Drexel University

NSF Awards · FY 2026 · 2026-09

Artificial intelligence (AI) companion chatbots are rapidly becoming part of teens' daily lives during critical stages of identity formation and development. Many of the AI companion chatbots are highly customizable and interactive. There is evidence that these chatbots can expose users to developing emotional attachment, excessive use, and overreliance. Current safety measures for AI chatbots are often inadequate or easily bypassed. This CAREER project seeks to address these issues by designing, developing, and assessing developmentally appropriate interventions to foster healthy AI interactions among teens. It will benefit society broadly by addressing the mental health of teens as impacted by emotional and cognitive attachment and overreliance on AI companions. It will enhance digital literacy and critical thinking among teens and their caregivers, helping them engage with AI technologies in more effective ways. The interdisciplinary research plan seeks to transform knowledge at the intersection of digital safety for teens, developmental psychology, AI ethics, and human-AI interaction through three main objectives. The first objective is to develop a novel empirical foundation that bridges teens' self-reported data and behaviors through triangulated research methods, examining their experiences with AI companion risks and parasocial relationships, as well as the ways they cope and build mental resilience against the potential negative impacts of AI. The second objective is to create reusable teen-centric sociotechnical design frameworks and a suite of interventions to enhance AI companion safety through co-design activities involving teens and their safety stakeholders. The third objective is to evaluate and longitudinally assess the age-appropriate suite of novel interventions in real-world contexts. The project builds upon well-established theoretical approaches to develop datasets, models, and tools. The project's activities include plans to benefit the public through developing a competitive workforce by providing training from middle school through graduate school, integrating research and education, and expanding education and public engagement in science and technology. 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 2026 · 2026-06

This project aims to develop theory and methodology required for statistical inference on spatiotemporal rates of change or gradients, followed by extending their use to assess boundaries that track significant changes in spatiotemporal response. The current stage of spatial and temporal data science bears witness to the recording of massive spatiotemporally indexed data for the purpose of tracking changes in spatial and temporal variables. This project outlines the details of the methodology and software development for quantifying and understanding change within large and complex spatiotemporally referenced datasets. These are closely related to machine learning and artificial intelligence, and the developments are motivated by substantive questions arising in various fields where assessing regions of rapid change in space and time is crucial. The focus of applications is on biomedical and neuroimaging datasets, and the project provides research training opportunities for graduate students. Extending the statistical inference to larger domains, we leverage a low-rank projection-based approximation to exact Gaussian processes. The project will also develop classes of highly scalable Bayesian factor models and Graphical predictive processes for jointly modeling highly multivariate spatiotemporal data. The project will conduct rigorous investigations into statistical inference for rates of change associated with predictive processes and graphical predictive processes. The project aims to derive probability distributions that facilitate posterior inference within a Bayesian setting. This is followed by extending the inference to smooth surfaces within space-time that track rapid directional change. 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 · 2026-06

Project Abstract Neuropathic pain is a common complication of spinal cord injury (SCI), characterized by symptoms of allodynia and hyperalgesia experienced at- and below the level of injury. This type of chronic pain can be spontaneous or evoked, and currently accepted therapeutics display limited efficacy. Neuroimmune interactions are thought to play a central role in the development and maintenance of neuropathic pain. Increased production of proinflammatory mediators after SCI alters the expression of voltage-gated channels on primary nociceptors, driving hypersensitivity and spontaneous activity. This results in aberrant sensory signaling extending from the peripheral dorsal root ganglia (DRG) into the spinal dorsal horn and ascending to supraspinal centers, driving neuropathic pain. Intercellular communications between infiltrating macrophages and neuronal populations in the DRG after injury have drawn considerable interest in the study of neuropathic pain, as these cells have critical contributions to both the development and resolution of chronic pain. Recent work highlights the therapeutic potential of small extracellular vesicles (sEVs) derived from lipopolysaccharide (LPS)-stimulated macrophages in preclinical models of inflammation and pain. Preliminary data from our lab revealed a dramatic resolution of established SCI-induced neuropathic pain and a more normal distribution of nociceptive primary afferents in the spinal cord after intrathecal injection of sEVs released from RAW 264.7 macrophages treated with LPS. However, how sEVs affect nociceptors and/or other cells found along the sensory neuroaxis remains to be established. We hypothesize that sEVs from LPS-stimulated macrophages attenuate aberrant nociceptor plasticity and hyperexcitability to resolve neuropathic pain after SCI via 1: direct internalization by nociceptors in the DRG, or 2: indirectly by affecting endogenous macrophage/microglia mediated mechanisms. Two specific aims have been developed to explore this hypothesis. Our first aim will utilize patch clamp electrophysiology recordings to determine how DRG nociceptors are affected by sEV administration both in vitro and in vivo. The second aim will deplete endogenous macrophages and microglia in hypersensitive SCI rats to determine whether these cells are necessary for the analgesic effect of sEV administration. The data from this proposal will explore how macrophage derived sEVs interact with the neuroimmune environment after SCI in a way that facilitates treatment of neuropathic pain.

NIH Research Projects · FY 2026 · 2026-06

ABSTRACT The development of effective therapies for cartilage regeneration and osteoarthritis (OA) treatment is challenged by our limited understanding of the complex molecular interactions that regulate the assembly, maintenance and degradation of the extracellular matrix (ECM). During the first funding cycle of this project, we identified a crucial role for decorin, a small proteoglycan, in regulating cartilage ECM integrity by providing physical linkages to stabilize aggrecan network and its fragments. In addition, we found that loss of decorin results in aberrant cartilage surface fibril remodeling during aging and after injury, contributing to full cartilage erosion and accelerated OA development. Building on these findings, our updated central hypothesis for this renewal is that, in addition to stabilizing the aggrecan assembly, decorin also attenuates aberrant cartilage surface fibril remodeling, and that increasing decorin content can ameliorate cartilage degradation in OA and improve the quality of tissue repair post-injury. To test this hypothesis, we will pinpoint the role of decorin in regulating collagen fibril structure on the cartilage surface, and evaluate the effects of increasing decorin levels in slowing OA progression and improving the repair of cartilage tissue after injury. In Aim 1, we will determine whether targeted ablation of decorin in cartilage superficial layer cells accelerates cartilage surface fibril remodeling and degradation in aged mice and in injury-induced post- traumatic OA using the destabilization of the medial meniscus (DMM) model. Next, we will elucidate if decorin directly attenuates force-induced collagen II fibril alignment at both the nanoscale individual fibril level and microscale cellular spheroid level, and if decorin directly strengthens the collagen II fibril network on the cartilage surface. In Aim 2, we will determine whether the overexpression of decorin by adeno-associated virus (AAV) therapy can ameliorate cartilage degradation and surface remodeling in a murine DMM model, in which, AAV-decorin will be intra-articularly administered at either an early “preventative” (before DMM) or a delayed “treatment” timepoint (4 weeks after DMM). Next, we will test if increasing decorin levels by AAV-decorin attenuates the degradation of cartilage explants under catabolic stimulation by inflammatory cytokine IL-1β. In Aim 3, we will test if increasing decorin in porcine chondrocytes by AAV-decorin improves the quality of nascent pericellular matrix and if AAV-decorin increases the preservation of degenerative cartilage matrix when integrated with our established matrix reinforcing tissue-penetrating hyaluronan (tpHA) hydrogel in explant culture. Lastly, we will evaluate if delivering AAV-decorin within the reinforcing tpHA-hydrogel further increases the quality of repair cartilage in a minipig partial thickness defect model in vivo. Validating our central hypothesis will establish decorin as an indispensable cartilage ECM constituent and will validate its therapeutic potential in slowing OA progression and improving the quality of regenerating cartilage.

NIH Research Projects · FY 2026 · 2026-05

Despite the success of antiretroviral therapy (ART), HIV remains incurable due to the persistence of viral reservoirs, particularly in the central nervous system (CNS). Myeloid cells—macrophages and microglia— serve as long-lived HIV reservoirs in the CNS and are implicated in neuroinflammation and HIV-associated neurocognitive disorders (HAND). Unlike CD4+ T cells, infected myeloid cells exhibit a state we define as semi‗quiescence, in which transcription from the HIV-1 promoter persists, but viral protein production is minimal. This persistent yet attenuated activity complicates efforts to eradicate the virus from the CNS. Our preliminary data show that ART-treated human monocyte-derived macrophages (hMDMs) maintain stable proviral levels over time, with reduced p24 Gag protein expression but active transcription. Chromatin immunoprecipitation (ChIP-qPCR) analysis of these cells revealed euchromatin markers at the viral LTR, consistent with transcriptionally active but translationally restricted infection. Strikingly, treatment with benzodiazepines (BDZs)—commonly prescribed to people living with HIV—reactivates viral protein production in these cells, suggesting they may act as latency reversal agents (LRAs) in the CNS. BDZs appear to target RUNX1, a transcription factor that interacts with the HIV-1 LTR, and may disrupt epigenetic control of viral persistence. We hypothesize that HIV-infected myeloid cells adopt a unique global epigenetic signature early in infection, orchestrated in part by RUNX1 and HIV Tat, which modulates effector function and maintains semi-quiescence. BDZs may override this regulation, reactivating latent virus and worsening neuroinflammatory outcomes. We aim to: 1) define the global epigenetic landscape of HIV-infected hMDMs under ART and characterize how RUNX1 and Tat occupancy correlates with gene expression and viral activity and 2) determine how BDZ exposure alters the global epigenetic state of infected and uninfected hMDMs, testing the hypothesis that BDZs promote viral reactivation via a euchromatic shift. This research will uncover new mechanisms of HIV persistence in myeloid reservoirs and inform safer therapeutic strategies for PLWH, especially those at risk for HAND.

NIH Research Projects · FY 2026 · 2026-05

Project Summary Human immunodeficiency virus (HIV) infection frequently co-occurs with cocaine use disorder (CUD). Despite high rates of psychostimulant use among people living with HIV (PLWH), and the worsening of HIV outcomes by chronic drug exposure - including increased risk for neurocognitive impairment -, targeted therapeutic strategies to reduce drug use in PLWH are lacking. CUD is characterized by difficulty in terminating drug use and high propensity to relapse after even protracted abstinence. This can be modeled in rodents through extinction learning (persistent drug seeking) and reinstatement (relapse to use) models. Extinction and reinstatement are mediated in part by projections to the nucleus accumbens shell (NAcS) from the infralimbic subregion of the medial prefrontal cortex (IL). HIV infection and chronic drug exposure have independent and interactive effects on the brain and behavior, including regulation of reward seeking. Our previous and preliminary findings identify impaired extinction learning in multiple mouse models of HIV infection (humanized mouse model with HIV-1 infection and wild-type mice with EcoHIV infection). We further observe increased cocaine-primed reinstatement in the EcoHIV model. These behavioral changes are accompanied by dysregulation of the IL and NAc. Thus, this proposal will apply in vivo electrophysiology, tract tracing, and circuit-specific chemogenetics to test the overarching hypothesis that EcoHIV infection impacts activity in glutamatergic projections from the IL to the NAcS and that modulation of these projections is sufficient to suppress drug seeking in animals with EcoHIV infection. We propose that alterations in these circuits resulting from infection impair cognitive control of behavior which promotes the maintenance of and susceptibility to relapse to cocaine seeking. Aim 1 will determine the effects of EcoHIV and/or ART on IL encoding of cocaine reward and seeking behavior using in vivo electrophysiology to track neuronal activity across behavior. This Aim will further assess interactive effects of EcoHIV and/or ART exposure with a history of cocaine administration on later neurocognitive performance. Aim 2 will investigate the ability of modulation of ILNAcS circuit activity to suppress cocaine reinstatement in EcoHIV-infected mice. This will be accomplished using chemogenetic modulation of the IL and of IL projections to the NAcS and through local administration of an mGluR2/3 agonist to the NAc. Aim 3 will test the effects of EcoHIV and/or ART on cocaine-associated alterations in activity within IL to NAc circuitry. This will be accomplished using multiplexed tract tracing and immunofluorescent labeling. This Aim will further identify EcoHIV and ART effects on glutamate receptor expression within the prefrontal cortex and NAC using western blot. Together, the results of these experiments will inform the mechanisms by which EcoHIV alters cocaine seeking and taking behavior and expand our understanding of the circuit-level consequences of EcoHIV infection which may support next- generation CUD and HAND therapeutic development for PLWH.

NIH Research Projects · FY 2026 · 2026-05

PROJECT SUMMARY People in recovery from alcohol use disorder (AUD) can experience a range of physiological and behavioral effects during withdrawal. These effects include aberrant food consumption, and increased alcohol drinking and seeking, which can increase stress and drive relapse. Ethanol dependence appears to dysregulate the glucagon- like peptide-1 (GLP-1) system, and clinical drugs that target this system are now being investigated for their ability to reduce food and alcohol intake. While GLP-1 is a gut peptide, it is also a neuropeptide, synthesized by neurons of the nucleus tractus solitarius (NTS), and its receptor (GLP-1R) is expressed throughout the brain. Several clinically approved GLP-1R agonist medications cross the blood brain-barrier, and work both peripherally and centrally. While these medications hold promise, they also induce undesirable side-effects, largely due to their effects in the hindbrain. Specific targeting of GLP-1Rs in regions of the forebrain could reduce the off-target effects of GLP-1 medications, while still suppressing aberrant food and alcohol consumption during AUD recovery. Thus, this proposal is designed to investigate the ability of GLP-1R in discrete CNS circuits to regulate binge-like food and ethanol intake and relapse during withdrawal. We will model ethanol dependence using chronic intermittent ethanol (CIE) exposure by vapor inhalation to test the overarching hypothesis that withdrawal from ethanol in the CIE model leads to physiological dysregulation, including dysregulation of the central GLP-1 system and associated disruption in reward taking and seeking. Thus, by increasing GLP-1R activity in the prefrontal cortex (PFC) and paraventricular nucleus of the thalamus (PVT), we can suppress CIE-induced behavioral dysregulation, including escalated binge-like eating and ethanol drinking, and reinstatement of seeking for palatable food and ethanol. Aim 1 is to examine the consequences of withdrawal from CIE on binge- like intake, and associated stress and metabolic system dysregulation. Aim 2 is to characterize the contribution of PFC and PVT circuit-specific GLP-1R signaling to dysregulated consumption of food and ethanol following withdrawal. Aim 3 is to characterize the contribution of PFC and PVT circuit-specific GLP-1R signaling to relapse- related appetitive behavior following withdrawal. To accomplish these aims, male and female mice will undergo CIE or Air exposure and withdrawal and be tested for: CIE effects on binge-like eating and stress-induced reinstatement of ethanol and palatable food seeking; effect of systemic GLP-1R and selective (PFC and PVT) GLP-1R pharmacological manipulation on palatable food and ethanol intake and stress-induced reinstatement; and the necessity of GLP-1R within discrete PFC and PVT circuits in regulating binge-like eating and ethanol seeking through circuit-specific knockdown of GLP-1R. Understanding the role of the forebrain GLP-1 system may aid with the implementation of novel therapeutics during alcohol recovery, to suppress both the development of new and relapse to disordered behavior, while limiting undesirable side effects.

NIH Research Projects · FY 2026 · 2026-04

PROJECT SUMMARY/ABSTRACT Autism is a neurodevelopmental disorder impacting 1 in 36 children in the US. Children with autism often experience multi-morbidity of other neurodevelopmental disorders (NDDs) and physical health outcomes like obesity and asthma at higher rates than typically developing peers. While prior work has observed associations between prenatal exposure to several classes of endocrine disrupting chemicals (EDCs) and autism, NDDs, obesity, and asthma, little is known regarding their associations with co-occurrence of these health outcomes. Phthalates and phenols are EDCs of particular concern, given their widespread occurrence in diet and personal care products, and strong potential to contribute to these outcomes in combination given shared mechanisms. Little work has considered how the sources of these chemicals may impact outcomes, limiting our ability to target exposure reduction strategies to optimize health for all children. I hypothesize that gestational exposure to phthalates and phenols will be associated with higher child health burdens and multi-morbidity in autism, and that patterns of maternal diet and personal care product use, as key exposure sources, contribute to differential chemical exposure among demographic subgroups and subsequent variability in child health outcomes across the population. In this proposal, I will use data from the Environmental Influences on Child Health Outcomes (ECHO) Program to address these gaps. ECHO is an NIH-funded consortium of longitudinal US-based cohort studies in which participants follow a common protocol and extant data is harmonized. In Aim 1, the K99 portion of this application, I will investigate how prenatal exposure to phthalates, phenols, and their mixtures drives phenotypic variability in autism and co-occurring NDDs, obesity, and asthma (n=4,250). In Aim 2, the R00 portion of this application, I will examine whether there are differences in measured biomarkers of these EDCs across the population according to diet and personal care product use source. Next, I will conduct mediation analyses to determine if demographic subgroups (e.g., rural versus urban dwelling) mediate associations between measured phthalate and phenol metabolites and exposure sources with child health outcomes (n=5,155). During the grant period, I will receive training in the autism phenotype, exposure science, and causal mediation analyses, guided by a mentorship team of experts in autism, epidemiology, and urban environmental health. Upon successful completion of the research and training included in this proposal, I will be well poised to develop and lead future projects focused on EDC exposure mitigation and interventions to reduce risk of child health outcomes related to gestational phthalate and phenol chemical exposure and their dietary and personal care product sources. This opportunity will prepare me well to achieve my goal of research independence.

NIH Research Projects · FY 2026 · 2026-04

Project Summary Drug use increases HIV risk and worsens health outcomes in people living with HIV (PLWH). While antiretrovirals are effective for both prevention – using pre-exposure prophylaxis (PrEP) – and for treatment – using antiretroviral therapy (ART) – drug use further impairs medication adherence. It is thus essential to develop strategies to enable people who use drugs to achieve abstinence and prevent relapse, which is expected to reduce HIV risk, burden, and infection. Progesterone and its metabolites regulate drug craving and immune function, making them potential therapeutic targets. However, PLWH and people who use drugs often experience menstrual cycle disruptions, and the impact of PrEP or ART on hormone regulation remains unclear. Understanding these interactions could reveal strategies to reduce drug-seeking behavior and to improve HIV treatment outcomes. In our preclinical work using the EcoHIV mouse model of HIV infection, we observe disrupted estrous cyclicity, altered cytokine expression, and increased risk for cocaine relapse-related behavior. We further observe that ART restores estrous cyclicity and partially reverses altered brain cytokine expression in EcoHIV-infected mice. However, it is unknown whether ART restores cycle regularity in cocaine-exposed, EcoHIV-infected mice or whether PrEP interacts with drug exposure to affect hormonal function. The medial preoptic area (mPOA) regulates both estrous cyclicity and cocaine-related behavior, and our findings suggest EcoHIV infection increases mPOA activation in cocaine-exposed females. Progesterone and its active metabolite, allopregnanolone, act on both neurons and astrocytes. Thus, modulation of mPOA astrocytic and neuronal activity may represent a novel target for reducing drug seeking and neuroimmune dysregulation among those at risk of or living with HIV. This proposal will test the overarching hypothesis that chronic drug exposure and EcoHIV infection interact with antiretrovirals to promote estrous cycle irregularity and cocaine reinstatement via dysregulation of the mPOA. Aim 1 will assess how PrEP and ART impact estrous cyclicity, ovarian reserve, mPOA cellular activity, and neuroimmune signaling following chronic cocaine exposure. Aim 2 will use chemogenetic tools to determine the role of mPOA discrete populations of astrocytes and neurons in cocaine reinstatement after PrEP or ART+EcoHIV. Aim 3 will evaluate whether allopregnanolone administration reduces cocaine reinstatement and alters neuroimmune signaling. Together, these Aims are to expected define the mPOA as a mediator of drug seeking and immune state following treatment with antiretrovirals, and further to identify hormonal strategies to suppress relapse in individuals taking PrEP or with virally suppressed HIV infection.

NIH Research Projects · FY 2026 · 2026-03

Epilepsy is a complex neurological disorder characterized by recurrent, unprovoked seizures affecting around 50 million people worldwide. There are over 30 marketed drugs to treat the symptoms of epilepsy, however, these drugs do not work in nearly a third of the patients leading to drug resistant epilepsy. In addition, there are various forms of genetic epilepsy and rare forms of epilepsy that do not respond to the existing drugs. Nearly 85 genes have been identified in genome wide association studies as causal for childhood and genetic epilepsy such as Dravet syndrome. The SLC1A2 encoding the Excitatory Amino acid transporter 2 or EAAT2 has been noted as a risk gene with at least three mutants in epilepsy patients and animal models have demonstrated that loss of EAAT2 induces neuronal hyperexcitability and recurrent epileptic seizures, while genetic or pharmacological upregulation of EAAT2 reduced epileptic seizures. EAAT2 is a glutamate transporter localized to the astrocytes and responsible for clearing >80% of glutamate from the synapse is downregulated in epilepsy leading to glutamate accumulation and excitotoxicity. In this study, we utilized the hybrid structure-based screening platform to design GTS467, a novel activator of EAAT2 to not only suppress seizures but to promote neuroprotection by restoring normal glutamate neurotransmission. GTS467 has good drug-like properties and high oral bioavailability in plasma and brain tissue was chosen as the lead candidate for in vivo studies at NINDS-epilepsy therapy screening program. GTS467 was tested in various murine models of epilepsy and results from the studies have shown that GTS467 not only reduces seizure burden but can also promote disease modification. In this proposal we aim to further optimize GTS467 (UG3 phase) and in IND enabling studies (UH3 phase) with a goal to deliver a clinical candidate as a disease modifying agent to treat acute and drug-resistant forms of epilepsy which is a significant unmet need.

NIH Research Projects · FY 2026 · 2026-03

Cocaine use disorder (CUD) is a highly prevalent in people living with HIV (PWH), and co-occurring HIV and CUD result in poorer clinical outcomes and more severe neurocognitive sequelae. Despite exacerbated risk for behavioral and cognitive deficits in PWH who use cocaine, there is limited understanding and an absence of targeted therapeutic strategies addressing the effects of CUD and HIV on the brain. Better definition of the interaction between cocaine use and HIV infection in the CNS is essential to address this knowledge gap. HIV and CUD both increase neuroinflammation via activation of inflammasomes, multiprotein complexes that regulate inflammation through production of the cytokines IL-1β and IL-18. NLRP3, the most widely studied inflammasome, is highly expressed in microglia, as well as other CNS myeloid cells. Cocaine exposure and HIV infection can both activate NLRP3. While processes regulating inflammasome activity are well-defined, the mechanisms by which HIV and cocaine affect them are not. Cocaine increases dopamine in the mesolimbic region. Increased dopamine appears to mediate the effects of cocaine effects on inflammasomes, as cocaine use upregulates NLRP3 expression and IL-1β in the mesolimbic region in vivo (when it increases dopamine levels), but not in microglia in vitro. HIV infection also disrupts dopamine reuptake and metabolism and increases inflammation in mesolimbic structures. This suggests that cocaine use and HIV infection interact via dopaminergic dysregulation, potentiating regional neuroinflammation and disrupting behaviors and cognitive processes defined by mesolimbic circuits. The mechanistic link between dopamine and inflammasomes is not clear, but mitochondrial dysregulation has been shown to regulate inflammasome activity in myeloid cells. Our preliminary data show that dopamine increases NLRP3 activity in human iPSC-derived microglia in vitro, and that in human macrophages, dopamine specifically enhances caspase expression and Gasdermin cleavage. In these human macrophages, dopamine also disrupts mitochondrial fission, and blocking the effects of dopamine on mitochondrial fission inhibits the dopamine-enhanced in inflammasome activity. We also show that HIV and cocaine interact to drive inflammation and disrupt reward-seeking behavior in vivo in EcoHIV-infected mice self- administering cocaine, which correlates with other studies showing that cocaine mediated inflammation impairs drug seeking behavior and cognitive function. Thus, we hypothesize that cocaine-mediated increases in dopamine potentiate inflammasome activation in microglia in the HIV-infected CNS by dysregulating mitochondria and enhancing neuroinflammation, which contributes to cognitive deficits and aberrant reward seeking. Our proposal addresses this hypothesis in in vitro, ex vivo and in vivo models at the single cell (Aim 1), circuit and behavioral (Aim 2) levels. This will generate of data from complementary human and rodent systems to overcome the limitations inherent in any single neuroHIV model and generate interconnected data sets correlating functional, and behavioral changes in response to HIV and cocaine use.

NIH Research Projects · FY 2026 · 2026-03

Project Summary HIV-1 associated neurocognitive disorders (HAND) affect 15 to 40% of people living with HIV (PWH), despite the use of anti-retroviral therapies (ART). Persistence of HAND in the presence of ART suggests that factors outside of viral replication contribute to neurocognitive impairment. The HIV-1 transactivator of transcription (Tat) is a neurotoxic viral protein that recapitulates cognitive impairment in the absence of viral replication and persists in virally suppressed PWH, likely generated from cellular reservoirs including microglia and astrocytes. Prior studies have separately shown that in the presence of Tat, the microglial transporter xCT is upregulated – increasing extracellular glutamate – and astrocytic EAAT2 is downregulated. Nonetheless, these mechanisms have been demonstrated with varying techniques and agnostic to how Tat expression within cellular reservoirs affects Tat-mediated toxicity and cognitive symptoms of HAND. Thus, we hypothesize that Tat expressed independently from microglia and astrocytes promotes aberrant glutamatergic neurotransmission causing NMDAR dependent excitotoxicity in the prefrontal cortex and cognitive impairment in HAND. In this proposal, we will use lentiviral transduction to model Tat expression from microglia and astrocytes, as the HIV-1 reservoirs of the CNS. We will then assess glutamate toxicity in this model in vitro and in vivo, by evaluating 1) EAAT2 or xCT expression and markers of gliosis [GFAP, Iba1], 2) extracellular glutamate levels in culture supernatants, 3) neuronal NMDA receptor expression and signaling via calcium levels. These outcomes will provide an understanding of how microglia and astrocytes respond to Tat and influence NMDAR- mediated neurotoxicity. To understand how these cell types drive toxicity and cognitive impairment in turn, lentivirus will be injected intracerebrally to prefrontal cortex of Sprague-Dawley rats. Two weeks after surgery, we will assess behavioral and molecular outcomes; or calcium levels in neurons and astrocytes. Animals will undergo testing in novel object recognition, spatial object recognition, and attentional set-shifting tasks, to assess learning and memory and cognitive flexibility. Brain tissue will then be assessed by immunoblot, RT- PCR, and calcium imaging to correlate cognitive impairments with molecular mechanisms; further paralleling the in vitro results to contextualize the contribution of Tat-mediated mechanisms to cognitive impairment. This study will elucidate the role of microglia and astrocytes as separate sources of Tat for their effects on glutamatergic neurotransmission and PFC-mediated cognitive functions. The proposal addresses a significant gap in the literature on microglia as the primary viral reservoir generating Tat, while accounting for the distinct impacts of each cellular reservoir on Tat-mediated glutamate toxicity and cognitive impairment. This will prompt future study into the microglial reservoir, and glutamatergic disease mechanisms that could be refined as therapeutic targets that are clinically relevant to neuropathology in PWH.

NIH Research Projects · FY 2026 · 2026-03

ABSTRACT After spinal cord injury (SCI), spasticity emerges in approximately 75% of individuals. Spasticity clinically manifests as hyperreflexia, co-contraction of antagonistic muscles, muscle spasms, and clonus which are a result of disrupted spinal excitability and inhibition after SCI. Current available pharmacological treatments for spasticity are limited and often have severe side effects and dampen overall motor output. Transcutaneous spinal cord stimulation (tSCS) has recently emerged as a promising clinical treatment for spasticity, however its mechanisms of action remain elusive. Our previous work suggests that KCC2, a chloride extruder, plays a critical role in decreasing spasticity following rehabilitation after SCI. KCC2 is a chloride extruder responsible for helping maintain low intracellular chloride in neurons to ensure proper hyperpolarizing GABAergic signaling. However, following SCI, KCC2 protein levels are decreased, disrupting chloride homeostasis and increasing motoneuronal hyperexcitability. Our preliminary data suggests that, similarly to activity-based therapies, tSCS can both increase protein levels of motoneuronal membrane-bound (active) KCC2 and decrease spasticity. However, it remains unknown whether this is coincidential or if there is a causal effect. In Aim 1, we will determine if tSCS improves spasticity after SCI by genetically increasing active motoneuronal KCC2 or knocking-down motoneuronal KCC2. We hypothesize that the upregulation of motoneuronal KCC2 via tSCS underlies improvements in spasticity after SCI. While human and computational studies have provided indirect evidence that tSCS activates large, myelinated primary afferents by quantifying motor responses, direct evidence is lacking. Additional studies are needed to further clarify how the activation of primary afferents through activity and stimulation-based therapies impacts functional recovery. In Aim 2, we will assess the role of VGlut1+ afferent activation on motor output, hyperreflexia, and KCC2 protein abundance and localization to assess the contribution of primary afferent activation during tSCS to improvements in spasticity. We hypothesize that tSCS activates vGlut1 afferents to produce TEPs, decrease hyperreflexia, and increase KCC2 after SCI to improve spasticity. Overall, we hypothesize that tSCS improves spasticity by increasing the amount of active, membrane-bound KCC2 in motoneurons following activation of VGluT1+ afferents.

NIH Research Projects · FY 2026 · 2026-03

Autistic adults universally face communication difficulties, yet no multi-dimensional measure of communication has been specifically validated in this population. The absence of such a measure is a barrier to advancing our understanding of communication strengths and challenges in autism – and how they may predict outcomes such as employment, health, and relationships. The objective of the current application is to develop and validate a comprehensive communication measure for autistic adults, using COSMIN standards for measure design. The project will use an iterative, mixed-methods, Community-Based Participatory Research (CBPR) approach, leveraging the PI’s existing team of autistic community partners as co-researchers in all study phases. The rationale for this approach is that research on marginalized populations should be conducted collaboratively with those affected, to ensure ethical, impactful, and scientifically sound processes and outcomes. The measure developed through this study, the C-SCAN (Communication Strengths, Challenges, and Nuances), will be grounded in both the established experimental literature on communication differences in autism, and the emerging literature on autistic adults’ internal experiences of communication. The C-SCAN will generate profiles of communication abilities and challenges, and will be designed for maximum accessibility to ensure valid data from the target population. Critically, the C-SCAN will be inclusive of the entire autism spectrum, accomplished by creating two versions: one for autistic adults to complete as a self-report measure (Aim 1), and one for proxy reporters (i.e., support people who will report on behalf of autistic adults who cannot complete the measure, even with support; Aim 2). Both instruments will be created through five rounds of a CBPR-Nested Delphi process involving (1) autistic adults or proxy reporters, as appropriate to the instrument version, (2) communication scientists, and (3) other professionals, such as clinicians, attorneys, employers, or direct support personnel. The research team, in collaboration with community partners, will draft instructions, response options, and item formatting based on best practices in accessible instrument design. For each instrument, we will test and refine content validity through an iterative series of cognitive interviews with a diverse sample of autistic adults and support people. Successful completion of the proposed project will result in two distinct versions of a multi-dimensional, community-driven measure of communication skills and experiences tailored for use by autistic adults. This contribution lays the groundwork for validating and disseminating a first-of-its-kind measure of a core feature of autism (communication differences) with robust links to outcomes, addressing community interests and needs. This innovative approach to instrument development in communication disorders research is expected to advance communication measurement, accelerating large-scale autism phenotyping research, outcomes research, and intervention planning.

NIH Research Projects · FY 2026 · 2026-03

Project Summary/Abstract: Opioid use disorder is a major public health crisis with widespread socioeconomic consequences. Most drugs of abuse, including opioids, increase dopamine levels in the nucleus accumbens, and disruption of nucleus accumbens dopamine signaling reduces opioid seeking behavior. The canonical mechanism through which opioids increase dopamine is through actions on inhibitory mu-opioid receptors located on midbrain GABA interneurons of the rostromedial tegmental nucleus and ventral tegmental area. Under basal conditions, midbrain GABA interneurons exert an inhibitory influence on dopamine neuron activity in the ventral tegmental area. Activation of mu-opioid receptors decreases midbrain GABA interneuron activity leading to disinhibition of ventral tegmental area dopamine neurons and subsequent increases in nucleus accumbens dopamine. We recently demonstrated a novel mechanism through which opioids increase dopamine levels in the nucleus accumbens. Preliminary observations in isolated nucleus accumbens brain slices, which do not include the midbrain, indicate that the opioid oxycodone increases evoked dopamine by reducing dopamine uptake rate. Given that there are no mu-opioid receptors on dopamine terminals in the nucleus accumbens, the effects of opioids on dopamine transmission must involve mu-opioid receptors on other neuron types. We thus propose that oxycodone enhances dopamine signals in the nucleus accumbens through actions on a putative local circuit. Consistent with this, prior electrophysiological and molecular evidence suggests that mu-opioid receptors are expressed on GABA and cholinergic interneurons in the nucleus accumbens, both of which are known to regulate nucleus accumbens dopamine transmission through actions on dopamine terminals. However, it remains unclear to what extent GABA and/or cholinergic interneurons modulate dopamine uptake and whether opioids exert their effects on dopamine uptake through local mu-opioid receptor actions on these interneuron populations. The proposed studies will define the anatomical, pharmacological, and local circuit mechanisms by which oxycodone reduces dopamine uptake in the nucleus accumbens. We will first quantify mu-opioid receptor expression on GABA and cholinergic interneurons in the nucleus accumbens before determining if oxycodone’s influence on nucleus accumbens dopamine signaling requires changes in GABA and/or acetylcholine receptor activity. Next, we will knock down mu-opioid receptors selectively on GABA or cholinergic interneurons, individually and in combination, to determine if the local effects of opioids on dopamine transmission in the nucleus accumbens depend on mu-opioid receptors on these interneuron populations. Completion of the proposed studies will reveal a novel framework for understanding opioid-induced dopamine modulation, will provide molecular tools critical for defining the role of this novel mechanism in opioid reinforcement, and will ultimately inform the development of alternative treatments for opioid use disorders.

NIH Research Projects · FY 2026 · 2026-02

Neurologic complications remain prevalent in nearly 50% of people with HIV (PWH) and persist despite viral suppression with antiretroviral therapy (ART). Though the exact processes mediating HIV neuropathogenesis are not well understood, co-morbidities such as substance use disorders (SUD), which are higher in PWH compared to the general population, exacerbate neuropathogenesis of HIV and worsen outcomes. Multiple substances of misuse are reported to increase HIV replication, induce inflammatory signaling, and amplify neurodegenerative phenotypes. Thus, there is a significant need to understand the intersection between SUD and NeuroHIV to improve longitudinal care and inform the public. The overlapping effects of distinct substances of misuse on HIV pathogenesis in the CNS suggest that a common pathway may be involved through presently undefined mechanisms. All addictive substances increase extracellular dopamine in the central nervous system (CNS), which signals neurons and other nearby glial cells expressing dopamine receptors. Our lab has shown that myeloid cells such as macrophages and microglia, which are major HIV reservoirs in the brain, express dopamine receptors more D1-like receptors (D1 and D5) than D2-like receptors (D2, D3, D4). Treatment of macrophages and microglia with micromolar concentrations of dopamine increased pro-inflammatory signaling, increased viral entry, and potentiated viral secretion in vitro. We recently found that a higher D1-like to D2-like ratio is associated with a more pro-inflammatory response in microglia. Further, we showed that dopamine increases activation of nuclear factor-kappa B (NF-κB) in macrophages, and that inhibition of NF-κB can block the pro-inflammatory effects of dopamine. Together, these data suggest that dopamine-enriched brain regions, such as the cortex and striatum, may be especially vulnerable to HIV and neuroinflammation in PWH and co-morbid addiction through the action of dopamine on microglia. Therefore, the central hypothesis of this proposal is that dopamine D1-like receptor activation promotes HIV infection and NF-κB-mediated inflammation in microglia to worsen neurodegeneration. This hypothesis will be tested using human induced pluripotent stem cell (iPSC)-derived brain human cortical assembloids and several orthogonal assays to explore the dopamine-mediated pathways that modulate HIV neuroimmune pathogenesis. We will use pharmacologic activation of dopamine receptors in cortical assembloids to assess viral kinetics (Aim 1), neuroinflammation (Aim 2), and neuronal degeneration of synapses and dendrites (Aim 3). Together, these studies will significantly advance our understanding of dopamine as an immunomodulatory signaling molecule in the context of substance use and HIV, as well as expand the approaches to studying neuroimmune pharmacology using human micro-physiological systems.

NIH Research Projects · FY 2026 · 2026-02

PROJECT SUMMARY Cocaine use disorder (CUD) is highly comorbid in people with HIV (PWH) and can accelerate infection, alter neuropathology, and exacerbate cognitive decline despite antiretroviral therapy (ART). Many of these effects are due to the infection and dysregulation of CNS-associated myeloid cells, especially microglia, which comprise a significant reservoir in this compartment. However, the precise mechanisms by which cocaine (Coc) dysregulates microglia to enhance HIV infection are unclear, partly due to the lack of translationally relevant human microglial models suitable for mechanistic evaluation of Coc-mediated changes in viral dynamics. Classically, Coc has been thought to act by blocking dopamine transporter (DAT) activity, exposing microglia to aberrantly high dopamine concentrations. Our data show that dopamine can increase HIV infection and inflammation in microglia and other myeloid cells. However, recent data show that Coc has other mechanisms of action beyond the modulation of dopaminergic tone, involving the ER protein sigma1 (σ1), which has diverse cellular functions including the modulation of cellular stress pathways such as the unfolded protein response (UPR). Viruses, including HIV, can exploit the UPR to amplify stress-induced protein production in the host cell, enhancing viral replication. Our preliminary studies indicate that Coc’s effects on σ1 may drive a Coc-mediated increase in HIV infection in microglia, potentially through increased stress response and independent of dopamine’s effects. My preliminary data show that both Coc and σ1 agonists increase HIV replication in human inducible pluripotent stem cell (iPSC)-derived microglia (iMg). These effects are blocked by σ1 antagonism but not by inhibition of DAT or dopamine receptors. We also show increased σ1 protein expression and recruitment to the ER/nuclear envelope space in HIV-infected iMg treated with Coc, and preliminary single-cell RNAseq data suggest changes in the UPR. Therefore, we hypothesize that Coc-mediated activation of σ1 increases HIV infection of microglia via activation of the UPR. In Aim 1, we will test the involvement of σ1 in driving Coc-mediated changes in HIV infection of iMg using pharmacological and genetic modulation, and we will also confirm the absence of dopaminergic involvement. We will assess changes in viral dynamics using AlphaLISA and immunofluorescence (IF) high-content imaging. In Aim 2, we will test the hypothesis that Coc induces greater σ1 activity in the presence of HIV infection utilizing confocal and high-content IF imaging of σ1 subcellular localization in cellular compartments like the nuclear envelope, ER, and mitochondria-associated ER membrane. Movement of σ1 to these compartments is a feature of σ1 activation. In Aim 3, we will use single-cell RNAseq to test the hypothesis that Coc-induced σ1 activity drives increased HIV infection in iMg via upregulation of UPR genes. The results from these experiments will not only define novel interactions between HIV and σ1 that could reveal new antiretroviral targets but will also broadly inform on the role of σ1 in microglia and potentially identify biomarkers for prevention strategies against CUD and its associated comorbid diseases.

NIH Research Projects · FY 2026 · 2026-02

Extreme weather events pose major risks for population health and mortality, particularly for incarcerated people who have limited control over their thermal environments. Several aspects of the prison built environment (such as overcrowding, insufficient heating or air-conditioning, and heat-retaining building materials) likely worsen extreme temperature exposure, yet there has been no comprehensive investigation of the health consequences of extreme temperature exposure inside US prisons. Research on non-institutionalized populations has established extreme heat and cold temperature exposures as acute contributors to cardiovascular and respiratory disease mortality, which are leading causes of death among the 1.2 million people imprisoned in the U.S. (and among the leading causes of death in incarcerated people over the age of 55, the fastest growing cohort in U.S. prisons today). This project’s overall objective is to assess extreme indoor prison temperatures in relation to mortality among incarcerated adults in the U.S. and identify prison conditions and policies that prevent these harms. Aim 1 will use state-of-the-art building science methods and leverage a unique database of prison conditions to develop the first estimates of daily indoor temperatures for facilities in the 20 largest state prison systems, including over 600 prisons and 800,000 imprisoned adults, representing over three quarters of the imprisoned adult population. Indoor temperature and humidity estimates and prison policy and conditions data will be linked with the latest data from Mortality in Correctional Institutions to examine associations with excess all-cause cardiovascular and respiratory disease mortality in prisons. Aim 2 will evaluate prison overcrowding and lack of air-conditioning as factors that may elevate risk for temperature-related mortality. Aim 3 will apply legal epidemiologic methods to develop a comprehensive database of temperature safety strategies and examine relationships with temperature-related mortality in prisons.

NSF Awards · FY 2025 · 2025-10

The challenges facing society today and in the near future are inherently complex systems problems. For example, improving transportation in cities or managing the growth of an international company both involve complex systems. The ability to recognize interactions and optimize connections between components in a system is called systems thinking. This type of thinking is vital for innovation and necessary for humanity’s longer-term survival. However, systems thinking is not intuitive for many people, and it can require significant mental effort. Most engineers benefit from the formal instruction provided in their undergraduate program. There are numerous methods to teach students about systems thinking but, unfortunately, assessing the effectiveness of these methods is a challenge. Assessment typically focuses on what students are able to produce rather than the mental effort required to produce it. Measuring mental effort is important because if mental effort can be measured and minimized, systems thinking is more likely to be adopted by students when they experience a real-world context. This research will test an approach to help students--more quickly and with less mental effort--solve complex systems problems using systems thinking. The research tests the effectiveness of priming students to think about the connections and interactions between components in a system using concept maps, a type of conceptual diagram to depict relationships within a system. This project tests the effects of concept maps to help students solve complex problems in engineering. The project will not only evaluate student solutions but measure their mental effort using a brain imaging technique. The expectation is that concept mapping makes complex systems problems mentally easier to solve, and this is measured via patterns of activation in their brain. Priming students for systems thinking with concept maps holds the potential for adoption across many college programs because of the minimal adjustments needed in teaching and the possibility of widespread application of concept maps in engineering. The project will use concept maps to prime students to think about the complex and dynamic relationships in engineering problems. Measurement of students’ brain activation will provide new data about the effects of this approach to help aid engineering students to solve complex engineering problems. Three cohorts of undergraduate engineering students will receive either multiple, single, or no concept map priming intervention. Assessment of students’ solutions to subsequent engineering systems problems will be correlated with patterns of brain activation. Brain activation will be measured using a non-intrusive technique called functional near infrared spectroscopy. Students will repeat the experiment to measure the effects of priming over time. The proposed research will extend current knowledge by measuring how changes in brain function persist, and how repeated educational priming interventions affect students’ ability to solve complex engineering problems. The results will offer a new type of evidentiary support for cognitive load theory in engineering education by demonstrating how priming students in ways that use specific regions and patterns of activation in their brain reduces subsequent cognitive effort to solve complex engineering problems. The research findings will be translated into short research briefs for college instructors to implement in their classroom. The project will also offer annual training in the brain imaging technique used in this project at engineering education conference workshops and a summer program for faculty and 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 2025 · 2025-10

Colleges and universities across the country use active learning to enhance student understanding of biology content knowledge. Active learning is both a style of teaching and way of learning that encourages students to engage with their instructors and peers to solve problems, explore ideas, and apply concepts to real-world settings. Studies have shown that active learning is more effective at improving students’ understanding of core concepts across STEM fields when compared to traditional lecture-based instruction. While there has been widespread adoption of active learning, little is known about the specific mechanisms that contribute to its effectiveness. The importance of this project is that it intends to define instructor and student behaviors and interactions across biology active learning classrooms and how these aspects of the course learning environment shape students’ understanding of biology content. Using video, survey, and interview data from a national sample of biology classrooms, the significance of this research is that it could result in practical guidance for instructors on how to support active learning in their classrooms This project goals include the identification of latent behavioral and social characteristics of biology active learning environments and how they impact students’ understanding of core biology concepts. In Aim One, course video data collected from a national sample of large introductory biology courses with various learning instructional models can be used to identify latent profiles of instructor and student behaviors in active learning environments. In Aim Two, social network surveys and concept inventories collected from students enrolled in the biology courses are intended to help describe the structure of classroom social networks across the latent profiles identified in Aim One. In Aim Three, semi-structured interviews conducted with students across varying network positions can lead to understanding how students perceive their roles, the resources exchanged, and the norms shaping student engagement during active learning. Social learning theories, social network analysis, machine learning, and a dual coding approach should lead to practical insights and inform strategies to foster student engagement and improve learning outcomes where active learning is used. An additional goal of the project is to support the PI’s development in advanced STEM education research methods, teaching, and mentoring. The project is funded by the National Science Foundation’s STEM Education Individual Postdoctoral Fellowship Program, which provides funding and professional development support for early-career scholars pursuing postdoctoral training in 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.

NIH Research Projects · FY 2025 · 2025-09

ABSTRACT Multiple factors contribute to the development of autism spectrum disorder (ASD), a developmental condition with early onset and heterogeneous phenotype. Prenatal diet is one of the few factors that has been associated with reductions in risk of ASD, and emerging evidence also suggests certain nutrients may mitigate the effects of other environmental exposures. At the same time, packaged and highly processed foods represent a major source of exposure to classes of chemicals linked with adverse neurodevelopment. The balance of risks and benefits in the diet, and effects on ASD, particularly within the context of other common risk factors, has not been well studied. The overarching goal of this project is to determine the role of diet and its complex interactions with other exposures in the development and presentation of autism spectrum disorder (ASD). This project will use existing data from up to 10,000 mother-child participants from the Environmental influences on Child Health Outcomes (ECHO) consortium, a large US program initiated with over 60 cohorts following a common protocol to study child health from gestation to adulthood. We address key gaps in the field under 3 related aims. 1) Examine complex interactions of prenatal diet and exposure to common chemicals on ASD. We focus on chemical exposures with diet as a major source and in common use, including pesticides, phthalates, and phenols, to better understand risks within the diet. We will first examine independent effects of under-studied but highly consumed “high burden foods” on ASD and related traits, and next use advanced mixture models to capture interactions between nutrients and measured levels of chemicals, and address potential mitigation of chemical exposure effects across sources by healthy components of the diet. We will utilize existing metabolomics data from prenatal measurements, which capture the biological effects of exposures, to determine pathways that may link these factors to ASD and bolster evidence for mechanisms that underlie associations. Next, we expand the consideration of the role of diet to: 2). Examine multi-exposure effects on ASD to determine key players in the prenatal exposome. Building from our prior work in ECHO, we will examine the ability of prenatal dietary factors to modify the effects of another common exposure rising in prevalence in the US in parallel with ASD: maternal metabolic conditions during pregnancy (which include obesity, gestational diabetes, and gestational hypertension). We will then use advanced data science approaches to determine how the wider set of prenatal risk factors across environmental, medical and lifestyle factors contributes to the gestational “exposome,” (the entirety of exposures), to influence ASD risk, and uncover key factors. As in aim 1, these analyses will be followed by mechanistic work using metabolomics data to determine key pathways underlying identified signals. As secondary outcomes across Aims 1 and 2, we will examine risk of not just ASD itself, but also its highly co-occurring conditions and ASD-related traits, to advance understanding of contributors to variability in ASD. Finally, we will make use of the large numbers in ECHO with information on childhood exposures to: 3). Determine dietary risks and deficiencies in children with ASD and examine how these contribute to phenotypic variability. These analyses will determine if autistic children experience worse nutrition than children without ASD, including higher intake of high burden foods, and assess whether these dietary differences contribute to symptom severity or risk of comorbidities, accounting for prenatal maternal exposures. Completion of these aims will aid discovery of novel interactions and exposures whose effects may be lessened or made worse by different aspects of diet. Ultimately, findings from this project will advance understanding of the role of diet in ASD and the broader ASD exposome, and present opportunities for interventions with the potential to reduce risks and improve the lives of autistic individuals.

NIH Research Projects · FY 2025 · 2025-09

Housing is closely linked to health outcomes, and stable housing is essential for overall health and wellbeing. Housing provides continuity in home environments, access to social support, reduced family stress, and improved long-term outcomes. For adults with chronic health conditions, housing stability is even more crucial due to heightened need for consistent access to services and support. Few studies have examined how housing influences access to appropriate care for people with chronic health conditions. Federal housing assistance from the US Department of Housing and Urban Development (HUD) plays a vital role in providing affordable housing options for families with limited financial means, including a subset of the 150 million Americans who live with at least one chronic health condition. HUD assistance includes programs like housing choice vouchers, multi-family housing, and public housing. Yet there is limited understanding of how newly receiving HUD assistance as an intervention to address housing instability impacts access to and utilization of appropriate treatment regimens for adults with chronic health conditions. Factors such as housing and economic stability, insurance enrollment factors, community characteristics, and individual attributes may further influence appropriate care for chronic health conditions and outcomes for these adults. Medicaid, as the largest public insurer in the US, and HUD, as the primary housing assistance provider, both play critical roles in serving impoverished adults with chronic health conditions. However, little national data exists on the connection between the two programs, making it difficult to identify ways to improve efficiency and effectiveness. The proposed research aims to address this gap by linking Medicaid and HUD datasets to each other and to additional sources of data on community factors, to examine the relationship between newly gained housing assistance and appropriate health service use and outcomes for a large national cohort of adults with chronic health conditions. This study will be the first to examine appropriate health care and housing outcomes of adults with key chronic conditions (including asthma, coronary heart disease, depression, and diabetes) who newly receive HUD assistance and how individual and community factors influence these outcomes. In addition to quantitative analyses, qualitative interviews with policymakers and advocates working in Medicaid, housing, and health will help illuminate connections between housing and appropriate health care. By producing a robust evidence base that highlights both the impact of housing assistance and mechanisms through which it can be optimized, this study will inform policy and public health strategies to improve housing stability and health care access for people with chronic health conditions and lay the groundwork for coordinated, systems-level interventions that are immediately actionable, to foster improved health outcomes for adults with chronic conditions.

NIH Research Projects · FY 2025 · 2025-09

Project Abstract: The mortality rate from influenza viral (IV) infection is highest in infants less than age six months, currently an age group not eligible for the available influenza vaccine, but the mechanisms for this clinical observation are not well understood. Vulnerability to respiratory viruses during infancy is likely manifested by an immature lung and immune system. To understand age-specific differences in hematopoietic and epithelial cell function at the air-blood interface in the developing lung, an age-appropriate pre-clinical neonatal murine IV infection model is employed. Previously, we demonstrated that murine neonates are exceptionally susceptible to IV infection. Differences in the dominant airway microbial communities in these first few months of life have been linked to susceptibility to respiratory infections. Commensal-derived signals establish an activation threshold of the innate immune system required for optimal antiviral immunity. Therefore, modulating early airway microbial communities presents a potential therapeutic strategy to prevent or ameliorate respiratory tract infections. Recently, we demonstrated that intratracheal administration of Lactobacillus rhamnosus (LGG), a probiotic, prior to IV infection improved neonatal survival. However, the specific mechanisms by which LGG acts, the cells on which it exerts the most effect and the dominant pattern recognition receptors it modulates remains to be determined. The goal of this project is to determine mechanisms by which these LGG-derived signals impact the function of 1. pulmonary epithelial cells, the target of IV infection, and 2. innate immune cells, such as alveolar macrophages (AMs), sentinel tissue-resident immune cells which drive immune cell recruitment, and neutrophils, which are pathologic in the developing lung during respiratory viral infection. We have identified an antimicrobial peptide as a potential signaling mediator between infected epithelial cells and AMs. Our recently published work demonstrates that murine neonates deficient in Catheliciden-related Antimicrobial Peptide (CRAMP) are protected during IV infection. Importantly, LGG pretreatment decreases CRAMP production. Here, we seek to investigate the pathogenic role of CRAMP as a signaling mediator to orchestrate the initial response to IV. The overarching hypothesis of this proposal is that in IV-infected neonates, LGG reduces CRAMP production by epithelial cells, which diminishes CRAMP-mediated alveolar macrophage (AM) activation through Toll-like receptor 2 (TLR2) and subsequent neutrophil chemoattractant production. Neutrophil infiltration is a potent driver of mortality. To test our hypothesis, we will: (1) Define IV tropism and the primary cell source of CRAMP in LGG treated and untreated IV-infected murine neonates and adults using single cell sequencing; (2) Evaluate the age- specific role of LGG and CRAMP-dependent TLR2 signaling in key innate immune cell production of neutrophil chemoattractants; and (3) Determine if CRAMP acts directly on neutrophils to increase oxidative stress. Our studies in an innovative neonatal pre-clinical animal IV model will bring forth new understanding of infant mucosal immunity to develop targeted therapeutics for the infant population.

NSF Awards · FY 2025 · 2025-09

Non-technical summary: This award supports research to accelerate the making of new inorganic materials, which are vital components of next-generation energy, optoelectronic, and biomedical devices. Often new materials are created through a trial-and-error approach that depends on the intuition of the researcher, but this is inefficient and wasteful of both materials and time. With support from the Solid State and Materials Chemistry program and the Ceramics program, both in the Division of Materials Research, the researchers predict how to make new inorganic materials using computational materials science and validate these predictions in the laboratory, setting up a feedback loop to further improve future predictions. Computational predictions rely on the understanding of material thermodynamic properties, and laboratory experiments use real time characterization to monitor how the material is made. The feedback loop is employed to make perovskite oxynitrides, which are inorganic materials with highly tunable properties. The impact of the starting materials, also known as precursors, from which perovskite oxynitride products form is being investigated, and formation pathway maps to perovskite oxynitrides from varied precursors and reaction conditions are being created. Through this project, the team of researchers bridges the gap between computer-aided materials design and practical synthesis in the laboratory, which benefits society by accelerating the creation of inorganic materials with useful functional properties. This award also supports activities to expose a broad age range of students to inorganic materials science through low-cost, hands-on science kits (grades K-12) and focused research experiences for undergraduate students at Drexel University. Technical summary: With support from the Solid State and Materials Chemistry program and the Ceramics program, both in the Division of Materials Research, this award supports research focused on clarifying the synthesizability of solid-state inorganic materials relevant for applications in energy generation and storage, catalysis, and optoelectronic devices. The research co-leverages computation and experiment in an integrated feedback loop to accelerate inorganic material synthesis and reduce waste to scale-up. Specifically, thermodynamic modelling employing the CALculation of PHAse Diagram (CALPHAD) approach provides synthetic guideposts, while ex situ and in situ solid-state reactions unveil reaction pathways and validate and improve computational predictions. The materials of interest are mixed anion perovskite oxynitrides which possess highly tunable optical and electronic properties sensitive to the choice of cations, smaller electronegativity of nitrogen with respect to oxygen, and anion ordering. These materials have been synthesized sparingly experimentally, and many more are predicted to be stable or metastable. The central hypothesis is that informed choice of precursor and precursor reactivity can minimize the nucleation barrier for synthesis of these materials, with high reactivities and low interfacial energies favoring the formation of metastable perovskite oxynitrides. To showcase the role of precursors, reaction conditions, and kinetics on formation of these materials, multi-variable phase space diagrams that capture and map precursor to intermediate to product are being created. This award also supports educational and outreach activities that are informed by the research direction, including incorporating new inquiry-based science activities on inorganic materials synthesis into low-cost kits for K-12 students and broadening the participation of undergraduate researchers in informed materials synthesis at Drexel University. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-09

Nontechnical Description This project will focus on developing new materials that can be customized to control how light behaves, thereby advancing optical technologies for applications in communication, information technology, energy, and sensing. Conventional optical materials are not easily tuned or adapted, which limits their use in reconfigurable devices. This research will utilize MXenes, a family of two-dimensional structures engineered to reflect, absorb, or guide light in precise ways. By combining advanced material-making, experimental testing, and computer modeling, the team will establish a novel design framework for producing customizable materials with exceptional optical properties. The framework will also include new digital tools for predicting materials behavior and minimizing trial-and-error during development. In addition to the research, the project will offer interdisciplinary training for graduate and undergraduate students and contribute to public science education by developing open-access learning resources through nanoHUB.org. These initiatives will help prepare a new generation of researchers in the field of advanced photonic materials. Technical Description The project aims to develop optical materials that are customizable, dynamically tunable, scalable, and reconfigurable while exhibiting advanced light-matter interactions, such as plasmonic behavior, epsilon-near-zero (ENZ) response, hyperbolic dispersion, and strong nonlinear effects. Conventional photonic materials do not provide sufficient control or adaptability for emerging applications in photonics and optoelectronics. To tackle this challenge, the team will integrate synthesis, characterization, and computational modeling to understand and engineer how the composition, structure, and arrangement of MXenes impact their highly versatile optical and electronic properties. To create a predictive materials-by-design framework, the research will proceed with three objectives: (1) synthesize different MXene films and perform structural and optical characterization using tools such as ellipsometry, spectroscopy, and microscopy to generate a digital twin model, a physics-informed framework capable of predicting optical properties; (2) explore ordered and disordered hybrid MXene composites to achieve ENZ behavior and hyperbolic dispersion, using quantum emitters as probes for optical anisotropy; and (3) investigate all-optical and externally driven modulation through nonlinear optical measurements such as Z-scan and second-harmonic generation, incorporating these results into an expanded nonlinear digital twin. This combination of predictive modeling, experimental feedback, and dynamic control will enable the rational design of MXene-based materials for advanced optical applications. The outcomes will deepen understanding of structure-property relationships in 2D materials and establish scalable strategies for reconfigurable photonics. 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.