs. 3. Project 3 is a timely investigation of the tumor-promoting potential of GLP1 and GIP receptor agonists in gastroenteropancreatic NETs as those agents have burgeoning clinical use and unprecedented levels of patient interest. The Iowa NET SPORE will support translational investigators through four interactive cores: A. The Administrative Core facilitates communication and collaboration between projects, cores, external colleagues, advisors and patient advocates. B. The Biospecimens Core provides access to multiple sources of rare NET tissue and guides scientific use and accurate tumor classification. C. The Biostatistics Core provides study design, data analysis, quality control and biostatistics education. D. The Clinical Core provides access to data in the NET Registry on >2,400 identified patients eager to participate in trials as well as clinical trial coordination and regulatory support to projects. We will recruit NET translational researchers via developmental research and career enhancement programs that successfully transition junior scientists to independent funding and introduce established scientists to the NET field. Together with patients, we will promote translational research in NETs through vertical and horizontal collaborations that will lead to improved management of patients with NETs and NECs. IMPACT: Achievement of these goals will result in scientific advances related to NETs and other cancers, translation of novel molecularly targeted therapies for patients with NETs and NECs, alteration in patient management, and prolonged as well as improved quality of life for patients with NETs and NECs.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT The purpose of this Ruth L. Kirschstein National Research Service Award is to provide support for Grace Maurer, a Ph.D. student in Dr. Anna Stanhewicz’s laboratory at the University of Iowa, to conduct research that will prepare her to become an independent investigator in the field of maternal cardiovascular health. As part of her proposed training plan, she will learn a variety of new technical, conceptual, intellectual, and professional skills and refine research skills currently under development. Women who experience gestational diabetes mellitus (GDM) are 7 times more likely to develop type II diabetes and 2 times more likely to develop cardiovascular diseases than women who had an uncomplicated pregnancy. Microvascular dysfunction, mediated in part by decreases in the vasodilatory molecule nitric oxide, is likely a key mechanism contributing to reductions in microvascular insulin-mediated dilation and subsequent overt disease development in this population. Understanding the mechanistic underpinnings of this microvascular dysfunction prior to overt disease in this high-risk cohort of women is required to determine the pathophysiology of disease and identify mechanism-specific interventional approaches and is therefore an important biomedical research priority. Additionally, physical activity and sedentary behavior influence vascular function and disease risk in clinical populations (e.g. obesity, type II diabetes) but have not been mechanistically explored in healthy women with a history of GDM. Supported by strong scientific premise and compelling preliminary results, Grace will use an innovative human approach – leveraging the cutaneous circulation as an in vivo model of global microvascular function – coupled with device-based assessments of physical activity and sedentary behavior to determine the extent to which insulin-mediated endothelin-1 responses attenuate microvascular vasodilation in women with a history of GDM (Aim 1), and delineate the degree to which device-measured free-living physical activity and sedentary behavior predict microvascular endothelial responses to insulin in healthy control and GDM women (Aim 2). The proposed research will be the first to assess the mechanistic role of endothelin-1 on microvascular insulin-dependent responses and to examine physical activity and sedentary behavior and their impact on microvascular responses in women who had GDM after pregnancy but before overt disease development. This F31 fellowship project addresses important NHLBI research objectives to: 1) investigate newly discovered pathobiological mechanisms important to the onset and progression of heart, lung, blood, and sleep diseases, and 2) develop and optimize novel diagnostic and therapeutic strategies to prevent, treat, and cure heart, lung, blood, and sleep diseases. Under the expert supervision of her mentors, Grace will complete the proposed research and highly individualized training plan to advance a novel line of investigation and facilitate development towards becoming a successful independent investigator.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT Nearly 11% of all pregnancies result in a preterm delivery. Prematurity is the leading cause of infant death and disability, making it a global health priority. The majority of preterm deliveries are due to chorioamnionitis, which involves infection and/or inflammation of the amnion, chorion and placenta. Chorioamnionitis is characterized by acute perinatal inflammation, and results in the fetal inflammatory response syndrome (FIRS). FIRS is defined by elevated IL-6 in the amniotic fluid and/or umbilical cord blood. FIRS is associated with an array of negative neonatal outcomes, including white matter brain injury, sepsis, necrotizing enterocolitis and death. We have shown that FIRS is dependent upon maternal IL-6 signaling in a murine model of sterile chorioamnionitis. We have also shown the chorioamnionitis epigenetically re-programs human and murine neonatal monocytes and macrophages. This epigenetic re-programming includes altered chromatin accessibility, dampened pro- inflammatory responses and improved survival during neonatal sepsis. This is consistent with trained immunity, where exposure to certain stimuli alters the epigenetic landscape of innate immune cells, allowing them to respond promptly and specifically to subsequent stimuli. Trained immunity has been well-described following exposure to the Bacillus Calmette-Guerin vaccine or the fungal ligand b-glucan, although it has also been reported to occur following exposure to pathogen-associated molecular patterns and cytokines. Trained immunity is generally protective against subsequent lethal infections, which is also consistent with our findings. However, a more in-depth evaluation of chorioamnionitis-induced trained immune changes is needed to improve outcomes in infants afflicted by this highly morbid condition. The central hypothesis of this proposal is that perinatal inflammation induces trained immune responses in offspring monocytes/macrophages that persist into childhood, are tissue-specific and depend on functional IL-6 signaling in both the dam and offspring. This hypothesis will be tested with the following specific aims: 1) Determine the persistence of chorioamnionitis- induced trained immune responses in offspring by assessing chromatin accessibility, histone tail modifications and cell function in human monocytes through age two and murine macrophages through adulthood, 2) Determine the tissue-specificity of chorioamnionitis-induced offspring trained immune changes by assessing chromatin accessibility and function in neonatal bone marrow progenitors and the global transcriptional and chromatin accessibility landscapes at a single-cell level in neonatal lung and intestine, and 3) Determine the requirement and sufficiency of IL-6 signaling in chorioamnionitis-induced offspring monocyte/macrophage trained immune changes by deleting IL-6 or IL-10 in murine dams or offspring, supplementing dams or offspring with recombinant IL-6 or exposing human neonatal monocytes to recombinant IL-6 and assessing monocyte/macrophage chromatin accessibility and function.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY The airway and lung undergo dynamic stretch-relax motions in breath, cough, and airway physiotherapy. Conversely, a misplacement of airway motion contributes to severe pulmonary diseases, including postoperative pulmonary infections after chest surgery and respiratory distress syndrome from mechanical ventilation. Encouraged by clinical outcomes, efforts have been undertaken to develop research tools that culture airway epithelial cells with dynamic stretch-relax motions. In these methods, epithelial cells from the airway or lung are cultured on a porous, flexible membrane; the membrane is stretched pneumatically; and microfluidic channels function to perfuse cells and deliver pressure. However, current methods fall short in several aspects. First, the pneumatic actuation enables only basic stretch-relax motions and requires complex pressure delivery equipment. Second, the porous membrane usually requires microfabrication and a cleanroom facility. Third, the microfluidic device format prevents easy access to cell cultures and differs from standard biological protocols. To overcome these limitations and advance the science, this proposal aims to prototype an electro-magnetic actuated, dynamic airway/lung epithelial cell culture system as an insert of a 12- well plate (we named it “MagniWell-12”). In our preliminary studies, we demonstrated the effectiveness of electro-magnetic actuation of a polydimethylsiloxane (PDMS) membrane, established a protocol of laboratory fabrication of porous PDMS membrane, and confirmed biocompatibility of airway epithelial cells on the membrane. In the proposed research, we aim to integrate a porous PDMS membrane, a membrane holder, a magnetic actuator, and to develop a peripheral heat dissipation system and control circuits (Aim 1). We also plan to reveal how stretch-relax culture in the device impacts airway epithelial cell biology and function (Aim 2). Upon completion of the proposed project, we expect to deliver a novel tool for dynamic cell cultures. In the future, the device developed in this project will be broadly applied to study airway physiology and diseases (e.g., coughing and ventilation) for future R01 applications. A fully developed MagniWell-12 is expected to eventually be commercialized through potential SBIR/STTR support.

NIH Research Projects · FY 2026 · 2025-08

PROJECT SUMMARY Substance use disorders (SUDs) are notoriously difficult to treat, especially when co-occurring with psychiatric conditions. However, pharmacologic treatment that effectively targets SUDs and psychiatric disorders simultaneously are lacking, and the shared mechanistic underpinnings of comorbid SUDs and psychiatric disorders remained to be elucidated. This proposal introduces an innovative framework to address this gap by systematically examining how psychiatric genetic risk factors and substances of abuse interact at molecular and cellular levels. The central questions are: (1) How are the cellular responses to drugs of abuse affected by genetic loading for psychiatric disorders? (2) Can we identify distinct molecular subtypes of SUDs arising from gene-drug interactions? These questions are driven by decades of genetic studies, including recent GWAS’s, that show overlapping genetic risk across SUDs and psychiatric disorders, pointing to pleiotropy and shared pathophysiology. Our overarching hypothesis is that genetic variants linked to SUDs and psychiatric disorders cluster into distinct “profiles” of drug response, which could serve as the molecular correlates of clinical subtypes of SUDs. This research represents a paradigm shift in addiction research by systematically interrogating the combined molecular and cellular effects of substance use and genetic loading for psychiatric risk rather than treating them separately, with greater real-world relevance. To identify molecular and cellular endophenotypes that reflect addiction subtypes, we use two complementary approaches. First, in a gene-centric approach, we will introduce specific mutations linked to SUDs and/or psychiatric disorders into isogenic iPSC-derived brain cell types and expose them to panels of drugs of abuse, as well as to soluble factors associated with these drugs. We then assess cellular response through high-dimensional assays, including molecular (e.g., chromatin state and epigenetic marks) and functional (e.g., neurotransmission) readouts. Second, in a clinical phenotype-centric approach, we will take patient cells with known SUDs and deep clinical phenotyping data. We identify “subtypes” of patients with similar cellular drug response profiles and search for genetic and molecular features that define these subtypes. This study brings high-dimensional phenotypic profiling—which has been successfully used in cancer research to develop biomarkers and predict drug response—to substance use research.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY Regeneration of the lung following severe injury is an imperfect process and frequently leads to permanently altered lung structure and dysplastic cell types. After severe injury, such as influenza or COVID-19, the alveolus can either regenerate in form and function (adaptive regeneration) or be replaced by airway-derived dysplastic epithelium (maladaptive repair). These maladaptive cells and structures do not participate in gas exchange and likely contribute to the long-term reduction in pulmonary function seen in some patients from severe lung injury, highlighting the need for the development of new therapeutics with which to promote functional adaptive alveolar regeneration. Developing these new therapies will require a comprehensive understanding of not only the progenitor cells and their functions after injury, but also how they signal and interact with other cells within the injured alveolar niche. The alveolus is composed of a fragile layer of epithelium surrounded by a dense network of mesenchymal cells which serve important roles in paracrine signaling within the alveolar niche. Recent work from our lab and others has demonstrated the heterogeneity of these cells, identifying two key populations of alveolar mesenchyme, those that express Pdgfra (alpha+) and those that express Pdgfrb (beta+). Based on my extensive preliminary data demonstrating a key role of alpha+ cell proliferation, plasticity, and Notch signaling in alveolar regeneration after viral injury in both mouse and human lungs, I will test the hypothesize that specific mesenchymal cell lineages that arise from injury-induced plasticity establish and maintain the maladaptive epithelial regenerative response, in part through Notch mesenchymal-epithelial signaling. In Aim 1 of this proposal, I will examine how alpha+ cell proliferation and plasticity are defined and maintained after viral injury. The proposed research in Aim 1 will further develop my skills in transcriptomic and epigenomic analyses and physiological impacts of injury on lung function. In the independent phase outlined in Aim 2, I will define the importance of Notch mediated mesenchymal paracrine signaling within the alveolar niche during adaptive vs maladaptive regeneration. My primary mentor, Dr. Edward Morrisey is an internationally renowned lung biologist who has identified many key cell types and pathways which drive regeneration of the injured lung. I have also assembled a diverse advisory committee of experts in bioinformatics, epigenetics, physiologic readouts of recovery of lung function after injury, and Notch signaling who will assist me in training of these areas. The proposed work will be conducted at the University of Pennsylvania, where I will benefit from the rich intellectual environment, wide-ranging resources, collaborative scientific community in pulmonary and mesenchymal biology, and the full support of the institution. Together, this proposal outlines a rigorous research and training plan that will establish the foundation to advance my career in lung and mesenchymal cell biology.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT CANDIDATE: Dr. Naomi Rodgers is an academic speech-language pathologist and Assistant Professor at the University of Iowa with expertise in scale development, qualitative methodologies, and experimental design in the study of the psychosocial aspects of stuttering. With this K23 mentored patient-oriented career development award, Dr. Rodgers will build on this foundation to develop new knowledge and skills needed to independently conduct clinical trials of multidimensional therapy for people who stutter, and to investigate factors related to intervention implementation. CAREER DEVELOPMENT PLAN: Dr. Rodgers will develop proficiency in (1) design and conduct of clinical trials of behavioral health interventions; (2) dissemination and implementation science; (3) team science and multi-site project management; and (4) school-based research. Developing these advanced skills will be critical to her success as an independent investigator who is committed to enhancing accessibility and implementability of effective stuttering therapy that improves psychological and communicative well-being for people who stutter across the lifespan in diverse clinical settings. ENVIRONMENT: Dr. Rodgers will train with a multidisciplinary team of extramurally funded mentors including: Dr. Elizabeth Walker (primary mentor), a leading applied researcher in the field of pediatric communication disorders; Dr. Geoffrey Curran (co- mentor), a leading implementation scientist; Dr. Gerta Bardhoshi (co-mentor), a leading school mental health researcher; and Dr. Anu Subramanian (co-mentor), a specialist in stuttering intervention and clinical education. RESEARCH: Although many school-based speech-language pathologists (SLPs) recognize that stuttering therapy should address cognitions and emotions alongside communication behaviors, status quo speech therapy often narrowly focuses on reducing stuttering frequency. There is a critical lack of high-level evidence for multidimensional approaches for school-age children who stutter (CWS), and it is unclear how to best support school SLPs in facilitating them. Avoidance Reduction Therapy for Stuttering (ARTS®) offers a theory-driven stutter-affirming approach to coaching CWS to reduce conditioned struggle behaviors in turn helping them develop comfortable, forward-moving communication. Aim 1 of this study involves partnering with topical experts and stakeholders to adapt ARTS® for school service delivery and develop a protocol to train school-based SLPs to implement ARTS® with school-aged CWS (aged 7-12 years). Aim 2 is to conduct a pilot randomized controlled trial with SLP-CWS dyads to evaluate preliminary effects of the ARTS® training and intervention on SLP and CWS outcomes, respectively. Aim 3 is to identify outcomes, barriers, and facilitators of implementing ARTS® in the schools, and to select and operationalize strategies to that we will evaluate in a subsequent fully powered hybrid effectiveness-implementation trial. The completion of these training and research aims are critical for Dr. Rodgers’ career development in creating, adapting, and evaluating evidence-based, implementable behavioral health interventions for people who stutter to enhance their quality of life and well-being.

NSF Awards · FY 2025 · 2025-08

Understanding and predicting air quality and how chemicals move and change in the atmosphere is important for protecting public health, supporting agriculture and energy systems, improving weather forecasts, and shaping environmental policies. To do this effectively, advanced computer models are needed that can connect atmospheric and chemical processes from local to global scales, while also making it easier for scientists to test new ideas, compare results, and work together. This project develops CheMPAS-A, a new atmospheric chemistry modeling system that incorporates additional chemistry features into a modern global weather model, the Model for Prediction Across Scales-Atmosphere (MPAS-A), and provides a seamless framework for simulating atmospheric chemistry from global to local scales. A key part of CheMPAS-A is a flexible, easy-to-use coding system that helps researchers quickly explore, test, and improve how atmospheric chemistry is represented, making science faster and more collaborative. By encouraging shared development, utilizing up-to-date software practices, and helping to train future scientists, CheMPAS-A transforms individual research into tools and knowledge that benefit both science and society. This project tackles two critical cyberinfrastructure challenges in atmospheric chemistry modeling: (1) creating stable, portable, high-performance, and user-friendly modeling software, and (2) developing an efficient, sustainable framework for integrating new scientific processes and algorithms. The project augments MPAS-A with a stable and functional chemistry capability by integrating the Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA) library. An innovative scripting capability called QUACS or Quick Updates to Aerosol and Chemistry Systems for Next Generation Multi-Scale Models enables the integration of custom parameterizations through a high-level, open-source, and globally used scripting language. QUACS empowers domain specialists and students to innovate. Enhanced configuration options and pre- and post-processing tools further improve flexibility and accessibility without compromising core stability. The outcome of this work is designed to accelerate scientific advancements and sustain scientific innovation in atmospheric chemistry modeling. This award by the Office of Advanced Cyberinfrastructure is jointly supported by the Division of Atmospheric and Geospace Sciences and the Division of Research, Innovation, Synergies, and Education in the Directorate for Geosciences. 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

Despite being linked to febrile disease nearly 150 years ago, malaria still kills more than 600,000 people each year; most of those individuals being children under the age of 5 in sub-Saharan Africa. These numbers highlight the urgent need to develop effective antimalarial vaccines. The plasmodium parasite replicates in an asymptomatic liver stage followed by the symptomatic blood stage. Our lab and others have found that circulating (TCIRCM) and liver resident memory (TRM) CD8+ T cells targeting liver stage malarial antigens can facilitate sterilizing immunity. The gold standard of inducing liver stage protection has long been immunization with Radiation Attenuated Sporozoites (RAS), which arrest in replication during the asymptomatic liver stage. It has been demonstrated in murine and human models that RAS immunization can provide sterilizing immunity to malaria in 100% of subjects. However, this protection drops precipitously in individuals with prior malaria exposure. Our lab and others have modeled this discrepancy and found that mice with prior malaria exposure have reduced CD8+ T cell responses to RAS immunization which drives this impaired protection. We have determined this to be a T cell extrinsic defect, implicating compromised functions of antigen presenting cells (APCs) as the primary driver of the T cell defect. Unfortunately, the mechanism nor the host and/or parasite- derived factors mediating this phenotype are unknown. Our long-term goal is to understand the biology that underlies the impaired CD8+ T cell responses observed in blood stage malaria experienced individuals. We have identified the blood stage malarial pigment hemozoin (Hz) as a candidate driver of impaired CD8+ T cell priming, as injection of synthetic Hz phenocopies our findings of CD8+ T cell impairment in plasmodium experienced mice. Moreover, Hz has been demonstrated to be taken up by APCs and we have found evidence that it impairs antigen uptake and chemokine-directed migration in these APCs. In Aim 1, we will determine the effects of Hz on CD8+ T cell priming using innovative approaches including intravital microscopy and scRNAseq. Importantly, we have designed an mRNA vaccine that elicits equivalent circulating CD8+ T cell responses in malaria experienced mice and naïve controls. In Aim 2, we will optimize mRNA LNP vaccination strategies to maximize both TCIRCM and TRM generation and protection in malaria experienced hosts utilizing cutting-edge LNP targeting strategies and cytokine encoding mRNAs. Finally, yellow fever virus (YFV) co-circulates in malaria endemic regions. Therefore, the YFV vaccine is recommended for individuals living in these regions. Despite the established impairment of malaria exposure on vaccine-induced T cell responses, it is unknown how malaria exposure impacts YFV vaccine efficacy. In Aim 3, we will incorporate a murine model of YFV vaccination to determine the impact of prior malaria exposure on YFV vaccine responses. The results of this proposal will provide a mechanistic understanding into CD8+ T cell mediated immunity to arthropodborne pathogens in malaria exposed individuals and define novel vaccination strategies to maximize immunity.

NSF Awards · FY 2025 · 2025-08

Von Neumann algebras were introduced to provide a mathematical foundation for the study of quantum mechanics and can be viewed as infinite-dimensional generalizations of matrix algebras. The groundbreaking work of Francis J. Murray and John von Neumann in the 1930s already demonstrated that von Neumann algebras are complex objects with exceptionally rich mathematical structures. Since then, the theory of von Neumann algebras has developed into an independent field, establishing fruitful connections with various branches of mathematics and science. Natural classes of von Neumann algebras arise from a variety of mathematical structures, such as groups of symmetries and their actions. This highlights the close relationship between von Neumann algebras and the mathematical areas of group theory and ergodic theory. The main goal of this project is to advance the connections among these research areas by addressing a range of open problems at their intersection. The project will also incorporate opportunities for the involvement of graduate students. In this research project, the principal investigator (PI) aims to obtain new classification and structural results for von Neumann algebras arising from groups and their actions on probability spaces. As a consequence, he will derive several new structural results for equivalence relations associated with group actions. In general, von Neumann algebras do not retain much information about the groups or actions from which they are constructed. However, Popa’s deformation/rigidity theory has revealed that many structural properties of these groups and actions can, in fact, be detected through their associated von Neumann algebras. Building on this foundation, the PI will develop new techniques to investigate this rigidity phenomenon within von Neumann algebras. The project will focus on several key research directions. First, the PI will expand the understanding of rigidity by identifying new classes of groups and actions that can be completely reconstructed from their von Neumann algebras. Second, he will investigate primeness and unique prime factorization for von Neumann algebras arising from actions of higher-rank lattices. Finally, the PI will pursue new rigidity results within the framework of measure equivalence of von Neumann algebras. 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 Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and its major short-term complication, pulmonary embolism (PE), represents a significant health issue in the US and worldwide. The mainstay of current DVT treatment is oral anticoagulant therapy. It decreases the risk of DVT reoccurrence but, unfortunately, does not mitigate inflammation or facilitate venous thrombus (VT) resolution, which correlates with postthrombotic syndrome (PTS) in humans. Even pharmaco-mechanical thrombectomy allows the removal of only limited amounts of thrombus and has minimal efficacy in preventing PTS. Therefore, significant therapeutic gaps exist in providing safer and more effective treatments for DVT and PTS. Given the thromboinflammatory nature of DVT, the major problem is that resolving or residual venous thrombus, even after partial removal via systemic or catheter-directed thrombolysis or stenting, confers local inflammation, leading to persistent fibrotic venous wall injury resulting in PTS. We propose to address this problem by testing the innovative concept that manipulating metabolic reprogramming by targeting dimeric pyruvate kinase M2 (PKM2) in platelets and neutrophils will inhibit acute venous thrombus formation and, at later stages, targeting PKM2 in macrophages will enhance efferocytosis, thereby limiting fibrotic venous wall injury and accelerating VT resolution. The concept builds upon our exciting findings that limiting PKM2 dimerization inhibits platelet activation, reprograms pro-inflammatory into anti-inflammatory macrophages, and enhances the macrophages’ efferocytotic activity—the ability to clear apoptotic cells that are known to exacerbate inflammation—and inhibits collagen synthesis in vein fibroblasts. Using human samples and cell-specific mutant mice, we propose further defining whether metabolic reprogramming by targeting dimeric PKM2 limits chronic inflammation and accelerates VT resolution. In Aim 1, we will define the regulatory role of PKM2 in acute DVT progression. In Aim 2, we will determine whether targeting PKM2 at later stages will limit local inflammation, accelerate VT resolution, and prevent PTS. A strength of the proposal is that we propose to test novel strategies to improve vascular integrity and motor function in the DVT-affected limb using the femoral vein thrombosis model in mice and rats. Our team has extensive collaborative expertise, which will increase the feasibility and the likelihood of success. The overall impact of the proposed research is high because the knowledge gained from this proposal will significantly move the field of DVT by defining novel mechanisms contributing to common pathways from acute to chronic inflammation and leading to fibrotic damage of the venous wall.

NIH Research Projects · FY 2025 · 2025-08

Abstract Staphylococcus aureus is a major human pathogen and a leading bacterial cause of death worldwide. Some S. aureus lineages, including ST398, commonly infect livestock but are rare in humans. These livestock- associated bacteria commonly acquire tetracycline resistance from the use of antibiotics for animal production. Recently, we discovered that over 5% of patients with cystic fibrosis (CF) are infected with ST398 S. aureus, suggesting that this livestock-associated lineage has jumped into the human population. It is not clear how these patients developed ST398 infections. The goal of this research project is to determine whether these ST398 infections persist in people with CF and to identify potential environmental sources such as food or water are the sources of these infections. We hypothesize that ST398 infections persist for 3 years in half of patients who become infected. We also hypothesize that ST398 infections are acquired indirectly from livestock through either contaminated water supply or from the food supply chain. We will test these hypotheses by prospectively collecting both clinical and environmental isolates of S. aureus and genome sequencing isolates that are tetracycline resistant, a common marker of this lineage. We will use phylogenetic and geospatial analysis to rigorously examine the relationship between strains of ST398 that infect patients with CF and that are found in water collected around the state of Iowa, bioaerosols collected near animal production facilities, or meat collected from local grocery suppliers.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY Sepsis is the most common cause of death in U.S. hospitals, and hospital risk-adjusted sepsis mortality varies by more than 40%—suggesting that an estimated 20,000 sepsis deaths could be avoided if top-performing sepsis care were delivered more widely. Sepsis quality improvement activities have focused on reducing variation in early clinical care, but the ways in which performance improvement (PI) is implemented vary widely. Trauma systems and other disease-specific regionalization programs have achieved impressive mortality reduction through standardized implementation of PI. The overall objective of this project is to identify organizational features and PI implementation practices likely to reduce sepsis mortality and then to validate that these practices are associated with improved outcomes. Our central hypothesis is that PI implementation practices (e.g., multidisciplinary sepsis committee, case review, use of an institutional sepsis registry) observed in top-performing hospitals can be adapted and widely applied to lower-performing hospitals to improve sepsis clinical outcomes. The specific aims of the proposed study are to (1) identify hospital-level implementation strategies and PI activities being used in top-performing hospitals, (2) validate the relationship(s) between specific implementation strategies and sepsis performance, and (3) develop consensus regarding implementation strategies most likely to be impactful in lower-performing hospitals using a community-engaged approach. The proposed project will accomplish these aims by (1) conducting site visits at 10 top-performing hospitals and 6 lower-performing hospitals identified based on hospital risk-adjusted sepsis mortality and performance on the sepsis quality reporting metric (SEP-1); (2) identifying PI implementation strategies that are related to low sepsis mortality; (3) conducting an inventory of PI activities identified in site visits in a national sample of 560 hospitals to measure the association between PI and clinical outcomes; (4) identifying those strategies most strongly associated with improved clinical outcomes; and (5) convening a panel of experts with practical knowledge and experience to identify strategies using a modified Delphi method that are most promising to implement feasibly in lower-performing hospitals. After successful completion of the proposed project, we expect to have identified organizational features and successful PI implementation strategies at top-performing hospitals (Aim 1) and validated those strategies in a larger sample of U.S. hospitals (Aim 2). Then we expect to have identified the most promising among those strategies for future implementation (Aim 3). These results will have a positive impact because they will serve as an important resource for developing best practices for sepsis PI implementation that have the potential to improve hospital performance and therefore reduce preventable sepsis deaths.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT NTSHSD2 neurons are activated by aldosterone and detect sodium deficiency. When activated, NTSHSD2 neurons drive robust sodium appetite, while their ablation reduces intake. As key regulators of sodium appetite, how NTSHSD2 neuron activity is controlled is of great interest. During sodium deficiency or mineralocorticoid excess, NTSHSD2 neurons exhibit increased spontaneous activity in ex vivo brain slice recordings, which we hypothesize is mediated by aldosterone-mineralocorticoid receptor (MR) signaling. However, the molecular mechanisms through which aldosterone-MR signaling acts to drive NTSHSD2 neuron activity are unknown. Further, sodium ingestion has been shown to rapidly decrease Fos expression by NTSHSD2 neurons, indicating active inhibition of NTSHSD2 neurons. Such rapid control is likely to be mediated by neural input, but the specific afferent neurons that regulate NTSHSD2 neuron activity are yet to be elucidated. The goal of this grant is to study mechanisms by which NTSHSD2 neuron activity is controlled. Aim 1 will determine how aldosterone-MR signaling regulates NTSHSD2 neuron activity. We propose a key role for genomic regulation by aldosterone-MR signaling for driving intrinsic activity of NTSHSD2 neurons during sodium deficiency and mineralocorticoid excess. Aims 2 and 3 will define the wiring diagram of inputs to NTSHSD2 neurons as these very afferents are also likely sensitive to alterations in extracellular fluid volume and/or sodium intake. This will be accomplished through single cell transcriptional profiling of NTS afferent neurons to identify their marker genes, which will then be leveraged to gain access to the afferent neurons using Cre driver mice. Connectivity to NTSHSD2 neurons will then be established by performing channelrhodopsin-2 (ChR2)-assisted circuit mapping (CRACM). Finally, we will also specifically investigate regulation of NTSHSD2 neurons by the central amygdala (CeA) – a GABAergic structure linked to appetite control with neurons that provide input to NTSHSD2 neurons. Our goal is to identify the information carried by these afferents and their effects on sodium appetite. The experiments proposed in this project will address significant gaps in our knowledge regarding the regulation of NTSHSD2 neurons by providing both molecular and circuit mechanisms for the control of their activity.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT. An aging population faces unique health challenges, including increased susceptibility to ionizing radiation (IR) toxicities due to oxidative and nitrative metabolic changes. Elderly individuals are particularly vulnerable to IR-induced cardiopulmonary toxicities due to age-related physiological changes that impair tissue repair and regeneration. Age-associated decline in metabolic efficiency generates increased reactive oxygen species [i.e., superoxide (O2•−)]. IR exposure may also induce bursts of O2•− and nitrative species [i.e., nitric oxide (NO)]. Excess O2•− can combine with NO to form peroxynitrite (ONOO-) that can damage proteins, lipids, and DNA leading to inflammation and fibrosis. O2•− can disrupt the mitochondrial electron transport chain (ETC) complexes I and III while ONOO- inhibits mitochondrial ETC complex II. Inhibition of the ETC complexes leads to increased residence time of electrons at specific sites in the ETC, disrupting ETC stoichiometry and further increasing O2•− formation, resulting in a state of persistent oxidative stress and subsequent cardiopulmonary damage. This proposal investigates the age-associated impact of nitro-oxidative metabolism on mitochondrial ETC complex efficiency and cardiopulmonary physiology. Utilizing genetically modified mice and an upper body irradiation (UBI) model, we will elucidate the impact of nitric oxide synthase 1 (Nos1) disruption and assess the efficacy of a superoxide dismutase mimetic (Rucosopasem) in ameliorating age-associated cardiopulmonary effects induced by IR. We hypothesize that age-associated, IR-induced disruptions in the assembly of mitochondrial complexes result in stochiometric mismatches and alterations in the generation of O2•− and ONOO- leading to differential IR-induced cardiac and pulmonary phenotypes based on age. Aim 1 will define the age- associated effects of UBI on the stoichiometry of the ETC complexes in WT and Nos1+/- murine models and the effects on cardiopulmonary pathophysiology. Aim 2 will determine the efficacy of a clinically relevant superoxide dismutase (SOD) mimetic, Rucusopasem, to target the alterations in mitochondrial ETC stoichiometry, reduce ONOO- and O2•− formation, and mitigate the age-related IR-induced effects on the cardiopulmonary system. Completing these studies may unveil age-associated differences in nitro-oxidative metabolism and mitochondrial dysfunction, potentially identifying targets to prevent or reduce IR-induced cardiopulmonary toxicities. Moreover, if treatment with a superoxide dismutase mimetic restores ETC complex function, this will identify a potential countermeasure strategy to mitigate IR-induced cardiopulmonary toxicities.

NIH Research Projects · FY 2025 · 2025-07

RFA-FD-25-007 Application | Overall Project Summary/Abstact The assurance of food safety that has been developed and sustained within the State Hygienic Laboratory (SHL) at the University of Iowa is a high-quality, performance-based effort that enhances public health, protects consumers and promotes preparedness. The SHL, in conjunction with its partner Manufactured Food Regulatory Program Standards (MFRPS) agency, the Iowa Department of Inspections, Appeals, and Licensing (DIAL), comprise a proactive regulatory, response and surveillance team. This team effort minimizes risks in food consumption for the public through efficient and effective sample collection, analysis and results reporting to support the U.S. Food and Drug Administration goal of an integrated food safety system. The culture of food safety at SHL is multidisciplinary, fully engaged at all levels and well-staffed with subject matter experts. The State Hygienic Laboratory has been engaged in maintaining quality systems in the laboratory in compliance with ISO/IEC 17025 since September 2013. SHL has maintained AIHA Laboratory Accreditation in both the Coralville and Ankeny lab locations, specifically for the food scope by providing the resources - including systems, equipment, and personnel - to ensure adherence to rigorous QA/QC protocols and appropriate accrediting authority/agency standards. Over the past nearly five years DIAL has been an active partner, collecting 75 samples per year in support of FDA LFFM Microbiological Human Food Testing, meeting the goal set each year of the previous award. The SHL is, and has been, an active and experienced participant in the FDA LFFM and the USDA FSIS FERN Cooperative Agreement Programs, providing laboratory testing for chemical, microbiological, and radiological contaminants in various food matrices for routine contaminants and threat agents. The State Hygienic laboratory has develop a series of projects within this proposal to meet the following aims: 1) Ensure laboratory capacity for the analysis of foods and food products related to chemical, microbiological, and radiological contamination that occurs as intentional, accidental or unknowing; 2) Strengthen and enhance preparedness of the state public health laboratory to provide organized, timely and efficient response in urgent and emergency situations/outbreaks; and 3)enhance currently validated analytical methods and strive to validate/verify additional methods to accomplish program growth. SHL has the expertise, facilities, and resources to execute the projects fully and hopes to continue as a valuable member of the FDA LFFM Cooperative Agreement Program for many years to come.

NIH Research Projects · FY 2025 · 2025-07

Abstract Melanoma, a deadly cutaneous malignancy, is increasing globally despite treatment advances. Melanocytic nevi ("moles") are often studied for early diagnosis, but their risk of progressing to melanoma is low. While BRAFV600E or NRASQ61R mutations are common in both melanomas and nevi, additional mutations in tumor-suppressor genes are needed for melanoma development. Similar to human nevi, BRAFV600E and NRASQ61R nevi in zebrafish remain benign. Even in tp53-deficient BRAFV600E and NRASQ61R fish, only a small percentage of nevi advance to melanoma. These findings emphasize the robust constraints on nevus growth and the need for cooperative transcriptional changes for melanocyte transformation. A knowledge gap exists in our understanding of the transcriptional mechanisms outside of somatic mutations that are necessary for transformation. The Sleeping Beauty (SB) transposon mutagenesis system has been utilized to identify novel genes associated with melanoma recurrence. It is unique in comparison to other genetic screens (i.e. CRISPR gRNA) in that transposon integration allows for gene silencing, activation or expression of truncated transcripts through an internal promoter within the transposon. We have established two transgenic nevi-prone zebrafish line, that harbors a germline T2/OncZ transposon, Tg(mitfa-BRAFv600e: T2/OncZ): mitfa-/- and Tg(mitfa-NRASQ61R: T2/OncZ): mitfa-/-. Introducing plasmids expressing mitfa into melanocyte stem cells in our transgenic mitfa-/- fish rescues melanocytes, achieved through injection and electroporation of plasmids carrying the mitfa-promoter driving expression of mitfa, thus inducing nevi formation. While rescued melanocytes propagate into nevi within 4 weeks, these zebrafish remain melanoma-free for up to ~1 year. Injecting mitfa-SB100 transposase plasmids into formed nevi at 6 weeks induces SB mutagenesis and results in transposition of the OncZ transposon, and thus anticipated to accelerate melanocyte transformation. Sequencing melanomas and control nevi will identify significantly enriched transposon integration sites and a short list of candidate genes will be identified. The function of such genes, predicted to be accelerators of melanomagenesis and in the context of both BRAF and NRAS- induced nevi, will be validated by in vivo and in vitro assays utilizing zebrafish and human melanocyte cell lines. Our proposal presents a novel in vivo application of the SB system to uncover unique accelerators of melanomagenesis. This approach combines established zebrafish lines with transgene electroporation techniques, allowing for precise spatial and temporal control over tumor initiation. We aim to identify new transcriptional mechanisms underlying nevi transformation, offering critical insights into melanoma biology and advancing genetic methodologies in cancer research.

NSF Awards · FY 2025 · 2025-07

This I-Corps project focuses on the development of simulation technologies for training surgeons in ear- and hearing-related healthcare. In this field, trainees must learn to use high-speed drills safely in the head and near vital structures like the brain, large blood vessels, and nerves. The work is precise, and the risks are high, so practicing on simulators before operating on patients is essential. The current gold standard for training is dissection of donated human temporal bones in simulation laboratories, where learners receive instruction, feedback, and evaluation from expert ear surgeons. This method teaches anatomy, hand skills, and proper techniques in surgery. However, the number of donated cadaveric temporal bones is decreasing, which limits access to hands-on training. Outside of the United States, the shortage is even worse. Many countries lack cadaveric materials, dissection equipment, and formal instruction. As a result, tens of thousands of trainees around the world have little to no access to basic surgical simulation for ear surgeries. Still, training programs must meet learners’ needs, the skill benchmarks required for accreditation, and the public’s expectations for high-quality surgical care. This growing demand is fueling interest in new surgical simulation technologies and opening opportunities in a $70 million global market. 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 unique surgical training kit designed to be affordable, portable, and regularly accessible. Each kit contains a series of 3D-printed artificial temporal bones, mock surgical instruments, and access to online, video-based instructional modules. The complete curriculum is flexible and self-directed, allowing learners to set up in minutes and train in any location, including at home. The training kits are distributed through a monthly subscription box and digital service. This delivery model provides consistent, structured exposure to simulated tissues, essential tools, and instructional resources. By offering safe, cost-effective, and repeatable practice opportunities, the solution aims to enhance surgical training for more trainees who can learn and offer patients more effective ear- and hearing-related procedures. 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

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.

NSF Awards · FY 2025 · 2025-07

This award supports development of a novel space plasma measurement methodology called plasma seismology that uses measurements of the velocity distribution function of particles at a single point in space to reconstruct the variation of the electric field over an extended spatial region. In space plasmas, the electric field plays a key role in collisionless wave-particle interactions that govern the acceleration of particles to high energy. Such a new capability may provide valuable information needed to understand the dynamics of space phenomena with significant societal impacts, such as severe space weather events that can impact our communication and navigation satellites as well as potentially cause severe damage to the electrical power grid. Further, by determining the electric field over an extended spatial range with fewer spacecraft, this innovative technique holds the promise to reduce the cost of future spacecraft missions. This project will also support the education and training of a graduate student in both the numerical and experimental investigation of kinetic plasma physics. This project will first validate the plasma seismology technique for electrostatic dynamics to determine the spatial variation of the electric field through single-point, time-series measurements of the electron velocity distribution function using kinetic electrostatic simulations. Second, the procedure for plasma seismology in electromagnetic plasmas relevant to space environments will be developed and validated using single-point, time-series measurements of the electron velocity distribution from kinetic electromagnetic simulations of plasma turbulence. Finally, the feasibility of the plasma seismology implementation will be confirmed by determining the spatial variation of the parallel electric field in laboratory experiments. Close coordination of the analytical, numerical, and experimental tasks will enable the development of the innovative technique of plasma seismology to be used as a new tool to probe the electric fields in laboratory and space plasmas over a greater spatial extent than currently possible with existing technological capabilities. 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.