University Of Missouri-Columbia

NSF Awards · FY 2025 · 2025-08

Roughly 550 million years ago, life on Earth underwent a major transformation. During this time at the end of the Ediacaran Period the first animals began to form hard shells, move across the sea floor, and interact in new ways, including hunting and burrowing. These innovations laid the foundation for the “Cambrian Explosion,” a burst of evolutionary change that produced nearly all major animal groups. However, the fossil record from this critical time remains incomplete, and major questions persist about how and why these changes occurred. This project investigates ancient rocks at the Nevada National Security Site (NNSS), a region that has been closed to paleontological study for over 70 years. By uncovering and analyzing fossils preserved in these rocks, this research will provide new insights into the earliest animals and how they shaped Earth’s ecosystems. In addition to advancing scientific discovery, the project supports student training, public science outreach, and national collaboration, helping connect society with its deep evolutionary past. This project will be the first to systematically investigate Ediacaran- to Cambrian-aged strata within the Nevada National Security Site (NNSS), with the goal of understanding biotic and environmental dynamics during the terminal Ediacaran Period. The study focuses on fossiliferous carbonate and siliciclastic units that may preserve cloudinomorph-grade taxa and associated trace fossil assemblages, with particular attention to characterizing evidence of early biomineralization, ecological interactions (e.g., predation), and taphonomic pathways. The research team will employ high-resolution imaging (including scanning electron microscopy and X-ray tomographic microscopy), geochemical analyses (e.g., elemental mapping, stable isotope chemostratigraphy), and stratigraphic correlation to document fossil morphology, reconstruct paleoecological settings, and assess facies changes and preservational controls. The project also aims to provide data relevant to defining the proposed Terminal Ediacaran Stage of the geologic time scale and will contribute to international stratigraphic efforts through collaboration with the Ediacaran Subcommission of the International Commission on Stratigraphy. Outcomes will include taxonomic revisions, refined geochronologic and paleoenvironmental interpretations, and increased understanding of early animal evolution. 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

The massive expansion in the production of data has led to natural computational challenges in uncertainty quantification. In particular, Bayesian methodology can account for sources of uncertainty, but requires techniques known to be computationally demanding. These difficulties are exacerbated when data are spatially and/or temporally correlated. The current solutions predominantly use either approximations or inefficient iterative methods such as Markov chain Monte Carlo (MCMC). This project resolves the computational challenges in uncertainty quantification with novel statistical methodology that does not require approximations and MCMC. Big data has impacted nearly every area of science, and as a result, methodological development and software for scalable, exact, MCMC free Bayesian methodology will have a substantial effect. Not only will the proposed methodology and software be an advancement in statistics, but it will be useful across a broad range of disciplines that deal with complex spatio-temporal processes such as neuroscience, climatology, demography, econometrics, ecology, meteorology, oceanography, and official statistics. The investigator will educate and train graduate students, and disseminate project findings through journal publications, public-use software, and conference presentations. The objective of this project is to develop conjugate distribution theory for scalable Bayesian hierarchical models that create a larger framework for statisticians and subject matter scientist to perform MCMC free Bayesian inference without approximating the posterior distribution. In particular, this project will develop and extend the generalized conjugate multivariate (GCM) distribution, which allows one to simulate directly from the exact posterior distribution for a particular large class mixed effects models. This exact sample is referred to as Exact Posterior Regression (EPR). In Aim 1, the investigator will develop extensions of GCM and EPR to new settings including ordinal and nominal data, exact MCMC free inference for certain hyperparameters, and theoretical connections to existing statistical models. Aim 2 involves extensions of EPR to multivariate spatio-temporal and multiscale spatial data, allowing one to leverage several sources of dependence to improve predictions and perform spatial change of support (COS) without the use of MCMC or approximate Bayesian methods. To achieve scalability, in Aim 3, the investigator will develop an exact Bayesian hierarchical model that repeatedly subsets the data in an informative manner that does not impose additional assumptions on the data. 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 · 2025-08

Project Summary Our research program focuses on understanding the relationship between the structure and function of organic solid-state materials. We are especially interested in understanding this relationship in the context of drug polymorphism, physicochemical properties, and crystallization mechanisms. Crystallization and structural determination are exceptionally important aspects of chemical synthesis, biochemistry, and pharmaceutics. While many compounds can be crystallized through standard techniques, some compounds such as oils, chiral compounds, and natural products are difficult to crystallize. Two additional challenges that arise when developing drug molecules include polymorphism and poor physicochemical properties (e.g., aqueous solubility). Polymorphism is the ability of a compound to exist in more than one form or crystal structure, and polymorphs often exhibit different properties. Poor aqueous solubility impacts bioavailability and causes many drugs to be rejected during discovery. Our group has taken a multifaceted approach toward addressing the structure-function relationship by using cocrystallization, mechanochemistry, and structural analysis as strategies for controlling and tuning behaviors of drug molecules. Cocrystallization involves combining at least two compounds into a unique solid phase, and the components typically interact through noncovalent bonds. Mechanochemistry is a chemical transformation that is either initiated or sustained by mechanical force, and the field has undergone a rapid re-emergence because it is a green technique and has shown promise in controlling polymorphism. Cocrystallization and mechanochemistry offer our group platforms for preparing pharmaceutical materials of interest, while interrogating how the resulting structure gives rise to drug function. Our laboratory recently developed a mechanochemical method to facilitate crystallization of beta blocker drugs that otherwise form oils when standard crystallization methods are used. We have also used cocrystallization to improve aqueous solubility of a biopharmaceutics classification system (BCS) Class II (low solubility) antibiotic while maintaining drug safety. Most recently, we demonstrated that mechanical methods can be used to reversibly interconvert pharmaceutical polymorphs. Over the next five years, our goals are to use mechanochemistry to control crystallization and polymorphism of drug molecules, elucidate mechanisms by which mechanochemistry facilitates such crystallization, and determine structural characteristics that afford enhanced physicochemical properties in BCS Class II and IV drugs. The methods outlined above will be complemented with several characterization techniques to determine how structural modification impacts drug behavior. Our long-term goal is to use the insight gained from this work to enhance our understanding of the crystallization process, develop novel strategies for synthesizing pharmaceutical solids with improved treatment efficacy, and address fundamental challenges in controlling drug polymorphism. Overall, we aim to impact the future of disease treatments by determining the role that the solid-state structure plays in drug function and efficacy.

NIH Research Projects · FY 2026 · 2025-07

ABSTRACT Nicotine addiction is associated with deficits in prefrontal cortical (PFC) mediated control over inhibiting behavior and regulating appetitive response. We have reported stimulation pattern-dependent dissociable modulatory effects of low-frequency non-invasive brain stimulation (NIBS; cTBS) when applied to the lateral PFC—right inferior frontal gyrus (r.IFG) on inhibitory control, corticolimbic resting state functional connectivity (rsF) and smoking behavior. We further identified a novel pattern showing that dorsomedial PFC (preSMA) rsFC with corticostriatal circuitry predicts regulation of craving efficacy and smoking lapse vulnerability, and that preSMA NIBS modulates corticostriatal rsFC. Our preliminary findings, along with the extant literature also suggest PFC location specific effects of continuous theta burst stimulation cTBS on changing the strength of cortico-limbic- striatal functional connectivity (FC) and reducing the concentration of excitatory neurometabolites in the respective circuitry target by cTBS. The goal of this proposal is to conduct a location control (vertex) crossover study of cTBS to examine the neurocircuitry and neurobiological mechanisms mediating the effects of cTBS to r.IFG and preSMA on inhibitory control and craving regulation, respectively, and evaluate associations between neural outcomes and smoking behavior over the subsequent 24-hours.

NIH Research Projects · FY 2025 · 2025-07

PROJECT SUMMARY Cell therapy is emerging as an important therapeutic tool for a range of intractable and non-druggable diseases. A wide spectrum of therapeutic cells coined as “living drugs” are being developed in recent years for treating a panoply of indications including cancer, hematopoietic diseases, diabetes, liver pathologies, inherited diseases, etc., with few of them in advanced stages of clinical trials, and some (KymriahTM and YescartaTM) approved by FDA for clinical use. A major bottleneck for realizing the full potential of cell therapies is a lack of tools and resources in large animal models such as pigs, which provide the best cost- benefit considerations for safety and efficacy studies, and for better translatability of findings to humans. A clear understanding of cell viability, functionality, and bio-distribution of transplanted cells in the diseased model is paramount for cell therapy research. From a bio-distribution standpoint, precise dosing, delivery of cells to desired sites, tracking the retention of cells in tissues, and clearance over time in vivo is critical. In this regard, novel tools for non- invasive imaging such as positron emission tomography (PET) in large animal models like pigs is essential for improving the accuracy and efficiency of cell therapies in vivo. To address this stated gap, the main goal of this proposal is to develop foundational tools and resources for non-invasively detecting and tracking the implanted cells and tissues in vivo. To achieve this goal, two Specific Aims are proposed. Aim-1 will generate and characterize PET-reporter cells. We plan to generate stable transgenic PET reporter cells by CRISPR/Cas knockin of dual bicistronic PSMA and NIS reporter genes into ROSA26 safe- harbor locus. Functionality of the resulting cells will be validated both in vitro and in vivo. Aim-2 will establish a line of CRE-inducible and CRE-activated dual PET-reporter minipigs: The sequence confirmed, and functionality validated cells will be used for generating live offspring via somatic cell nuclear transfer (SCNT; or cloning). We expect that a successful outcome of this proposal will lay a foundation for non-invasive imaging in pig models- a great need; and will open-up promising new avenues for cell and tissue therapy research.

NIH Research Projects · FY 2025 · 2025-07

ABSTRACT Head and neck squamous cell carcinomas (HNSCCs) are an aggressive form of cancer that is difficult to treat due to the complexity and heterogeneity of the tumors. Resistance to drug and radiotherapy resulting in disease recurrence is common as HNSCCs are genetically very heterogeneous among patients. Studies of the HNSCC genome, transcriptome, and metabolome have revealed new altered targets, but translating these findings to clinical improvements in treating patients is a long road ahead. Therefore, there is a critical need to innovate strategies to facilitate precision in clinical decision-making. Recent studies by Gevaert Lab (Advisor) and Sunwoo Lab (Co-mentor) have shown HNSCCs can be classified into various subtypes with distinct genetic and epigenetic signatures. It is urgently important to know if these subtypes respond differently to the standard-of- care treatments. This proposal will test if the drug and radiation response in patient-derived tumor organoids (tumoroids) is correlated with DNA methylation patterns in these patients. Aim 1 will establish a high-throughput automated HNSCC tumoroid platform by precise bioprinting tumoroids in 96- and 384-well plates to generate self-assembled identical tumoroids, which will capture tumor heterogeneity of patients. Aim 2 will establish a methodology to perform high-throughput tumoroid screening using 18-F-Fluorodeoxyglucose (FDG), a radioisotope used for clinical imaging of cancer. The FDG influx rate inside tumoroids will be compared to the standardized uptake values (SUV) of the patient tumors (from positron emission tomography (PET) scans) for validation. Aim 3 will examine the standard-of-care and emerging treatment response among the five heterogeneous HNSCC subgroups. I hypothesize that DNA (hypo/hyper) methylation plays a key role in HNSCC treatment resistance to drugs and immunotherapy. This knowledge will significantly improve the future treatment plans and overall survival rate of HNSCC patients. In addition, this project will have two significant innovations: 1) An automated high-throughput strategy to generate HNSCC tumoroids for drug, radiation and immunotherapy screening. 2) A high-throughput screening strategy of tumoroids with gold-standard clinical imaging biomarkers, which are used in clinic for accurate assessment of treatment response. These innovations will enable higher clinical relevance, speed, and automation while reducing variability in both measurement and analysis in organoid-based head and neck cancer research. My career development activities at Stanford University will ensure gaining knowledge and expertise in head and neck cancer, bioprinting, strengthening scientific networks, improving study design skills, and achieving scientific and professional independence. With the successful completion of aims, a future prospective R01 grant will advance the technology further to make it more clinically relevant and suitable for identifying new drug and immunotherapy targets of head and neck cancers. In summary, the project will allow us to measure the sensitivity to standard-of-care treatments for HNSCC subtypes based on their epigenetic footprints and pave a way to develop an effective and precision therapy for these patients.

NIH Research Projects · FY 2026 · 2025-07

Project Summary My laboratory will use a combination of magnetic tweezers-based force and torque measurements, single molecule fluorescence measurements, and computational methods to study the activity of two genome maintenance systems: (1) the human transcription factor IIH (TFIIH) and (2) the type IA topoisomerase of mycobacteria. Both of these systems require the coordinated movements of multiple components to accomplish their functions. We will make use of two different single molecule methods to simultaneously measure orthogonal degrees of freedom. Using this approach we will be able to follow complex protein-DNA dynamics in real-time in order to better understand these systems. We will also use molecular dynamics simulations to determine the molecular motions underpinning the experimental observations. TFIIH is a DNA unwinding enzyme that plays a major role in two of the most important cellular functions, transcription of DNA to RNA and repair of damaged DNA. Because of this dual function, TFIIH is a potential target for chemotherapeutics. It has also been linked to human disorders of DNA repair. TFIIH is a large, multidomain protein complex. The core TFIIH complex includes both a DNA helicase domain and a DNA translocase domain. Evidence from biochemical studies and high resolution cryo-EM structures suggest that in the nucleotide excision repair pathway, these domains work in concert to open a bubble in DNA. A major limitation of such studies, however, is the inability to directly observe the active dynamics of the enzyme on the structure of DNA. Over the next five years, we will develop and conduct simultaneous single molecule force and fluorescence assays to observe TFIIH in action to understand how the helicase and translocase domains coordinate their activities. Type IA topoisomerases are a class of enzyme that are found in virtually all organisms. These enzymes remove excess supercoils from DNA to maintain genome integrity. While many chemotherapy drugs and antibiotics target other topoisomerases, there are currently no drugs in use against type IA topoisomerases, making them an important potential target for novel therapeutics. The type IA topoisomerase of Mycobacterium tuberculosis has been identified as a potential target for antibiotics against drug-resistant tuberculosis. Mycobacteria type IA topoisomerases contain unique C-terminal domains which are required for passage of one strand of dsDNA through a protein-mediated DNA-gate in the other strand. The details of this strand passage activity and its coupling to gate opening are unclear. We will use a combination of single molecule force and fluorescence assays and molecular dynamics simulations to probe the activity, conformational dynamics, and drug-response of mycobacteria type IA topoisomerases. Single molecule methods offer the opportunity to understand the mechanisms of enzyme activity by following dynamic molecular processes in real-time. Combining different single molecule methods will allow us to measure different aspects of the enzyme-DNA interactions, deepening our understanding of these processes.

NIH Research Projects · FY 2025 · 2025-07

Project Summary/Abstract The tear film on the ocular surface provides a protective barrier and serves as physiological lubricant to the ocular surface for ocular comfort and visual clarity. A lipid layer produced by the Meibomian glands (MGs) in the inner surface of eyelids constitutes the outermost layer of the tear film, with its function to prevent the evaporation of aqueous tear secreted by the lacrimal glands. Meibomian gland dysfunction (MGD) is the most prevalent cause of dry eye disease (DED) in the world with significant socioeconomic impact and public health concerns. To date, treatments for MGD or DED are mostly palliative for temporary symptom relief without targeting to improve MG function and abnormal evaporative loss of tears. It is well recognized that older age and female sex are the two significant risk factors for developing MGD and DED, although the prevalence varies widely among different age groups and sexes. For years, sex hormones have been postulated to play an important role in the maintenance of a normal tear film and ocular surface health. Like the related sebaceous glands (SG) of the skin, androgens are known to increase lipid synthesis and enhance the MG function. In contrast, a higher serum estrogen level was a significant predictor of worsening MG function in women. However, this consensus is unable to explain the higher prevalence of DED in postmenopausal women whose estrogen levels are reduced. In our preliminary study using estrogen receptor (ER) knockout (KO) mice, we found that loss of ER isoform α (ERα), but not ERβ, markedly increased the androgen receptor (AR) in the acinar cell nuclei of the meibomian glands in female KO mice. This finding suggests a crosstalk regulation at the hormonal receptor levels, i.e. ERα has an antagonistic effect on AR nuclear translocation in female MGs. In this application, we propose a new therapeutic target for MGD treatment by increasing the lipogenic function of AR via ER suppression. Up to date, a battery of pharmacological ER inhibitors has been widely used to block ER activity in ER+ breast and other cancers with satisfactory efficacy and clinical safety profiles. We will explore the therapeutic implications of two popular ER inhibitors, tamoxifen (a selective ER modulators or SERM) and fulvestrant (a selective ER downregulator or SERD) for better management and treatment of MGD. In Aim 1, ER inhibitors will be administrated systematically to suppress ER-related activity in wild type (WT) mice, a condition resemblance of ERα deletion in KO mice. It’s expected that treatment by ER inhibitors will augment AR activity and increase lipogenesis in the MGs of female mice. In Aim 2, a combined treatment of androgen and ER-inhibition is proposed to evaluate whether elevation of both androgen and AR can circumvent age-associated hormonal decline and maintain or restore MG function in aged mice. The outcomes from this proposal will establish a brand new therapeutic paradigm in targeting the regulation of sex hormones and their receptors for MGD and pave the avenue for a potential investigational new drug (IND) application of using currently available ER inhibitors for age-related MGD in postmenopausal women.

NSF Awards · FY 2025 · 2025-07

Generative artificial intelligence (AI) services are becoming ubiquitous and directly impacting the daily activities of citizens. These services build on large AI models that require massive amounts of data and computing resources to be trained. Unfortunately, academic users do not have access to such resources and may leverage smaller AI models for specialized applications with limited data. This project seeks to leverage FABRIC (https://portal.fabric-testbed.net), an NSF-funded national distributed computing/networking research infrastructure, to efficiently and securely train AI models and employ them to accelerate research and advance scientific discovery. This project seeks to empower faculty and students with generative AI capabilities to foster innovations in computing and related scientific disciplines. The research activities will lead to the development of new algorithms and techniques for efficient, scalable, and secure language model (LM) pretraining and inference using FABRIC. Specifically, new approaches will be developed to enable (a) efficient LM training for heterogeneous graphics processing unit (GPU) clusters and high speed networking using model parallelism and network-aware cost models; (b) scalable and secure processing of LM training jobs using combinatorial optimization techniques while ensuring fair-share of cluster resources; and (c) efficient CPU-based LM inference using combinatorial optimization techniques to achieve high cluster utilization. A secure, end-to-end operational prototype will integrate the University of Missouri (MU) research computing with FABRIC. As a result, users can leverage FABRIC for LM training and inference on domain-specific datasets at no charge. The proposed research will foster advances in applications of AI to disciplines such as health informatics, and bioinformatics. It can enable breakthroughs in solving pressing problems (e.g., food safety, disease diagnosis, drug discovery) using generative AI. The research findings will be disseminated in the form of publications, demos, presentations, and tutorials. Open-source software and datasets will be made available to the public. These resources will be of immense value to other universities with pressing need for generative AI technologies. New curriculum will be developed for computer science and informatics students. Students will be involved in research in this project. Software and training materials will be developed for broader use by the education and research community. The project website is hosted at https://github.com/MU-Data-Science/LaMB. This repository will be maintained for 3 years after the completion of the project. 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

A central theme of this project is the study of geometric properties of convex bodies based on information about their sections and projections. This branch of convex geometry is called geometric tomography. An important instance of this theory is x-ray tomography, which has numerous applications in science, medicine and engineering. The PI has developed a new approach to geometric tomography in which the geometric properties of convex bodies are expressed in terms of integral transforms, enabling the use of certain analytical methods to solve geometric problems. In this project, the PI plans to further develop these techniques and apply them to a range of problems at the interface between convex geometry, functional analysis, harmonic analysis and probability. For example, can one find an algebraic equation whose solutions are sections of a given solid? Can one estimate the volume of a solid from data involving areas of certain sets of sections or projections of this solid? Which random variables are stable, i.e. have the property that the sums of several copies of these variables always reproduce the same variable up to a constant? The PI will continue to work with students and early career stage mathematicians, to introduce them to this evolving area of research. The problems considered in this proposal connect several areas of mathematics - convex geometry, functional analysis and probability. However, the strategy of solution is common for most of the results - the question is translated into the language of the Fourier transform and then treated as a problem from harmonic analysis. The PI plans to consider the lower-dimensional and non-symmetric versions of the Busemann-Petty problem asking whether a convex body with uniformly smaller areas of plane sections necessarily has smaller volume. Another direction is to study comparison problems and lower estimates for the Radon transform associated with volumetric results about convex bodies. The PI plans to study algebraic properties of the Radon transform related to the problem of Arnold, going back to Lemma 28 from Newton's ``Principia." The problem is to characterize those convex domains whose cut-off area is an algebraic function of the parameters of the cutting plane. A connection with functional analysis is the study of embedding and duality problems. An old problem about norm dependent positive definite functions is related to embeddings of normed spaces and stable random vectors. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-07

Project Summary We previously discovered a subpopulation of dopaminergic neurons that reside in the rat spinal cord. Following spinal cord injuries (SCI), these neurons undergo plasticity and release a low level of dopamine (DA) to modulate lower urinary tract (LUT) activity. However, we found the effects of DA on the recovered micturition reflex cannot simply be interpreted by activation of either the D1 or D2 receptor alone nor by simultaneous stimulation of the two. Instead, stimulating D1 receptors appears to synergize the effect induced by D2 activation on voiding in SCI rats. Recently, a D1-D2 receptor heterooligomer (heteromer) was uncovered in the brain which is linked to several neurological behaviors or disorders. In the preliminary data, we detected D1-D2 heteromer levels in the rat lower spinal cord, and the expression of this receptor complex is upregulated following SCI. Accordingly, we hypothesize that spinal D1-D2 heteromers regulate the micturition reflex in rats with SCI and stimulation of this receptor complex improves involuntary micturition function. Using multiple experimental approaches, including co-immunoprecipitation, ELISA, in situ proximity ligation assay, RNAscope, quantitative PCR, western blot, micturition reflex and functional recordings, we will 1) determine whether spinal D1-D2 receptor heteromers tonically regulate micturition reflexes in rats with SCI, 2) test whether co- stimulating spinal D1 and D2 receptors increases heteromer formation and improves involuntary micturition function in rats with SCI as a potential strategy for translation, and 3) elucidate whether the D1-D2 complex acts on micturition function via an intracellular Gq/11-PLC-Ca++ signaling pathway. This project will challenge traditional concepts concerning DA receptors in the spinal cord, aid in further appreciation of DA-ergic machinery regulating the micturition reflex, and establish plausible pharmacotherapeutic targets for SCI- induced urinary disorders.

NIH Research Projects · FY 2026 · 2025-07

Project Summary As the biomedical community tackles grand challenges like site-specific pharmaceutical delivery and organ regeneration, strategies employing simple products serving a singular function are suboptimal. Instead, novel, multi-dimensional strategies need to be developed to achieve the next breakthroughs especially in fields like immunoengineering and regenerative medicine. Nowhere is this effort more necessary than in the use of bioactive peptides where considerable hurdles exist in achieving spatiotemporal control over their delivery. While a wide range of biomaterials have been employed to attempt to achieve this goal, they have been mostly non- bioactive in nature minimizing their maximum drug loading and device fabrication potential while often leading to limited higher order structure of associated peptides. To address this issue, the long-term goal of the Ulery Laboratory is to engineer the physicochemical properties of biomaterials to allow them to directly modulate cell and tissue responses. These novel biomaterials, defined as biomodulatory materials, are being utilized individually or in combination with other bioactive factors to produce desirable biomedical outcomes. Our recent progress in this research space has focused on leveraging peptide amphiphile micelles to create complex nanoparticles and hydrogels. By generating novel biomaterials from bioactive peptides, we have been able to create self-adjuvanting vaccines, anti-inflammatory therapeutics, cell-targeted cancer therapies, and bone regenerating products. While exciting in its own right, we have been able to achieve these results with peptides that do not have the peptide chemistry that lends to their stabilization through other means like stapling and cyclization. In this Maximizing Investigators’ Research Award, we will build on our previous efforts to engineer peptide-based biomodulatory materials that can serve as translational platform technologies for a variety of biomedical applications. First, we will use a combination of computational and experimental techniques to generate design rules for micellar nanoarchitectures to allow for the rapid production of micellar systems from new bioactive peptides. In addition to nanoparticle shape, we will characterize the influence that other physical properties such as charge, stability, and product entrapment have on peptide amphiphile micelle function. Finally, we will focus on programming multiple cell recruitment and differentiation outcomes into hydrogel systems to achieve coordinated complex bioactivity. These efforts are well suited as a foundation to continue to build our laboratory’s research program upon including progressing into the new application areas such as treatments for autoimmune diseases, tumors, and neural disorders.

NIH Research Projects · FY 2025 · 2025-06

Modified Project Summary/Abstract Section Broad Objectives: The proposed research will examine how the specific ways adolescent friends provide social support to each other in text message conversations are associated with their perceived friendship quality and emotional adjustment (i.e., depressive symptoms). Though past research has emphasized the importance of high-quality social support for adolescents' adjustment, less is known about how specific support processes in digital contexts relate to adolescent well-being. The project will involve multimethod data collection with adolescent friend dyads and aims to increase understanding of how friends’ texting behaviors relate to positive and negative adjustment outcomes in adolescence. Specific Aims: Three specific aims are proposed. For each aim, a coding system previously used for in-person observation of social support interactions will be implemented on adolescent friends’ text message conversations. Additional codes specific to digital communication (i.e., emojis, time to reply) will be added to this original coding system. I will examine the associations between the types of responses (i.e., positive responses, negative responses, emojis, and time to reply) adolescents receive from their friends following problem disclosures in text messages and adolescents’ friendship quality and depressive symptoms (Aim 1a). I will also examine how these types of responses that adolescents provide for support in response to friends’ problem disclosures in text message conversations relate to adolescents’ own depressive symptoms and friendship quality (Aim 1b). Interactions between positive and negative responses will also be examined to assess whether receiving or providing negative responses attenuates any benefits of receiving or providing positive responses (Aim 2). Finally, biological sex and age differences in these associations will be tested (Aim 3). Method: Data will be collected from friend dyads (N = 200 adolescents; 100 dyads) between 14 and 18 years old. Participants will complete surveys on their friendship quality and emotional adjustment and two weeks of text messages exchanged between the friends will be collected. Text message data will be coded for statements in which adolescents discuss personal problems and the specific ways friends respond to these problem statements. Significance: The proposed research will use a unique multimethod design to promote understanding of how adolescent friends’ supportive interactions in digital contexts relate to friendship and emotional adjustment. The findings of the proposed research aims can inform social and behavioral interventions among adolescents and identify behaviors associated with greater risk for negative adjustment outcomes. Training Goals: The applicant will acquire training in collection and analysis of smartphone data of technology-mediated communication (Goal 1), enhance her skills in advanced statistical analyses used for dyadic data analysis (Goal 2), and will acquire additional professional development skills (Goal 3). These training goals will support the applicant’s larger career goals of becoming an independent researcher in adolescent peer relationships, technology use, and adolescent adjustment.

NSF Awards · FY 2025 · 2025-06

Given that plants cannot outrun their predators, they often rely on chemical defenses to protect themselves and their offspring (seeds). These chemical defenses, often unique to particular plants or groups of plants, are valuable resources for developing natural pesticides that may carry fewer risks for ecosystems and for consumers. This project focuses on a group of plants in the tomato family that produce a promising class of natural insecticides called acylsugars. These sticky sugars are produced by gland-tipped hairs and act as traps for insect predators, but they are non-toxic to humans and degrade quickly in the environment. While most acylsugar research has examined their importance in leaf defense, this research will explore their role in protecting the fruit and its enclosed seeds, studying the tomatillos and their wild relatives. Many of these species cover their fruit in a balloon-like sac that develops from the outer organ of the flower (the calyx), and they decorate this inflated calyx with dense sticky acylsugar-coated hairs. This research will investigate the relationship between the repeated evolutionary origins of the inflated calyx across tomatillos and the production of insecticidal acylsugars, providing the foundation for developing novel natural insecticides. This project is built upon a collaborative network of tomatillo researchers from the U.S. and abroad and will advance international collaborations. It will provide training opportunities for early career researchers including high school students, undergraduates, graduate students, and a postdoctoral fellow. In order to trace the coordinated evolution of inflated fruiting calyces and acylsugar defenses, the research will build the first comprehensive phylogenetic tree for all 310 species in the tomatillo clade. The phylogeny will be estimated using target sequence capture relying on existing collections of DNAs and herbarium specimens as well as new field collections. The researchers will use recently described Solanaceae fruit fossils, including two in the tomatillo clade, to calibrate the tree, and apply methods including state-dependent diversification to estimate transition rates to and away from the inflated calyx state. They will specifically test the hypothesis that gains of inflation are irreversible and that they proceed via an intermediate stage in which the calyx expands to cover the fruit but does not inflate. Finally, the project will explore the coupling of this physical defense (calyx elongation and inflation) with chemical defenses. In particular, the researchers posit that independent gains of inflated fruiting calyces are correlated with increased production of glandular trichomes and sticky, insecticidal acylsugars. Together, these three aims will allow the researchers to trace the assembly of a complex plant defense syndrome, which like many trait syndromes, combines convergently-evolved morphological and biochemical innovations as an adaptive response to a shared ecological driver. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-06

Cerebral small vessel disease (CSVD) could be caused by resistance artery narrowing, small cerebral artery embolism, capillary rarefaction and other etiologies. The prevalence of CSVD increases significantly with aging, and accounts for 25% of ischemic stroke and 45% of dementia, with hypertension being the preeminent risk factor. Mechanistically, an exaggerated myogenic response (vasoconstriction to increased pressure) and endothelial dysfunction are major causes of excessive resistance artery narrowing. Our preliminary data on rat supracerebellar artery (SCA) suggested that under steady-state myogenic vessel tone, the phosphorylated myosin light chain (pMLC) polarized to the outer layer smooth muscle cells (VSMC). This novel observation suggested a previously unknown signaling mechanism that drives MLC phosphorylation predominantly in the outer VSMC layers of the vessel wall, which subsequently maintains the SCA myogenic tone. Cell adhesion molecules, both integrin α5β1 and N-cadherin, are capable of mediating mechanical force-induced VSMC contraction. Preliminary data has suggested that, similar to pMLC, the clustering of N-cadherin peaked in the outer layer VSMC of SCA, and its expression increases in SCAs of spontaneous hypertensive rats, while increased integrin α5β1 expression was also reported in experimental hypertension. These results lead us to hypothesize that the transmural MLC phosphorylation gradient is at least in-part regulated by vessel wall tension through integrin α5β1− and N-cadherin-mediated mechanotransduction, and augmentation of these molecules inappropriately increases cerebral artery myogenic tone during aging combined with experimental hypertension. As a corollary, alterations in cellular adhesion and remodeling may contribute to cerebrovascular dysfunction and ultimately sequelae such as a decline in cognitive function. We will compare between young and aged groups of a genetic hypertensive rat model (SHR vs. WKY). A multi-level experimental approach will be employed, using pressurized blood vessels and isolated VSMCs along with confocal/super-resolution microscopy, immunofluorescence, and atomic force microscopy (AFM), to test these specific aims: Aim1: Demonstrate that comorbid aging and hypertension increases the recruitment of integrin α5β1 and N-cadherin to the outer VSMC layers in cerebral arteries; Aim2: Demonstrate that VSMCs isolated from aged and hypertensive animal show increased mechanically-activated contractile signaling mediated through integrin α5β1 and N-cadherin; and Aim3: Determine the effects of inhibiting integrin α5β1 and N-cadherin on the cognitive function of aged and hypertensive animals. These studies will establish the basic biology of cellular remodeling involved in the maintenance of myogenic tone in cerebral small arteries in association with aging and hypertension, and will potentially provide targets for the development of novel therapeutic approaches directed at reducing excessive cerebral vessel myogenic responsiveness.

NIH Research Projects · FY 2026 · 2025-05

The Sudden Infant Death Syndrome (SIDS) remains the leading cause of death in the post-neonatal period. Rare traces from infants who died of SIDS indicate cardiovascular collapse during autoresuscitation, the integrated cardiovascular and sympathetic response necessary to sustain life in severely hypoxic conditions. There is evidence of serotonergic dysfunction in SIDS, including reduced serotonin (5-HT) and reduced 5- HT2A receptors across multiple regions necessary for autoresuscitation. Most SIDS infants have reduced 5- HT2A receptors within the nucleus of the solitary tract (NTS) and medial accessory olive (MAO). Along with the fastigial nucleus of the cerebellum (FN), the NTS and MAO are key components of a brainstem-cerebellar circuit that increases drive to the rostral ventrolateral medulla (RVLM). Ultimately, the activation of the NTS- MAO-FN-RVLM circuit augments sympathetic activity, a response necessary for heart rate and blood pressure recovery from severe hypoxia. The MAO is the sole source of climbing fibers to Purkinje cells (PCs); the latter provide critical neuromodulation to the FN. Prenatal and/or postnatal intermittent hypoxia (IH) are associated with key risk factors for SIDS. IH may compromise autoresuscitation by inducing damage to vulnerable MAO and PCs while also reducing 5-HT2A activity across the entire circuit. Our overarching hypothesis is that an important subset of SIDS infants has reduced drive through 5-HT2A receptors within the NTS-MAO-FN- RVLM circuit. Prenatal or postnatal IH damages the MAO, PC cells, and reduces serotonergic function, compromising the ability of the circuit to restore blood pressure during autoresuscitation, resulting in sudden death. To test these hypotheses, we use a combination of delicate DREAD- and pharmacological- based experiments that manipulate serotonergic inputs to the NTS-MAO-FN-RVLM in infant rats, assessing the extent that drive through 5-HT2A receptors is necessary and sufficient for cardiovascular recovery and survival during autoresuscitation. Rodent studies run in parallel with studies using tissue from SIDS infants and controls. For the first time we examine 5-HT receptor binding and expression in the cerebellum, as well as the integrity of PCs and climbing fibers in SIDS versus controls. The proposed studies are innovative experimentally and conceptually – in particular, the cerebellum's role in successful cardiovascular recovery in autoresuscitation has never been tested experimentally. We pair rodent and human studies to maximize the potential for translational outcomes and clinical impact. From our studies will emerge a new concept that reduced drive through 5-HT2A receptors within a key brainstem-cerebellar circuit underlies a significant proportion of SIDS deaths. The knowledge generated will potentiate the development of key biomarkers and prophylactic strategies to reduce SIDS incidence worldwide. This research therefore aligns with the mission of the National Heart Lung and Blood Institute to support research promoting the prevention and treatment of heart, lung, and blood diseases to enhance the health of all individuals.

NSF Awards · FY 2025 · 2025-05

The objective of this Rapid Response Research (RAPID) project is to collect time-sensitive data on how housing infrastructure, risk perception, and warning communication influence people’s ability to take protective action during nighttime tornadoes. On 14-15 March 2025, a deadly outbreak of nocturnal tornadoes occurred across the Midwestern United States. When tornado disasters occur at night, they significantly increase fatality and injury rates, as they are difficult for the public to receive warnings and take protective action, as many are often asleep in homes that may lack adequate wind-resistant features or safe sheltering options. By integrating tools and methods from civil engineering and the social and behavioral sciences, the project aims to advance interdisciplinary knowledge about nighttime tornado sheltering vulnerability and decision-making processes. Using a convergent mixed-methods design and guided by the Protective Action Decision Model (PADM), the project conducts engineering assessments of wind damage across residential housing types and collects survey data on how households responded to the tornado outbreak. Project findings provide new understanding of converging social, behavioral, and built environment factors that facilitate or hinder effective protective action during nighttime tornado threats and will inform public warning systems, safe housing guidance, and emergency planning. Results are broadly shared with weather forecasters, emergency managers, and researchers as well as supporting student training and education across engineering and social science programs. 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 · 2025-05

Growth standards for the cranium and face have not kept pace with advances in imaging technology. Craniofacial growth models currently used in clinical practice rely on two-dimensional (2D) views of a three- dimensional (3D) structure, the craniofacial complex. While this approach has served the discipline well for the better part of a century, recent advances in 3D imaging mean that significant progress in treatment can only be expected once growth standards advance to incorporate growth in three dimensions. The proposed study accelerates the science behind clinical treatments by developing growth models using state-of-the-art cone- beam computed tomography (CBCT). Models will be rooted in dense longitudinal data from the investigators’ prior NIH-funded projects to ensure a robust and rigorous approach that clinicians can rely on. New technologies beget new approaches and analytical methodologies to propel the field forward. The potential for inclusion of a detailed assessment of craniofacial growth in clinical treatment has reached a watershed moment. While CBCT imaging technology has been available for two decades, the ability for clinicians to easily collect data from those images has lagged. Software allowing for autolandmarking of cephalometric points and measures are in development and will soon be available in commercial packages (e.g., InVivo, Dolphin). Through three innovative aims, the proposed work will collect and utilize 40,000 CBCT (3D craniofacial) images of children and young adults to create new growth standards based on the three-dimensional nature of the craniofacial complex and consider age, sex, race, ethnicity, facial type, and dental maturation. Assessment of growth, growth milestones, and prediction of future growth will be included in models for clinical and research use. In Aim 1, a large and racially/ethnically diverse database of clinically-relevant craniofacial phenotypes, will serve as the foundation of analyses in the proposed work. Resulting growth models will also be available to the craniofacial community via web interfaces such as FaceBase and the AAOF Legacy Collection website to maximize adoption in clinical practice. Through Aim 2 we will use shape-based approaches to capture global differences and analyze variation and covariation in anatomical regions across ages, sexes, and races. In so doing, we will also test shape groupings against clinically established facial types. Improvements in diagnostic abilities and treatment strategies will directly result from those analyses. To integrate these new approaches to assessment and prediction of growth, Specific Aim 3 will determine the degree to which dysmorphic growth and growth variation resemble that of normal growth, and whether divergence in growth trajectory provides added clinical utility. The overall impact of the proposed research will be a shift in clinical management of pediatric craniofacial patients toward more evidence-based treatment planning, utilizing references and predictions based on a large, racially diverse sample of modern U.S. children.

NSF Awards · FY 2025 · 2025-05

As stationary organisms that are faced with surviving constantly changing environments, plants have evolved specialized features to protect against environmental stresses. One of these features is an exterior protective barrier on aerial plant surfaces called the cuticle. The cuticle acts as a physical barrier between the plant and its environment, functioning to limit the loss of water and gasses. Although many key genes that function in making the cuticle have been identified, a holistic view of how the cuticle is built is missing. This project will engineer two novel, parallel synthetic biology systems that are normally devoid of a cuticle (yeast cells and plant roots) to build a cuticle from scratch and decipher the complexities of the biochemical pathways underlying this unique plant feature. Systematically determining how a cuticle is built will lead to important applications such as the breeding of crop plants with customized cuticles that may have enhanced tolerance to environmental stresses, as well as cuticle-inspired chemicals for the biorenewables industry. Moreover, this project will train the next generation of multi-disciplinary scientists, and build teaching and research initiatives with the ultimate goal of increasing the proportion of the scientific workforce who are from STEM-underrepresented backgrounds. This multi-disciplinary project will build and test two synergistic synthetic biology chassis in systems that do not naturally produce a cuticle (i.e., plant roots and the yeast Saccharomyces cerevisiae) to systematically refactor the transcriptional regulatory network, and the metabolic pathways that assemble the protective, hydrophobic cuticle barrier. These two synthetic chassis will be used to comprehensively model and quantitatively understand the integrated mechanisms that assemble a functional plant cuticle. The root chassis will be used to study the coordinated activation of cuticle assembly by plant transcription factors. This chassis will provide temporal transcriptional and metabolic data to enable the development of dynamic predictive models that provide a holistic view of cuticle metabolism and its associated regulation. A second chassis relies on multiple engineered yeast plug-and-play systems expressing different genetic complements capturing the gene redundancies within the pathway that will be assessed for the production of synthetic cuticle constituents. The metabolic data generated from these strains will be the inputs for kinetic modeling, which will provide the first kinetic understanding of this complex pathway. The coordinated development of the plant root and yeast chassis in combination with the proposed computational framework will provide a novel platform for discovery, and systematic analysis of cuticle assembly. This award was co-funded by the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences and by the Plant Genome Research Program in the Division of Integrative Organismal 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 · 2025-05

The project addresses a new process and catalyst design for on-purpose conversion of ethane to the commodity chemical acetonitrile. Ethane (a low-value and catalytically refractive component of natural gas) is reacted with ammonia over a bifunctional metal/zeolite catalyst to produce acetonitrile in a process that potentially offers both environmental and economic benefits with respect to existing technology. The project focuses on fundamental aspects of the catalyst design and the reaction mechanism to enhance catalyst performance and durability. Beyond the technical aspects, the project features educational and outreach activities targeting underrepresented minorities in STEM disciplines. This research will break ground for fundamental research for the direct ethane dehydrogenative C-N coupling with ammonia gas over bifunctional metal/zeolite catalysts. Specifically, the project targets catalyst structure/performance relationships and the fundamental understanding of the influence of metal functionality on C-H bond activation in the presence of ammonia. The project investigates the influence of cobalt (Co) and Platinum (Pt) metal sites on the Brønsted/Lewis acidity of the zeolite, in a catalyst design that would optimize metal/acid-site bifunctionality. Additionally, through the combination of operando DRIFT-MS and relaxation-type transient experiments, the project will identify the surface reaction intermediates as related to the kinetics and mechanism of the reaction over the tandem bifunctional metal/zeolite catalyst. The fundamental knowledge obtained from the project could be the basis for an efficient ammodehydrogenation catalyst design. With the support of this project, the PI will help address the problem of the loss of Mississippi’s STEM talent by recruiting and retaining promising chemical engineering students, especially from underrepresented groups. The investigator will work closely with various outreach programs at Mississippi State University. Students involved in this project will gain the skills to succeed in both industrial and academic career paths. This project is jointly funded by the CBET Catalysis program and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-05

Project Summary Phenylketonuria (PKU) is an autosomal recessive condition characterized by a deficiency in the ability to metabolize phenylalanine (Phe) into tyrosine (Tyr). Even with treatment, individuals with PKU experience higher-than-normal levels of Phe in the blood and brain. Whereas PKU is relatively rare (1 in 15,000 in U.S.), the rate of heterozygous carriers in the general population is much higher with an estimated incidence of 1 in 60 – representing approximately 5.5 million individuals in the U.S. Despite prior assumptions that such carriers were spared any adverse consequences, nascent evidence suggests that PKU carriers experience a marked reduction in their capacity to metabolize Phe. Previous work from our group has shown that elevated Phe levels in individuals with PKU are associated with significant cognitive and neurologic deficits including impairments in executive function (e.g., working memory), processing speed, attention, and fine motor control. Little is known, however, regarding the potential impact on heterozygous carriers, and whether carriers experience Phe-related disruptions in neurocognitive function. To begin to address this gap in the literature, we propose to conduct a principled investigation of the acute effects of Phe ingestion on metabolic, neurophysiologic, and cognitive markers in a sample of genetically-confirmed heterozygous PKU carriers (n=18) and non-carriers (n=18). A double-blind crossover study will be conducted in which participants perform an fMRI n-back working memory task, resting state scan, and a battery of select cognitive tests at 3 timepoints: baseline (pre-load), 2 hours and 4 hours after starting oral administration of Phe or placebo. Blood and brain levels of Phe and Tyr will also be assessed at each timepoint. The study’s specific aims center around the overarching hypothesis that PKU carriers will be less efficient at metabolizing the ingested Phe, which will result in higher and more prolonged elevations in blood Phe as compared to the non-carriers. Resulting elevations in brain Phe concentrations (Aim 1) will then lead to disruptions in neurocognitive processing as evidenced by poorer cognitive performance (Aim 2), atypical patterns of neural activity (Aim 3a), and decreased functional connectivity (Aim 3b). The present work has potential to significantly impact health guidelines and personalized medicine for a significant portion of the general population (1 in 60 of whom are PKU carriers). For example, high protein weight loss diets may be contraindicated for heterozygous carriers of PKU. The present study would also increase our scientific understanding of PKU as well as foster the emergence of several lines of related research (e.g., elucidation of the precise neurophysiologic mechanisms by which non-PKU variants of PAH have an impact on behavior and cognition).

NIH Research Projects · FY 2026 · 2025-04

Periodontitis is one of the most prevalent diseases. In the United States, 42% of adults are affected by periodontitis, with 7.8% having severe cases. Destructive periodontitis is characterized by irreversible loss of periodontal tissues, including periodontal ligament (PDL) and alveolar bone. While many efforts have been made to develop tissue engineering-based approaches to reconstructing the structures and functions of the lost/damaged periodontal tissues, none of those approaches can achieve predictable and long-term functional periodontal tissue regeneration. One of the major obstacles is the difficulty in regenerating well-organized Sharpey’s fibers that are the terminal ends of PDL principal fibers and are embedded in alveolar bone and cementum. Without these highly oriented Sharpey’s fibers, there would be no functional connection between PDL and alveolar bone/cementum; and the integrity of the periodontal tissues would be impaired, leading to tooth loss. To date, there is no effective bioengineering approach to regenerating PDL Sharpey’s fibers. The overall objective of this proposal is to develop a bio-inspired scaffold (periopatch) for Sharpey’s fiber and periodontal tissue regeneration. The hypothesis is that integration of crucial biophysical and biochemical cues into a bio-inspired matrix will provide a suitable microenvironment to guide periodontal ligament stem cells (PDLSCs) migration, growth, and form well-aligned PDL principal and Sharpey’s fibers. In the preliminary study, tubular architecture of the matrix and tenascin-c (a PDL glycoprotein) were identified as the pivotal biophysical and biochemical factors, respectively, to regulate PDLSC migration and form PDL principal fibers. A unique pyrophosphate/alkaline phosphatase (PPi/ALPase) system in the tubular matrix were further developed to precisely control mineral deposition at the PDL/bone interface to guide Sharpey’s fiber formation. In addition, a bioengineering technology was developed to integrate these crucial elements into a bio-inspired triphasic scaffold for functional Sharpey’s fibers and periodontal tissue regeneration. Based on these exciting preliminary data, three aims are proposed in this proposal. Aim 1 will focus on developing and optimizing a bio-inspired tubular matrix to guide PDL principal fiber formation. Aim 2 is to rebuild the microenvironment for Sharpey’s fiber formation. Aim 3 will focus on regenerating Sharpey’s fibers and periodontal tissues using a periodontal fenestration defect model. Successful completion of this project will address one of the major challenges in periodontal regeneration, making a significant step toward regenerative periodontal therapy in clinic settings.

NSF Awards · FY 2025 · 2025-04

Non-technical summary/abstract Contemporary life and society depend heavily on energy and materials sources. Certain sources are non-sustainable, meaning that they cannot be replenished quickly once consumed, while others are sustainable and can be regenerated. Unfortunately, non-sustainable sources are running out rapidly; thus, the nation could benefit both environmentally and economically from an improved use of sustainable sources. Plants are promising sustainable sources, which offer fuels, materials, and nutrients. Yet, these valuable components cannot be easily taken out from plants, because they are trapped in plant skins. Typical plant skins are composed of complex species, such as i) an intense network of numerous, cross-linked large molecules, known as cellulose, ii) a bunch of small molecules known as lipids which line up and assemble into plant cell membranes, and iii) glycoproteins, molecules formed by sugar-like molecules connected with proteins. These species build up a hard protection layer to plants, which cannot be broken down easily. This project will develop special biomaterials to break down such a protection layer. A series of enzymes, special proteins which speed up the breaking-down of cellulose, lipids, and glycoproteins, will be placed in the scaffolds and gaps of a solid crystal, known as Ca-MOM. These enzymes will cooperate to degrade the protection layer of plants without generating adverse by-products. The Ca-MOM crystal will stabilize and help re-collect the enzymes, making them reusable. Meanwhile, the positions of the enzymes in the crystal scaffolds will also be probed to understand the performance of the enzymes in the developed biomaterials. These efforts will not only produce biomaterials to efficiently and sustainably break down plant skins to allow for the extraction of valuable energy resources and materials but also understand how enzymes function in these biomaterials. The demonstrated strategy will also improve the progress of science because it can be adapted to breaking down of other natural sources which contain valuable components and require multiple enzymes to cooperate. The research efforts will be bridged with an educational plan to bring research opportunities to local underrepresented groups by involving them in green chemistry research. This principle investigator will also develop an educational program called Green Chemistry- Green Planet in order to introduce the green chemistry concept to local elementary students through established programs such as the North Dakota (ND) 4-H and Operation Military Kids programs in ND. Technical summary/abstract Plants are sustainable sources of energy and materials, yet the valuable components are protected by plant cell walls. The challenges to break down these cell walls are the difficulty in degrading the intense cellulose network, the major cause of cell wall stiffness, and complexities due to other components such as lipids and glycoproteins, which also enhance viscosity and stiffness. Using cellulases and accessory enzymes to degrade cellulose and other components is the green choice of plant biomass degradation due to their specificity and biocompatibility, yet the challenge is the need of multiple enzymes including proteases which damage the partner enzymes. This project will overcome this challenge by immobilizing three celluases, a lipase, and a protease on Metal-Organic Materials (MOM) via enzyme-MOM co-crystallization. In the resultant co-crystals, each enzyme is partially exposed to the reaction medium for substrate contact while partially buried under MOM surfaces for enzyme protection to reduce proteolytic damage. The developed biocatalysts will be demonstrated on the degradation of a model plant biomass, followed by probing the structure-property relationship of the resultant multi-enzyme/MOM biocatalysts differing in MOM ligands using Electron Paramagnetic Resonance spectroscopy. The hypotheses are 1) simultaneous immobilization of 5 enzymes enhances the cost efficiency of and accelerate plant biomass degradation with reduced proteolytic damage and 2) the biocatalytic performance of the developed biocatalysts depends on the structural basis of enzyme exposure on MOM surfaces and MOM ligands. These hypotheses will be tested through three objectives: 1) develop a 5-in-1/Ca-BDC biocatalyst for the rapid biodegradation of plant biomass, 2) determine the structural basis of the 5-in-1/Ca-BDC biocatalyst, and 3) establish the structure-property relationship of the 5-in-1/Ca-MOMs the biocatalytic performance of the developed biocatalysts. The educational plan of this project will provide opportunities for averagely 1 Native American student, 2 undergraduate students, and 1 local high school student per year to participate in green chemistry research. In addition, an educational program called Green Chemistry - Green Planet will be developed to enhance the science knowledge of numerous K-12 students via the North Dakota (ND) 4-H system and the Operation Military Kids program in ND. 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 · 2025-04

During pregnancy, the mouse and human placenta contain appreciable quantities of serotonin (5- hydroxytryptamine; 5-HT), but a scant amount is known about the actions of this catecholamine within the placenta. In the mouse, 5-HT is concentrated in parietal trophoblast giant cells (pTGCs) at the periphery of the spongiotrophoblast layer and at the interface of the placenta and maternal decidua and may have local and as yet uncharacterized paracrine effects. Concentrations of placenta 5-HT can be affected by extrinsic factors, including selective serotonin reuptake inhibitors (SSRI) and endocrine disrupting chemicals, that can detrimentally affect placental architecture and may render the fetus prone to diseases later in life. Thus, it is essential to understand the source of 5-HT and paracrine actions of this compound within the placenta. In mouse conceptuses where the 5-HT transporter gene (Scl6a4/SERT) is mutated, we have recently shown that the pTGCs also appear to be targeted, but in this case, there is marked expansion, rather than shrinkage of the pTGC layer, and upregulation of gene-sets involved in nutrient acquisition and metabolism and those linked to blood clotting. We hypothesize that 5-HT exerts key paracrine actions within the placenta, pTGCs acquire it via SERT from maternal sources, and disruption in pTGC accrual of 5-HT leads to placental dysfunction and compromises fetal brain development. Relevant to these observations is that selective serotonin-reuptake inhibitors (SSRIs), which block SLC6A4/SERT transport activity, are commonly prescribed anti-depressants for pregnant women, and women using SSRI have been reported to deliver lower birthweight infants and have placental-fetal vascular mal-perfusion, consistent with the inference that 5-HT might play a role in placental homeostasis in the human. Based on these facts, we surmise that compromised SLC6A4/SERT activity affects allocation of 5-HT within the placenta, thereby interfering with placental function, including the ability to supply 5-HT to the fetal forebrain. To test our hypothesis that the pTGCs play a central role in 5-HTapportionment, we have created conditional knockout (KO) mice that lack Slc6a4 /SERT selectively in pTGCs and spiral artery TGC (Spa-TGCs), which may also be important for 5-HT accumulation by the placenta. Specific Aim: We will determine whether disturbances in pTGC/Spa-TGC 5-HT acquisition via SLC6A4 affect placental and subsequent brain development and function. This aim will address whether mice that conditionally lack Scl6a4/SERT in pTGCs and Spa-TGCs have lowered accumulation of 5-HT and develop placental and neural transcriptomic and histopathological changes. Experiments will confirm the role of pTGCs in 5-HT accrual in the rodent placenta, help us understand how 5-HT availability affects the placenta and brain, and whether maternal treatment with SSRI could obstruct such processes. Results may offer insight into how placental abnormalities contribute to later-in-life diseases with a fetal origin, presumably paving the way for novel early diagnostic and remediation strategies to prevent such disorders.

NSF Awards · FY 2025 · 2025-04

Energy storage technologies are critical for advancing renewable energy integration and ensuring a stable energy supply for large-scale applications such as industrial processes and solar power generation. Among these technologies, thermochemical energy storage systems, which store and release heat through reversible chemical reactions, offer significant potential due to their high energy density and long-term storage capabilities. This project focuses on improving the efficiency and reliability of calcium-based thermochemical systems, which are pivotal for sustainable energy practices. By enhancing the understanding of particle behavior and system dynamics, this project aims to overcome current limitations, such as low thermal conductivity and particle agglomeration. The results of the research will benefit the energy sector and the broader economy. The broader impacts include advancing energy sustainability, reducing carbon emissions, and fostering education and outreach initiatives. This research seeks to develop a comprehensive multiscale understanding of thermochemical energy storage systems through small-scale computational simulations and large-scale experimental validation. Using advanced molecular dynamics and machine learning techniques, the project will explore particle configurations and reaction dynamics at the micro-level. These simulations will be complemented by macroscopic experiments designed to ensure homogeneity and practical relevance. By integrating these methodologies, the project will validate and refine a physics-informed neural operator model, bridging the gap between atomistic and macroscopic scales. The outcomes will provide critical insights into system optimization, inform scalable design strategies, and establish a framework for addressing challenges in related energy technologies. This effort is expected to have a lasting impact on energy storage innovation, environmental sustainability, and STEM 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.