Drexel University

NIH Research Projects · FY 2025 · 2022-09

Modified Project Summary/Abstract Section Autism is a common neurodevelopmental condition that affects functioning and well-being in a myriad of domains across the life course. The proposed Autism Center of Excellence, “Public Health and Autism Science advancing Effectual Strategies across the life course” (PHASES) application proposes to employ an overarching public health research framework to examine health determinants, health differences, and health services delivery and their impact on health outcomes. Projects in our center highlight different stages of the life course – early childhood, adolescence to young adulthood, and older adults. Project 1 addresses predictors of age of diagnosis among young children with autism, with emphasis on variation in access to universal, high-fidelity screening during primary care visits, with a goal of ensuring access to early detection for all. Projects 2 and 3 examine Medicaid claims and other national data to address key issues arising from the disproportionate burden of co-occurring health conditions in autistic adolescents and young adults (Project 2) and middle age-to-older adults (Project 3). Each of the 3 studies targets unique groups characterized by potentially modifiable adverse outcomes: young children with delayed autism detection, autistic adolescents and young adults with co-occurring conditions, older autistic adults with co-occurring health and cognitive deterioration. The three Center Aims address the following research goals at three different key life stages: Aim 1 investigates modifiable health determinants for autistic individuals; Aim 2 evaluates variation in health and health services in persons on the autism spectrum; and Aim 3 examines the relations between health services delivery and health outcomes. The Center will be supported by three cores facilitating synergy across projects: the Administrative Core streamlines communication and collaboration across projects; the Dissemination and Outreach Core facilitates engagement with stakeholders and expands our existing activities to emphasize bidirectional communication between our team and the community; and the Data Core ensures quality, integrity, and security of data from large sources (e.g. Medicaid, Medicare, electronic health records). Overall, the Center will address preventable adverse outcomes and promote wellbeing in individuals on the autism spectrum, with a focus on several priorities identified by the Interagency Autism Coordinating Committee, including research across the lifespan and improving health outcomes for all autistic persons.

NIH Research Projects · FY 2025 · 2022-09

Researchers at state and local health departments producing small area estimates often face a lose-lose situation. On one hand, there is a wealth of evidence of racial disparities in many health outcomes and their risk factors, but stratifying data by space and race (in addition to factors such as age and sex) only exacerbates the issues associated with small area estimation by dividing a dataset with small sample sizes into a larger dataset with smaller sample sizes. On the other hand, while the use of complex statistical models can be used to produce more precise estimates from limited data, estimates produced by state and local health departments may be treated as “official statistics” and thus these agencies may be reluctant to rely too heavily on statistical models for fear of the bias they may introduce. The objective of the proposed work is three-fold. Our first task will be to develop statistical models for the analysis of multivariate spatial data that allow users to pre-specify an upper bound on the model’s informativeness — i.e., a measure of the weight given to the model as compared to the data when producing model-based estimates. This work will build on the rich spatial statistics literature and recent research that provides insight into how to quantify the informativeness of spatial models. We will extend this approach to the setting of multivariate spatial data for the purposes of calculating demographic group-specific estimates and age-adjusted estimates. Because we envision these methods being useful for researchers at state and local health departments, we believe a thorough case study of our methods should be conducted to assess their suitability. To this end, our second task will be to partner with the Philadelphia Department of Public Health and use the methods we’ve developed to conduct a rigorous analysis of heart disease mortality and its risk factors in Philadelphia. This analysis will produce yearly census tract-level estimates for rates of death due to several forms of heart disease and estimates of the prevalence of key risk factors by age, sex, and race/ethnicity. The product of this research will include a collection of reports — one focused on city-level trends and one focused on neighborhood-level trends — an interactive online dashboard, and peer-reviewed publications that add context to our findings. Finally, we recognize that few state and local health departments have staff who are trained in advanced spatial Bayesian statistical methods, a fact that could serve as an impediment to the use of the methods we develop. To remedy this, our third task will be to partner with the CDC-funded GIS Capacity Building Project, which provides training in geospatial analyses to state and local health departments. This month-long training program begins by introducing users to the ArcGIS software package and concludes with an overview of a tool created by the GIS Capacity Building Project — the Rate Stabilizing Tool (RST). For this project, we will partner with the GIS Capacity Building Project to incorporate the methods we develop into the RST in a “black-box” framework and provide additional training on the use of spatial Bayesian methods in disease surveillance.

NIH Research Projects · FY 2025 · 2022-09

Abstract Chronic pain is the most prevalent, disabling, and expensive public health condition in the United States. The goal of this project is to elucidate how to harness body’s own analgesic mechanisms to provide pain relief. We propose to investigate 30-150 nm small extracellular vesicles (sEVs) that transport mRNAs, miRNAs, proteins, and lipid mediators to recipient cells via circulation. Uptake of sEVs induce gene expression changes in recipient cells and thus, sEVs play an important role in intercellular communication. We observed that sEVs from RAW 264.7 macrophage cells show therapeutic and prophylactic efficacy in a complete Freud adjuvant (CFA) mouse model of inflammatory pain. Our preliminary studies show that mouse serum derived sEVs also conferred prophylaxis when injected intrathecally in naïve recipient mice that, two weeks later, received a hind paw injection of CFA. Thus, mice that received sEVs can remember this stimulation for at least 2 weeks and show an attenuated response to CFA. How this long-term memory develop is unknown. Though chronic pain is prevalent, an immunization strategy has not yet been tested and our studies will provide the rationale and mechanistic basis for such a strategy. Here we propose to test the hypothesis that monocyte/macrophage-derived sEV subsets in serum are necessary and sufficient to attenuate inflammatory pain hypersensitivity and confer prophylaxis. We will also investigate if monocyte/macrophage sEVs recruit, or promote anti- inflammatory phenotype switching of immune cells in dorsal root ganglion and spinal cord by quantitative immunophenotyping in situ, before and after CFA treatment. Recent studies show that microglia, the resident macrophages of the central nervous system can enhance or suppress responses to a delayed secondary insult through epigenetic modifications. We hypothesize that monocyte/macrophage-derived sEVs impart epigenetic immune memory in spinal microglia of recipient mice, granting the capacity to attenuate pain from a future insult and contribute to the prophylactic effect of sEVs. The studies proposed will elucidate the role of sEVs in immune regulation and memory.

NIH Research Projects · FY 2024 · 2022-09

PROJECT SUMMARY Access to cognitive behavioral therapy (CBT), the first-line treatment for disorders characterized by recurrent binge eating (i.e., eating large amounts of food within a discrete-time period, characterized by a sense of loss of control) is limited. CBT for binge eating is intensive (16-20 sessions), expensive ($1,882 per patient), and requires access to clinicians with specialized training. Self-help CBTs for binge eating are accessible and cost- effective, however, outcomes are best when the self-help treatment is paired with periodic contact with a highly trained clinician. Clinicians likely improve outcomes because they are trained to utilize specific behavior change techniques for facilitating improvements in two key treatment targets including treatment adherence and skills utilization during self-help CBT program. Given the limited availability of expert clinicians, it is critical to understand how to enhance outcomes from self-help CBTs without clinician involvement. Recent technological advancements have shown the potential to closely approximate the behavior change techniques typically implemented by expert clinicians to enhance treatment adherence and skills utilization during self-help CBT without clinician involvement. In particular, technology-based intervention factors such as Advanced Digital Data Sharing with Coaches and Just-in-time adaptive interventions (JITAIs) have shown promise in emulating behavior change techniques used by an expert clinician. Advanced Digital Data Sharing systems can perform key behavioral tasks typically accomplished by expert clinician (e.g., identify areas for intervention and generate recommendations on how to intervene on target behaviors). Coaches (individuals with bachelor’s degree in health-related fields) may use the recommendations generated by this system and provide support to patients via weekly emails for improving treatment adherence and skills utilization. Thus, Advanced Digital Data Sharing system may allow coaches to function in a more skilled way without receiving extensive training in behavior change techniques. JITAIs are a smartphone intervention design that conducts real-time analysis of behavioral data related to treatment targets and determines the time of delivery and content of momentary interventions designed to improve treatment adherence and skills use. To date, no study has tested whether these technology-based intervention factors can independently and synergistically improve treatment targets and outcomes from self-help CBTs for binge eating without clinician involvement. The proposed study will use a full factorial design with 76 individuals with binge eating to identify the independent and combined synergistic efficacies of two intervention factors (i.e., Advanced Digital Data Sharing with Coaches and JITAIs) hypothesized to 1) improve treatment adherence and skills utilization, and 2) enhance treatment outcomes when combined with a self-help CBT program without clinician involvement. Results of the study will inform development of effective and highly disseminable self-help CBT program for binge eating.

NIH Research Projects · FY 2025 · 2022-09

Treatment of prostate cancer patients relies heavily on therapeutic strategies depriving tumor cells of the transcriptional activity of the Androgen Receptor (AR). Despite their initial efficacy, androgen-deprivation therapies (ADT) are eventually circumvented by the emergence of castrate-resistant prostate cancer (CRPC), which is characterized by skeletal metastases in more than 90% of patients. We have recently demonstrated that approximately 30% of bone-metastatic prostate cancer cells lack AR (ARNeg) and express Interleukin-1β (IL-1β). Our hypothesis is that ARNeg cancer cells, by secreting IL-1β, establish a supportive bone habitat, allows ARPos cells to withstand androgen-deprivation and AR inhibition. Thus, a major goal of this proposal is to define the modalities by which ARNeg/IL-1β cancer cells sustain skeletal colonization in prostate cancer under androgen-deprived conditions. This proposal is structured in three aims: Aim 1. IL-1β involvement in ADT resistance; Aim 2. Role of bone stroma in IL-1β induced regulation of ARPos cells; Aim 3. Regulation of IL-1β expression by AR. The proposed studies will employ animal models of metastasis, human cell lines, PDX-derived cells and human tissue amples to ascertain the functional role of IL-1β in skeletal colonization of prostate cancer cells, discriminating between direct autocrine-paracrine effects on cancer cells and targeting cells of the tumor- associated bone stroma. Furthermore, we will identify the bone stroma cells targeted by IL-1β and evaluate three stromal factors secreted in response to IL-1β for the ability to induce AR signaling and expression of AR- regulated genes. Finally, using a combination of molecular biology approaches we will define the mechanism for the transcriptional regulation of IL-1β by the AR and the translational control exerted on this cytokine by miRNAs. Our studies will define the unique role of ARNeg prostate cancer cells in metastases and provide conceptual and pre-clinical ground for complementary strategies to improve therapeutic outcomes.

NIH Research Projects · FY 2026 · 2022-08

ABSTRACT African American and Hispanic populations have worse adult health than their White peers (hereafter “health disparities”). These health gaps often begin in childhood and persist to adulthood. Far less research has identified population-level interventions that reduce variation in risk factors across population subgroups. The scant evidence on effective population-level interventions is a significant barrier to reducing health gaps and therefore improving overall population health. Rigorous prior studies have revealed the plausibility for large-scale nutrition interventions to reduce gaps in children’s academic performance—a strong predictor of adult educational attainment, which is one of the most prominent health promoting factors. These prior studies have illuminated the intermediary mechanisms in the pathway between school-based nutrition interventions, (junk) food availability near schools and children’s academic performance. No longitudinal studies have thoroughly investigated the population-level influences on academic performance of large-scale nutrition interventions together with modifiable food-related factors near schools. This longitudinal study capitalizes on a series of natural experiments generated by large-scale interventions that enhance nutrition standards for foods and drinks available to children in schools. The study will determine (a) the effectiveness of population-level school nutrition interventions in improving children’s academic performance and reducing related gaps among African American and Hispanic vs. White peers; (b) the extent to which modifiable, food-related factors near schools influence longitudinal changes in academic performance and related disparities; and (c) the degree to which school nutrition intervention effectiveness varies by the food-related factors near schools. To generate valid inferences about the population-level effectiveness of these interventions on academic performance, this study uses the strongest possible approach to evaluate non-randomized exposures: a difference-in-differences analysis that includes within-child change in exposures. Difference-in-difference analyses will also examine the effects of child-level changes in modifiable food-related factors near their schools and changes in academic performance (and disparities). This study is unparalleled because we use powerful longitudinal data on academic performance among a large population of 11.8 million children. Interventions in and around schools hold potential to reduce gaps given they apply to all children, and use existing infrastructures and networks that facilitate their large-scale implementation and population-level impact. Given its robust design, the study will have a significant impact on evidence-based nutrition interventions to mitigate health gaps; identify opportunities to enhance educational attainment; and broaden the scope of interventions to improve health for all Americans.

NIH Research Projects · FY 2024 · 2022-08

Abstract Approximately 5.4 million adults in the United States (1 in 45) are believed to have autism spectrum disorder (ASD), but there is a lack of services available to support them in reaching their full potential. Although typically conceptualized as a childhood disorder, ASD-related service needs persist into adulthood. The core social and communication impairments of ASD, reported difficulties with change, and a high rate of co-occurring mental health conditions often result in limited participation in major life areas that are determinants of health, including social and community participation, employment, housing, and transportation. The transition to adulthood is not only associated with developmental challenges, but also a “services cliff” whereby supports and services that were previously available through the education system are no longer available. Peer- delivered interventions have emerged as a potent, evidence-based modality for enhancing outcomes among other clinical populations, such as adults with serious mental illnesses, with effectiveness in enhancing social networks, empowering participants, reducing the use of inpatient services, and increasing life satisfaction. At present, there is limited research on the effectiveness of autistic-led peer support interventions, especially those that target broad aspects of community functioning. The proposed study seeks to refine, manualize, and test a pilot autistic peer support program aimed at supporting community participation among autistic young adults, with the goal of preparing it for large-scale testing and future dissemination and sustainability. The first aim of this proposal is to enhance the structure of a pilot autistic-peer delivered intervention (Community Autism Peer Specialists, or CAPS) that is currently in use as a Medicaid-reimbursed service in Philadelphia. This will include developing a manual and fidelity tool to facilitate evaluation and systematic implementation. The second and third aims are to conduct a hybrid type 1 effectiveness-implementation randomized controlled trial with 40 young autistic adults to test the feasibility and acceptability of the intervention and research procedures, while also examining proposed target mechanisms of action (e.g., self-efficacy, working alliance, perceived social support) and clinical outcomes such as community participation, loneliness, and resilience. This work will gather additional evidence and implementation information to support a fully-powered R01- funded clinical trial. The proposed efforts will involve substantial engagement of a diverse group of autistic adults in all phases along with multiple community partners, including a Medicaid payer. The project has tremendous potential to expand service options for autistic adults and is uniquely poised to have broad, scalable impact.

NIH Research Projects · FY 2025 · 2022-08

ABSTRACT It remains unclear why some tissue injuries regenerate and heal while others fibrose and scar. It is evident, however, that the inflammatory response underlies these divergent outcomes. This immune system’s response to injury depends on a multitude of cell types and organ systems that remain in communication to evolve collectively, guiding tissue-level outcomes. My lab’s expertise is in the design of local drug delivery systems for immune modulation. We will leverage these delivery platforms to explore immune systems interactions after local therapeutic delivery, with applications toward tissue healing and arresting inflammatory disease progression. Theme 1: How does cell-targeted delivery of therapeutics alter monocyte & macrophage crosstalk? Macrophages are a primary component of the innate immune system, acting as first-responders to injury and initiating the activation of other cell types – including their replacement by monocyte precursors recruited from the bone marrow. Promoting a pro-regenerative macrophage phenotype is a promising therapeutic avenue under widespread investigation. However, little is known about how macrophage polarization alters monocyte recruitment and differentiation. This project area builds on my experience in therapeutic macrophage polarization to develop cell-targeted therapeutics that promote a pro-healing macrophage phenotype at the injury site, exploring the hypothesis that altered monocyte recruitment and differentiation, not the long-lasting generation of pro-healing macrophages, is the critical axis supporting an immunoregenerative response. Theme 2: How does the promotion of early post-injury inflammation alter adaptive immune response? The magnitude and temporal sequence of cell signals, including chemokines and cytokines, is a critical regulator of cell migration, differentiation, and polarization; these processes guide evolution of the injury immune microenvironment and resulting tissue-level outcomes. It has been recently observed that exogenous delivery of inflammatory signaling promotes tissue healing after ischemic injury. Here, we will explore the hypothesis that beneficial effects result from the recruitment and differentiation of regulatory T cells by macrophage-derived signals, which can be re- capitulated by sequential biomolecule release from injectable hydrogels. If successful, this project will elucidate new design principles for guiding the injury immune microenvironment toward a functional orientation that supports tissue healing. Theme 3: Can remote drug delivery systems modulate damaging systemic inflammation? A sequela of dysregulated systemic inflammation often results from significant tissue insults (heart attack, kidney injury) or chronic inflammatory disease (inflammatory bowel, rheumatoid arthritis). Such insults are associated with deleterious multi-organ effects, including renal and pulmonary fibrosis, atherosclerosis, and heart failure. This area of research explores the capacity to develop refillable drug reservoirs for delivering immunomodulatory drugs to distant immune organs, thereby modulating inflammation at the primary cell sources.

NIH Research Projects · FY 2025 · 2022-08

Black/African American (Black) young adults have among the highest cigarillo smoking prevalence in the U.S. Cigarillos contain more tobacco and higher levels of carcinogens per gram than cigarettes, with inhalation levels as high as or exceeding that of cigarette smoking. Cigarillo smoking causes multiple cancers and pulmonary and cardiovascular diseases. Outcome expectancies (e.g., utility values and anticipated emotions) are associated with Black young adults’ cigarillo smoking. Additionally, some Black young adults consider cigarillos to be less harmful and addictive than cigarettes, which is associated with their cigarillo use. Cigarillos are under the Food and Drug Administration (FDA)’s regulatory authority. The FDA is positioned to inform individuals about the health harm and addiction potential of cigarillos. Public education messaging is one effective strategy to provide accurate health information and increase harm perceptions, prevent and reduce tobacco use, and reduce tobacco-related health disparities. However, there has not been health communication studies examining effective cigarillo public education messaging for Black young adults, and how to optimize such messaging. This K99/R00 career award will help fill these gaps in identifying effective health communication strategies to communicate cigarillos’ harms to Black young adults ages 18 to 30 years. The specific aims of this proposed study are to: 1) develop and pilot test candidate cigarillo harm messaging among Black young adults at-risk for established cigarillo use; and 2) test the efficacy of cigarillo harm messaging on harm perceptions and use intentions, and explore its effects on use behaviors among Black young adults at-risk for established cigarillo use. With my mentors, I will develop and test the effects of public education messaging about cigarillos’ health harm and addiction potential alone as well as combined with messaging about outcome expectancies. I will pilot test candidate messages with Black young adults at-risk for established cigarillo use to examine their visual attention and self-report rating of perceived message effectiveness. Through an online randomized controlled trial, Black young adults at-risk for established cigarillo use will be randomly assigned to receive 1 of 3 message conditions: 1) harm; 2) harm contextualized with outcome expectancies; or 3) control messages to test intervention message effects on cigarillo harm perceptions, use intentions, and use behaviors. Participants will view two condition messages daily online for four weeks and complete self-report measures of cigarillo harm perceptions, use intentions and use behaviors at baseline, 1- and 3-month follow up. This K99/R00 career award will position me as a tobacco researcher focused on health communication for young adults at-risk for increased use of harmful tobacco products. It will provide the FDA with a sound scientific base on effective cigarillo public education messaging. These findings will also inform designing effective public education messages for other cigar and tobacco products.

NIH Research Projects · FY 2025 · 2022-07

Corticothalamic control of social motivation Abstract Social impairments are a common symptom among psychiatric disorders such as depression, schizophrenia, and autism. However, the mechanisms by which the brain processes social information and uses it to guide social behaviors remain unclear. In humans and rodents, the medial prefrontal cortex (mPFC) is thought to exert top-down inhibitory control over social behaviors, but the distinct neural circuitry involved has yet to be elucidated. While non-specific global activation of mPFC neurons decreases sociability, recent reports indicate these effects are mediated by activity changes in the posterior paraventricular thalamus (pPVT), a midline thalamic nucleus known to play a role in motivated and emotional behaviors. This proposal aims to determine whether parvalbumin (PV) interneurons in the mPFC gate activity in pPVT-projecting mPFC neurons to regulate social motivation. Our pilot data indicate that chemogenetic activation of mPFC-pPVT pathway suppressed social motivation in male but not female mice. Based on this observation, we hypothesize that pPVT-projecting mPFC neurons exert top- down inhibitory control over social motivation in a sex-specific manner. In male mice, we predict that effective social engagement requires suppressed activity of the mPFC-pPVT circuit mediated by activation of nearby PV interneurons. This hypothesis will be tested using a combination of transgenic mice, viral optogenetic constructs, behavioral testing, in vivo calcium imaging, and patch-clamp recording. Aim 1 will use optogenetics to precisely activate or inhibit axonal terminals of mPFC neurons in the pPVT to reveal how manipulating this circuit regulates social motivation. Aim 2 will combine pathway-specific calcium imaging via fiber photometry, chemogenetics, and transgenic mice to determine whether mPFC-pPVT neurons are silenced during social interaction in a manner that is dependent on PV interneuron activity. Aim 3 will determine if physiological differences exist in the mPFC-pPVT circuit between male and female mice. This study will provide the first sex-specific evidence that the mPFC-pPVT pathway represents a previously overlooked component of the social brain, especially in female mice, and novel insights into the circuit mechanisms by which the PV interneurons in the mPFC play in the regulation of social motivation.

NIH Research Projects · FY 2025 · 2022-07

Project summary Diabetic foot ulcers (DFUs) occur in 15% of diabetic patients, leading to over 82,000 lower limb amputations annually in the United States and a 5-year mortality rate of up to 74%. The reasons for impaired DFU healing are complex, but the downstream effects of chronic inflammation are major contributors. Our research has shown that while initial pro-inflammatory activation of immune cells is critical for the initiation of healing processes, prolonged activation directly impairs wound healing. Recognizing that transition from the early inflammatory phase to the late resolution phase is required for successful healing, we developed a composite biomarker that uses the change in the ratio of 4 early stage pro-inflammatory gene markers to 3 late stage inflammation-resolution gene markers over 4 weeks to predict responsiveness to treatment. By using a ratio of these early-stage to late-stage genes, referred to here as the Inflammation Index, higher values indicate wounds that are earlier in the healing process (and further from healing), while lower values indicate a wound that is later in the healing process (and closer to healing). Thus, a decrease in this index over time is linked to healing, while an increase is linked to exacerbating inflammation and non-healing. In our preliminary studies (3 cohorts of 21 subjects), the change in the Inflammation Index correctly predicted healing in 10 out of 10 healing wounds (responders), and it correctly predicted non-healing in 9 out of 11 non-healing wounds (non-responders), with an area under the ROC curve of 0.9. This biomarker utilizes debrided wound tissue so that it can be easily incorporated into standard wound care practice without adding any new techniques or time into the visit. Expression of the 7 genes that comprise the composite biomarker is measured using qRTPCR, a widely available, low-cost, and reliable technique. Finally, the use of a ratio self-normalizes the gene expression values to reduce patient-to-patient variability and increase reproducibility. In this project, we will develop and internally validate detection of this composite ratio-based biomarker; establish proof of concept of its prognostic utility; lay the foundation for a specific Context of Use (COU); and ultimately ensure that is ready for Phase II clinical trials. The proposed COU is a prognostic biomarker to identify individuals who are not likely to heal their ulcer when treated with the standard of care, for use in the personalization of treatment and/or the refinement of entry criteria for clinical trials of new treatments. In the R61 phase of this project, we will optimize biomarker measurement and standardization, and determine the quality control (QC) metrics that can be used to determine if the biomarker is accurately measured. We will also validate storage/shipping conditions and measure reliability and reproducibility. After meeting rigorous milestones the biomarker will progress to the R33 phase of the project, in which we will measure its ability to predict healing in response to the standard of care, in order to ultimately personalize treatment for patients with hard-to-heal ulcers and to refine entry criteria for clinical trials of new treatments.

NIH Research Projects · FY 2026 · 2022-07

ABSTRACT/SUMMARY Inhibitors of the mTOR pathway are among the most promising interventions to target age-related dysfunction, however, there is a critical need to further define the pro longevity effects to facilitate clinical development of mTOR inhibitors. The current proposal will significantly advance this effort providing new targets for intervention and novel markers to monitor individual responses to mTOR inhibition. The overarching goal of this research program is to develop a mechanistic understanding of novel downstream targets of rapamycin, in order to facilitate safer and more effective strategies to promote healthy aging. Cellular senescence occurs in both somatic and stem cell populations and contributes to age-related dysfunction, and our laboratory has shown that mTOR inhibition using rapamycin, can prevent entry into the senescent state. The mTOR pathway also regulates senescence a n d pluripotency in a variety of stem cell populations. The central hypothesis of the application is that mTOR inhibition by rapamycin prevents senescence and enhances pluripotency by increasing the lncRNA H19. The rationale for this hypothesis is our observation that rapamycin increases levels of the non- coding RNA (lncRNA) H19. We find that levels of H19 decrease during senescence and in pluripotent cells. H19 plays a central role during development and differentiation, and maintenance of adult stem cell populations. Rapamycin increases H19 levels, prevents senescence and maintains pluripotency. The results suggest that increasing H19 levels in response to mTOR inhibition may play a dual role, inhibiting senescence while simultaneously increasing pluripotency in adult stem cell populations. The proposed work will provide transformative data regarding a novel mechanism for lifespan extension and improvement of late-life function in multiple tissues.

NIH Research Projects · FY 2025 · 2022-06

PROJECT SUMMARY Nearly 14% of US households with children were food insecure before the start of the COVID-19 crisis, and this number increased dramatically during the pandemic. Food insecurity (FI)— inadequate access to enough food for every person in a household to live an active, healthy life—threatens critical early childhood growth and can put children at risk for poor short- and long-term health. FI is also a major source of inequity among children: compared to white households with children, Black households are 3 times as likely and Latinx households over twice as likely to experience FI. The degree to which household FI impacts children’s diet and weight may vary depending on caregivers’ shielding behaviors (e.g., skipping meals to prioritize feeding their children), characteristics of the neighborhoods where families live (e.g., healthy food access), and participation in food assistance programs. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is an important evidence-based program that supports equitable child health by providing families with children aged 0–4 access to nutritionally and developmentally appropriate foods and counseling. However, only half of those who are eligible for WIC participate; among those who do participate, nonredemption or partial redemption of the monthly benefit is common. Maximizing the effectiveness of this cornerstone food assistance program requires understanding the multilevel factors that influence families’ participation and use of the benefit. The goal of the proposed exploratory sequential mixed-methods study is to inform implementation of WIC and other food assistance policies by analyzing how household FI is associated with weight trajectories among young children, and how this association is modified by neighborhood environment and public food assistance programs. We will accomplish this goal through the following specific aims: Aim 1: Conduct in-depth qualitative focus groups with caregivers with low incomes to investigate families’ food purchasing, feeding practices, and food insecurity during the COVID-19 crisis and economic recovery, including recent changes in WIC and neighborhood characteristics. Aim 2: Assess whether FI at age 2 to 36 months predicts weight gain trajectories to age 3 and 6 years before and after onset of the COVID-19 crisis. Aim 3: Assess interactions between FI and (focus group-identified) neighborhood environments in early life as predictors of child weight gain trajectories to age 3 and 6 years before and after onset of the COVID-19 crisis. We will integrate qualitative and quantitative findings in an integrative report to inform WIC program recommendations to best support families’ healthy feeding choices and children’s healthy growth in the context of multilevel contributing factors. The evidence we produce can be used to improve WIC implementation to support families with young children in metropolitan areas long-term and in times of crisis.

NIH Research Projects · FY 2024 · 2022-05

Research Abstract The spinal cord appears, at least in part, to structure movement through combining a limited number of stereotyped ‘motor modules’. Module structure and combination is often dysfunctional in motor system diseases, such as spinal cord injury (SCI). The long-term goal of this research is to identify mechanisms of motor module structure and recruitment, to enable artificial activation or restoration to ameliorate maladaptive motor control. The objective of this proposal is to determine how spinal motor modules are activated in the spinal cord and how these modules then recruit motoneurons from the motor pools in the simpler spinal bullfrog model. The central hypothesis is that motor modules are partially independent, generate both rhythm and pattern, and recruit particular motoneurons across coactivated motor pools in turn. The rationale underlying this proposal is that frogs have unique physiology allowing chronic survival despite destruction of supraspinal centers, permitting the intrinsic capacities of the spinal cord to be studied within the intact musculature over an extended period of time. This proposal builds off historical research which activated motor modules through electrical stimulation or excitatory neurotransmitters. I will test the central hypothesis through two specific aims: 1) Evaluating independence of module activation during manipulation of spinal state, and 2) Discerning the granularity of recruitment of motor pools contributing to motor modules. I utilize two innovative methods to refine these investigations: 1) a new type of electrode which can record from many single motor units simultaneously and 2) a new mathematical tool to identify state-dependent effects between a spiking neuron with continuous signals, such as muscle activity. The proposed research is significant as it will bridge modularity research in the spinal wiping reflexes with hierarchical models of spinal motor pattern generation (e.g. locomotion). A more refined understanding of motor module organization may clarify muscle and motor pool recruitment in higher species, including humans, where direct analysis is often obscured or impossible due to increased complexity. The expected outcome of this work is an understanding of how modules are activated by the spinal cord and their capacity to be flexibly combined. This work will have a further positive impact by validating new tools and techniques for experimental use, and lay the groundwork for proactively activating motor modules in a task-dependent fashion in neuroprostheses. Towards this end, I have finished my neuroscience coursework and proposed cross-disciplinary training in biomedical engineering through Drexel University’s neuroengineering initiative to increase his quantitative skills to better pursue these questions. This training plan will combine the historically-strong program of spinal cord biology and motor control within the Department of Neurobiology and Anatomy with the quantitative rigor of formal mathematics and engineering, further equipping me to accomplish these aims and pursue a successful career as an independent research scientist.

NIH Research Projects · FY 2026 · 2022-04

PROJECT SUMMARY Spinal cord injury (SCI) is a devastating event sustained by as many as 1.3 million Americans. While not often appreciated, cardiovascular disease and susceptibility to infection are leading causes of mortality and morbidity in individuals living with SCI. One major reason thought to underlie these issues is SCI-induced dysregulation of the sympathetic nervous system. In this proposal, we will use a clinically-relevant contusion rodent SCI model to test the hypothesis that intracellular sigma peptide (ISP) will promote sufficient sprouting of serotonergic axons onto neurons in the spinal sympathetic circuit below the SCI to normalize sympathetic activity after injury. Furthermore, we hypothesize that administering a combining ISP and inhibition of soluble tumor necrosis factor alpha (sTNFα) with XPro1595 – which target different root causes of sympathetic hyperreflexia after SCI (i.e., interrupted supraspinal input the spinal sympathetic circuit and sTNFα-induced maladaptive plasticity of the spinal sympathetic circuit, respectively) – will have synergistic effects on improving cardiovascular and immune function after SCI.

NIH Research Projects · FY 2026 · 2022-02

PROJECT SUMMARY The purpose of this K01 proposal is to provide Alina Schnake-Mahl, ScD MPH with the protected time and resources to pursue the additional training needed to reach her long-term goal of an independent academic career in health policy and social epidemiology, focused on generating evidence to inform law and policies that reduce health inequities in infectious diseases. This proposal builds on Dr. Schnake-Mahl’s background as a social epidemiologist with expertise in health policy. It also leverages her experience with applied health care research and evaluation, and a cohesive mentorship team, to improve our understanding of the social determinants of COVID-19 and influenza disparities. Over 878,000 people have been hospitalized for COVID- 19 over the last year, and between 140,000 to 710,000 people are hospitalized for flu annually. Studies have found wide disparities in COVID-19 and influenza, but gaps remain with respect to the interactions between the social determinants of these disparities. This project uses diverse and multi-disciplinary approaches to examine the determinants of disparities and effects of policy exposures on disparities. The specific aims are to: 1) use multilevel analysis to describe the social determinants of racial and geographic disparities in influenza and COVID-19 outcomes in US cities; 2) use non-experimental causal inference methods to estimate the effect of PSL and rent control laws on rates and disparities of influenza and COVID-19 outcomes in US cities; 3) use agent based modeling to understand mechanisms linking two key social determinants, occupational exposures and housing overcrowding, and influenza disparities. The training goals are designed to expand skills and knowledge through training in infectious disease epidemiology, casual inference methods for policy analysis, and systems approaches including agent-based modeling. Training in this set of complementary approaches will position the candidate to pursue innovative research in the area of infectious disease disparities as part of a future R01. The proposed work has substantial potential to make a significant public health impact as these aims will advance our understanding of the social determinants of COVID-19 and influenza disparities and provide a strong evidence-base for policies and interventions that may address these inequities and reduce the overall burden of COVID-19 and influenza. Furthermore, this K01 develops specific topic area (infectious disease) and methods (advanced causal inference for policy analysis and systems dynamics) expertise whose extension to other infectious disease indicates applicability beyond the scope of this proposal. The proposed work is feasible and realistic within the award period and will allow Dr. Schnake-Mahl to continue to build research skills, extend professional networks, generate numerous publications, and compete for other NIH funding. In summary, this K01 award will support and stimulate the career development activities of Dr. Schnake Mahl and allow her to successfully move into the next phase of her career as an independent investigator.

NIH Research Projects · FY 2025 · 2022-02

PROJECT SUMMARY Title: Plasmodium vivax Erythrocyte Invasion Mechanisms and Humoral Immune Response in Duffy Negative Africans Individuals of African ancestry were thought to be protected from Plasmodium vivax because they lack Duffy antigen expression on the surface of their erythrocytes rendering P. vivax unable to invade their red blood cells. However, an increasing number of P. vivax cases reported across Africa and in Duffy-negative individuals challenges this conventional dogma, raising the possibility that some P. vivax lineages have evolved to use ligands other than Duffy Binding Protein for erythrocyte invasion. The intrinsic invasion mechanism and immune response of Duffy-negative individuals to P. vivax are largely unknown. In this application, we will investigate the expression and function of erythrocyte binding genes in Duffy-negative P. vivax and the antibody response of Duffy-negative individuals to P. vivax antigens. There are three specific aims: 1) to identify genes with differential expression between Duffy-positive and Duffy-negative P. vivax by RNA-seq; 2) to determine in vitro binding and invasion activities of P. vivax candidate ligand proteins to Duffy-negative red blood cells; and 3) to examine in vivo antibody levels to targeted P. vivax antigens associated with erythrocyte invasion in Duffy- negative patients. The proposed research will be conducted in Ethiopia, where malaria is a major public health problem and about 30% of the 1.2 million confirmed malaria cases were P. vivax. As our study sites have a large number of P. vivax cases and a significant proportion of Duffy-negative individuals, we have a unique opportunity to study the invasion mechanisms of P. vivax in Africa. We have a collaborative team and logistics in place for sample collection and processing. Our established lab culture facility closes to the health centers and successful P. vivax transcriptome data obtained from cultured schizonts have demonstrated the feasibility of this research. Comparison of P. vivax transcriptomes between Duffy-negative and Duffy-positive individuals from both in vitro and in vivo samples will provide the first description of genetic and functional attributes of P. vivax that permit infection of Duffy-negative erythrocytes. This research will significantly enhance the understanding of invasion mechanism of P. vivax in Duffy- negative individuals and lay a foundation for molecular and biochemical characterizations of P. vivax ligand-receptor interactions. Knowledge of P. vivax invasion mechanisms and host immune responses will have important implications for P. vivax vaccine development and vivax malaria risk assessment both within and outside Africa.

NIH Research Projects · FY 2024 · 2021-09

Abstract Men in the United States have an exceptionally high prevalence of overweight and obesity, i.e., 71.3%, and 42% of men are currently attempting weight loss. However, men are dramatically underrepresented in weight loss programs. Men find conventional weight loss program (i.e., group-based, education and counseling- orientated, dietary/calorie-focused) unappealing because they involve receiving counseling, focus on replacing “masculine” foods (e.g., meat) with “feminine” ones (e.g., salad), and provide minimal personalization or autonomy. As such, attempts have been made to increase recruitment and appeal through targeted recruitment and adaptations to standard weight loss programs. However, these efforts have been disappointing. Mobile applications (mHealth apps) have attractive features, but have low male enrollment and poor efficacy as conventionally delivered. A gamified mHealth program offers the possibility of engaging men and enhancing efficacy given that (1) video gaming is highly appealing to men; (2) gamification features (e.g., digital rewards for attaining “streaks” and milestones, competition) are known enhance enjoyment and motivation and facilitate desired behaviors; and (3) “neurotraining” video games featuring repetitive action mechanics, adaptive difficulty, and feedback can train inhibitory control, a basic brain capacity to inhibit intrinsically-generated approach responses that is strongly linked to body mass and the consumption of high- calorie foods. Inhibitory control training (ICT) games have been successful at reducing consumption of targeted foods/beverages and improving short-term weight loss. For instance, in our preliminary work we demonstrated that a weight loss workshop plus a short, daily ICT produced greater weight loss for individuals with higher- than-average implicit preferences for high-sugar foods, compared to a robust attention control (i.e., the workshop plus a sham training), and we found that adding gamification elements (e.g., story, music, levels) to a rudimentary game produced additional 8-week weight loss for men (4.1% vs 2.5%). This project extends previous work by evaluating the independent effects of gamification and ICT on long-term engagement and outcomes. As such, 243 men with BMI ≥ 25 will be recruited, with 15 participating in usability testing and 228 assigned to a 12-month mHealth weight loss program that prescribes digital self-monitoring and dietary and physical activity targets. Utilizing an efficient 2 x 2 factorial design, participants will be randomized to receive either a standard or fully-gamified program, comprised of a behavior change program featuring team-based competition, and digital reinforcers for attainment of streaks and milestones, and also randomized to receive either sham or active inhibitory control neurotraining. Aims include evaluating the efficacy of gamification and ICTon weight loss, diet and physical activity at 12 months, as well as evaluating hypothesized mediators (engagement and inhibitory control) and moderators (baseline frequency of video game play and implicit preferences for ICT-targeted foods).

NIH Research Projects · FY 2024 · 2021-09

PROJECT SUMMARY In response to the NIH U54 Faculty Institutional Recruitment for Sustainable Transformation (FIRST) Program (RFA-RM-20-022), Drexel University proposes to establish a robust, transformative and sustainable program to support diverse early career scientists engaged in health disparities research spanning population science to intervention research. This proposal, a collaboration across Drexel University led by Drexel’s Dornsife School of Public Health and College of Nursing and Health Professions, leverages our nationally and internationally recognized NIH and other extramurally supported research, our community-based clinical practices serving diverse, underserved communities, and our shared core values of social justice and health equity guiding our pedagogy, research and hiring practices. Our proposal also strongly reflects Drexel University’s unwavering commitment and newly instituted strategic goals to promote inclusive excellence and ensure diversity, equity, retention, and promotion across for diverse faculty across their career pathways. Our proposed program will create a collaborative structure involving multi-level inputs from University leaders, academic units and faculty to catalyze sustainable institutional change that supports scientific and inclusive excellence in the conduct of health disparities research. With support from the FIRST program, we will hire and mentor a diverse (gender, race, ethnicity) group of 10 early-stage faculty in three clusters who are competitive for tenure-track research positions with joint or secondary appointments across relevant departments, programs, or colleges, Using evidence-based, multi-level mentorship strategies at the individual, department, college and university levels, we will form a scientifically rigorous and supportive learning community in which FIRST faculty will engage in individual and group activities leading to submissions of competitive NIH R01 research proposals. FIRST faculty will be hired who are committed to diversity and whose research addresses one of 3 pillars of health disparities research: detecting (defining/measuring health disparities), understanding (identifying determinants of disparities), and/or reducing (intervene, evaluate, translate, scale, policy) health inequities in cross-cutting thematic areas (aging, chronic disease, and/or environmental determinants). Developing and supporting a cadre of diverse researchers has been identified as an evidence-based strategy for advancing new methodologies, measures, and novel multi-level/multi-modal interventions that address inequities and improve individual and population health outcomes. We will deploy a multi-level and multi-methods evaluative approach guided by critical and intersectionality theories to evaluate nuanced experiences of bias and structural discriminatory practices as well as program successes at the individual, department, mentor, college and University levels of achieving inclusive excellence. Our FIRST Program is co-led by nationally/internationally recognized leaders in population health, intervention science, mentorship of racially/ethnically diverse faculty and evaluation of programs seeking inclusivity.

NIH Research Projects · FY 2024 · 2021-09

Summary/Abstract The reactive oxygen species (ROS) including hydrogen peroxide (H2O2) are key signaling molecules that mediate diverse biological processes, including cell migration involved in tissue repair, immune response, and cancers. The central molecular targets of ROS are protein cysteine residues that form various thiol oxoforms, including S-glutathionylated cysteines, termed as S-glutathionylation. This protein S-glutathionylation regulates protein activity in a number of signaling pathways. Despite the continuing advance on identification of glutathionylated proteins, identification of the specific glutathionylated cysteines that control definite biological functions has been challenging. To provide the insights into the glutathionylation-susceptibility of global cysteines, we have developed a chemical proteomic approach, termed clickable glutathione, that enables to study S- glutathionylation. In this proposal, we will develop an integrative strategy combining our chemical proteomic platforms with functional biological analyses to streamline identification of glutathionylation-susceptible cysteines that control cell migration. First, we aim to identify glutathionylation-sensitive cysteines in mammalian cell lines during cell migration induced by D-amino acid oxidase (DAAO) with D-Ala, which produces spatiotemporal and magnitude-controlled levels of H2O2. We will use our quantitative proteomics and bioinformatic analyses to identify a group of cysteines highly susceptible to glutathionylation and functionally related to migration. Because of the importance of localized H2O2 production, the strategy will be extended to the use of localized DAAO/D-Ala systems to determine localization-dependent glutathionylation of global cysteines. Second, we aim to determine regulatory roles of the identified glutathionylated cysteines in cell migration. In preliminary studies, we identified the redox-active glutathionylated cysteines in three proteins, PP2Cα, ARHGEF7, and NISCH, which increase cell migration in functional analyses. We will investigate glutathionylation-susceptibility of three proteins and their downstream signaling pathways mediated by glutathionylation. Lastly, we will apply a combination of chemical proteomics, bioinformatics, and functional screening analyses to find new glutathionylation-susceptible proteins that regulate cell migration.

NIH Research Projects · FY 2025 · 2021-09

PROJECT SUMMARY Over the last several decades, cardiovascular disease (CVD) incidence and the prevalence of CVD risk factors have steadily increased in the Central American region, in contrast to other countries of the Americas where CVD is no longer increasing or on the decline. The rise of CVD in the region has occurred in tandem with increases in urbanization and widening social inequities, and poses a growing, untenable burden for its limited public health and health care systems. While research in high income countries highlights interventions on social determinants of health as levers to prevent cardiovascular disease, less is known about the specific, intervenable social determinants that can help prevent CVD in Central America. Training and mentoring of the local workforce in identifying relevant research questions, in the use of appropriate research methods, and in the dissemination of results to the scientific community, the public, and policy makers is critical to identify and develop interventions to prevent CVD in the region. To this end, researchers from Drexel University and the Institute for Nutrition of Central America and Panama (INCAP) have partnered to establish a training program focused on developing the research capabilities of trainees and local capacity building in the conduct of policy- relevant research on the influence of social determinants and place-based factors on CVD risk across the lifespan. Key elements include: (1) a focus on factors at multiple levels (from cities, to neighborhoods, to persons) and over the lifecourse, (2) the use of rigorous state-of-the-art methods; (3) an emphasis on the value of interdisciplinary approaches; and (4) dissemination and translation of research findings into policy actions. The program leverages the SALURBAL Study, a unique multidisciplinary collaboration focused on the region. Training activities will include (1) training of up to 3 PhD students or up to 5 Masters students; (2) support for up to 4 postdoctoral fellows and 11 visiting faculty fellows promoting the development of junior and mid-career faculty; (3) annual workshops and periodic webinars and journal clubs on social determinants of health, CVD and lifecourse epidemiology, and research methods; (4) support for the development of data management and analytical capacity on site; and (5) enhanced south-south collaborations in mentorship and research. As a result of the program we expect to see an increase in the number researchers with Masters or Doctoral degrees at INCAP, an increase in the number of publications and grant proposals submitted by local researchers, larger numbers of mentoring relationships, publications, and grant proposals involving collaborations between INCAP and other countries in the region, greater capacity for data management/analysis at INCAP, and greater engagement of local investigators in CVD research and dissemination activities, including policy translation in the region. We also expect to see a continuation proposal to this training program submitted by INCAP as lead at the end of the this initial phase of the program.

NIH Research Projects · FY 2025 · 2021-08

PROJECT SUMMARY Prenatal air pollution exposure has been repeatedly identified as risk factor for autism spectrum disorder (ASD), with support for associations with particulate matter less than 2.5 microns in diameter (PM2.5), ozone, and nitrogen dioxide (NO2). Research from other fields suggests diet may be a key modulator of air pollution risks in pathways relevant to autism, yet only one study, examining the joint effects of folate and air pollution, has been published on ASD risk. However, a range of dietary factors beyond folate, including polyunsaturated fatty acids (PUFAs) and vitamin D, may serve to offset effects of exposures. In addition, given that nutrients do not act in isolation, studying single nutrient-pollutant interactions may provide only part of the picture. Further, time- windows for such modification have not been identified. In the proposed study, we will address these gaps and examine how prenatal diet may modify air pollutant associations with ASD-related outcomes in two prospective cohorts. The Nurses’ Health Study 3 (NHS3) is an ongoing, large prospective cohort of nurses from across the US that includes a pregnancy sub-cohort (n>7,000). The Early Autism Risk Longitudinal Investigation (EARLI) is a high-risk cohort that followed mothers who already had a child with ASD through a subsequent pregnancy until that child was age 3 (n~200). ASD-related outcomes will be captured in both studies according to Social Responsiveness Scale (SRS) scores, as well as ASD diagnosis, allowing us to consider both dimensional traits across the population and diagnostic-level risks. Both studies will have air pollution exposure assignments for PM2.5, NO2, and ozone from the same method and prenatal nutrient data from validated food frequency questionnaires. Using these data, our aims are to: 1) Examine modification of air pollutant-ASD associations by folate, vitamin D, and PUFAs; 2) Evaluate interactions between air pollutants and nutrients on ASD-related outcomes within a multi-exposure framework; and 3) Examine time windows in the air pollution-ASD relationship when dietary nutrients might be most impactful. Aim 1 analyses will use linear and logistic regression to examine associations with SRS scores and ASD diagnosis, respectively, within strata of nutrients defined by deficiency status and prior interaction in each cohort. In Aim 2, we will use Bayesian Kernel Machine Regression (BKMR) to consider nutrient-pollutant interactions within the context of broader diet, accounting for a wider set of nutrients and considering potential combined effects on ASD outcomes. In Aim 3, we will use distributed lag models to consider potential critical windows of air pollutant associations with ASD-related outcomes in which nutrient modifiers may have strongest effects. In this proposal we address a critical, yet understudied, area of research. Due to the widespread occurrence of air pollution exposure, and because diet is a readily accessible, individual- level modifiable factor, findings from this project present the potential for a large public health impact.

NIH Research Projects · FY 2025 · 2021-07

Abstract Adults attempting weight loss through lifestyle modification (LM) typically find maintenance of behavior change difficult. Outcomes might be improved if participants are provided with sustained sources of accountability and support and ongoing opportunities to reflect with others on goal progress. This study proposes that sharing digital data (i.e., body weight from wireless scale, physical activity from wearable sensor, and dietary intake from smartphone app) with other parties has the potential to improve long-term weight loss. The benefit of device data sharing has not yet been rigorously tested, and traditional LM programs do not yet incorporate digital data sharing in a systematic way. The proposed study will enroll adults (N = 320) with overweight/ obesity in a 24-month LM program and instruct them to use digital tools for self-monitoring of weight, physical activity, and eating on a daily basis. Groups will meet face-to-face weekly in months 1-3 to initiate weight loss. In months 4-24, intervention contact will be remote and will include the following: quarterly group meetings held via videoconference; brief phone calls with the coach held twice per quarter; and monthly text messages with the coach, with a small group of fellow group participants, and with a friend or family member outside of the program. A 2 x 2 x 2 factorial design will test the independent effects of three types of data sharing partnerships: Coach Share, Group Share, and Friend/Family Share. Half of the participants will receive Coach Share and half will not; half will receive Group Share and half will not; and half will receive Friend/Family Share and half will not. In Coach Share, the behavioral coach will view digital self-monitoring data throughout the program and will directly address data observations during intervention contacts. In Group Share, participants in a given LM group will view each other’s self-monitoring data in their small-group text messages. In Friend/Family Share, a friend or family member outside of the group will view the participant’s data via automated text message. Each party with whom data are shared will be trained to respond by eliciting reflection from the index participant on his/her goal progress, which is a key component of self-regulation, and supporting the participant’s motivation to meet program goals. Amount of intervention contact between the participant and each party (Coach, Group, Friend/Family) will be comparable across treatment conditions, isolating the effects of data sharing components. Outcomes will be measured at months 0, 6, 12, and 24. The study will determine if Coach Share, Group Share, and Friend/Family Share each improve long-term weight loss, PA, and calorie intake (i.e., outcomes will be compared for participants who are randomized to engage in that data sharing partnership, versus those who are not). The study also will examine if effects are additive when participants are assigned to engage in more than one type of data sharing partnership. Mediators and moderators of intervention effects will be examined. As digital technology makes data sharing increasingly feasible, it is critical to determine how to optimize these partnerships to improve long-term outcomes in LM.

NIH Research Projects · FY 2026 · 2021-07

Women who inject drugs (WWID) experience disproportionate rates of HIV infections due in part to challenges negotiating HIV prevention tools such as condoms with male partners. In contrast, pre-exposure prophylaxis (PrEP) is a discrete biomedical prevention strategy that can be taken without involving sexual partners. There is strong evidence that WWID find PrEP acceptable, however, they face multilevel barriers to uptake and adherence, including trauma, substance use, and economic insecurity. This randomized controlled trial will test whether adding a trauma-focused expressive writing (EW) intervention to contingency management (CM) reduces HIV acquisition risk (primary outcome) among WWID initiating PrEP. CM will target objectively verified PrEP adherence and stimulant/opioid abstinence, and outcomes will be compared with an attention-control condition using neutral writing plus CM. HIV acquisition risk will be operationalized as syringe sharing or condomless sex during objectively measured periods of PrEP non-adherence. WWID who are at risk for HIV (e.g., report syringe sharing or condomless sex and no PrEP use within 30 days) will be linked to HIV testing and PrEP care at a large syringe services program operating a low barrier PrEP clinic in Philadelphia. A cohort of 240 WWID initiating PrEP will be enrolled and immediately begin a 3-month CM period, and those completing a run-in period will be randomized (1:1) to EW+CM (n=120) or Attention-Control+CM (n=120). Follow-up assessments will be conducted at 3, 6, and 12 months post-randomization and will include review of medical records to verify on-time receipt of long-acting PrEP and collection of scalp hair to quantify monthly levels of tenofovir among those taking oral PrEP. At 3 and 12 months a purposive subset of 60 WWID (30 from each condition), will participate in qualitative interviews designed to contextualize primary and secondary outcomes. The specific aims of this trial are to: (1) Determine the efficacy of EW+CM for improving the proportion of participants achieving reductions in HIV acquisition risk at 12 months. (2) Examine key secondary outcomes such as greater PrEP persistence, reductions in substance use, PTSD symptoms, depression, entry into drug treatment, and cost-effectiveness over 12 months. (3) Evaluate mediating pathways through which the intervention operates (e.g., mediated by reductions in substance use or emotional expression and processing in EW essays) and moderators of these relationships (e.g., more pronounced among those with higher PTSD severity at baseline). This novel RCT has the potential for substantial impact by generating one of the first evidence-based interventions to address HIV acquisition risk among WWID in the era of PrEP, including a cost-effectiveness analysis to inform implementation and scale-up if EW+CM is efficacious. The long-term outcome of this research program will be a reduction in HIV through a replicable model that optimizes PrEP engagement among WWID.

NIH Research Projects · FY 2025 · 2021-07

PROJECT SUMMARY/ABSTRACT Spinal cord injury (SCI) is a devastating condition that affects about 250,000 Americans with 17,700 new cases annually costing upwards of $2 million each. There is very little that can be done to treat these patients that improves their prospects for even partial recovery or the amelioration of symptoms that negatively impact their quality of life. SCI research continues to advance, but bolder and more innovative breakthroughs are needed, if the efforts are to translate into therapies that improve symptoms, alleviate pain, and restore functionality. As highlighted by the NIH-hosted SCI-2020 meeting, a new generation of SCI researchers is desperately needed, one that is thoroughly educated in all of the needed background and history of the field while also equipped to bring new technologies and insights into the field through strong collaborative interactions with scientists from other fields. Drexel University College of Medicine is home to the Marion Murray Spinal Cord Research Center, which has over three decades of history advancing the SCI field while simultaneously educating and training doctoral students to take the field forward. Within the Center is the Drexel SCI Training Program, which consists of well-funded and vibrant investigators who study SCI from many different perspectives, and mentor trainees in many different approaches. These include engineering, electrophysiology, cell transplantation, rehabilitation and others. The center has extensive multidisciplinary collaborations with Drexel investigators from other fields, many of whom are involved in the SCI Training Program. The Center is based within the Department of Neurobiology and Anatomy, with the students affiliated with the Neuroscience Graduate Program. SCI students are exposed to a multitude of training experiences, including but not limited to what the Neuroscience Graduate Program offers, with flexibility that welcomes students from other graduate programs to transfer into the program in order to conduct SCI-relevant research. The program has existed for over thirty years, with consistent success of the students securing F31 funding to fund their senior years, and then achieving success in their careers after completing the program. T32 funding for the program will enable expansion of the research and the number of trainees, thus improving the prospects of SCI patients, for whom treatments have remained elusive for too long.