University Of South Florida

NIH Research Projects · FY 2025 · 2025-09

Not Applicable

NIH Research Projects · FY 2025 · 2025-09

Acid-base homeostasis is critical for normal physiological function. Chronic metabolic acidosis is an independent risk factor for the progression of chronic kidney diseases (CKD) and can contribute to increased morbidity and mortality in patients with CKD. Patients with KCNJ16 (the gene encodes the inwardly rectifying potassium channel Kir5.1) mutation display metabolic acidosis; however, the underlying mechanism is still not fully understood. The overarching goal of this study is to unmask the interaction between Kir5.1 and Kir4.2 channels and how such interaction regulates acid-base balance in the kidney. Mentored K99 Phase: Our preliminary data revealed that loss of Kir5.1 impairs renal ammonia metabolism in the proximal tubule. I hypothesize that loss of Kir5.1 depolarizes the proximal tubule cell membrane and inhibits the exit of HCO3- through NBCe1, resulting in increased intracellular pH (pHi) and thus, impairs the proximal ammonia metabolism. Specific Aim 1: Determine the role of Kir5.1 in regulating proximal tubule membrane potential and pHi .To test this hypothesis, I will use: 1) FluoVolt membrane potential kit and 2) pH-sensitive BCECF dye to measure the membrane potential and pHi of isolated proximal tubules from SSWT rats under the stimulation (VU206, agonist) and inhibition (VU720/VU992, antagonists) of Kir5.1 and compare the membrane potential and pHi of isolated proximal tubules from SSWT and SSKcnj16-/- rats. Independent R00 Phase: This phase of the project will develop an independent line of investigation into the physical and functional interactions between Kir5.1 and Kir4.2. Insights gained from these experiments will further explain the physiological mechanisms underlying inwardly rectifying potassium channels' regulation of acid-base balance. Previous studies suggest potential interactions between Kir5.1 and Kir4.2. However, the functional interactions between Kir5.1/4.2 in the kidneys still remain largely unknown. I hypothesize that Kir5.1 physically and functionally interacts with Kir4.2, and the Kir5.1/4.2 complexes determine the membrane potential of the proximal cell. Specific Aim 2: Investigate the physical and functional interactions of Kir5.1 and Kir4.2 in the proximal tubule. To test this hypothesis, I will: 1) use immunofluorescence and co-immunoprecipitation on isolated proximal tubules from SSWT rats to study the physical interaction between Kir5.1 and Kir4.2; 2) generate the Kir4.2 KO rat based on Dahl SS rat background (SSKcnj15-/-) to evaluate the effect of Kir4.2 on acid-base status, kidney function and blood pressure in SS hypertension; 3) use Western blot, immunofluorescence and patch clamp to study the expression and channel activity of Kir4.2 in SSKcnj16-/- rats and vice versa. The results of this proposal will unmask the molecular mechanisms of acid-base regulation by Kir5.1 and the physical and functional interactions of Kir5.1 and Kir4.2, which will not only help define the role of inwardly rectifying potassium channels in the proximal tubule but also contribute to developing new therapeutic strategies for metabolic acidosis.

NSF Awards · FY 2025 · 2025-09

Algorithms permeate our modern world, driving everything from navigation, information storage, and data retrieval. In contrast, biological information is inherently physical, carried by molecules whose shapes determine their interactions with the environment. This NSF-funded program aims to explore and harness the interface between the deoxyribonucleic acid (DNA) “software” and the geometric “wetware” of molecules. The research will begin by developing mathematical tools to distinguish molecules based on their 3D shapes and structures. These tools will then be used to create a new programming framework: “algorithmic shape encoding.” Using small DNA tiles as modular pieces in a molecular-scale 3D jigsaw puzzle, the team will construct increasingly complex structures—drawing inspiration from nature’s ability to link form and function. The expected outcomes include breakthroughs in self-assembling materials, biocomputing, and optical communication systems. In addition to scientific discovery, this program will foster interdisciplinary training across mathematics, engineering, and chemistry from high school to the postdoctoral levels. DNA, with its predictable structure and ability to self-organize at nanometer precision, offers a powerful platform for designing next-generation materials. This project builds on the well-established tensegrity triangle motif to create a diverse set of 3D DNA motifs that self-organize into authentic 3D DNA building blocks. In Aim 1—Unit Design: Encoding Information in 3D DNA Motifs—researchers will identify key structural features of DNA motifs that can encode information through molecular shape. This will involve developing computational tools to predict and constrain topologies and verifying motif structures using X-ray and related techniques. In Aim 2—Algorithmic Shape Encoding for Large 3D Nanomaterials—the focus will shift from individual motifs to overall structural organization. The team will (1) design and characterize quaternary structures with defined chirality, and (2) develop periodic, hierarchical, and fractal-based arrays that require supramolecular-level algorithms rather than sequence-level design. Finally, the project will prototype optical materials capable of light-based computation and readout, paving the way for new advances in nanomaterials and biomimetic systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-09

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Dr. Merkler from the University of South Florida (USF), Dr. Dempsey from Boston University, and Dr. Richards from the Foundation for Molecular Evolution are investigating peptidylglycine α-monooxygenase (PAM), the enzyme responsible for making a diverse family of neuropeptides in humans and many other organisms. Their experimental procedures will provide the first understanding of how full-length PAM binds to biologically relevant neuropeptide precursors. In addition, their work will provide new insights into the interaction of PAM and the molecular precursor for atrial natriuretic peptide (pro-ANP), setting the scene for discovering why PAM is present in tissues that do not make neuropeptides. The project will provide training for a number of graduate, undergraduate, and high school students in the use of a broad array of modern biochemical methods. The results of these studies will form the basis for a series of interactive, in-person talks at the Museum of Science and Industry (MOSI), located close to the USF campus, that will be tailored for students in grades 3-5, 6-8, or 9-12, and members of the general public. These talks will aim to not only improve scientific literacy in Florida but also inspire young people to pursue scientific research in neuroscience and medicine. This research project will provide a detailed molecular understanding of how the full-length, bifunctional form of PAM is able to recognize and modify a wide range of neuropeptide precursors as substrates. They will also provide the first information about how the dynamical properties of PAM impact both catalytic mechanism and communication between the two active sites, which are located in different domains of the enzyme. In addition, we will explore the structural basis of how bifunctional PAM binds to pro-ANP, a peptide that is not a substrate for the enzyme. Our studies will yield the first molecular understanding of the PAM/pro-ANP complex, test current hypotheses about the importance of this complex for cells in tissues that do not make or secrete α-amidated peptides. These project objectives will be accomplished using a multidisciplinary approach that combines biochemical assays, peptide synthesis, hydrogen/deuterium exchange (HDX) measurements, computational modeling, and cryogenic electron microscopy (cryo-EM). 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

Chronic subdural hematomas (cSDH) are one of the most common neurosurgical conditions in the United States. cSDH is a progressive hemorrhage in the subdural space between the dura and the arachnoid mater. The bleed is characteristically encased by a neomembrane made of a dura-mater-facing outer membrane (OM) and an arachnoid-mater-facing inner membrane (IM). These neomembranes have been implicated in the continued pathology and recurrence of the condition. It is hypothesized that damage to dural border cells and subsequent pro-inflammatory and pro-angiogenic signaling cascades can exacerbate neomembrane growth. However, little has been reported on the cellular and molecular architecture of the tissue or its exact role in cSDH pathophysiology. The overall goal of this proposal is to develop an understanding of the cellular and molecular pathogenesis of chronic subdural hematomas. My goal is to address the following questions: What cells are the membranes made of, and how are they distributed? What are the molecular changes across different regions of the tissues? Are there novel markers that correlate with cellular diversity or disease severity? I hypothesize that the molecular characterization of neomembranes will identify key markers associated with angiogenesis, pro-inflammation, and fibroproliferation that will correlate with cSDH severity. AIM 1) In the total cohort of 31 patients, I will stage cSDH disease severity of patients by collecting clinical and radiographical outcomes (AIM 1A); identify cellular and morphological diversity through immunohistochemistry (AIM 1B); and characterize protein and genetic diversity through immunofluorescence staining and bulk RNA sequencing (AIM 1C). AIM 2) Next, I will characterize the spatial transcriptome and proteome across the neomembranes via NanoString GeoMx Digital Spatial Profiler (DSP) and correlate the spatially resolved – omics datasets to the patients’ clinical and radiographical databases (AIM 2A), and then will validate the most enriched gene and protein signatures using a variety of molecular techniques (AIM 2B). Our preliminary data shows a distinct distribution of cells and proteins across the outer membrane. Dura-facing sides have a highly vascular area, intermediate layers consist of acellular or sinusoidal cellular regions, and hematoma-facing sides have high cell densities. These cell densities include large lymphocytic and eosinophilic infiltrates. Further molecular characterization is required. I expect that I will be able to subtype cSDH into different stages of the disease through the creation of transcriptomic and proteomic spatial atlases in this study. I aim to identify key insights on cSDH pathophysiology by identifying factors associated with angiogenic and pro-inflammatory cascades in cSDH. This study is significant because it will generate novel molecular information on cSDH. The use of the Nanostring GeoMx DSP to create whole transcriptomics and proteomics atlases is highly innovative. This study will help identify markers of interest that can serve as therapeutic targets for improving cSDH intervention and cSDH staging and give key insights on pathogenesis that have not yet been reported.

NIH Research Projects · FY 2025 · 2025-08

From 2010 to 2020, the number of new HIV infections in Eastern Europe and Central Asia increased by 43%, while in Kazakhstan, the estimated number of people living with HIV infection (PLWH) increased by 133%, an indication that the key populations transmitting the infections are poorly understood and not effectively linked to harm reduction services, warranting a need for effective training and capacity building for efficient surveillance. Molecular epidemiology approach to reconstruct viral transmission networks forms an explicit part of the Ending the Epidemic program (https://www.cdc.gov/endhiv/index.html). As part of a NIDA-funded grant, we have obtained key information through molecular epidemiology approaches and provided pin-point data regarding high-risk communities in which currently emerging infections suggest their prioritization for intervention. While our NIDA grant has been instrumental in training a handful of young Kazakhstani scientists in cutting-edge molecular epidemiology tools, capacity for such skills is scarce in Kazakhstan. Here, we propose a D43 training program, Molecular Virology Epidemiology in Kazakhstan (MoVE-Kaz), to build capacity for molecular epidemiology research in Kazakhstan. Our specific aims are: 1. To build a pool of well-capacitated Kazakhstani faculty who conduct molecular virology research, we will: a) collaborate with international mentors from Yale University, SUNY-Downstate, and Katholieke Universiteit Leuven in Belgium for the training of two cohorts of 6 Kazakhstani health professionals and young scientists in Molecular Virology (12 trainees total), b) engage local and international mentors to mentor the trainee in applying molecular epidemiology tools for investigating Public Health problems, c) train Kazakhstani health professionals and scientists in the field of molecular virology and epidemiology through short- and long-term training within Kazakhstan, and in New Haven and Leuven. 2. To enhance research capacity for HIV molecular epidemiology in Kazakhstan, our MoVE-Kaz program will train young Kazakhstani physicians and scientists: a) in basic and advanced concepts of molecular virology and epidemiology through two 3-month certificate courses, b) to develop hands-on research skills through an 18-month research certificate course molecular virology for studying transmission and emergence of infection, drug resistance, and viral variants – applying this knowledge to improve HIV surveillance and patient care, c) in ethical conduct of research that meets international standards, and d) in developing competitive grants to fund research in molecular virology and epidemiology. Given the continued surge of HIV in CA, we believe the topic and timing of the training grant is compelling. With our experienced and internationally recognized team of experts in phylogenetic analysis, we believe that we can make a substantial leap in capacity-building for young individual scientists in Kazakhstan.

NSF Awards · FY 2025 · 2025-08

Sea ice is a key feature of the Southern Ocean that shapes the physical structure of the water column and regulates phytoplankton community dynamics and primary production. Phytoplankton are the base of the food chain, and the type of phytoplankton present, along with their overall productivity, impact the abundance of zooplankton and larger animals. Phytoplankton communities and production are also an important link for carbon export to the deep sea, a critical service provided by the Southern Ocean. However, sea ice extent and duration are decreasing in the Antarctic Peninsula region of the Southern Ocean, potentially affecting carbon export. This project aims to evaluate physical and chemical characteristics of sea ice in the Weddell Sea near Seymour Island and quantify effects of melting sea ice on phytoplankton and zooplankton growth and carbon export. This work will promote the progress of polar science and allow for better predictions of the ecosystem effects of changing sea ice conditions, such as shifts in krill abundance and its ability to support macrofauna and fisheries, and changes in carbon export. This project will further support the training of new undergraduate and graduate polar scientists and confer key transferable skills, such as data analysis and visualization and science communication. This project brings together an interdisciplinary team of physical, chemical, and biological oceanographers to comprehensively evaluate characteristics of sea ice in the Weddell Sea near Seymour Island and parse the effects of sea ice melt on biological systems and carbon export through a dual approach involving environmental observations and replicated factorial incubation experiments. Snow pits and ice cores will be used to characterize physical (snow density, hardness, temperature, and grain size and shape) and chemical parameters (δ¹⁸O, nitrate + nitrite, and Fe concentrations) of sea ice. Physical characteristics will be used to better calibrate satellite observations and improve future remote sensing. Chemical parameters will help determine how much meltwater is derived from sea ice and will further constrain the impact of sea ice melt on macro and micronutrient availability in the surface mixed layer. The spatial evolution of sea ice melt across the Weddell Sea continental shelf will be quantified through conductivity, temperature, and depth transects extending from Seymour Island to the shelf break. These transects will also include seawater sampling, zooplankton tows, and deployment of an in situ particle imager to characterize microbial, phytoplankton, and zooplankton communities and calculate particle flux. Experimental incubations will constrain the impacts of changing salinity, light, and nutrient regimes associated with ice melt on biological productivity, particle formation, and export potential. Broader Impacts include training an undergraduate and a graduate student and a synthesis workshop to share results and build a network of scientists interested in the impacts of ice-melt on polar systems. 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

The USF Health Expanding Research in AD/ADRD (ERA) PREP is committed to developing a cohort of postbaccalaureate students with limited research experience to foster their transition to AD/ADRD research-focused doctoral programs to pursue a PhD or MD/PhD degree. The USF academic community, notably the Byrd Alzheimer’s Center and Research Institute (referred to as the Byrd Institute), is rich with many investigators focused on molecular, cellular, pathological, clinical, and regenerative aspects of Alzheimer’s disease and related disorders (ADRD). This makes USF an ideal location for a PREP in AD/ADRD. The mission of the USF Health ERA PREP is to train a pool of post-bac students to enter PhD and MD/PhD programs with the goal of expanding the research workforce dedicated to prevention, treatment, and cure of AD/ADRD. This team will be led by Prof. Paula C. Bickford and Prof. Gopal Thinakaran (CEO of the Byrd Institute). Drs. Bickford and Thinakaran have a long track record of excellence in research and a commitment to successfully mentor young researchers into successful scientific careers. We have selected 12 faculty mentors as program faculty for our ADRD PREP application. Many of us have mentored “gap” year students in our labs on AD/ADRD research who have successfully transitioned to advanced degree programs. This formal PREP program will enhance the ability to attract and train a pool of post-bac scholars interested in AD/ADRD. We are committed to recruiting a pool of recent baccalaureate graduates who have not previously had the opportunity to participate in medical research and will provide them with mentors and strong research training. USF has a strong track record of recruiting a pool of undergraduate and graduate students. The PREP program will entail intensive exposure to hypothesis-driven research experience with an established mentor with a funded research program in AD/ADRD. This mentored research will accelerate training and enhance the number of highly skilled researchers dedicated to AD/ADRD research. The program will help PREP scholars develop a research project, hone critical thinking skills, learn experimental techniques, data collection, analysis, and interpretation of the results, and brainstorm each other’s research projects with the program faculty. We will offer workshops on how to thrive and establish skills for long-term career success, including aspects of professional development. Monthly social gatherings and workshops will foster engagement and engender a strong community of scholars to thrive.

NIH Research Projects · FY 2025 · 2025-08

PROJECT ABSTRACT Improving speech understanding in the presence of background noise by individuals fitted with cochlear implants is an enormous challenge. Although audibility can sometimes be a limiting factor for benefit, more frequently it is because the cues that are often responsible for sound source segregation by individuals with normal hearing, are limited or unavailable. This proposal will alter binaural cues, in the form of magnified ILDs, and use behavioral and neuroimaging techniques to establish both the extent and the mechanisms of benefit.

NSF Awards · FY 2025 · 2025-08

The increasing demand for expertise in quantum computing and cybersecurity presents both a national challenge and an opportunity. By 2035, quantum computing is expected to generate nearly $700 billion in value, yet the talent pipeline remains limited, with only one qualified candidate for every three job openings. Meanwhile, the number of cybersecurity jobs are projected to grow by 35% between 2021 and 2031. Despite the urgent workforce needs in both domains, there is a lack of integrated, experiential learning opportunities that foster cross-disciplinary skills. This project addresses that gap by creating cloud-based educational modules that blend quantum computing and cybersecurity through hands-on, collaborative learning experiences. The project supports national priorities by preparing a future-ready STEM workforce and promoting collaboration across institutions of different types. This award supports the development of a cyberinfrastructure-based platform for experiential learning in quantum computing and cybersecurity. The project includes the design and implementation of new interdisciplinary learning modules, integration of these modules into existing courses, and delivery of the faculty development workshop and the student summer camp. Modules will include tutorials and hands-on labs using cloud platforms, making them scalable and adaptable across different institutional contexts. Faculty and students at the New York Institute of Technology and the University of South Florida will collaborate on course development, module testing, and implementation. Through formative and summative evaluation, the project will improve teaching materials and support nationwide dissemination and adoption. This initiative will contribute to curriculum innovation, faculty training, and the preparation of a skilled workforce equipped to address the emerging challenges and opportunities in quantum computing and cybersecurity. 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 · 2025-08

Collaborative Research: BUILD: Bridging the Unmet Industry Learning Demands for Research Administrators A robust support infrastructure providing responsible stewardship and vigilant oversight for grants is integral to the research enterprise. The future of the field will leverage technology to optimize performance and manage risk to realize operational excellence and improve economic impact for the research enterprise. Skilled research administration professionals are needed to ensure that federal investments are protected. BUILD will design and deliver online curriculum that will bridge the unmet need for this critical workforce. To educate and retain a large student body, BUILD combines the low-cost solution of asynchronous coursework with the effective retention strategies of high impact practices, which include peer support, mentoring, learning cohorts and e-portfolios. Upon completion of all courses, electronic portfolio and passing the comprehensive examination, students receive a Certificate of Foundations of Research Administration and Research Development. BUILD brings together multiple institutions with differing levels of research activity and resources to create effective virtual education that will fit any research support environment. To realize its transformational potential, BUILD will establish a model that can be implemented nationwide, contributing resources that are shareable by design – instructional and empirical – to support effective education. The impact includes the 280 students served and mentors and graduate students trained. Outcomes include asynchronous courses, an online textbook, mentor orientation materials, and an open access repository of curated educational resources. BUILD uses a mixed methods approach, with qualitative measures used primarily for fidelity of implementation, to document the content and quality of materials, instruction, and interaction in the proposed activities. Quantitative assessment includes data on program quality and predictors of successful outcomes. A randomized control trial will assess the impact of mentoring on achievement and retention. Knowledge gained through this project addresses the complexity of pursuing and managing externally supported research, modernizes training activities to expand research capacity, and catalyzes a stronger, more agile workforce. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT SSR42 is a 1,233 nt regulatory RNA bearing no ORFs, that exhibits enhanced stability during stationary growth and maintains extensive nucleotide sequence conservation (>98% across diverse strains). Characterization of SSR42 by others has shown that SSR42 mutants are impaired in their ability to lyse rabbit- and sheep- erythrocytes, have reduced survival upon challenge by neutrophils, and engender limited intracellular toxicity towards HeLa cells. Additionally, an SSR42 mutant has significantly decrease bacterial burden in a murine model of skin abscess formation. Herein, we demonstrate that an SSR42 mutant also has impaired hemolytic activity towards human erythrocytes, limited cytolytic activity towards human leukocytes, and increased proteolytic capacity. In addition, SSR42 also regulates numerous secreted virulence factors known to be central to S. aureus infection. Furthermore, our SSR42 mutant has a decreased ability to survive and disseminate in the liver, heart, lungs, and spleen of mice during sepsis, and decreased viability during murine pneumonia, all by several orders of magnitude. Previous work by our group revealed that SSR42 is found only in S. aureus strains. Not only this, but it is the most highly expressed, S. aureus-specific transcript in stationary phase cells. Indeed, only RNAIII is present in more copies after 15h growth. This means that 20% of the total RNA (minus rRNA) in stationary phases cells belongs to SSR42, and 45% to SSR42 and RNAIII combined. The importance of the Agr system, and thus RNAIII, is clear and undeniable; thus the paucity of knowledge for how SSR42 mediates its role, and is itself controlled, demonstrates a major knowledge gap in S. aureus pathogenesis research. Accordingly, in the present application we will dissect the role and regulation of this important, yet understudied component of the S. aureus regulatory machinery by: Aim #1: Determining the Mechanism by which SSR42 Regulates Virulence Factor Production: We will perform RNA EMSAs coupled with mutational genetics to explore SSR42 mediated RNA:RNA interaction. We will then determine the importance of such events in the S. aureus cell. Aim #2: Defining the Impact of SSR42 on S. aureus Virulence Factors Expression in vivo: Next, we will perform a longitudinal study of virulence factor production by S. aureus during both localized and disseminated disease to understand the impact of SSR42 on the severity and timing of infection. This will be achieved using cutting edge mass-spectrometry to detect virulence factors in infected tissues. Aim #3: Dissecting the Hierarchical Control of SSR42: Given the powerful nature of SSR42 as a regulator, and its profound ability to impact infection, we consider it of primary importance to understand how it too is controlled. Herein we have generated a testable map of SSR42 regulation using a novel high-throughput screen which we will interrogate via classical genetic approaches, providing a comprehensive understanding of SSR42 regulation.

NIH Research Projects · FY 2025 · 2025-08

Abstract Clostridioides difficile is the leading cause of nosocomial infection. The use of b-lactam antibiotics, especially cephalosporins, is a major risk factor for infection, but high dietary zinc concentrations have also been shown to increase infection rates. Current treatments of C. difficile infection (CDI) are plagued by high recurrence frequency due to C. difficile spores, which are the main vehicle of transmission and highly resilient against harsh environmental conditions. We hypothesize that penicillin-binding proteins (PBPs), the target of b-lactam antibiotics, may play important roles in C. difficile cephalosporin resistance while serving as valuable targets for novel antibiotic development, especially targeting C. difficile sporulation in recurrent infection. Despite PBP’s biological and clinical importance, our understanding of PBPs has mostly relied on studies of a few model organisms. Most recently, we have demonstrated, for the first time, that the structures of several C. difficile PBPs contain a zinc ion in their active site, a feature never observed in PBPs from model organisms but likely prevalent in other bacteria. We have also developed a series of diazabicyclooctane (DBO) compounds as potent anti- sporulation reagents by inhibiting PBP3, a PBP critical for sporulation. Here we propose to 1) elucidate the roles of PBPs and other peptidoglycan transpeptidases in the pathogen’s complex life cycle and determine the b- lactam resistance profile through biochemical/structural analysis and gene knockout/knockdown experiments; 2) apply a structure-based design approach to develop new PBP inhibitors targeting C. difficile sporulation. Taken together, the proposed studies will deepen our understanding of PBPs across bacterial species and provide new knowledge about the unique properties of C. difficile PBPs, particularly those related to the risk factors of CDI and future drug discovery to address current treatment challenges. The results will also facilitate the development of new combination therapies for recurrent CDI by using existing CDI drugs such as vancomycin and anti- sporulation inhibitors.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT Mutations in the CDK13 gene cause “Congenital Heart Defects, dysmorphic Facial features, and Intellectual Developmental Disorder” (CHDFIDD); the link to this congenital heart disease (CHD) has spurred great interest about its molecular mechanism of action. We have developed genetic mouse and iPS cell models to investigate how mutations in this kinase lead to the associated cardiac pathologies. Several recent reports have provided additional evidence that also supports our hypothesis that reduced CDK13 function affects transcriptional and post-transcriptional RNA processing to disrupt cellular function. Consequences of inadequate CDK13 function may lead to defects in RNA splicing; in addition, depending on the level of CDK13 functional deficiency, compensatory mechanisms may be activated in the cell in an effort to remove aberrant RNAs. This could include the increased expression of spliceosome components, exosome factors, or RNAses. Therefore, we will test the hypothesis that CDK13 deficiency induces heart defects through disruption of RNA processing, generating functional deficiencies at the cellular level and impairing normal heart development. To accomplish this, we propose three integrative aims, including studies in both mouse and human iPSC models. For Aim 1, we will employ Cdk13 mutant mice with the genetic lesion specifically targeted to cardiomyocytes within the first heart field (FHF) or the second heart field (SHF). We will also delete Cdk13 from neural crest cells (NCC) as part of a systematic strategy to characterize the cardiac phenotype. We will also employ cellular and molecular biology approaches to determine the role of Cdk13 in cell proliferation, differentiation, and migration. In Aim 2, we will employ a cell based approach, using the innovative induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) model. This model will facilitate the testing of mutations in the CDK13 gene that are associated with CHDFIDD, based on published studies. Our approach will yield important new information on how each mutation contributes to the individual defects. Our preliminary studies have established proof of principle with the generation of iPSCs with CDK13 mutations corresponding to those found in CHDFIDD patients. Our characterization of the CDK13 mutant iPSC-CMs will establish a high throughput model of CHDFIDD that will facilitate both mechanistic studies and approaches to intervention and potential treatments. In Aim 3, we will focus on the molecular mechanisms of Cdk13 function. We and others have observed abnormal RNA processing associated with insufficient CDK13 function; our preliminary data highlights important potential links to RBFOX1 as well as several ribosomal proteins. We have designed a chemically inhibitable CDK13 line that will facilitate the study of a complete or partial loss of CDK13 function and facilitate a dissection of the molecular mechanism disrupted in CHDFIDD patients. Our proposed studies will provide important insights into CDK13 function and possible approaches for the treatment of CHDs and heart disease.

NIH Research Projects · FY 2025 · 2025-08

Project Summary/Abstract Melanoma is a highly aggressive cancer from melanocytes, accounting for 1% of skin cancer cases yet causing most skin cancer deaths. The 5-year survival for metastatic melanoma patients is below 30%. The mechanisms driving melanoma metastasis are poorly understood, necessitating thorough investigations to enhance patient survival rates. While targeted therapies like BRAF and MEK inhibitors can lead to initial regression, relapses occur quickly. Immunotherapy offers lower response rates (30-50%) and substantial toxicity, highlighting the need for novel therapeutic targets. The human genome consists of 98% non-coding regions, many of which produce non-coding RNAs essential for cancer development, including melanoma. Circular RNAs (circRNAs), known for their closed structure and degradation resistance, are attracting attention for their potential roles in cancer. However, their specific functions and mechanisms in melanoma metastasis remain largely unexplored. By analyzing RNA-sequencing data, I identified circPMS1 as the most upregulated circRNA in melanoma cells compared to melanocytes. Using previously developed genetic tools for stable circRNA overexpression, I assessed the oncogenic potential of circPMS1. Overexpression of circPMS1 enhanced both melanoma and melanocyte migration and invasion in vitro. Conversely, CasRX-mediated silencing of circPMS1 resulted in decreased migration and invasion. Furthermore, circPMS1-overexpressing cells formed more metastases in lungs and liver when injected into NSG mice, while silencing circPMS1 significantly reduced metastasis formation. Despite the presence of a predicted ORF and IRES, I demonstrated that circPMS1 does not translate into a protein. This leads to my hypothesis that circPMS1 interacts with proteins that influence the metastatic potential of melanoma cells. To investigate this, I pulled down tagged circPMS1 and identified six potential interacting proteins via mass spectrometry. Four of these proteins (ABLIM, CAPZA2, PDLIM7, LMO7) contain LIM domains that may bind nucleic acids and are involved in cytoskeleton rearrangement and metastasis in other cancers. However, the effects of RNA binding on these LIM domain proteins’ biology remain unstudied. In the light of these findings, I hypothesized that circPMS1 has pro-metastatic functions in melanoma by altering the expression, activity, and/or localization of its protein binding partners. In the F99 phase, I will characterize these partners and elucidate the molecular mechanism underlying circPMS1's metastatic phenotype using in vitro assays and genetically engineered melanoma mouse models. In the K00 phase, I will examine the role of circPMS1 in melanoma brain metastasis through in vitro and transplant models, developing therapeutic strategies to target circPMS1 and inhibit its pro-metastatic functions. Additionally, I will identify and characterize circRNAs associated with melanoma brain metastasis through RNA-seq, CRISPR screenings, in vitro assays, and transplant models. The F99/K00 award will provide essential training to become an independent investigator, enabling me to identify circRNAs as potential therapeutic targets for melanoma metastasis.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY The blood-brain barrier (BBB) is a vital defender of the central nervous system (CNS) that allows for nutrient exchange while blocking the entry of toxic factors or immune cells. However, its disruption is common in CNS disorders and can drive their disease progression. As such, our long-term goals are to identify the mechanisms governing BBB function and evaluate their therapeutic potential to preserve or restore BBB integrity and limit disease progression. The overarching objective of this proposal is to investigate the role of FoxO1, nmMLCK, and HDAC6 in BBB dysfunction and disease progression using animal and cell culture models of multiple sclerosis (MS), a chronic CNS disorder affecting an estimated one million adults in the US. During barrier maturation, the transcription factors FoxO1 and β-catenin are inactivated and removed from a silencer region in the Cldn5 promoter. However, we have shown that inflammation-induced BBB-dysfunction requires their concurrent re-activation and occupancy at the silencer region. This process involves nmMLCK. In a follow-up study, we defined an insulin receptor (IR)-Akt2-FoxO1 axis that can be targeted with an IR agonist to limit FoxO1 activation, claudin-5 loss, and barrier dysfunction in BBB-ECs and mice induced with experimental autoimmune encephalomyelitis (EAE), a model of MS. Here, we provide preliminary data showing the importance of nmMLCK and its regulation by histone deacetylase 6 (HDAC6) in barrier dysfunction. Global knockout mice are resilient to EAE, including paralysis, BBB dysfunction, and claudin-5 loss. In tandem, we explored mechanisms for nmMLCK activation and identified that it is robustly deacetylated in IL-1ꞵ-stimulated BBB-ECs. Using inhibitors, we found that tubastatin A attenuated barrier dysfunction, implying that HDAC6 is responsible. Thus, we hypothesize that FoxO1 and β-catenin are essential for mediating inflammation-induced claudin-5 repression, driving BBB dysfunction. To address this, we have developed a two-part approach that focuses on the relative contributions of FoxO1 deficiency in BBB-ECs (Aim 1) and HDAC6/nmMLCK/β-catenin signaling-dependent downregulation of claudin-5 (Aim 2) to BBB disruption and disease progression. The multi-faceted approach combines in vivo physiological analyses in EAE with complementary co-culture systems using BBB-ECs, astrocytes, pericytes, and myelin-reactive T cells. Multiple innovative models are proposed, including transgenic mice with inducible BBB-EC-specific knockout of FoxO1, nmMLCK, or HDAC6 and pharmacologic approaches to inhibit them; new molecular tools like TetOn overexpression systems for FoxO1 and HDAC6; and state-of-the-art histopathology techniques to detect and characterize perivenular inflammatory lesion formation which occurs around CNS microvessels in white matter lesions. In sum, the proposed research is significant, as data derived from these studies will provide new mechanistic insights into the pathophysiology of BBB dysfunction during inflammation, which has the potential to provide a basis for developing new therapeutic targets for CNS disorders that involve BBB dysfunction.

NIH Research Projects · FY 2025 · 2025-07

Abstract S. aureus possesses 4 major secreted proteases carried on the core genome: a metalloprotease (aureolysin), a serine protease (V8), and two cysteine proteases (Staphopain A and Staphopain B). In addition, most strains encode up to 9 serine-protease-like enzymes (Spls) carried on the vSab pathogenicity island. Despite the first of these enzymes being identified >45 years ago, we have only recently begun to understand their importance to S. aureus infection. Using a 10-protease gene deletion (Protease Null (PN)) we revealed that secreted protease are key mediators of S. aureus disease. Importantly, their role is biphasic as: (i) Secreted protease deletion leads to markedly increased mortality of infected animals during sepsis; whilst (ii) the PN strain also displays impaired survival in human blood, decreased resistance to phagocytosis, and impaired ability for dissemination and survival during septic infection. The explanation for these seemingly contradictory findings stems from their differing roles, and substrates, during infection. The enhanced mortality of mice is driven by a role for these enzymes in controlling the stability of virulence factors (VF). Thus, in the absence of secreted proteases, VF exist unchecked, accumulating to high levels and causing aggressive and deadly infections. Conversely, virulence attenuation is mediated by a key role for these enzymes in attacking the host, cleaving proteins that facilitate nutrition, immune evasion, inflammation, inactivation of host defenses, tissue destruction, and dysregulation of host processes. However, despite this important knowledge, much remains unknown about how these enzymes are regulated, how they regulate the progression of infection, and how they interact with the host. As such, herein we will dissect the role and regulation of secreted proteases by exploring: Aim #1: The Regulation of S. aureus Secreted Proteases: Secreted proteases are produced by S. aureus alongside its many VF, to modulate their stability, and control the course of infection. During the previous period of support, we identified two non-canonical regulators that profoundly influence protease production. Thus, in this aim we will explore how each of these (a novel regulatory RNA and a unique two-component system) modulate protease activity. Aim #2: The Role of S. aureus Secreted Proteases: During septic infection, the PN strain demonstrates marked decreased in dissemination/survival within mouse organs. This attenuation is mediated by a key role for these enzymes in attacking the host. We know that not all proteases are required for this phenotype, thus we will unravel which proteases contribute to survival during a disseminated septic infection. We will next understand how the proteases mediate their role in vivo using cutting edge mass-spectrometry. Finally, we will conclude this aim determining the role of the Spls during pneumonia.

NSF Awards · FY 2025 · 2025-07

Many homes in the U.S. use carbon-based point-of-use filters to purify drinking water —whether in the refrigerator, under the sink, or attached to the faucet. These filters are common in cities with lead problems, in rural areas with private wells, and among people who prefer not to drink tap water. While these filters are popular, scientists still do not fully understand how they affect water quality over time. In some cases, the filters may even make water quality worse by increasing the concentrations of contaminants like nitrite to unsafe levels. This research aims to understand how the design and use of the filters can impact the quality of household water. Outcomes of this research can be used to improve the safety of filtered water. The researchers will work closely with local community members to communicate results to the public. Activated carbon block (ACB) point-of-use (POU) filters exist in almost every U.S. home, yet fundamental knowledge regarding ACB POU filter water quality tradeoffs, filter nitrification, microbial colonization, use patterns, and long-term operation is still lacking. ACB POU filters are installed in urban neighborhoods in response to high lead levels, in rural areas to treat private wells impacted by regulated and emerging pollutants, and as a personal choice to avoid tap water. However, consumers do not expect water quality to worsen after installing ACB POU filters, let alone suspect high nitrite concentrations. The goal of this research is to redesign ACB POU filters by investigating the motivations to install, water quality tradeoffs created, and patterns of use once a filter is in place. The project will: (1) advance the knowledge of water quality tradeoffs by investigating ACB POU filter microbial colonization, nitrite production mechanisms, and the impacts on target contaminant treatment efficiency; and (2) develop a mechanistic understanding of ACB POU filter component and operational status impacts on microbial colonization and filtrate quality using technical and human behavior inputs. The research includes developing a novel flow pathway approach, normalized by surface area, to reduce experimental space and influent water volume requirements. This scale of investigation of POU filter components and operation could transform filter research and inform certification methods. The project has a strong focus on increasing scientific communication by disseminating results to relevant policy groups, industry collaborators, utility partners, professional associations, and to community groups within the Tampa Bay Area to ensure research communication to the broadest possible audience. 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

Summary/Abstract Patients with diabetes mellitus (DM) manifest coronary microvascular endothelial dysfunction, characterized by impaired endothelium-dependent relaxation. Impaired endothelium-dependent vasodilation decreases coronary blood flow and myocardial perfusion, resulting in cardiac dysfunction/diabetic cardiomyopathy, and myocardial ischemia with no obstructive arteries (INOCA), which increase morbidity and mortality in the diabetic population. Our recent studies indicate that dysfunction of small-conductance calcium-activated potassium channels (SK channels) play a key role in DM-induced endothelial dysfunction in animal and human coronary microcirculation. However, the mechanisms responsible for diabetic dysregulation of endothelial SK channels and coronary microvasculature remain undefined. Our pilot data indicate that DM causes excessive phosphorylation of CaMKII (p-CaMKII), O- GlcNAcylation of CaMKII (OG-CaMKII), and oxidation of CaMKII (ox-CaMKII), along with increased mitochondrial ROS (mROS) production in the heart and endothelial cells. Moreover, our preliminary studies demonstrate that chronic p-CaMKII, ox-CaMKII and O-GlcNAcylation during DM reduce endothelial SK channel activity, or coronary microvascular relaxation, and/or myocardial blow flow in both male and female mice. These results suggest that CaMKII posttranslational modification plays an important role in diabetic dysregulation of endothelial SK channels, coronary microvascular function and myocardial perfusion. Thus, the overall goal of this project is to investigate how CaMKII posttranslational modifications during chronic DM alter endothelial SK channel activity, coronary microvascular endothelial-dependent relaxation, and myocardial blow flow. Our central hypothesis is that sustained and excessive posttranslational modification of CaMKII during chronic DM dysregulates endothelial SK3/SK4(IK) channel activity, eNOS signaling, and endothelial function, resulting in coronary microvascular dysfunction and myocardial hypo-perfusion. We will test our hypothesis by employing multiple innovative approaches from cellular/molecular analyses and microvascular biology to physiology and pathophysiology. These approaches include type-1 and type-2 diabetic mouse models in combination with knock-in mouse models of oxidation-resistant CaMKII (MMVV), O-GlcNAcylation-resistant CaMKIIδ (S280) and a transgenic mouse model of endothelial cells expressing synthetic CaMKII inhibitory peptide (AC3-I) in both male and female animals, as well as endothelial ion channel recordings by patch clamp methods, measurement of microvascular reactivity in-vitro by a vessel myograph, contrast echocardiography to measure myocardial blood flow reserve in-vivo, immunoprecipitation (IP), LC/MS-MS, and site-directed mutagenesis, amongst other methods. The impact of sex differences on diabetes induced CaMKII posttranslational modification and related coronary microvascular dysfunction will also be analyzed. This integrated proposal will result in the identification of novel pathways, molecular targets, and novel therapeutics strategies for improving coronary microvascular function in diabetic patients with coronary heart disease.

NIH Research Projects · FY 2025 · 2025-07

Project Summary Malaria affects almost half the world’s population and causes more than half a million deaths annually. Children with underdeveloped immune systems in malaria-endemic areas have the highest mortality rate but no vaccine candidates are explicitly identified for this group. Global efforts to control the disease have had limited success, with no blood-stage vaccine being approved yet. However, the WHO recommends two sporozoite protein-based vaccines, RTS, S/AS01, and R21/Matrix-M, for human use but achieving broad implementation and evaluation of global efficacy remains a challenge. Therefore, there is an urgent unmet need to discover new vaccine candidates or improve the efficacy of known antigens to develop a new generation of malaria vaccines for children. Previous studies in our lab identified a novel vaccine candidate, PfGARP, using phase display screening of malaria-resistant children's serum and P. falciparum T7 Phage-based cDNA library. Our work has culminated in the discovery of Pf Glutamic Acid Rich Protein A (PfGARP-A) and a comprehensive, full-length Research Article in Raj et al. Nature, 2020. During the screening phase of our approach, we identified antigens from C- terminus regions of PfGARP overlapping with each other and interacting only with the antibodies from the plasma of malaria-resistant children. The above findings indicate that the lower molecular weight recombinant PfGARP (rPfGARP) antigens might have the crucial domain for functional antibodies and can generate growth inhibition activity comparable to PfGARP-A. In our preliminary approach, we immunized the mice (n=5/antigen) with DNA vaccine using the smaller fragments of the immunodominant regions as PfGARP-B, PfGARP-C, PfGARP-D, and a 324 bp N-terminus fragment of PfGARP (PfGARP-E as negative control) and harvested polyclonal serum. Our preliminary data demonstrate that polyclonal serum generated against PfGARP-B and PfGARP-C in mice specifically interacts with P. falciparum in western blot, flow cytometry, Immunofluroscent microscopy, and shows significant parasite-killing activity in growth inhibition assay (GIA) comparable to PfGARP-A. The study aims to develop human- usable recombinant protein and LNP-mRNA-based platforms for PfGARP-B & C antigens using in vitro assays and humanized murine model (in vivo) against P. falciparum, the deadly human malaria parasite. These studies will form the core supporting data for further development of the lower molecular weight rPfGARP antigens, which could help reduce the production cost and make it easier to use with other blood stage proteins as fusion antigens with the ultimate goal of an efficacious malaria vaccine for humans that has better efficacy against children.

NSF Awards · FY 2025 · 2025-07

This I-Corps project focuses on the development of a new gene therapy designed to treat diabetes in pets through a single, long-lasting injection. Diabetes is a growing health issue among companion animals, with hundreds of thousands of dogs and cats affected in the United States alone. Current treatments often require daily insulin injections, which can be stressful, expensive, and difficult for pet owners to manage. The technology addresses that challenge by creating a simpler, more effective solution that helps regulate blood sugar levels with just one treatment. The therapy works by helping the animal’s body produce a natural protein that improves how it uses insulin and protects against damage caused by diabetes. The scale of the problem is significant, with the number of diabetic pets increasing and limited treatment options available. This therapy has the potential to reduce long-term veterinary costs and make diabetes care more accessible. Early results also show improvements in both body and brain health, supporting the potential for wider therapeutic benefits. The project also looks at how this treatment can be scaled up for use in veterinary clinics, filling a major gap in long-term care for pets with chronic diseases. 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 gene therapy platform designed to express a molecule with antioxidant and tissue-repair properties. The therapy targets metabolic dysfunction in diabetic animals by enhancing insulin sensitivity, reducing weight gain, and protecting against diabetic neuropathy. The approach involves a single intramuscular injection of a viral vector engineered to deliver the gene encoding this protein, resulting in sustained systemic expression. Preclinical studies in diet-induced diabetic mice demonstrate significant improvements in glucose regulation and cognitive function, with plasma protein levels maintained for several months post-injection. This method contrasts with existing treatments that rely on frequent insulin administration, offering a long-acting, low-maintenance alternative. The therapy’s design allows for scalability to larger animals, such as cats and dogs, using standard veterinary injection techniques. The scientific innovation lies in the use of a gene-based delivery system to achieve durable therapeutic effects from a single administration, reducing the need for ongoing intervention. Users benefit from improved disease control, reduced treatment burden, and lower risk of complications such as hypoglycemia. 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

Whereas traditional cameras form images exclusively through use of optics, computational-imaging systems are transforming how to see and what can be seen by sharing the imaging task across frontend optical hardware and backend computational algorithms. In such computational-imaging systems, the optical hardware collects informative measurements that are subsequently analyzed by computation to produce high-quality, human-interpretable images. Although these systems promise unprecedented access to previously unobserved physics and biology, existing mathematical techniques used to study their performance capabilities and jointly optimize their constituent frontend optics and backend algorithms are imprecise and deficient for many emerging applications. Consequently, this project aims to introduce new mathematical tools to tackle these deficiencies and establish a framework for unlocking the maximum potential of computational-imaging systems, especially in applications – such as single-photon lidar, focused-beam microscopy, and imaging with no line of sight – wherein images are to be computed from extremely weak and noisy measurements. Societal benefits include the integration of art-infused initiatives as a high-impact pedagogy that aims to improving student engagement in science and engineering. The convention for assessing the conditioning of computational-imaging systems is based on computing condition numbers and singular values. This computation presupposes an interest in worst-case performance over some fixed, pre-chosen discretization. Unfortunately, this approach can lead to incorrect conclusions, including the impossibility of imaging even where imaging is possible, especially when conditioning is not spatially uniform. With the proliferation of computational imaging in myriad applications, the time is ripe for a precise and unified framework for studying the fundamental limits of computational-imaging systems. This project will achieve this goal by using the notion of information orthogonality to separate ill-conditioned spatial directions from well-conditioned ones, allowing for more precise characterizations of conditioning. Precise characterizations will enable system-level design optimizations and new, efficient algorithms that augment existing reconstruction methods to yield substantial improvements in imaging quality and efficiency and even unlock new imaging capabilities and modalities. While this project focuses on computational-imaging systems and corresponding inverse-imaging problems, it will also contribute more generally to the theory and practice of inverse problems. 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

Lithium is a critical component of batteries that power everything from smartphones to electric vehicles. Current methods for extracting lithium are often inefficient, costly, and harmful to the environment. This project will design new molecular binders that selectively capture lithium ions from natural sources such as salt lakes and geothermal brines. It will result in materials that capture and release lithium more efficiently and sustainably. This work will strengthen the U.S. supply chain for critical materials, promote energy security, and reduce environmental impact. In addition to its scientific contributions, the project will train students in advanced chemical research, support workforce development in science and technology, and inspire the next generation of STEM leaders through educational activities and outreach initiatives. The key challenge in this field is how to selectively extract lithium ions from an aqueous solution containing many other ions. Existing processes often use crown ethers and other macrocyclic receptors with cavities that trap lithium, but exclude larger metal ions. These receptors typically show weak lithium binding, low selectivity over competing ions, and costly syntheses. This project introduces a new approach to designing acyclic molecular receptors that exploit strong noncovalent forces, particularly ion-dipole and electrostatic interactions, to achieve selective lithium binding. The project team will design and synthesize a series of acyclic molecular receptors and systematically evaluate their lithium binding in solution. Promising candidates will then be immobilized onto solid supports, and their separation performance will be assessed under conditions typical of industrial practice. The results will advance fundamental understanding of how noncovalent interactions can be exploited for selective ion binding. Overall, the project will establish the molecular-level principles needed to develop sorbents with improved efficiency, selectivity, and sustainability for lithium extraction. This project will promote national self-reliance for critical minerals. Additional benefits will derive from extensive outreach activities at pre-college level, and incorporating virtual reality experiences for chemistry education. 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 · 2025-06

Hands-on training helps students bridge theoretical knowledge with practical application in cybersecurity. While remote platforms offer excellent opportunities for learning software security, no comparable resources exist for hardware security education. Key topics in hardware security require access to physical development boards, creating a significant barrier for learners without these resources. In this interdisciplinary project, a remote platform will be designed to provide open access to physical hardware for beginners to advanced-level hardware security experiments. By providing a scalable, accessible, and innovative educational resource, this tool will advance hardware security education, support the development of skilled practitioners in this field, and respond to national security needs. The remote platform will consist of an array of hardware security development boards, comprising microcontrollers, Field Programmable Gate Arrays (FPGAs), built-in power side-channel measurement and fault injection hardware. The software will include a user-friendly front-end based on JupyterLab and an open-source backend for C and FPGA development. The project will also develop extensions for collecting important educational benchmarks and usage statistics, enabling the evaluation of pedagogical strategies for remote hardware labs. Students will design and conduct complex hardware security experiments on remote physical boards using Python to control the hardware and analyze outputs. By combining innovative hardware tools with scalable software solutions, the platform will enhance both the accessibility and effectiveness of hardware security education and foster advancements with teaching and learning in the field. This project is supported by the Secure and Trustworthy Cyberspace (SaTC) program, which funds proposals that address cybersecurity and privacy, and in this case, cybersecurity education. The SaTC program aligns with the Federal Cybersecurity Research and Development Strategic Plan and the National Privacy Research Strategy to protect and preserve the growing social and economic benefits of cyber systems while ensuring security and privacy. 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 · 2025-06

This I-Corps project is based on the development of an educational software platform for high school math instructors and students. Learning disparities in high school math education are caused by various factors including varying levels of prior knowledge and learning needs and limited availability for personalized support. These factors together contribute to significant barriers in learning math for many students, impacting their college academic paths and their success in Science, Technology, Engineering and Mathematics (STEM)-related fields. This technology addresses these issues by providing an artificial intelligence (AI)-driven, interactive visual learning software platform to support instructors in detecting potential learning gaps. Currently, instructors rely mainly on static instructional methods that do not adapt well to students’ personalized learning needs. In addition, these static methods pose challenges for instructors to detect students’ learning disparities and in identifying the causative factors associated with these disparities. This technology platform can dynamically analyze students’ learning performance while generating clear, contextualized, and actionable insights for instructors. By integrating advanced technologies into real educational practices, this technology may benefit math education student outcomes. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of an artificial intelligence (AI)-driven educational software platform to support high school math instructors. This technology is an adaptive platform that integrates large language models (LLMs), data analysis, and interactive data visualization techniques. The goal is to enable instructors to identify students’ learning disparities, analyze the influential factors, evaluate algorithmic accountability, and implement effective strategies to close the performance gaps. The process used is guided by a framework derived from Bloom’s Taxonomy for aligning the analytical process with educational methodologies to enhance educational outcomes. The solution leverages LLMs to interpret the analytical results within real math learning contexts, ensuring generated insights are understandable, trustworthy, and actionable for educators. In addition, the platform offers contextualized explanations about learning disparities for educators, enabling them to make informed, data-driven decisions while enhancing their confidence in engaging with AI. For students, this platform may transform the passive math learning process into interactive, adaptive, and data-driven experiences. For teachers, the platform’s contextualized interpretations may demystify the instruction and learning process, supporting targeted and effective teaching practices. 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.