University Of Florida

NIH Research Projects · FY 2025 · 2024-09

ABSTRACT: Background-subtracted fast-scan cyclic voltammetry (FSCV) is unrivaled in its ability to monitor neurochemical dynamics. This approach permits highly localized analysis of multi-neurochemical release and reuptake events at single cells, in tissue slices, and in intact animal subjects over the course of seconds, hours, weeks, or months. However, it is used almost exclusively for quantification of dopamine (DA) over short (< 2 minute) time windows, and exploited almost entirely by users with formal training in voltammetry. This under-utilization is stunning, because FSCV is attractive in almost any neurochemical monitoring application where cellular-scale spatial resolution, speed, and accuracy are essential. The transfer of electrons across the electrode/solution interface is the source of the signal and it is fundamentally dictated by the physical properties of that interface at any given moment, which change (a lot!) over the course of an experiment. This can confound data interpretation, particularly when experimental conditions also change in an uncontrolled fashion. This is the biggest factor that has restricted the broad application of this technique to additional molecules and user groups. To address these issues, we plan to use standard FSCV instrumentation to continuously monitor the physical properties of the dynamic carbon/solution interface using electrochemical impedance spectroscopy during fast voltammetric experiments, and to directly map this information onto shifts in electrochemical performance, in real time. This will enable reliable prediction of - and thus correction for - shifts in voltammetric performance that develop as experimental conditions change. The first goal is to enable continuous mapping of impedance information onto electrochemical performance. This will provide a predictive framework for correcting impedance-related shifts in electrode performance when the system impedance is known. The second goal is to develop, evaluate, and optimize an automated feedback mechanism to account for distortions to the voltammetric data that result from uncompensated shifts in system impedance. This will simplify interpretation of complex FSCV data, improving quality and enabling multi-transmitter monitoring. Performance will be validated by recording the effects of cocaine on coordinated glutamate and DA signaling in striatum, which has been implicated in cocaine abuse. The project is innovative, because it will shift researchers from traditional methods of calibration that use static characterization factors acquired in irrelevant recording environments, to an entirely new way of thinking about signal standardization that accounts for ongoing shifts in system impedance during the course of the experiment. It is significant, because it minimizes distortion of complex FSCV data, enabling measurements of coordinated neurochemical signaling and providing for improved quantification, especially in instances where a traditional approach to calibration is precluded. Ultimately, this work will enable countless new neurochemical investigations.

NIH Research Projects · FY 2025 · 2024-09

Project Summary Alcohol Use Disorder (AUD) is characterized by attenuated capacities to recognize and interpret the emotional states of others. Extant cross-sectional studies have described these deficits and confirm their association with interpersonal difficulties. However, no current data adequately inform the capacity for change in emotion processing during early abstinence, the putative cognitive/affective mechanisms underlying such change, or resultant impacts on treatment adherence, relapse, or other clinically-relevant recovery outcomes. The proposed project addresses these three critical gaps. The fundamental approach involves longitudinal assessment of emotion processing from treatment initiation to discharge (~3 months). We will recruit recently-abstinent individuals in residential treatment for AUD. We will also recruit a matched sample of community controls, facilitating characterization of practice effects. In addition to longitudinal collection of emotion processing performance, indexed via multimodal computerized assessment tasks, we will also interrogate non-affective cognitive functions (e.g., inhibitory control) and intrapersonal measures of affect processing (e.g., emotion regulation). In addition to surveillance of treatment adherence (e.g., dropout, readmission), treatment outcome indices will be provided by both patients and clinicians, and will include post-discharge assessments of functioning (e.g., quality of life; resumption of use). We will delineate the growth function(s) indexing change in social cognition over the first three months of abstinence, allowing us to test the hypothesis that these functions improve, as well as describe what constitutes normal vs. maladaptive rates of recovery. We will employ statistical models facilitating causal inference to test the hypotheses that alterations in executive functions, intrapersonal affect processing, and mood constitute underlying mechanisms of AUD-associated deficits in interpersonal emotion processing. We will test the hypothesis that change in emotion processing will drive subsequent improvements in a range of clinically- relevant outcomes, and examine putative mediators (e.g., social support) of these relationships. Execution of the proposed project will provide actionable data guiding identification of at-risk patients for whom intervention may be most impactful, as well as critical periods for intervention delivery. Results will directly contribute to the development of interventions designed to enhance emotion processing by facilitating selection of the most appropriate mechanistic targets. Resulting data will determine the breadth and magnitude of clinically-relevant recovery outcomes impacted, facilitating estimation of potential intervention efficacy. Our laboratory has the requisite experience to execute these aims, the ongoing relationships with treatment facilities required to collect the data, and the expertise to translate findings into social cognitive interventions.

NSF Awards · FY 2024 · 2024-09

The process of learning and maintaining knowledge of a language is significantly influenced by both individual capacities and social interactions. Previous studies have focused on understanding how individual variability in linguistic background and cognitive skills may impact language outcomes. However, the impact of the speaker’s social network for language acquisition and maintenance remains unclear. This project extends the inquiry to consider how the characteristics of the immediate social network of speakers influence their ability to learn and use a language. Specifically, this project focuses on heritage speakers of Spanish, an increasing community of people in the US who grow up with a strong familial or community connection to Spanish, while also being fluent in English. Heritage speakers provide a unique lens through which to study the interplay between individual capacities and social factors in language learning. This project includes the creation of the Bilingual Experience ARchive (BEAR), an online repository that provides access to language and social network data and modeling tools for bilingual language science. This project is driven by two principal questions: First, do the compositional and structural features of a speaker's personal social network predict their language learning outcomes? Second, how do these network characteristics influence language outcomes over time? Utilizing interdisciplinary methods from language science, social network science, and cognitive science, this research involves participants from a university-level heritage language program. During the project, participants engage in tasks designed to both map their personal social networks and measure their language skills through written and oral tests. The assessments in this project include (1) a personal social network interview, (2) measures of written and oral fluency in both languages, (3) measures of sensitivity to the subjunctive verb mode in the heritage language, and (4) measures of attention and executive functioning that have been shown to play a role in language learning. Participants are tested at the beginning and at the end of a semester. The longitudinal approach used in this project allows for an analysis of how changes in social networks over time correlate with language learning outcomes. 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 · 2024-09

Strengthening American Infrastructure (SAI) is an NSF Program seeking to stimulate human-centered fundamental and potentially transformative research that strengthens America’s infrastructure. Effective infrastructure provides a strong foundation for socioeconomic vitality and broad quality of life improvement. Strong, reliable, and effective infrastructure spurs private-sector innovation, grows the economy, creates jobs, makes public-sector service provision more efficient, strengthens communities, promotes equal opportunity, protects the natural environment, enhances national security, and fuels American leadership. To achieve these goals requires expertise from across the science and engineering disciplines. SAI focuses on how knowledge of human reasoning and decision-making, governance, and social and cultural processes enables the building and maintenance of effective infrastructure that improves lives and society and builds on advances in technology and engineering. Cities and towns across the United States have witnessed rapid growth of electric bike (e-bike) usage in recent years. Along with this growth has been an increase in e-bike crashes, highlighting the urgent need to improve bicycle infrastructure. This SAI project seeks to improve bicycle infrastructure planning and design across U.S. communities to promote safer and more widespread e-bike use. Until now, transportation planners and engineers typically design bicycle infrastructure with a traditional, non-electric bike in mind. This is problematic because e-bikes are faster, heavier, and larger than traditional bicycles, creating new challenges for planning and designing bicycle infrastructure. This project strengthens American bike infrastructure to prepare for an e-bike future by studying how different types of bicycle facilities affect cyclists' and e-cyclists' perceptions of comfort and safety, as well as their riding behavior. The research helps transportation planners make better infrastructure investment decisions to increase bicycle use, enhance rider safety, and promote transportation equity. Cyclists' perceptions of the bicycle infrastructure they interact with play a major role in shaping their cycling behavior and infrastructure-related choices. However, little is known about whether and how the comfort and safety perceptions of e-bike users and traditional bike riders differ. Grounded in social and behavioral theories, this project advances knowledge of e-bike users' infrastructure needs and preferences by developing a social and cognitive psychological account of cyclists' and e-cyclists' comfort and safety perceptions across cycling environments. A multidisciplinary research team develops and tests a novel socioecological theory of planned behavior model by collecting and analyzing multi-sourced, complementary datasets such as survey, interview, bike trip trajectory, and surface street imagery data. The integration of these datasets, coupled with state-of-the-art generative AI technologies and modeling approaches, advances bicycle infrastructure research on both theoretical and methodological fronts. Numerous stakeholders, including transportation agencies, bikeshare operators, and bicyclist organizations are engaged throughout the project for co-design activities to maximize societal impacts. 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 · 2024-09

Plasticity is a hallmark feature of the neural system controlling breathing. As one example, acute intermittent hypoxia (AIH) elicits plasticity in multiple respiratory motor systems including phrenic, intercostal, hypoglossal and laryngeal (Mitchell and Baker, 2022). Recent work from our lab demonstrates that interactions between time of day and hypoxic episode duration have important implications, regulating the magnitude and dominant mechanism driving phrenic long-term facilitation (LTF), a well-studied model of AIH-induced respiratory plasticity in anesthetized rats. Given the potential impact of anesthesia and invasive physiological manipulations in prior studies, it is crucial to understand how the daily rest/active cycle influences AIH-induced respiratory motor plasticity in unanesthetized, freely-behaving rats with intact physiology. One major hypothesis guiding this proposal is that the daily rest/active cycle determines the magnitude and mechanism of diaphragm and ventilatory LTF, both forms of AIH-induced respiratory motor plasticity studied in unanesthetized rats. The importance of these findings is reinforced by the fact that AIH is being used in ongoing clinical trials to improve breathing (and non-respiratory) function in individuals with spinal cord injury and ALS. Given the reverse diurnal rhythm of rodents and humans, our ability to harness AIH as a therapeutic modality will be enhanced through greater understanding of circadian effects on respiratory outcomes. Since the endogenous circadian clock is the predominant organizer of daily behavioral and physiological rhythms in mammals, including natural 24-hr rest/active cycles, a second major goal of this proposal is to test the hypothesis that a local circadian clock within phrenic motor neurons regulates mechanisms giving rise to AIH-induced respiratory motor plasticity. Currently, there is no information available concerning how the endogenous circadian clock influences any form of respiratory plasticity, presenting a novel research opportunity with significant scientific and translational potential. Collectively, these findings will provide important insights to help guide the design of clinical trials using AIH as a therapeutic modality. Elucidating circadian regulation of respiratory plasticity will have both biological and translational significance that may guide development of new strategies to treat severe neuromuscular disorders that compromise breathing.

NIH Research Projects · FY 2025 · 2024-09

ABSTRACT Neural systems, including the system controlling breathing, exhibit plasticity, a change in future behavior based on prior experience. In anesthetized rats I will monitor phrenic nerve activity, serving as an electrical proxy for diaphragm muscle activation and respiratory motor output. Among the various forms of phrenic motor plasticity, phrenic long-term facilitation (pLTF) is extensively studied, which can be induced by repeated exposures to brief episodes of low oxygen, known as acute intermittent hypoxia (AIH). AIH has shown promise as a therapeutic approach for improving breathing and motor functions in individuals with spinal cord injuries or ALS. The induction of pLTF by AIH involves two distinct mechanisms: the Q and S pathways. The Q pathway requires the activation of carotid chemoafferents which project to brainstem raphe neurons inducing spinal serotonin (5-HT) release, and activation of phrenic motor neuron 5-HT2 receptors. In contrast, the S pathway relies on spinal tissue hypoxia, glial ATP/adenosine release, and activation of phrenic motor neuron A2A receptors. These pathways interact through "cross-talk inhibition," where the balance between Q and S pathways regulates AIH- induced pLTF. Notably, the complete abolition of plasticity occurs when both serotonin and adenosine-dependent mechanisms are equally activated. Therefore, shifting the balance away from equal activation of the Q and S pathways may enhance the induction of pLTF by AIH. In human studies, sustained hypercapnia or acute intermittent hypercapnic-hypoxia (AIHH) with isocapnic maintenance during recovery is necessary for long-term facilitation (LTF). Preliminary data from rat studies suggest that AIHH induces approximately double the pLTF compared to AIH alone. The enhanced pLTF induced by AIHH versus AIH is likely attributed to concurrent increase in Q pathway dominance and the simultaneous reduction of cross-talk inhibition from S pathway activation. Accordingly, this proposal aims to uncover the mechanism(s) behind the enhanced pLTF induced by AIHH compared to AIH. I hypothesize that AIHH enhances Q pathway dominance by increasing carotid chemoreceptor activation and amplifying serotonergic raphe neuron activity (Aim 1). I also hypothesize that AIHH alleviates S pathway constraints by increasing spinal tissue blood flow during hypoxic episodes, preventing a dramatic drop in spinal tissue PO2, and minimizing glial ATP/adenosine release (Aim 2). Participating in this research will provide me with new methods and insights, furthering our understanding of respiratory motor plasticity. It may also impact the design of clinical trials, considering the exploration of AIH as a treatment to enhance both respiratory and non-respiratory motor function in individuals with spinal cord injuries and ALS. Additionally, this research aligns with my broader career goal of transitioning to independence by eventually applying for a K99, allowing me to contribute significantly to the investigation of AIH/AIHH as a treatment for clinical populations (e.g., ALS, spinal cord injury).

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY Knowledge about the human microbiome has increased exponentially in the last twenty years, leading to its association with a wide variety of conditions and diseases. However, many of the mechanisms underlying the relationships between microbes and their human hosts have not been elucidated, particularly at the tissue level. The human extracellular matrix (ECM) provides important structural and biochemical cues for the development and homeostasis of all human tissues. Extensive ECM remodeling is a prominent feature of several diseases linked to human microbiome dysfunction including pulmonary cystic fibrosis, inflammatory bowel disease, and cervical cancer. Yet, regardless of tissue or body part, host cells (e.g. fibroblasts, macrophages, and neutrophils) are considered the primary drivers of ECM degradation, even though human-associated microorganisms are known to secrete active proteases. Thus, crucial ECM-microbiome interactions should be included in existing paradigms of host ECM remodeling. To address this important knowledge gap, our lab develops in vitro and ex vivo models using biomaterials and tissue engineering strategies to explore the fundamental mechanisms behind ECM-microbe interactions. We hypothesize that commensal microbiota can degrade human ECM and that ECM remodeling, in turn, alters host cell behavior. The proposed research program will initially answer three key questions: 1) What environmental conditions enable bacterial degradation of host ECM? Our preliminary data demonstrates that commensal bacteria grown in complete growth medium can degrade individual ECM components in vitro. Because environmental factors influence bacterial metabolism, we will explore how factors such as pH, and nutrient source impact ECM degradation by gut and vaginal bacterial species. 2) How do human-associated bacteria remodel host ECM? In parallel to question 1, we will use metaproteomics and inhibition studies to identify the specific proteases and carbohydrate degrading enzymes involved in ECM degradation. Additionally, we will develop an ex vivo tissue culture model to characterize the extent of bacterial ECM remodeling. 3) What are the consequences of microbiota-driven ECM remodeling for host immune cells? Because the ECM regulates cell behavior, we will test the hypothesis that ECM modified by the microbiome impacts host cell function. We will generate in vitro biomaterial platforms that capture the properties of native ECM and incubate them with microbiota culture supernatant. We will then expose innate immune cells to the remodeled matrices and evaluate their phenotype. This ESI-MIRA award will enable my group to discover interactions between bacterial microbiota and host ECM, shedding light on the microbiome’s underexplored contributions to tissue maintenance and dysfunction. Ultimately, the vision for my research program is to determine the impact of the human microbiome on ECM remodeling and leverage this new knowledge to develop novel diagnostics and therapeutic strategies.

NIH Research Projects · FY 2025 · 2024-09

Gene editing is moving towards the clinic, but several challenges must be addressed in order for it to be applied to skeletal muscle disease. Adeno-associated virus (AAV) is one of the most promising technologies to enable delivery of gene editing machinery to skeletal muscle, but at least four major hurdles stand in the way of using it to safely and effectively edit genes in this tissue. These include 1) maximizing delivery of editing enzymes to muscle, 2) maximizing spread of editing enzymes across nuclei of the myofiber syncytium, 3) avoiding sustained expression of editing enzymes, and 4) integrating solutions to each of these problems in a single AAV so as to minimize total viral dose required. Given that exciting new myotropic capsids that have emerged in the literature, this proposal is primarily focused on addressing the latter 3 issues. We have previously developed ways to shuttle Cas enzymes throughout myofibers and now propose to use creative new approaches that rely on tried- and-true mechanisms to access and edit even more myonuclei in skeletal muscle. We have also developed ways to use small molecules to control AAV-delivered gene expression and propose to further develop this technology to achieve fully “off” transgene states with maximally “on” states when desired, so that Cas enzyme expression can be turned off when no longer needed. Finally, we will integrate these technologies with the latest miniaturized Cas enzymes and package all components, including guide RNAs, into a single AAV vector. We will test approaches in mouse models of myotonic dystrophy and Duchenne muscular dystrophy. Ultimately, the insights we make here will be apply to gene editing for any skeletal muscle disease and enable the next generation of therapies for muscular dystrophies.

NIH Research Projects · FY 2025 · 2024-09

The University of Florida (UF) proposes to develop a nation-wide digital course to upskill biomedical researchers’ expertise in artificial intelligence (AI). The AI Passport for Biomedical Research (AIPassportBMR) overall objectives are to provide biomedical researchers the opportunity to augment their skills in a concise and comprehensive course based on innovative learning techniques and will be the first scalable, self-correcting AI training program that is dynamic enough to withstand constant evolution of AI technologies. AIPassportBMR will focus on technical skills while providing mentorship on how to expand biomedical research into the AI field with highly collaborative sessions that include national leaders in medical AI. Designed as a digital experiential learning community, this program will enable predoctoral trainees and early-stage investigators in biomedical, behavioral, and clinical sciences to acquire the multidisciplinary skills necessary to integrate AI into their research while creating a nationwide community of mentors and peers. Our approach aligns with the objectives outlined in the IPERT initiate to provide innovative research skills development and mentoring through the following three overarching aims: Aim 1. AIPassportBMR Program: Develop the educational and technological infrastructure for community-driven experiential biomedical AI training using a See-Practice-Share-Reflect learning approach, Aim 2. Real-World Evaluation: Implement, evaluate, and fine-tune AIPassportBMR using an implementation mapping framework and Cognitive Theory of Culture to align instructional design with learners’ scientific and educational needs, Aim 3. AI Digital Community of Practice: Build a support mosaic network of peers, mentors and coaches and the capacity for sustainable nationwide dissemination of the AI research training program. To further expand AIPassportBMR, the digital community learning platform program will be disseminated nationwide to build capacity for biomedical AI workforce development and support replication for all biomedical researchers.

NIH Research Projects · FY 2025 · 2024-09

Modified Project Summary/Abstract Section Rates of mental and behavioral health disorders are increasing among adolescents coinciding with increases in overall time spent engaging with social media and other online activities. This trend has led to a strong media narrative that online engagement is spilling over into offline mental and behavioral health. However, empirical evidence is relatively weak and mixed between positive, negative, and null effects. Some evidence suggests there may be benefits from online engagement. For instance, youth who identify as sexual and/or gender minorities (SGM) may benefit from receiving emotional support in designated online spaces that support SGM identities. Other research finds health disparities for girls’ mental health related to online engagement as well as increased exposure to cyberbullying among SGM youth. There is a strong potential of high impact interventions that consider adolescents embedded within the online context but this area of research is limited by cross-sectional, self-report methods and an almost exclusive focus on time spent online and unidirectional associations rather than bidirectional within-person mechanistic processes and rich assessments of online engagement. Passive assessment of online engagement and mental health indicators can provide ecologically valid data on naturalistic adolescent online behaviors and experiences, recognizing that adolescents both shape and are shaped by their online environments. Informed by the Compensatory Internet Use Theory (CIUT), this study leverages multiple data streams (e.g., survey data, ecological momentary assessment (EMA), passive digital trace data from smartphones) to test mechanistic within-person processes that underlie bidirectional links between offline mental and behavioral health and online behaviors and experiences, identifying potentially modifiable targets for future prevention and intervention development. We will recruit both a clinical and non-clinical sample of adolescents age 13-15 (n=450) with an overrepresentation of SGM youth to participate in the following research activities: (a) three bursts of a 21-day EMA of moods and motivations for engaging online; (b) three pre-burst and three post-burst surveys of mental and behavioral health and online experiences; and (c) passive assessment of digital trace data related to online behavior (e.g., social networking, messaging, music, typed language) and proximal indicators of mental health (e.g., sleep, activity). To address study aims, natural language processing will be utilized to detect hidden mental states in language data and dynamic structural equations modeling will be used to estimate between-person differences in within-person adaptive and maladaptive mechanistic pathways leveraging all data streams. These results are a necessary next step in understanding how real world, ecologically valid assessments of online engagement longitudinally and acutely impact mental health as well as identifying modifiable targets to promote youth mental health and reduce health disparities in the digital age. This is a mental health disparities grant and no gender affirming surgery or hormone-based interventions are provided as part of this research grant

NIH Research Projects · FY 2025 · 2024-09

ABSTRACT Trauma remains the leading cause of death among people younger than 46 years of age and is the leading cause of years of potential life lost among those younger than 65. With more lives saved, trauma morbidity has increased, which has consequently revealed a lack of understanding of the impact of trauma survivorship on the patients’ quality of life and long-term recovery. Severe injury when followed by chronic critical illness leads to persistent anemia, and the use of blood transfusions is associated with a linear increase in infectious complications. These conditions are due to prolonged bone marrow dysfunction associated with an exaggerated catecholamine response, chronic stress, and systemic inflammation. The Principal Investigator (PI) has demonstrated significant productivity over the last decade, especially in the last five years, in this research field. The PI’s laboratory has conducted human and rodent research to establish that there are unique bone marrow transcriptomic differences related to inflammation, the innate immune response, and known inhibitors of erythropoiesis following trauma. The laboratory has also discovered that chronic stress after trauma contributes to persistent anemia with impaired iron and erythropoietin function along with the prolonged loss of hematopoietic stem progenitor cells (HSPC) from the bone marrow. Chronic stress after trauma also induces an altered microbiome with decreased alpha and beta diversity and changes in microbial composition leading to a persistent ‘pathobiome’. All of these factors influence outcomes. We hypothesize that there is a unifying interaction between stress, inflammation, and the microbiome and this has an overall role in the regulation of HSPC and erythroid progenitor cell fate and function following trauma and critical illness. Therefore, the overarching goal for this application is to build upon this foundation and expand our understanding of HSPC fate and function following trauma, including examining interventions aimed at reducing stress/inflammation and restoring the microbiome, thus, improving long-term outcomes. Severely injured patients with chronic critical illness at risk of long-term morbidity as well as our novel preclinical rodent model of multicompartmental trauma and chronic stress will be employed. We intend: (1) to directly link changes in HSPC and erythroid progenitor cell fate and function with changes in the microbiota by examining specific mechanisms, including how stress-induced changes following trauma create a pathobiome that maintains altered erythroid progenitor function. With these studies, we will (2) explore the unique interplay of the microbiome, the stress response, and HSPCs and erythroid progenitor cell fate in different cohorts of trauma, evaluating both age and sex; and (3) consider possible interventions that restore the microbiome and/or reduce chronic stress/inflammation which reestablishes HSPC homeostasis to improve bone marrow function and long-term outcomes. Focusing on longitudinal interactions between the dysregulated stress response, the pathobiome, and HSPC fate is a novel, under-explored area of research that could improve the long-term management of severe trauma.

NIH Research Projects · FY 2024 · 2024-09

PROJECT SUMMARY Implantable Medical Devices (IMDs) stand on the brink of a healthcare revolution, providing an unprecedented means of managing and preventing a myriad of diseases. However, the potential of IMDs is currently impeded by the challenges of limited interfacing with dispersed neurons, invasive and voluminous designs, and excessive costs, factors that impede their widespread adoption. This project aims to address these limitations by pioneering a novel generation of IMDs: wireless microdevices. The proposed devices will be battery-free, injectable microchips capable of deployment anywhere within the body, integrating energy harvesting, telecommunication functions, and capabilities specific to diverse applications. The development of the microdevice will necessitate interdisciplinary integration spanning integrated circuits, wireless powering, materials science, and microfabrication. Key innovations central to this research include the design of compact, reconfigurable integrated circuits; enhancement of power transfer efficiency; and the application of cost-effective, inkjet printing-based techniques for efficient device assembly and fabrication. Importantly, this project will introduce for the first time a precise injection technique designed to enhance placement accuracy and minimize tissue damage. The project's validation of injectable bioelectric devices in animal models opens avenues for engaging collaboration with neurosurgeons, neurologists, and industry stakeholders. Together, we envisage translating the technology into clinical trials, implementing targeted health interventions, and potentially shifting the perception of IMDs from a last-resort solution to an elective option at earlier disease treatment stages. By developing wireless microdevices that are injectable, scalable, versatile, and fully addressable, this project represents a technological breakthrough, aiming to redefine the future of implantable medical devices. This resonates deeply with my career aspiration to be at the forefront of transforming the IMD field.

NIH Research Projects · FY 2025 · 2024-09

Project Summary Nonmuscle Myosin IIB (NMIIB) is an ATPase motor complex that generates force on actin filaments. This force generation is an essential driver of the actin re-organization that occurs in dendritic spines, actin dense post- synaptic structures, that allows spines to enlarge when stimulated. When a neuron is stimulated, actin mobilization in spines, spinal enlargement, and then actin stabilization of the enlarged structures occurs, and this dynamic process results in plasticity. Spine plasticity in regions of the brain such as the hippocampus (HPC) and basolateral amygdala (BLA) contributes to the molecular basis of learning and memory storage. While NMIIB is known to be a critical contributor to the structural plasticity underlying learning and memory, surprisingly little is known about its action and regulation in mature excitatory neurons. Previous work from our group established that NMIIB is a driver of actin polymerization in rodent hippocampal neurons and that it is regulated as a part of the NMDA receptor pathway upon synaptic stimulation. Inhibiting NMIIB in the HPC results in disruption of memory. Our group has also discovered a regionally specific role of NMIIB in the BLA. Methamphetamine (METH) exposure induces the actin cytoskeleton of a subset of spines to remain constitutively active in an NMIIB-dependent manner. Upon NMIIB inhibition, this overactive population returns to normal motility. Accordingly, NMIIB inhibition after METH exposure disrupts METH-associated memories and drug seeking, establishing NMIIB as a therapeutic target. With new advances in molecular level imaging, a comprehensive cellular biological study of NMIIB is now possible to elucidate its regulation of synaptic actin dynamics. To support this, I have generated and validated a novel endogenously tagged NMIIB knock-in mouse line containing both 3x FLAG and Halo tags as a tool compatible with super resolution imaging and biochemical analysis. Super resolution imaging is necessary to address our questions about NMIIB localization and dynamics because at 300nm, myosin filaments are just at the diffraction limit and any non- filamentous myosin structures will be even smaller. Preliminary data shows NMIIB interacts with proteins in the shaft and at tips of spines, suggesting that dynamic changes in subcellular localization are occurring on a scale < 1 micron and therefore super resolution, and even more specifically, single molecule localization microscopy (SMLM) is most suitable to investigate. In Aim1 we will determine the subcellular distribution on NMIIB in neurons from our tagged NMIIB line using stochastic optical reconstruction microscopy (STORM) in fixed samples. We will also treat neurons to simulate synaptic plasticity to determine if that changes NMIIB distribution. In Aim 2 we use live neurons from NMIIB mice to track the subcellular location of NMIIB and measure its trafficking dynamics within the spine using single particle tracking photoactivatable localization microscopy (spt PALM). This will enable us to image NMIIB dynamics in live cells under basal conditions and then image the same cells during synaptic activation.

NIH Research Projects · FY 2024 · 2024-09

PROJECT SUMMARY Dementia with Lewy bodies (LBD) and Parkinson's disease (PD) are characterized pathologically by the presence of Lewy bodies, composed of misfolded alpha synuclein (α-syn) inclusions. These disorders are progressive, and result in the degeneration of dopaminergic neurons in multiple motor and non-motor basal ganglia circuits. There are no known disease altering drugs, hence there is an unmet need for delivering viable treatments to slow down progression of LBDs. Furthermore, there is a growing body of literature suggesting the role that lipids play in LBD pathogenesis. We have developed a promising mRNA-based immunomodulatory approach (ACT), which shows efficacy of reducing α-syn pathology burden in a preclinical model. We also show that ACT restores the lipidome to normal levels and hence visualizing the inter-brain distribution of lipids along with key enzymes involved in lipid metabolism would help comprehend their roles and alterations over time in the aging and diseased brain. Systems biology approaches provide a holistic examination of interactions between the metabolome, and environment in an attempt to comprehend pathomechanisms involved in LBDs. Imaging mass spectrometry (IMS) is a new technology that has the ability to map a wide range of small molecules with high spatial resolution, and the ability to quantify them, without a priori labeling, and hence can be harnessed to elucidate the role of the metabolome in driving neurodegeneration. Here we propose to generate a spatial atlas of the lipidome to identify lipid markers of disease progression in Aim 1, and assess lipid alterations resulting from ACT using MSI in Aim 2.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY This K99/R00 Pathway to Independence Award is designed so that the candidate will achieve her long-term goal of establishing an independent research career focused on the neural control of breathing. Specifically, I will study how genetic factors influence mechanisms of respiratory motor plasticity. This proposal has been tailored to supplement the candidate’s background in neuroscience and respiratory physiology with additional knowledge and technical skills necessary for targeted gene manipulations and cell-specific molecular analysis. These skills will be applied to a well-studied model of respiratory motor plasticity known as phrenic long-term facilitation (pLTF), a prolonged increase in phrenic motor output triggered by moderate acute intermittent hypoxia (mAIH). Hypoxia-induced adenosine release from spinal glia initiates signaling mechanisms that undermine serotonin- driven pLTF. Factors that increase spinal adenosine levels, such as inflammation and the daily active phase, further constrain pLTF. Understanding how specific factors undermine phrenic motor plasticity has the potential to reveal molecular targets for precision interventions, a necessary step to optimize therapeutic efficacy of AIH in ongoing clinical trails to preserve/restore breathing ability in people with spinal cord injury and ALS. Apolipoprotein (APOE) alleles (E2, E3 and E4) predict whether healthy individuals express respiratory plasticity, although little is known concerning how it does so. Exciting preliminary data lead us to hypothesize that APOE4 undermines pLTF through an adenosine-dependent mechanism, particularly during the rodent active (nocturnal) phase, when spinal adenosine levels are high (Aim 1). ApoE4 biases microglia (a regulator of neuroplasticity) towards a pro-inflammatory state and inflammation abolishes pLTF by a spinal adenosine mechanism. Since both hypoxia and inflammation stimulate phrenic motor neuron-microglia signaling and elicit ATP/adenosine release, we propose that neuronal ApoE4 exacerbates phrenic motor neuron-microglia signaling, increasing spinal adenosine levels. When combined with adenosine levels that are already elevated in the daily active phase, pLTF is suppressed or abolished (Aim 2). Since nearly all lung and CNS disorders are associated with systemic and/or neural inflammation, the candidate will determine how a widely-studied model of inflammation (lipopolysaccharide; LPS) and ApoE4 interact in disrupting phrenic motor neuron-microglia communication in the daily rest vs active phases (Aim 3). The aims of this proposal are supported by abundant preliminary data and will yield novel information providing a fundamental framework for understanding how ApoE4 and inflammation disrupt respiratory motor plasticity. A dedicated mentoring committee of successful scientists will contribute invaluable expertise and guidance, expanding the candidate’s scientific background and productivity while also providing a strong foundation for success in achieving her scientific and career goals.

NIH Research Projects · FY 2025 · 2024-09

Project Summary/Abstract Type 1 diabetes mellitus is an autoimmune disorder in which the patient’s pancreatic islets are destroyed by their own immune system, leaving them unable to produce insulin to manage their blood glucose levels. Currently, this disease affects about 1.6 million people in the United States and roughly 180 new patients are diagnosed each day. Clinical islet transplantation is a potential solution that involves injecting donor islets into the patient’s liver to secrete insulin and regain blood glucose control. A challenge of this therapy, however, is decreased islet viability due to mechanical stress and adverse inflammation at the infusion site. The utilization of islet encapsulation or islet-loaded porous scaffolds can provide a means to protect islets from these stresses; however, encapsulation can result in insufficient engraftment and incomplete immunosuppression, while traditional scaffold fabrication methods generate inconsistent pores and rough surfaces that can lead to unfavorable and unpredictable host responses to the implant. To address these challenges, this proposal seeks to develop a multi-functional biomaterial scaffold that improves the vascularization, engraftment, and immunoprotection of transplanted pancreatic islets for the treatment of Type 1 diabetes mellitus. In Aim 1, we will alter scaffold porosity and rung thickness to identify the specific geometric features that will result in robust host engraftment with minimal fibrosis. For Aim 2, we will incorporate depots of synergistic immunosuppressants into the 3D-printed scaffold material for controlled local drug delivery. We will characterize the kinetic release curves of the drug eluting scaffold in vitro and optimize the drug loading parameters necessary for sufficient local immune protection. Islet-loaded, therapeutic scaffolds should provide local drug release resulting in the suppression of adverse immune reactions in an allograft rat transplant model, preventing rejection of the cell cargo. Broadly, results from this work will provide a better understanding of the roles that scaffold geometry and local therapeutic release play in cell-based therapies, while improving experimental outcomes in islet transplantation.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY/ABSTRACT A high proportion of older adults are currently or soon will be at risk for the well-known decline in walking and balance abilities that occur with aging. Preserving those abilities has become a major public health priority. Balance training can enhance functional abilities or attenuate functional decline; however, age-related motor deficits may impair practice-based motor learning and behavioral performance. Due to the crucial roles of the spinal cord in balance and walking performance, it is important to consider that age-related neural impairment of the spinal cord is a likely contributing factor. Specifically, the spinal cord in older adults has fewer neurons, is less excitable, and conducts signals more slowly. Despite ample evidence of impaired spinal cord neuronal structure and function with aging, the potential benefit of an intervention targeting spinal control of balance and walking control has been largely unexplored. This dearth of research may be due in part to the lack of a clinically feasible intervention. However, the recent emergence of transcutaneous spinal direct current stimulation (tsDCS) as a non-invasive intervention creates new opportunities for understanding spinal cord contributions to balance and walking performance. The proposed study will be among the first multi-session trial to investigate the effects of tsDCS as an adjunct therapy to dynamic balance training in older adults. We propose to include 30 participants 65 years of age or older with balance/walking deficits, who will receive active or sham tsDCS while performing a dynamic balance training intervention. Balance and walking performance assessments will be conducted after each of the five intervention sessions to examine the intervention's effects over time. Spinal excitability will be assessed immediately before and after tsDCS at the first and last intervention sessions. Behavioral assessments will only be carried out at baseline and 1 day post-intervention to investigate the pre vs. post intervention effect, with a 10-day period considered for the retention effect. During behavioral assessments, prefrontal cortical activity will be measured to provide insights into the demand for increased executive control. The first aim of the study will be to acquire preliminary effect size and response variance data to assess whether active adjuvant tsDCS therapy combined with dynamic balance training enhances practice-related gains in balance and walking performance and retention over time. The second aim of the study will be to establish evidence of increased spinal excitability following tsDCS, positively correlating with gains in balance and walking functions. The overarching hypotheses of the proposed study are that the positive effects of tsDCS on practice-related enhancements and retention in balance and walking function will be related to increased spinal excitability. The long term deliverable of this line of research will be a clinically feasible multi-modal intervention to assist in preserving motor function and independence in older adults. The knowledge and experience gained from this study will enable us to conduct larger studies to better understand the effects of aging on the spinal cord and to test rehabilitation interventions to promote healthy aging among older adults.

NIH Research Projects · FY 2025 · 2024-09

Project Summary/Abstract BV is driver of the HIV epidemic, increasing HIV risk up to 60%. Bacterial Vaginosis (BV) is the most common vaginal condition among women of reproductive age, with a prevalence of 20-60% globally. Mediated by a non- optimal vaginal microbiome and characterized by vaginal inflammation, symptoms can cause extreme discomfort, including burning, vaginal malodor, and vaginal itching. A poorly understood component of BV are its effects on infiltrating immune cells. Tissue resident macrophages may play a role in increased HIV risk, but have not been investigated in the context of BV. The objective of this proposal is to determine the effects of a non-optimal vaginal microbiome on inflammatory macrophage activation and training towards an HIV permissive phenotype by establishing an ex-vivo macrophage stimulation model. Here we propose to assess changes in macrophage activation when exposed to vaginal fluid from a global cohort of women (BV and healthy). Macrophage activation will be characterized using both targeted analyses (HIV associated inflammatory markers) and multi-level proteomics (epigenetic, total proteome). Vaginal fluid will be characterized using metagenomics and metabolomics. Computational analyses and machine learning will allow for determination of the role of unique microbial combinations on macrophage activation. We expect to identify specific microbial compositions that correlate with an HIV promoting macrophage phenotype. This approach is highly innovative because it couples machine learning with an ex vivo macrophage stimulation model to study microbiome- macrophage interactions. Furthermore, vaginal fluid obtained from a global cohort of women in the US, South Africa, and Ghana will be obtained using a citizen scientist model of recruitment which empowers and educates participants. BV frequently recurs, and the vaginal microbiome is complexly variable among women. Completion of the proposed project will advance the field of HIV prevention science, by providing a tool to directly examine macrophage mediated-HIV risk. Additionally, it will provide a platform to test personalized, microbiome-informed, probiotic interventions. Further, these finding will be paradigm-shifting as there is no precedent data to determine if immune cells within the tissue micro-environment can be trained by a non-optimal vaginal microbiome, nor studies to determine how this impacts HIV risk. Trained immunity has been linked to increased risk of HIV infection, but has not been previously studied in the context of bacterial vaginosis. Completion of the proposed study will reveal the effects of the vaginal microbiome on macrophage activation, identifying previously unassessed novel mechanisms of inflammation. This multi-variate approach allows for deep proteomic and metabolic characterization of the macrophage, which will provide data to determine the effects of vaginal fluid on the macrophage training, differentiation and activation. Such models are necessary due to the complexity of the biological processes, which cannot be readily assessed in direct clinical studies.

NSF Awards · FY 2024 · 2024-09

Throughout history, infectious diseases have shaped human societies in profound ways. The Black Death pandemic of the 14th century was one of the deadliest in human history, killing an estimated 30 to 60 percent of Europe’s population. This project aims to unravel the complex relationships between climate, agriculture, human behavior, and disease outbreaks during the Black Death and subsequent centuries-long plague pandemic. By integrating mathematical models with archaeological and historical data, the researchers will reconstruct how environmental and social factors combined to create conditions ripe for catastrophic pandemics. Broader impacts will arise from the integrated datasets and modeling tools that will be made freely available and support infectious disease research. The crucial insights will aid management of modern outbreaks and may improve public health in the future. The project will develop computer simulations that integrate models of disease transmission, human demographics, land use, and climate. These models will be combined with diverse sources including human skeletal remains, tree-ring data, pollen records, and historical documents using a technique called data assimilation. This approach allows researchers to fill in gaps in the fragmentary historical record and test hypotheses about how factors like climate-driven food shortages, urbanization, and trade routes affected plague outbreaks. The researchers will collect new bio-archaeological data on age, health status, and migration patterns from skeletal remains at plague burial sites across Europe. By reconstructing the environmental and social conditions surrounding major outbreaks over several centuries, the project aims to identify recurring patterns that cannot be revealed from contemporary pandemics alone. 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 · 2024-09

Unrealistic optimism is the tendency for people to overestimate the chances that good things will happen to them and underestimate the chances that bad things will happen to them. Unrealistic optimism influences people's decisions about many aspects of life, such as in health, education, and the workplace. Researchers, however, do not know whether unrealistic optimism is helpful or harmful in these situations. Unrealistic optimism might impair decision making and stop people from trying other options. On the other hand, unrealistic optimism might help people cope with challenges or find motivation for difficult tasks. By learning whether unrealistic optimism is helpful or harmful, this study show educators, managers, and coaches how to help everyone make great decisions and have the best chances of success. This study aims to reconcile contradictions in prior research by determining whether unrealistic optimism helps or hurts and explaining why. The study distinguishes between different outcomes of unrealistic optimism (focal, alternative, and tertiary outcomes) and measures unrealistic optimism by comparing participants’ expectations to data-based predictions. The study follows minor league baseball players attempting to reach the Major League Baseball for 3 years and high school juniors attempting to get into college for 2 years. Bayesian model testing determines how unrealistic optimism affects focal outcomes (reaching Major League Baseball, getting accepted to top universities) and influences alternatives. The study also measures variables that explain the consequences of unrealistic optimism. Results from this research have the potential to reconcile debates in social science by testing competing hypotheses, collecting new, insightful data, and introducing an overarching framework that can accommodate conflicting evidence and organize future research on unrealistic optimism. 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 · 2024-09

Despite advances across the cervical cancer care continuum – screening, treatment, and survivorship care, people with obesity or type 2 diabetes (T2D), and people living in poverty or rural areas are significantly more likely to die from cervical cancer. More than 41% of people in the United States have obesity, and obesity and T2D often co-occur. People living in poverty or rural areas are more likely to be diagnosed with these conditions. Thus, there is a critical need to adapt evidence-based interventions that address challenges to engaging in cervical cancer screening among people with obesity or T2D living in rural areas or in poverty. Training: I am shifting my research from examining the etiology of chronic conditions (cancer, obesity, and T2D) and associated health-protective behaviors to developing and adapting interventions that prevent cancer in individuals with chronic conditions. The proposed K01 career development training builds upon my prior experience by focusing on three areas that require additional training: (1) enhancing skills in biomedical informatics and biostatistics, (2) building skills in developing evidence-based interventions to address cancer prevention, and (3) developing expertise in multi-level implementation science theories and methods. Accordingly, the proposed K01 will provide protected time to receive the necessary training to advance my expertise and propel me to become an independent cancer implementation scientist. Research: The availability of large real-world health data sets with electronic health records and claims data provides an opportunity to better identify populations to be targeted for interventions. We will analyze OneFlorida+ Clinical Research Network data using latent class analysis to examine which degree combinations of factors (obesity, T2D, poverty, or rurality) are associated with risk profiles of cervical cancer diagnosis. We will then use Intervention Mapping to guide the process of adapting the PatIent Navigation for the Prevention of CervIcal CaNcer intervention (PINPOINT). The Health Belief Model will be used to address factors influencing screening behaviors. Proctor’s Framework for Implementation Outcomes will be used to evaluate the PINPOINT intervention. The overarching hypothesis of this proposal is that the PINPOINT intervention will be acceptable and feasible in supporting cervical cancer screening for people with T2D or obesity who are living in poverty or rural areas. Summary: Findings will inform an R01 grant application to the NCI to test the effectiveness of the developed intervention in a fully powered sample. By the end of this award, I will have developed expertise, positioning myself to become an independent cancer prevention implementation scientist.

NIH Research Projects · FY 2025 · 2024-09

Reveal myeloid cell-mediated targeting through nano-bio interface. Project Summary/Abstract Nanomedicine based on ultra-small nanoparticles (usNPs), such as dendrimers, gold NPs, quantum dots, and protein-based carriers (e.g., albumin), are at the forefront of clinical translation for targeting cancer and inflammatory disorders. Myeloid cells such as inflammatory monocytes (ФIMs) can traffic to the inflamed tissue and mediate the targeting of NPs to inflammation. However, the lack of mechanistic understanding of NP interaction with ФIMs and ФIM-mediated NP targeting to inflammation has significantly limited the rational design of tissue- or cell- specific delivery systems. A critical obstacle is that when NPs are injected into the blood, multiple serum proteins adsorb to the NP surface, forming a ‘NP proteome’. The NP proteome masks NP interaction with the cell surface and alters the NP cellular tropism. It is now recognized that it is the NP proteome rather than the NP physiochemical properties that dictate the NP cell tropism and more broadly their in vivo targeting behaviors. Toward this end, the overarching goal of my research program is to understand usNP–myeloid cell interactions and myeloid cell- mediated NP targeting to inflammation from the perspective of ‘NP proteome’ and to leverage myeloid cell recruitment to design inflammation-targeting nanotherapeutics. My research team has made significant strides in using animal models to characterize the trafficking of ФIMs to inflamed tissue and how ФIMs trafficking dynamics affect the deposition of usNPs. We also showed NP proteome is a critical mediator of usNP–ФIM interactions. Over the next five years, my research team will address key knowledge gaps that limit the rational design of inflammation- targeting nanotherapeutics. Specifically, for usNPs that carry drug payload on their surfaces, we will i) determine the fundamental mechanisms that govern usNP–ФIM interactions: we will establish a structure-property relation between the molecular properties of surface payload and NP proteome, and understand how NP proteomes are ‘read’ by ФIMs; ii) determine how myeloid cell recruitment mediates the targeting to inflammation for NPs carrying different payloads. The anticipated results will transform the current understanding of NP-myeloid cell interactions and have broad implications for nanotherapeutic targeting behaviors in vivo (e.g., tropism towards myeloid cells, biodistribution, targeting to inflammation), clearance, and toxicity (e.g., complement activation). iii) guided by this knowledge, we will develop a translatable nanotherapeutic that selectively delivers an immune modulator to target ФIMs and remove immunosuppression. As ever more nanotherapeutics are being tested in the clinics for various diseases and through diverse delivery routes (e.g., inhalation, intratumoral delivery), we envision this research program will set up the foundation for future studies to understand how NP proteome formed in the serum samples of various disease conditions and biological fluids (e.g., pleural fluid, tumor interstitial fluid) can determine the in vivo targeting behaviors of nanotherapeutics.

NSF Awards · FY 2024 · 2024-09

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Stephen A. Miller of the University of Florida will convert post-consumer waste plastic and bio-based feedstocks into a novel family of sustainable polymers with properties suitable for replacing incumbent packaging plastics. Despite what is taught in most textbooks, the ester functional group is generally more stable than the amide functional group, as proof of concept experiments and computations indicate. This relative stability will be exploited to synthesize exemplary polymers via Amide to Ester Polymerization (ATEP), an unexplored polymerization pathway particularly suited for the chemical recycling/upcycling of post-consumer polyesters (e.g., water bottles and polyester clothing) and nylons (e.g., backpacks and fishing nets), yielding polyesteramides. Convergent chemical recycling will transform mixed waste streams of polyesteramides and polyesters into a single monomer suitable for repolymerization. Alternatively, the polyesteramides will be degraded via hydrolysis under environmentally relevant conditions (e.g., seawater). Long-term studies will establish polyesteramide degradation rates, while computational studies will explain how they can degrade in water over relatively short timescales—necessary to combat the plague of plastics accumulating in the environment. The U.S. plastics industry directly employs over one million people and generates $550 billion in annual shipments. More sustainable polymers—whether from post-consumer materials or bio-based feedstocks—are expected to exceed a 40% market share by 2030. Inclusion of the proposed ATEP polymers could further accelerate this amazing growth and expand the variety of materials applications. While polyester aminolysis is much more facile than hydrolysis or alcoholysis, the formed bis-amides have minimal demand because of their presumed stability. ATEP creates an application for these bis-amides and is a novel kinetic pathway for their polymerization, generally yielding polyesteramides with properties excelling those of the original polyester. Key polymer properties include melting temperature and glass transition temperature, and these measured properties will be correlated to polymer structure. For example, aminolysis of post-consumer PET (polyethylene terephthalate) followed by ATEP will yield polyesteramides with a tunable glass transition temperature that depends on the nature of the amine originally employed for aminolysis. Polymer upcycling will be achieved when the glass transition temperature substantially excels that of the precursor PET (72 °C). The complexities of ATEP will be unraveled by pursuing specific project goals: (1) optimizing PET aminolytic depolymerization conditions and applying them to a variety of commodity polymers, including polyesters, nylons, and others; (2) optimizing ATEP and comparing polyesteramide properties to those of extant polymers; (3) further developing the thermodynamic and kinetic rationale of ATEP via computational methods; (4) applying ATEP to a variety of bio-based diacids; (5) establishing polyesteramide structure/property relationships; and (6) investigating practical depolymerization conditions, including environmental degradation and chemical recycling. Exploring the many facets of ATEP will greatly expand the fundamental understanding of polymerization/depolymerization chemistry. 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 2024 · 2024-09

Project Summary: The purpose of this pilot study is to explore postpartum women’s oral health knowledge, attitudes, and behaviors (KABs) during and after pregnancy in Florida, and to identify specific barriers and facilitators to dental service use, unmet dental needs, and the intent to use dental services in the postpartum period. Oral health is integral to overall health, particularly for maternal and infant health outcomes. Despite its importance, many women face barriers to accessing dental care during pregnancy, such as financial constraints and lack of awareness, leading to untreated disease and poor systemic health. This study addresses a gap in understanding the specific oral health needs of postpartum women, especially given recent policy changes expanding Medicaid eligibility for postpartum women in Florida. This study addresses the oral health needs of postpartum women in light of recent Medicaid policy changes in Florida that expand eligibility for this population. To capture diverse perspectives, the study will develop and administer a survey in both English and Spanish, targeting Florida’s growing Hispanic population, which represents 26.4% of the state’s residents, with 22.2% identifying Spanish as their primary language. By including Spanish-speaking participants, the study aims to provide more nuanced insights into the factors influencing dental service use. Data will be collected from postpartum women at UF Health Shands Hospital through anonymous surveys. The study will analyze key barriers and facilitators to dental service utilization, unmet needs, and intent to seek dental care postpartum, while examining relationships between socio-demographic and clinical factors and oral health KABs. The findings will inform larger-scale studies and interventions, including a planned focus group study, and provide preliminary data for a career development award application by Dr. Cilia Zayas. This pilot study will lay the groundwork for developing strategies to improve dental health outcomes for a diverse postpartum population in Florida.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY Opioids exert a plethora of behavioral effects that include clinically beneficial analgesia and untoward euphoria that leads to their abuse. Furthermore, prolonged exposure to opioids is associated with the development of dependence and tolerance that drive relapse and contribute to overdose and grave side- effects. All of these effects are mediated by the μ-opioid receptor (MOR), strategically positioned in neurons that form reward and nociceptive circuits. Furthermore, MOR signaling is involved in development of addiction to a wide range of drugs of abuse. The overarching goal of our efforts is to dissociate the behavioral effects associated with activation MOR signaling in neural circuits to curb the development of dependence. Our strategy to achieve this goal is to use large scale, unbiased approaches to identify novel modulators of MOR signaling and then apply high throughput chemical biology strategies to target these components with small molecule compounds. By conducting an unbiased forward genetic screen we have recently identified several novel receptor-like components that exert “anti-opioid” activity by modifying MOR signaling. Proof-of-principle experiments with knockout mice show that elimination of these elements profoundly alters behavioral responses to opioids diminishing the dependence and tolerance while increasing analgesia. Based on these observations we propose to use high throughput approach to develop pharmacological tools for redirecting MOR signals to specifically manipulate with opioid responses modifying addictive behaviors. Specifically, we plan to follow up on the discovery of the diverse set of compounds identified in high- throughput screening campaign, optimizing them using medicinal chemistry for achieving selective and specific alterations of MOR signaling. We will characterize the compounds and undertake their development efforts culminating in studying the effects on modifying opioid responses with circuit specific resolution using innovative optical strategies for recording neuromodulation in brain slices. Finally, we will investigate in vivo actions of the developed tool compounds testing their activity in rodent models of pain and addiction using a comprehensive battery of behavioral assays. These efforts will be paralleled by conducting in vivo pharmacokinetics, pharmacodynamics and toxicology studies. It is expected that this effort should result in a development of precision tools for understanding opioid receptor signaling and dissociating opioid effects with circuits and molecular specificity.