Virginia Commonwealth University

NIH Research Projects · FY 2025 · 2025-07

Project Summary Human cytomegalovirus (CMV) is a β-herpesvirus exquisitely adapted to horizontally transmit in the face of robust preexisting immunity, replicate while causing minimal damage, maintain life-long latency, and reactivate sub-clinically to reach new hosts. Central to this strategy of coexistence with the host are virally-encoded “temperance factors” that actively restrict CMV replication and spread. The RL13 temperance factor, a virion- associated envelope glycoprotein, is clearly important in vivo as an intact RL13 gene is present in all CMV genomes sequenced from clinical materials. In cell culture RL13WT CMV isolates initially form small foci that grow slowly with little or no release of infectious virus into the culture medium. However, within a few cell culture passages mutations that disrupt RL13 invariably emerge and quickly outgrow the RL13WT parental virus. Consequently, the vast majority of CMV strains used for research are RL13null mutants. How and why RL13 represses CMV replication remain unknown. Our overarching hypothesis is that in vivo RL13 is turned on or off to modulate CMV replication in different settings. Thus, RL13 may be turned off at sites of entry to enhance spread and promote dissemination, then turned on during the convalescent phase to limit the production of cell-free virus that would be rapidly inactivated by neutralizing antibodies, then again turned off at sites of virus shedding (kidney and salivary glands) in order to drive high level release of cell-free virus into urine or saliva for transmission to new hosts. Recent studies have identified amino acid substitutions in the CMV glycoprotein M (gM) and Immediate Early 2 (IE2) proteins that independently counteract the temperance effects of RL13. We hypothesize (i) that RL13 repression is mediated through interactions with gM that alter virion morphogenesis, egress, or infectivity; and (ii) that under different circumstances or cell types in vivo, RL13 transcription is activated or repressed by cell type-specific expression of certain IE2 isoforms. These hypotheses will be explored through the following Aims: AIM 1. Determine the mechanism by which RL13 restricts CMV replication. Genetic and molecular techniques will be used to explore potential interactions between RL13 and gM to elucidate the molecular mechanisms whereby RL13 impairs assembly and/or release of infectious CMV virions. AIM 2. Determine how IE2 isoforms modulate RL13 temperance activities. Genetic and molecular approaches will determine how amino acid substitutions in IE2 or altered expression of IE2 isoforms impact RL13 expression or repression. RL13 has a seemingly paradoxical but clearly important role in the natural history of CMV infections. The proposed studies may reveal that RL13 is a “master regulator” that can be activated or repressed to control virus production as circumstances in vivo require. The results will be among the first to elucidate the functional basis of viral proteins that restrict, rather than enhance, viral replication and spread.

NIH Research Projects · FY 2026 · 2025-07

Adolescence is a key developmental stage during which many youth experiment with substances (e.g., alcohol, nicotine, cannabis). Some experimenters progress to regular use, potentially leading to substance use disorders. Whether and how early youth initiate substance use (SU) and how quickly they transition to heavier use is influenced by demographic, environmental, and genetic factors. Internalizing (INT) and externalizing (EXT) behaviors, sensitivity to reward, and cognitive control/impulsivity have all been associated with SU trajectories. However, questions remain about whether these associations are causal or reflect shared risk factors, whether INT behaviors are risk or protective factors, and whether INT/EXT effects are interactive. Changes in reward sensitivity and development of cognitive control across adolescence may further impact SU trajectories and may moderate the role of INT/EXT on SU. Data from longitudinal twin studies also suggest a change in the relative importance of environmental and genetic factors on individual differences in both SU and behavioral correlates, with family environment more critical in early adolescence and genetic factors increasing in importance with age. However, few studies have large enough samples that are epidemiologically informed by the US population in terms of sex, race/ethnicity and socio-economic status and are genetically informative, with assessments of key domains across this critical developmental period. The nationwide Adolescent Brain Cognitive Development (ABCD) Study, which assesses youth (N=11k+) from age 9-10 until young adulthood, provides a unique opportunity to investigate the role of demographic, environmental, and psychological factors in the rate of transition from substance initiation to regular and/or heavy use, controlling for potential confounding by genetic factors to inform when prevention might be most successful. The ABCD sample was enriched with >1000 twin pairs, primarily collected at four sites with long histories of twin research (Minnesota, Colorado, Missouri, & Virginia), and including siblings and twins recruited at other sites. This unique genetically informative subsample, especially when analyzed jointly with the remaining population-based sample on whom genomic data and a rich set of sociodemographic and environmental variables are available, affords great opportunities. We have assembled investigators from the four twin sites, who each bring unique expertise and rigor in assessment and genetic epidemiological methods. Their skills are relevant to the study of SU trajectories and the simultaneous changes in EXT/INT behavior and reward sensitivity/cognitive control. In addition, each site has existing twin family data from longitudinal assessments of SU and its correlates, which serve as validation samples to test assumptions used in ABCD analyses and validate conclusions drawn from ABCD analyses. Our team of investigators already has a track record of collaboration including publications as well as curation of an online resource. We have three aims:

NIH Research Projects · FY 2025 · 2025-07

Project Summary/Abstract Head and neck cancer is the sixth most prevalent cancer worldwide, with 90% of cases diagnosed as head and neck squamous cell carcinoma (HNSCC). Though initial treatments with DNA damaging agents such as radiation and cisplatin are effective in limiting tumor progression, 50% of HNSCC patients will experience tumor relapse. Therapy-induced senescence (TIS), a dormant yet metabolically active cellular state, may be a contributing factor to tumor cell proliferative recovery. TIS is characterized by morphological and enzymatic changes as well as the release of secretory proteins collectively called “SASP” (senescence associated secretory phenotype). This includes the release of cytokines, chemokines, growth factors and other proteins that impact paracrine and autocrine signaling. The cGAS-STING (cytosolic GMP-AMP synthase stimulator of interferon genes) pathway, a key component of the innate immune response, is activated with the presence of damaged cytosolic DNA, ultimately promoting the expression of interferon-associated genes necessary for the release of proinflammatory cytokines and chemokines, including a variety of SASP proteins. Thus, the cGAS-STING pathway may be an important underlying mechanism in the regulation of TIS. Our preliminary data demonstrated that STING expressing HNSCC cells recovered proliferation approximately 12 days following senescence induction by cisplatin while STING knockout cells remained growth-arrested. This finding generated the hypothesis that cGAS-STING may be necessary for proliferative recovery via the secretion of signaling proteins. RNAseq and proteomic mass spectroscopy of STING wildtype and knockout cells treated with cisplatin to induce senescence revealed multiple growth factor and cytokine candidates. qRT-PCR identified that leukemia inhibitory factor (LIF) was induced by cisplatin and was downregulated with STING suppression. A member of the IL-6 family, LIF has been found to contribute to tumorigenesis, tumor cell invasion, and migration in studies of oral squamous cell carcinoma, nasopharyngeal carcinoma, pancreatic ductal adenocarcinoma, and other solid tumor types. Additionally, LIF has been explored as a therapeutic target via the development of small-molecule LIF inhibitors and humanized monoclonal antibodies. Thus, we hypothesize that cGAS-STING may facilitate proliferative recovery via its regulation of LIF. We seek to characterize the impact of cGAS-STING on proliferative recovery via LIF both in vitro and in vivo as well as evaluate the potential of LIF as a therapeutic target to combat tumor relapse. Previous studies of cGAS-STING have predominantly focused on its role in the innate immune response; thus our proposed studies will provide critical investigation of the cell autonomous functions of cGAS- STING and LIF that may influence the overall function of cGAS-STING in the tumor cell response to chemotherapy and potentially other treatment modalities that promote senescence in head and neck cancer.

NIH Research Projects · FY 2026 · 2025-06

Cognitive fluctuations (CF) are a hallmark of Lewy body dementia (LBD), presenting as spontaneous, unpredictable episodes of reduced attention and alertness. In addition to being common, CF in LBD are associated with greater impairment in activities of daily living, worse quality of life, and greater healthcare costs. Despite their high prevalence and negative impact, the mechanisms underlying CF are poorly understood. This project aims to elucidate the role of central cholinergic degeneration in CF in LBD, addressing critical gaps in understanding. This project will also establish a paradigm for assessing CF in real-time and focus future therapeutic development. CF in LBD have been linked to alterations in resting-state EEG, specifically reduced dominant frequency and increased dominant frequency variability. Preliminary data suggest that these EEG alterations, reflecting dysregulated cortical rhythms, are associated with CF. Cholinergic degeneration, particularly in the basal forebrain and midbrain, is more pronounced in LBD compared to other dementias and is associated with various cognitive and motor symptoms. However, there is less evidence supporting the role of central cholinergic deficits in CF. Our central hypothesis is that cholinergic deficits in cortical and thalamic circuits lead to dysregulation of cortical states, manifesting as increased low- frequency EEG activity and clinically as CF. In Aim 1, we will determine the association between cholinergic degeneration and CF in LBD. This cross-sectional study will compare cholinergic degeneration in LBD patients with CF to a group of Lewy body disease patients without CF. We will use T1-weighted MRI, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI) to assess cholinergic network dysfunction. CF will be evaluated using the Clinical Assessment of Fluctuations scale (CAF), the psychomotor vigilance task (PVT) administered over 48 hours, and quantitative analysis of EEG over 48 hours. In Aim 2, we will isolate the effects of cholinesterase inhibitors on CF in a pre-post interventional study. In LBD patients with CF, we will determine the effect of a cholinesterase inhibitor on CF as measured by the CAF, the PVT administered over 48 hours and the quantitative EEG features over 48 hours. We will also assess the relationship between changes in network connectivity using rs-fMRI and changes in CF. In Aim 3, we will examine the longitudinal association between cholinergic degeneration and CF progression. This 2-year cohort study will monitor LBD patients with CF and Lewy body disease patients without CF over 2 years with annual MRI, CAF, PVT over 48 hours, and EEG over 48 hours. Our approach, integrating MRI, EEG, and clinical assessments, aims to provide a comprehensive understanding of CF dynamics and establish relevant outcome measures of CF. This research will also guide the development of new therapeutic strategies targeting the cholinergic system. The anticipated impact includes establishing a paradigm for monitoring CF with EEG and repeated cognitive testing, ultimately leading to better treatments and enhanced quality of life for individuals with LBD.

NSF Awards · FY 2025 · 2025-06

This project aims to serve the national interest by improving curricula in undergraduate computing education to prepare students for the challenges of understanding and managing Technical Debt (TD) in software systems. Technical debt arises when software developers make technical compromises that may bring short-term benefits but result in lower software quality in the long term, often leading to challenges in maintaining and evolving software. By integrating technical debt concepts into computing curricula at multiple levels, the project intends to contribute to building a strong foundation for students to develop high quality software, and prepare them to become part of a more effective and competitive STEM workforce. The project plans to develop an innovative inquiry-based learning tool, called TD-Tutor (Technical Debt Tutor), to help students recognize, evaluate, and manage technical debt. TD-Tutor will enhance outcomes for student populations from different backgrounds and types of institutions, aligning with NSF’s mission to advance STEM education and workforce development. TD-Tutor will be implemented, used, and evaluated at three curriculum levels: introductory programming, mid- level software engineering, and senior level decision-making courses. The tool will feature annotated examples, interactive exercises, and conceptual feedback to guide student learning, and will incorporate guided inquiry and spiral learning approaches. Pre- and post-evaluations will assess the tool’s impact on student learning, skill development, and readiness to manage software quality. The NSF IUSE: EDU Program supports research and development projects to improve the effectiveness of STEM education for all students. Through the Engaged Student Learning track, the program supports the creation, exploration, and implementation of promising practices and tools. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-06

PROJECT SUMMARY Opioid Use Disorder (OUD) is a prevalent issue in the United States, characterized by the chronic misuse of opioids, resulting in severe consequences such as fatal overdoses, infectious diseases, increased crime rates, and socioeconomic burdens. Despite the availability of treatment options, OUD remains a significant global challenge. The current FDA-approved therapies for OUD include methadone, buprenorphine, and naltrexone. However, these treatments have limitations, including failure to treat all OUD patients, frequent clinic visits, and low retention rates. To address these challenges, this project aims to develop and explore alternative approaches fordrug delivery that can optimize therapeutic outcomes for individuals with OUD. Specifically, this proposal investigates the therapeutic potential of Nor-Levo-α-acetylmethadol (nor-LAAM). Nor-LAAM is an active metabolite of Levo-α-acetylmethadol (LAAM), an FDA-approved drug to treat OUD. LAAM is a high- efficacy agonist at Mu Opioid Receptors (MOR) and was administered orally three times a week, showing promising results in reducing opioid-positive urine tests, incarceration rates, and prolonged abstinence. However, it was reported that LAAM is associated with cardiovascular risks, specifically QT prolongation and torsades de pointes (TdP). Previous studies have shown that QT prolongation is primarily attributed to the parent drug LAAM itself rather than its metabolite nor-LAAM, as nor-LAAM exhibits a higher IC50 of 12 μM to inhibit HERG potassium channels compared to 3 μM of LAAM. Additionally, nor-LAAM is more potent at MOR than LAAM. This proposal involves utilizing biodegradable polymers to develop nor-LAAM-loaded polymeric microparticles (Nor-LAAM-MP) with in vitro sustained release capabilities (≥1 month) suitable for subcutaneous administration to treat OUD. We hypothesize that these microparticles will enable a controlled release of nor-LAAM, thereby reducing dosing frequency and drug dose and enhancing patient adherence while mitigating the risk of drug-related adverse effects and potential toxicities. We plan to conduct pharmacokinetics, efficacy, and safety studies. By completing this project, we can enhance our understanding of the therapeutic potential and safety profiles associated with nor-LAAM-MP for treating opioid use disorder.

NSF Awards · FY 2025 · 2025-06

The Annual Digital Forensic Research Conference (DFRWS) is a long-running security and privacy conference that focuses on topics around digital forensics and attracts a variety of academic, industry, and law enforcement participants. This award will support student travel to the 25th edition of this conference, to be held in July 2025. Funding this travel will expose undergraduate and graduate students to state-of-the-art digital forensic research while connecting them to the larger community of digital forensics researchers and practitioners. Students will also be encouraged to present posters on their own work to both promote their ideas and get expert feedback. This grant will provide travel support to about 6 U.S.-based students who otherwise have limited travel funding and so might not be able to attend. The conference will reach out widely to the digital forensics and related communities to solicit applications from a wide range of institutions, disciplines, and backgrounds. Criteria for selection include first-time attendance, participation in poster sessions, availability of travel funding, and students' ability to benefit from and enrich the conference. Through these efforts, the award will support digital forensics workforce development of value to national security. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-05

Project Summary This project seeks to advance our etiological understanding of Major Depression (MD) by clarifying the interrelationships, over developmental time, of genetic and environmental risk factors. These analyses will be conducted using data from Denmark and Sweden - two of the best and most complete population-based registers in the world. Our investigative team brings together individuals with expertise in medical and psychiatric epidemiology, genetic epidemiology, psychiatric nosology, and psychiatric molecular genetics as well as deep experience working in Swedish and Danish registers. We propose seven specific aims. The first two involve harmonizing a wide range of information relevant to risk for MD across the two registers, along with their unique extensions, and then continued development of a methodological innovation key to this proposal: Family Genetic Risk Scores (FGRS). FGRS permits us to assess, based on extensive pedigree information, profiles of multiple genetic scores – capturing risk for MD, related disorders, and other traits that could help dissect etiology - in every individual with family-linkage in the Danish and Swedish populations. Our third aim is to further develop and validate registry-based measures of environmental stressors that reflect i) chronic psychosocial adversities and ii) stressful life events, both of which predispose to MD, although over different time scales. The fourth aim will be to describe differences in the FGRS profiles associated with key clinical characteristics of MD (e.g., age at onset, recurrence, diagnostic stability) and psychiatric comorbidity (e.g., with anxiety or alcohol use disorders) in Denmark and Sweden. The fifth and sixth aims are to integrate what we have learned about MD and its risk factors to develop comprehensive etiologic models for MD that take into account genetic, environmental, and developmental factors, as well as possible differences among subtypes of MD. All analyses using FGRS will be paralleled using polygenic scores (PGS) in the set of individuals genotyped as a part of three Danish biobanks. We hope these analyses can better flesh out etiologic heterogeneity within the broad MD syndrome. The final aim, using molecular genetic resources from Danish biobanks, is to explore the impact for GWAS approaches, guided by our previous aims, to inform on molecular mechanisms of MD. In sum, this project will find substantial power, reproducibility, and robustness in working across comparable nation-wide health, socio-demographic, and familial registers from Denmark (sampling from ~9,500,000 individuals, ~300,000,000 person-years of observation) and Sweden (sampling from ~17,000,00 individuals, ~500,000,000 person-years of observation) and leveraging extensions into primary care registers of Sweden and >500,000 genotyped individuals in Danish biobanks. This project is of relevance to the US as it seeks to gain much needed insights into the etiology of MDD that could guide, in the future, nosology, prevention, and/or intervention. 1

NIH Research Projects · FY 2026 · 2025-05

PROJECT SUMMARY/ABSTRACT Bulimia nervosa (BN) is a common and devastating illness that often emerges in adolescence, a time of dynamic neural maturation and cognitive development. Dieting and impulsivity are implicated in the onset and maintenance of BN. Yet, the few existing first-line treatments for adolescent BN primarily target dieting and produce suboptimal outcomes. Impulsivity is a complex, multi-faceted process, and the neural circuits subserving each facet change with development. The precise facets involved in adolescent BN remain unknown, hampering targeted interventions. Suboptimal exploration is a neurocognitive process that may underlie impulsivity and be salient to understanding adolescent BN. The overarching aim of this K23 Mentored Patient-Oriented Career Development Award is to test the hypothesis that adolescent BN is characterized by the altered development of exploration strategies and associated neural circuitry using an accelerated longitudinal design. Cohorts of early (aged 12-15), middle (aged 14-17), and late (aged 16-20) adolescent girls with BN and group-matched controls will be recruited. Each cohort will enroll 40 participants (20 BN/20 controls, N = 120). Adolescents will complete a bandit task that uses computational modeling to parse exploration strategies during fMRI scanning to decipher the neural correlates of exploration strategies. At 1- and 2-year follow-ups, adolescents will remotely complete the bandit task and clinical measures to examine developmental shifts in exploration strategies and their cross- sectional and prospective associations with BN symptoms. This design will test the following hypotheses: 1) adolescents with BN will not show shifts in exploration strategies over time, whereas controls will rely more on directed exploration and less on value-free random exploration over time (Aim 1); and 2) adolescents with BN will show altered neural activation and effective connectivity patterns during exploration that will be similar across BN age cohorts, but neural patterns will differ across control age cohorts (Aim 2). Links between exploration strategies and associated neural activation and effective connectivity and BN symptoms at baseline and over time will be examined (Exploratory Aim). The research will serve as a platform for mentorship and hands-on training in concepts and skills to support the candidate’s transition to independence. Specifically, the study will provide training in neurodevelopmental methods (e.g., adolescent recruitment and retention, longitudinal analysis, Training Aim 1) and computational modeling of brain and behavior data (Training Aim 2). The candidate will receive conceptual training in translational, transdiagnostic reward processing models to help her develop more precise models of adolescent BN (Training Aim 3). The research will support the candidate’s first R01 by yielding preliminary data on the neuro-computational and -developmental bases of BN and generating insights into developmentally sensitive clinical targets. Ultimately, the candidate’s research program will inform mechanistic, age-appropriate interventions that promote lasting recovery from this pernicious illness.

NSF Awards · FY 2025 · 2025-05

Confessions are an exceptionally powerful form of legal evidence; they pave the way to conviction and punishment. U.S. law requires that upon taking a criminal suspect into custody, police must issue Miranda warnings about the suspect’s rights to silence and counsel. During questioning, police are prohibited from using coercion that “overbears the suspect’s will” to extract a confession. Understanding perceptions of custody and coercion is essential because violations of these laws and principles can lead to inaccurate outcomes, such as false confessions and wrongful convictions. Moreover, when a confession is false, an innocent person is punished while the true perpetrator remains at large, which poses a significant threat to public safety. Judges and juries are tasked with evaluating custody and coercion in legal proceedings, and these decisions have serious and enduring consequences. Psychological science can deepen understanding of perceptions of custody and coercion and thereby help legal decision makers to assess custody and coercion in a transparent and consistent manner. Police interviews of subjects in custody are difficult to study in a way that is simultaneously scientifically rigorous, ethically conscious, and ecologically valid. This research harnesses Virtual Reality (VR), an innovative technological tool, to study perceptions of custody and coercion. The study introduces late adolescents and emerging adults to police interrogation in an immersive 3D environment. Study participants virtually “experience” an interrogation, scripted from a real case. Four VR conditions are designed to assess whether and how the type of interrogation strategy, which is a key factor that judges consider when evaluating the voluntariness of the interaction, affects perceptions of custody and coercion, as well as decision-making with respect to confessions. The investigators also compare outcomes across two non-VR conditions (standard 2D video and a transcript), which mimic real-world materials that judges evaluate in disputed confession cases. This research generates actionable data and findings about people’s interrogation experiences in order to promote fairer, more accurate legal processes and outcomes that ultimately benefit countless individual defendants, victims, and society at large. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-05

ABSTRACT Posttraumatic stress disorder (PTSD) is a commonly occurring condition following exposure to traumatic events with significant clinical, quality of life, and economic impact. PTSD is moderately heritable. Significant advances have been made through efforts of consortia and large-scale genetic studies to shift PTSD from a disorder with low genetic discoverability to one with a growing number of identified, replicable common genetic variants and significant genetic correlations with other neuropsychiatric and substance use disorders. In addition, the integration of multi-omics approaches (i.e., information from the genome, epigenome, proteome, and transcriptome) has identified pathways and tissues associated with the disorder. Rare non-coding functional variants are also an important component of genetic risk. The integration of rare variants with common variants into these multi-omics approaches has not to date been done for PTSD. The proposed study seeks to fill this gap by building upon prior work by our group 1) observing rare-variant based genes and pathways associated with PTSD from a pilot study using a whole exome sequencing (WES) dataset, and 2) identifying additional genes associated with other neuropsychiatric and substance use disorders by integrating rare variants from WES datasets and other omics datasets. We aim to leverage existing large-scale WES and whole genome sequencing (WGS) datasets and biorepositories and use these integrative approaches to identify additional genetic signals for PTSD. To do so, we will develop analytic pipelines to analyze available datasets for PTSD phenotypes from the UK Biobank (500K WES/WGS) and the All of Us study (245K WGS). Our analyses will impute, harmonize, and integrate phenotypic information available from these select biobanks to increase sample sizes and in turn power to detect effects and prioritize genes associated with PTSD using rare variant information from WES/WGS data. We further propose to jointly analyze existing gene-sets associated with PTSD with rare variants from sequencing data to improve genetic detection. We will also leverage the genetic correlation among other conditions to increase statistical power by jointly analyzing sequencing datasets of PTSD and other comorbid disorders. The overarching goal of this work is to integrate rare variants from large scale sequencing biobank datasets and available omics information to capitalize on the full frequency spectrum of variants to identify additional, novel genetic signals associated with PTSD. The knowledge gained and pipelines developed from study goals will be critical for future R01-scale efforts to extend this approach to other datasets and phenotypes and identify targets for prevention and treatment of PTSD.

NIH Research Projects · FY 2026 · 2025-05

Project Summary. Dental caries continues to remain a major public health burden in the US. Future dental treatment plans are expected to benefit from development of advanced statistical methods for efficient caries experience (CE) assessment by integrating various statistical challenges encountered in discrete caries data. Publicly available nation-wide survey databases, such as the NHANES, are important, but somewhat under- utilized resources for such evaluations and practical interpretations, mainly due to some unique statistical complexities posed by these large databases, including unequal sampling weights, data granularity, complex hierarchical structure, and possible spatial association (between tooth surfaces) determining disease progression. The popular DMFT/DMFS summary indices for assessing CE are plagued with various inconsistencies. Furthermore, these databases contain a large number of CE predictors, and confounders (such as socio-demographics, smoking status, etc), leading to further complexities in conducting prudent cross- sectional evaluation. Effective analysis and pragmatic summarization of the cross-sectional association between a variety of CE factors and caries outcomes, incorporating the aforementioned complexities within a unified paradigm are often beyond the capabilities of existing statistical tools and software packages, available for complex surveys. Furthermore, those currently available statistical methods for handling spatial discrete responses might be computationally prohibitive for analyzing large observational data, such as NHANES. In this project, we address these challenges, and propose a single-number, nationally-representative summary of CE index, from about 24,500 adult dentate subjects, who are part of the nationwide NHANES 2011- Mar 2020 complex survey. We further refine this index, and present a pragmatic validation using the NHANES database. We have the following 3 high-impact aims: (1) construct and validate a pragmatic, interpretable, single index model using DMFS/T counts, (2) refine and validate the index for spatially-referenced tooth-surface level binary D/M/F/S outcomes, and finally (3) produce free software (R package) for the estimation and computation of this personalized CE index for any future patient. This proposal will generate new knowledge on national-level CE evaluation via the development of this comprehensive and unique index, which will also unravel the complex covariate-response relationship to assess tooth-surface-level CE by moving away from the traditional DMFT/S summary indices. Our fully generalizable methods are also expected to stimulate future research in developing principled data-analytic tools for understanding burden of other diseases, and related comorbidities.

NIH Research Projects · FY 2025 · 2025-04

Abstract Funds are requested to acquire a Zeiss LSM 900 fluorescence confocal microscope to support the research efforts of multiple NIH-funded investigators at the Virginia Commonwealth University (VCU). The microscope will meet increasing demand multicolor 3D imaging of cell cultures and tissue samples in automated manner. Numerous research questions, developed in recent years, require visualization of these specimens at multiple scales, from cell population down to subcellular structures (vesicles, endoplasmic reticulum tubules, cytoskeletal filaments). None of the microscopes currently available at VCU (confocal or structured illumination) have the combination of imaging speed, ease of magnification changes and ergonomic operation, needed to execute these tasks robustly for large number of samples. The requested Zeiss system is configured around an Axio Imager Z2 upright stand and equipped with a motorized (piezo) stage with a 4-slide holder. The microscope has 3 high-sensitivity fluorescence confocal detectors, a transmitted light detector and a color camera for wide-field imaging. These features will make the LSM 900 a significant upgrade of the only upright VCU confocal microscope, Zeiss LSM 700 and its wide-field counterpart, Zeiss/MBF Neurolucida. The former system has experienced heavy usage since its installation in 2013. However, performance of the LSM 700 no longer meets requirements of contemporary experimental protocols and its further maintenance no longer guaranteed by the manufacturer (Zeiss). The new system will be housed in a well-established and highly productive Microscopy Shared Resource (MSR) facility. MSR is directed by the PI, who has expertise in multiple aspects of microscopic imaging. During the past five years (2019 - 2023), 135 different laboratories, representing 312 investigators from 17 different departments at VCU have used the MSR and its services (widefield fluorescence, confocal, TIRF, SIM, electron microscopy, image analysis, and sample preparation). The projects conducted by these researchers represent a broad range of studies (cell biology, microbiology, neurobiology, bioengineering, virology, pharmacology, physiology, etc.). Representative studies of major users (from 12 labs; 5 departments) and minor users (from 3 labs; 2 departments), who are funded by NIH, have been highlighted in this proposal. Acquisition of a versatile confocal/wide-field microscope will have a major impact on research at VCU as it will preserve and expand the capacity of a well-used core facility and attract additional users (whose needs cannot be met by the equipment available at VCU).

NSF Awards · FY 2025 · 2025-04

This project aims to serve the national interest by developing STEM courses that will prepare students to apply knowledge from mathematics courses to other disciplines. Undergraduate students are increasingly asked to make connections and articulate problems from disciplines outside of mathematics in quantitative terms. College faculty also need to understand and meet the changing educational needs of students, and most institutions have limited resources to address this critical challenge. The National Consortium for Synergistic Undergraduate Mathematics via Multi-institutional Interdisciplinary Teaching Partnerships (SUMMIT-P) has been working since 2016 to address these issues by forming and strengthening faculty partnerships across disciplines and institutions. These partnerships have reduced the separation between disciplines, resulting in undergraduate courses that make explicit connections between mathematics and numerous other disciplines. This Level 2 IUSE Institutional and Community Transformation project, led by West Virginia University, Virginia Commonwealth University, and Western Michigan University, includes approximately 40 new institutions that will adapt the SUMMIT-P model to form local faculty teams. The SUMMIT-P team plans to study the experiences of students in these revised courses while also collaborating with national professional societies to ensure the long-term sustainability of the consortium’s work, significantly expanding the scope and positive impact of SUMMIT-P to thousands of additional college students. The goal of this project is to assist institutions with the adaptation of a known model for developing and implementing cross-disciplinary STEM courses. The project will also work to broadly disseminate the SUMMIT-P model to institutions beyond the intended 40 project participants. The project will support the development of sustainable collaborations that aim to minimize traditional disciplinary silos. Additionally, the proposed work will advance understanding of the student experience in these interdisciplinary courses, using previous student outcomes in SUMMIT-P courses combined with new data focused on long-term student impact. The project’s research plan is designed to advance understanding of how choices made by institution-based teams affect positive impact of the change process, as well as the institutional qualities and resources that are critical to lasting change. Additionally, the research team plans to study the effectiveness of faculty partnerships formed using SUMMIT-P change processes in creating significant and lasting curricular change that results in positive long-term student impact. The NSF IUSE: EDU Program supports research and development projects to improve the effectiveness of STEM education for all students. Through its Institutional and Community Transformation track, the program supports efforts to transform and improve STEM education across institutions of higher education and disciplinary communities. 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 · 2025-04

PROJECT SUMMARY Manganese uptake has been shown to be essential for oxygen tolerance, oxidative stress resistance, and virulence in streptococci. Through our work with the oral commensal Streptococcus sanguinis and the work of others, the role of manganese in oxidative stress resistance is partially understood. Yet, many fundamental questions remain. We have previously shown that S. sanguinis strains containing mutations in the high-affinity manganese ABC transport system lose the ability to grow in aerobic serum. This growth defect can be corrected by the addition of manganese. We have identified suppressor mutants that have regained the ability to grow under these conditions, and yet are indistinguishable from the parent transporter mutants with regard to cellular levels of manganese. Genome sequencing of these suppressor strains identified mutations in a gene encoding a highly conserved integral membrane protein of unknown function. Complete deletion of this gene produced the same phenotype. Until recently, no structural or functional studies had been performed with the suppressor protein encoded by this gene or any other member of the large family to which this protein belongs. Recently, an integral membrane protein of unknown function in humans was characterized as an acyltransferase and was shown to have predicted structural homology to the S. sanguinis suppressor protein family, although the structure of the human protein was not determined experimentally. Based on that data and our new preliminary data, we hypothesize that the suppressor protein is an acyltransferase that incorporates polyunsaturated fatty acids into the S. sanguinis membrane, and that oxidative stress results in lipid peroxidation leading to further toxicity. We will test this hypothesis by determining the crystal structure of the suppressor protein and characterizing its function. This multidisciplinary application proposes to determine the first crystal structure of any protein belonging to this large superfamily and the first functional characterization of a bacterial member of this family. This project promises to provide fundamental new insights into fatty acid incorporation and oxidative stress resistance in streptococci and other bacteria of great importance to human health.

NIH Research Projects · FY 2026 · 2025-03

/// PROJECT SUMMARY \\\ Brain disorders such as psychiatric and substance use disorders are leading causes of disability worldwide. The molecular study of brain disorders remains challenging due to the lack of direct access to the diseased tissue in living patients. Extracellular vesicles (EVs) are a diverse group of nanoscale particles released by cells into the extracellular environment2. They carry a cargo of RNA, DNA, lipids, and proteins, and are critical for a variety of processes such as intercellular communication, synaptic plasticity, immune response and the disposal of cellular debris. EVs can cross the blood-brain barrier and methods are available to isolate EVs derived from brain cells from peripheral fluids such as blood. Because EVs contain a rich repertoire of biomolecules derived from their cell of origin, they have been heralded as a novel approach that provides a unique window into the disease processes in the brain and discover powerful non-invasive biomarkers that can be used to improve diagnosis, prognosis or to evaluate treatments. To the best of our knowledge there are no previous studies, as rigorous as proposed here, directly linking the RNA cargo of brain EVs isolated from serum to processes in brain. The main goal of this project is to better understand what can be learned about normal and disease processes occurring in the brain by studying brain EVs isolated from peripheral blood, and derive novel biomarkers for SZ. Tissue donors involve 16 schizophrenia (SZ) cases and 16 matched controls (CTR). For each donor, post-mortem brain tissue from the prefrontal cortex and serum is available. We will isolate three types of brain EVs from serum (BEVS), each focusing on a different class of brain cell-types. To catalogue the RNA cargo of BEVS we will generate two sequence libraries to assay a broad range of RNA species (e.g., messenger RNA, circular RNA, microRNAs, long non-coding RNA). To be able to link BEVS RNA abundance levels to processes in brain, we will perform single nucleus RNA-seq (snRNA-seq) on the brain samples to assay the cell-type specific expression of genes and transcripts. Successful completion of this project means that we have gained insight into what can be learned from normal and disease processes occurring in brain by studying BEVS isolated from peripheral blood. In addition we will have identified novel sophisticated biomarkers that eventually may be used to improve diagnosis, prognosis and treatment in the clinic.

NIH Research Projects · FY 2026 · 2025-02

PROJECT SUMMARY Cardiovascular (CV) events after receipt of potentially cardiotoxic chemotherapy are emerging as the leading causes of morbidity and mortality for survivors of breast cancer (BC), the most common cancer in North American women. The objective of our proposal is to test whether a tailored exercise intervention that commences and continues throughout receipt of adjuvant chemotherapy can attenuate physical inactivity and fatigue, and preserve exercise capacity, left ventricular (LV) function, and health-related quality of life (HRQOL). We showed feasibility of our proposed intervention and performance of the outcome measures in R21CA226960 (Section 3.C.2). We now propose a pragmatic, multicenter, randomized controlled trial of a home-based physical activity intervention plus a healthy living intervention (HLI), versus HLI alone, in 150 women receiving anthracycline-based chemotherapy for BC, to preserve exercise capacity, LV function, and HRQOL, and reduce fatigue. Novel features of this proposal include: 1) Performance of physical activity during receipt of cancer treatment where exercise intolerance originates. 2) Creation of patient communities that enable cancer patients to support one another during treatment. 3) Delivery of aerobic and strength activities suited to one’s individual lifestyle in the home guided by instruction from a central location, provided by exercise and behavioral specialists experienced in working with immunocompromised individuals or those with other pre-existing activity limitations. 4) Use of newly developed magnetic resonance and cardiopulmonary exercise testing methods to measure components (e.g., LV function and myocardial tissue characteristics) that contribute to peak oxygen consumption (a measure of maximal exercise capacity). This new information will provide mechanistic insight into how physical activity during cancer treatment helps preserve exercise capacity. 5) Assessment of physical activity, sedentary behavior, and exercise capacity to help to unravel associations among physical activity, HRQOL, and fatigue in cancer patients. 6) Measurement of systemic inflammation and LV myocardial fibrosis – both implicated in cancer treatment- associated CV dysfunction and modifiable through programs incorporating activity and exercise. 7) The first rigorous study of how dietary fatty acid intake affects exercise capacity among patients receiving treatment for breast cancer. We will partner with the Wake Forest NCI Community Oncology Research Program Research Base network in a novel and cost-effective collaboration. Ultimately, increasing physical activity during chemotherapy may lead to improved long-term outcomes for those with breast and other cancers, and establish a new paradigm for more effective and patient-centered care.

NIH Research Projects · FY 2026 · 2025-02

Substance use during pregnancy can lead to negative maternal and infant outcomes, contributing to the U.S. overdose crisis. Polysubstance use in pregnancy is particularly salient considering that the increase in number of substances used carries the compounded risk for both the mother and fetus of each individual substance, as well as potential negative interactions between substances. Prenatal polysubstance use in the U.S. is increasing, and characterization of use patterns is critical. Current research supports the relationship between prenatal individual substance use and environmental factors such as geographic location. However, there is limited research examining relationships between such factors and prenatal polysubstance use. The overall objective of this research will be to better understand prenatal polysubstance use in the U.S. by approaching the characterization in two ways (qualitative and quantitative), and triangulating findings. Specifically, this project will: 1) conduct qualitative interviews among pregnant or postpartum women engaging in prenatal polysubstance use, and 2) utilize an existing national pregnancy survey (CDC PRAMS) to quantitatively establish outcomes of polysubstance use behaviors among pregnant women. First, 20 qualitative interviews will be conducted with pregnant or postpartum women engaging in polysubstance use to understand practices of such use. Second, the findings of these interviews will inform an exploration of present-day patterns of pregnant polysubstance use using CDC PRAMS data. These patterns will be characterized using latent class analysis (LCA) to define unique groups of polysubstance use, using the following environmental factors as external validators: economic stability, education access and quality, healthcare access and quality, neighborhood and built environment, and social environment. The strength of this approach lies in the specificity of quantitative analyses, while being complemented by depth of qualitative data. This research will be the first to our knowledge to assess prenatal polysubstance use in the U.S. using both quantitative and qualitative methods. This dissertation project will lay the foundation for future research to identify modifiable factors for prevention and treatment, with the goal of decreasing the burden of prenatal polysubstance use and addressing the overdose crisis.

NIH Research Projects · FY 2026 · 2025-02

SUMMARY Electrolyte imbalances are the cause or the consequence of a variety of endocrine, renal, cardiac, and hepatic disorders. It has been envisioned that self-testing of electrolyte levels by patients will revolutionize the management of chronic conditions such as hypoparathyroidism, arginine vasopressin deficiency, congestive heart failure, and kidney failure, akin to the revolution witnessed in diabetes management through self-testing of blood sugars. However, in contrast to the widespread success of minimally invasive self-monitoring devices for glucose, there are currently no products designed for quantitative measurements of blood electrolytes by non- healthcare professionals. Although blood gas/electrolyte analyzers have been prevalent in hospitals for decades, the minimum required blood volume is hundreds of times greater than that of a typical glucose strip, and the analyzer price is hundreds of times higher than that of a glucometer. These limitations prohibit their use in decentralized settings such as patients’ homes for self-monitoring. Using the calcium ion as an example analyte, we have recently developed a novel colorimetric ion sensor (ultrasensitive ion-selective liquid optode) capable of detecting electrolytes in only a few microliters of whole blood. The optode is a non-volatile and viscous oil that contains hydrophobic sensing chemicals including an ionophore to recognize the analyte ion, a dye as the optical reporter, and an ion exchanger to maintain the charge balance. The target electrolyte from blood is selectively extracted into the sensing oil to change the oil color. The oil is uniquely formulated to yield an exceptionally large color response within the very narrow clinical range of the electrolyte, ensuring high-precision and high-confidence measurements. In this project, we aim to 1) develop ultrasensitive ion-selective optodes to measure blood electrolytes, including calcium, sodium, potassium, magnesium, and chloride ions, for the management of corresponding diseases, 2) select the calcium sensor as an example to conduct a clinical validation study using venous and fingerprick blood samples from patients with thyroid and parathyroid disorders; 3) design a multiplexed sensing platform for simultaneous measurements of multiple electrolytes in a drop of blood. The handheld electrolyte monitor will consist of a stepper motor-based liquid control module, a mini camera serving as the optical detector, and a single-use colorimetric sensor. The permanent component will cost a few hundred dollars, while each disposable part will cost no more than a dollar. The required blood (1-3 microliters) can be easily obtained through finger pricks using small-sized lancets without the finger squeezing that often causes hemolysis. If successful, this home-use technology will empower patients to self-monitor their blood electrolytes in a timely and frequent manner, minimizing complications and risks associated with their chronic diseases.

NIH Research Projects · FY 2026 · 2025-01

PROJECT SUMMARY Reduced exercise capacity is the hallmark symptom of heart failure (HF) and the primary morbidity experienced by women treated for breast cancer (BC). No established therapies exist to mitigate treatment-related declines in exercise capacity and lower HF risk in BC survivors. We found that meeting physical activity (PA) recommendations during the first 3 months of BC treatment was associated with preserved exercise capacity. Yet, nearly 80% of women were inactive during treatment. While center-based aerobic PA and/or strength training programs maintain exercise capacity during and after BC treatment, they are structured programs and typically have low adherence due to time constraints, travel barriers, persistent fatigue, and compromised immunity during BC treatment. Generalizability of these trials is limited as only the most motivated and physically active individuals enroll. Thus, there is a need for feasible and practical PA programs to engage women with BC. Recent work highlights the value of lifestyle PA to reduce HF risk by improving exercise capacity. Interventions that target lifestyle PA, such as vigorous intermittent lifestyle physical activity (VILPA), can heighten access for women with BC and attract time-limited and less physically active participants. VILPA is characterized by brief bouts of vigorous PA completed during activities of daily living and is associated with a 48% reduction in cardiovascular (CV) mortality compared to inactivity. Small amounts of VILPA (3 minutes/week) have shown improvements in exercise capacity in non-cancer populations. However, the efficacy of a VILPA solution for preserving exercise capacity in BC patients is unknown. Additionally, the mechanisms underlying PA benefits are unknown, which creates a major gap for refining PA-based interventions and maximizing efficacy. In this K99 project, prior to testing VILPA in a clinical trial (R00), I will examine mechanisms underlying the association of PA to preserve exercise capacity. I will test if increased PA participation in the first 3 months of BC treatment is associated with preserved muscle quality and/or mitigated inflammation (both contributors to exercise intolerance). In the R00, following the ORBIT model of behavioral interventions, I will conduct a Phase IIb randomized trial testing the preliminary efficacy of VILPA versus a healthy living comparator to preserve exercise capacity during BC treatment while prospectively assessing inflammation and muscle quality. Through this award, I will learn 1) CV and exercise capacity outcome assessments, 2) systemic inflammation related to cardiac injury, 3) design and implementation of behavioral clinical trials, and 4) analytical approaches for behavioral clinical trials. With guidance from outstanding mentors, I will gain skills to launch an independent career and deliver lifestyle interventions targeting mechanisms that contribute to reduced exercise capacity. Findings from this proposal could change clinical care of cancer patients by providing a feasible and accessible PA solution to improve CV outcomes for women with BC and potentially other cancer types.

NIH Research Projects · FY 2026 · 2025-01

Cisplatin is a potent first-line therapy for many solid malignancies such as breast, ovarian, lung, testicular and head and neck cancer. Nephrotoxicity is a primary dose-limiting toxicity and the major obstacle for the clinical use of cisplatin. Approximately 30% of patients that receive cisplatin treatment (either alone or in combination with other chemotherapeutics) will develop kidney damage and that ∼50% of cancer patients showed signs of nephrotoxicity 4 years posttreatment with cisplatin The mechanistic basis for cisplatin-induced kidney damage is not fully understood and no efficient management strategies are currently available. The endocannabinoid (EC) system, which has been initially focused on the central nervous system, also plays important roles in the peripheral organs, including the kidneys. The most well-characterized ECs are anandamide (AEA) and 2- arachidonoylglycerol (2-AG). The biosynthesis of AEA is through the hydrolysis of N-arachidonoyl-phosphatidyl- ethanolamines via at least three distinct biosynthetic routes. The 2-AG is produced by diacylglycerol lipases (DAGLα and DAGLβ), which hydrolyze 2-arachidonoyl-containing diacylglycerols (DAG) to generate 2-AG. After production, ECs bind to the local cannabinoid receptors (CB1 and CB2) in an autocrine or paracrine manner. It has been shown that EC system participates in different kidney diseases, including cisplatin nephrotoxicity, and that interventions of CB receptors are promising therapeutic strategies. Surprisingly, the majority of studies focus on CB receptors, and little is known about roles of ECs metabolic enzymes in kidney damages. It is important to address this significant gap and imperative to investigate the role of ECs enzymes in kidney diseases. Given the fact that 2-AG is 50-fold more abundant than AEA in kidneys and has a similar affinity to CB receptors, we focused on the 2-AG-producing enzyme DAGLs. Our preliminary data showed that DAGLα gene KO protected the kidneys against cisplatin nephrotoxicity in mice, while no difference was observed in DAGLβ KO mice. Furthermore, a selective DAGL inhibitor, DO34, protected against cisplatin-induced damages in human kidney tubular cell line HK-2 cells. Based on the above information, the hypothesis to be tested is that over produced 2-AG contributes to the cisplatin nephrotoxicity and that inhibition of DAGLα protects the kidneys against cisplatin-induced nephrotoxicity. Two Aims are proposed. Aim 1: To determine whether inhibition of DAGLα protects the kidneys against cisplatin-induced nephrotoxicity. Aim 2: To establish that inhibition of DAGL will not interfere with the antitumor actions of cisplatin. Studies will involve both pharmacological and genetic interventions as well as systemic and kidney-targeted approaches for DAGLα inhibition. The findings from these proposed studies will identify that the activation of DAGL/2-AG production is a novel molecular mechanism in cisplatin-induced nephrotoxicity and suggest new therapeutic strategies for the prevention and treatment of cisplatin-induced nephrotoxicity by inhibition of DAGLα, either using DAGL inhibitor DO34 or kidney-targeted delivery of DAGLα siRNA, given that FDA has recently approved several siRNA-based drugs.

NIH Research Projects · FY 2026 · 2024-12

Summary Paclitaxel is a drug commonly used for the treatment of breast, lung, and ovarian cancer. Chemotherapy- induced peripheral neuropathy (CIPN) is one of the most common and serious adverse effects experienced by cancer patients treated with paclitaxel. CIPN can be a dose-limiting factor for chemotherapy, leading to premature termination of treatment, thereby influencing survival and quality of life. Currently, no therapies have been identified that address the underlying pathogenic mechanisms of CIPN. Therefore, the identification of alternative forms of therapy is a crucial medical need. This proposal focuses on a promising target: NLRP3 (which encodes NOD-, LRR- and pyrin domain-containing protein 3) inflammasome. Our preliminary data suggest for the first time that NLRP3 inflammasome contributes to CIPN produced by paclitaxel in mice. Paclitaxel treatment increased the expression levels of NLRP3, caspase-1 and IL-1β in the dorsal root ganglia (DRG) of mice. Furthermore, paclitaxel-induced neuropathic symptoms were completely absent in null mice lacking NLRP3 compared to wild type mice. Collectively, our preliminary results suggest that NLRP3 inflammasome inhibition represents a promising novel strategy for the treatment of CIPN. This project will test the central hypothesis that NLRP3 inflammasome activation contributes to paclitaxel-induced CIPN and that inhibition of NLRP3 inflammasome alleviates these effects. The main goal of the project is to determine whether dapansutrile, an oral selective NLRP3 inflammasome inhibitor currently in phase II clinical studies for the treatment of gout flares, alleviates and prevents paclitaxel-induced CIPN in a mouse model of naïve and tumor-bearing animals. We will determine the effects of dapansutrile after acute and chronic oral administration in mice treated with paclitaxel and cisplatin. We will then determine if dapansutrile reverses ongoing pain of paclitaxel-induced CIPN by capturing the motivation to seek relief using the conditioned place preference (CPP) test. Finally we will address if dapansutrile treatment would prevent CIPN while enhancing or at least not interefering with anti-tumor efficacy of paclitaxel in tumor- bearing mice. If successful, our project will provide a rationale for development of NLRP3 inflammasome- based medications to treat this side effect of cancer chemotreatment.

NSF Awards · FY 2024 · 2024-10

Understanding what selective forces led to these emergence of human ancestors requires a detailed knowledge of the environmental conditions in which these species lived and how they exploited their environment. To achieve this goal, this study collects environmental and dietary information to unveil the small-scale ecology where hominin species lived and the diets they consumed. Ecological information is compared with that obtained from localities where no hominins lived. Dietary information is compared to assess whether species consumed different diets. The study trains students in geological and paleontological methods and analyses. The results are shared with the scientific community, as well as museums and K-12 students. This study combines paleontological and geological investigations, focusing on known hominin and non-hominin localities to address landscape variation, niche differentiation, habitat diversity, and mammal community structure in a region where hominin species shared resources and habitats. Investigators directly assess hominin divergence in diet through microwear analysis of molar teeth and dental nitrogen analysis in the different genera to ascertain meat eating, as well as possible differences in levels of C3 and C4 isotopes among the species. The investigators: (1) survey for hominin and faunal fossils, including microfauna, (2) reconstruct 3D sedimentary and structural architecture of encasing sedimentary rocks, and (3) analyze biomarkers. This research contributes to the debate regarding which hominins belong to the genus Homo through understanding behavioral and morphological differences among hominin species that lived in the same localities. 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 2024 · 2024-10

This project will contribute to the national need for well-educated computing professionals by supporting the retention and graduation of high-achieving, low-income computer science students with demonstrated financial need. In this program student coursework will be augmented with projects involving multidisciplinary teams of undergraduate students, who will work together to develop software. Students will receive guidance from faculty mentors who will provide the students with technical, professional, and interpersonal development opportunities. Over its six-year duration, this project will fund scholarships to 54 unique full-time students who are pursuing bachelor’s degrees in computer science. The program will provide two-year scholarships to transfer students and will provide them with a holistic model of support including a new scholars retreat; faculty, peer, and industry mentoring; and academic and professional development activities. The project will pursue the following three specific aims. First, is to establish a new program to support academic and social integration, retention, graduation, and post-baccalaureate success of transfer students in computing majors with financial need. Second, is to strengthen and broaden partnerships with campus partner such as Academic Affairs and Student Affairs, as well as community college collaborators, to better address pre- and post-transfer needs in computing across the two- to four-year pathway. Third, is to investigate how the program model impacts the academic and social integration of transfer students majoring in computing. A comprehensive external evaluation will be undertaken, focusing on the objectives and activities of the project and encompassing both formative and summative components. The findings of this project will be disseminated through presentations and publications, reaching the communities involved in computing and engineering education as well as the broader educational research community. Employing both quantitative and qualitative research methods, the project will assess the impact of these interventions on transfer success, contributing valuable knowledge to STEM education. This project is funded by NSF’s Scholarships in Science, Technology, Engineering, and Mathematics program, which seeks to increase the number of low-income academically talented students with demonstrated financial need who earn degrees in STEM fields. It also aims to improve the education of future STEM workers, and to generate knowledge about academic success, retention, transfer, graduation, and academic/career pathways of low-income students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-10

The implementation of active learning approaches in STEM undergraduate courses has significantly increased over the past few decades. Classrooms traditionally dominated by lectures have been reworked into environments where students actively participate in discussions, problem-solving, group work, and hands-on projects. Improvement in students' overall academic achievement in these environments has consistently been reported, but researchers have found that some students encounter barriers that significantly limit their participation and impact their learning experiences in these courses. Understanding these obstacles and how these students interact with peers and instructors in small-group settings is crucial for developing more effective educational practices. Despite this need, no rigorous studies have yet examined these interactions in undergraduate mathematics classrooms. Addressing this research gap is crucial for the STEM curriculum, considering the pivotal role these courses play in the STEM pipeline and their strong impact on student retention in STEM disciplines. This project will use surveys, interviews, and classroom observations to conduct a thorough analysis of the interactions among students working in small groups in undergraduate mathematics classrooms. This analysis will provide foundational knowledge about the relationship between active learning instruction and effective learning environments that engage all students. The primary goal of the research is to explore the experience of students and instructors during group activities in these classrooms; closely analyzing their interactions and characterizing learning opportunities (OtLs) within groups. The project team will work with instructors who incorporate teaching practices focused on fostering the engagement of all students in the context of teaching semester-long introductory undergraduate mathematics courses. Specifically, the research will examine the extent to which moving into more central roles of participation is available to all students within small-group social ecologies, carefully attending to the influence of classroom norms and belonging-oriented instruction on these participation shifts. The analysis will center on group interactions and OtLs before, during, and after the participation of instructors in coaching and professional learning opportunities focused on social ecologies and promoting students’ sense of belonging in mathematics. The research will be conducted at two institutions serving different regions of the United States, both of which have had a sustained commitment to active learning in introductory mathematics. The use of two sites will enable the exploration of how OtLs may vary among students in different institutional contexts with established instructional practices. The project will aim to capture comprehensive rich data on students' and instructors’ perceptions of group interactions through surveys, interviews, and classroom observations centered on small groups. The project will seek to provide four major contributions to STEM education research. First, is to advance foundational knowledge about the relationship between active learning instructional approaches and effective learning environments that engage all students. Second, is to broaden explanatory knowledge about students’ OTLs and experiences of belonging in active learning undergraduate mathematics classrooms. Third, is to increase understanding of how students experience sociohistorical and socio-mathematical classroom norms, and how those experiences are associated with OtLs. Fourth, and finally, is to extend core understanding of instructional practices that support effective learning environments in undergraduate mathematics classes. This project is supported by NSF's EDU Core Research (ECR) program. The ECR program emphasizes fundamental STEM education research that generates foundational knowledge in the field. Investments are made in critical areas that are essential, broad and enduring: STEM learning and STEM learning environments, broadening participation in STEM, and STEM workforce development. 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.