George Washington University

NSF Awards · FY 2025 · 2025-08

Many viruses in the environment threaten human health. Enteric viruses that cause diarrhea in humans are commonly found in municipal wastewater. Treated wastewater is increasing being used in farming, in industrial processes, in recreation, and in other proposes. It is imperative to guarantee that disease-causing viruses are effectively removed from this water source. Treatment can be challenging because of the small size of viruses and their tendency to stick together with bacteria to infect humans more easily. This project will determine how these enteric viruses from wastewater cause human illnesses. This project will use cross-disciplinary tools in laboratory experiments and environmental surveys to address the question. The study outcomes will aid in the effective management of wastewater and will help protect public health. This project will also train students and help the public learn more about environmental viruses. Advancing knowledge about the association between viruses and bacteria in aquatic environments is necessary to develop effective pathogen control strategies. This project will fill research gaps on the transmission, occurrence, and health impacts of bacteria-associated enteric viruses in aquatic environments and provide insights into the control of viral pathogens and protection of public health. The objectives of this research are to i) elucidate the impact of bacterial association on infectivity, environmental persistence, and disinfection resistance of enteric viruses; ii) investigate the occurrence, abundance, and removal of emerging bacteria-associated viruses in wastewater treatment and natural environments; and iii) explore the health impacts of bacteria-associated viruses through examining host responses. A suite of microbiology, omics, surveillance, and immunology tools will be integrated to achieve these objectives. The research will also be integrated into education to i) develop new education modules to foster students’ understanding in environmental pathogens and water disinfection; ii) increase the number of students from diverse educational backgrounds pursuing careers related to water; and iii) raise the understanding of the public about environmental pathogens and their control. The outcomes of this project will provide a framework to evaluate the fate and transport of pathogens interacting with other substances in complex environments. In addition, this project will extend the boundaries of environmental engineering and environmental virology to include immunology, which will enhance the understanding of health risks posed by environmental pathogens through host-pathogen interactions beyond mere infection. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-08

Project Summary Ovarian cancer (OC) is the most lethal malignancy of the female reproductive system with poor responses to immunotherapies due to a highly immunosuppressive tumor microenvironment. In contrast, higher levels of infiltrating lymphocytes are associated with better survival in OC, emphasizing the need to develop strategies to enhance immune cell recruitment and activation. One strategy is the use of DNA methyltransferase inhibitors (DNMTis), which include the FDA approved 5-Azacytidine and 5-Aza-2’-deoxycytidine, to increase the expression of transposable elements (TEs) to promote an antitumor immune response. The removal of DNA methylation upregulates TEs which form double-stranded RNAs (dsRNAs) that can be sensed by immune sensors, triggering type I interferon signaling in a response termed “viral mimicry”. Following type I interferon induction, immune cells are recruited and activated to promote antitumor immunity. However, many cancers exhibit high baseline levels of TE expression without signaling an immune response. This highlights the potential role of post-transcriptional regulation, such as RNA methylation, in the negative regulation of the viral mimicry response. Indeed, RNA methylation, specifically N6-methyladenosine (m6A), has been shown to promote the degradation of TE RNA and prevent dsRNA formation. In OC, the main m6A writer, METTL3, has been described as an oncogene. Additionally, other m6A readers are overexpressed compared to normal tissue and associated with poor survival and reduced immune cell infiltration. These specific aims will test the overall hypothesis that m6A modulates transposable element RNA to limit dsRNA sensing and dampens the viral mimicry response. Aim 1 will determine how m6A of TEs change throughout the transformation of fallopian tube cells, the common cell of origin for high-grade serous OC. Aim 2 will elucidate the role of m6A in regulating TEs and downstream immune signaling following epigenetic therapy. Collectively, the proposed aims will investigate the role of m6A in regulating TE RNA and downstream innate immune signaling during OC transformation and in response to epigenetic therapy. Results from these studies will provide insight into the potential for pharmacologically inhibiting m6A alone or synergistically with epigenetic therapy to promote antitumor immunity in OC.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT The majority of drugs prescribed to pregnant individuals lack dosing information specific to this population. Dosing is different in this population due to anatomic and physiologic changes during pregnancy that substantially affect drug exposure. A lack of appropriate dosing data in pregnant individuals is an unmet public health need that can result in therapeutic failure and maternal and fetal morbidity. Our objective for the Dosing and Safety of Understudied Drugs Administered to Pregnant Individuals per Standard of Care (PregDose) Study is to create the research infrastructure to address these dosing knowledge gaps and determine optimal dosing for commonly used drugs in pregnancy. We will accomplish this goal through an integrated approach that is centered on a prospective, multi-center, opportunistic study of understudied drugs in pregnant individuals. In AIM 1, we will enroll pregnant individuals who are on a drug(s) of interest per standard of care. Biological samples and markers of drug efficacy will be collected throughout pregnancy and in the postpartum period. Postpartum samples will also include cord blood and infant blood to better understand fetal/neonatal exposure. Using an aliquot of each sample, in AIM 2 we will establish a biorepository to aid future precision- dosing studies. In AIM 3 we will use sophisticated pharmacokinetic (PK)-pharmacodynamic (PD) modeling to determine optimal dosing. This modeling will identify key determinants of drug exposure-effect to inform a pregnancy precision dosing tool. The PIs and research team have a successful history in maternal pharmacology and possess the skills, access to patients, and research environment needed to complete these projects. Dr. Rebecaa Clifton is a biostatistician, the PI of the Maternal-Fetal Medicine Units (MFMU) Data Coordinating Center and will oversee all study efforts. Dr. Watt is a pediatrician, experienced trialist and pharmacologist, serves on the PRGLAC Implementation Working Group, and has led similar opportunistic dosing studies in children and lactating individuals. Dr. Torri Metz is a maternal fetal medicine specialist with extensive experience in obstetric drug trials. Importantly, this study will leverage the infrastructure and resources of the NICHD-funded MFMU Network and Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. Key MPRINT co-investigators have the expertise and resources to develop the assays to measure drug concentrations (Momper), support the PK-PD modeling (Quinney, Momper, Bies), and develop the model-informed precision dosing tool (Quinney, Bies). To maximize scientific exchange and accelerate research in the field, all information, data, protocols, resources, and methods developed by PregDose will be shared through the MFMU and MPRINT Hub and with the research and clinical community at large.

NIH Research Projects · FY 2025 · 2025-08

Project Summary The expression of noncoding, repetitive regions of the genome termed Transposable Elements (TEs) have shown strong preclinical potential as immunogenic agents that sensitize tumor cells to immune-modulating therapies. Hypomethylation of the genome, dysregulated heterochromatin silencing, and mutations in regulatory transcription factors results in elevated TE expression. Transcription of retrotransposons, a class of TEs that rely on an RNA intermediate, result in type-I interferon (IFN) signaling and improve immune cell recruitment and cytotoxic removal of tumor cells in cancer models including ovarian, colorectal, breast, and melanoma. However, it remains unclear how durable interferon responses induced by TEs can be harnessed therapeutically. Therefore, characterization of TE regulation and downstream activation of the type-I IFN response is critical to improving the immunogenic potential of tumor cells. In the F99 phase of this proposal, I will investigate how mutations in p53, a known regulator of TEs, derepresses retrotransposon transcription in ovarian cancer. Specifically, I will determine how wildtype and R175H p53 differentially bind and recruit cofactors at TE loci. I will examine the viral signaling cascade activated by TE RNA, known as MAVS/MDA-5, in both wildtype and R175H p53 settings to assess blunted signaling activation in response to high TE transcription. Overall, this work will determine how mutations in p53 alter its chromatin binding to derepress retrotransposons and identify how the ovarian tumor cells circumvent downstream IFN activation. In the K00 phase of this proposal, I will utilize my experience studying TEs to profile how disruptions in nuclear architecture during tumor cell migration contribute to TE expression and type-I IFN signaling. I will compare publicly available matched primary and metastatic RNA-sequencing data to assess TE derepression and type I IFN signaling across metastatic events. I will validate the re-expression of TEs across metastasis using both in vitro microfluidic micron-sized constrictions and in vivo mouse metastatic models. These models will determine the impact of tumor cell migration on TE expression, implicate the disruption of nuclear lamina architecture to TE derepression, and profile the activation of type I IFN. The proposed research will inform the mechanisms of TE regulation and the downstream IFN response during tumor evolution, and this will identify critical targets that mediate TE sensing needed to promote the immunogenic potential of TEs as therapeutic targets in immunologically “cold” tumor types. These mechanisms will inform how TE re-expression can further sensitize tumors to immune-modulating therapies to improve cancer patient outcomes.

NSF Awards · FY 2025 · 2025-08

The objective of this project is to support research on mathematical conceptualization for planning and taking infrastructure investment decisions based on real options and risk tradeoff. Protecting civil infrastructures against natural hazards is crucial to the welfare of communities. Such protections involve major capital expenditure and often take years to complete. Yet not taking actions comes with detrimental consequences in the forms of economic loss, physical damage, casualty, and population displacement. There are difficult tradeoffs between taking early action when uncertainty is high and deferring them when uncertainty is low. While popular in finance, options theory has been utilized at only a basic level in civil engineering applications, typically focusing on a single element, ignoring system effects and uncertainty sources, risk tradeoffs, and assuming risk neutrality. This project contributes to fundamentally changing the framing of the underlying protective investment decision problem and advancing the needed mathematics and algorithms to achieve this. The project involves four key research thrusts designed around: (1) advancing real options analysis methods under multiple uncertainty sources; (2) risk trade-offs and risk behavior modeling; (3) network-wide impacts and interacting options; and (4) machine learning approaches for information-rich environments. This project builds on concepts from optimal stopping theory, the Black-Scholes model, chance-constrained stochastic integer programming via p-efficiency, approximate dynamic programming, partially observable Markov decision processes, deep reinforcement learning, multi-agent extensions, and more. “Learn-to” algorithmic approaches that embed machine learning within optimization algorithms for speed-up, and explainable artificial intelligence for actionable protocols are developed. Educational and outreach activities include educational modules/mini-videos; presentations to decision-makers; input from local decision makers; involvement of undergraduate students and cross-university events and courses. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-07

NSF’s Secure and Trustworthy Cyberspace (SaTC) program is interdisciplinary and highly competitive. New principal investigators who do not have experience with SaTC expectations and norms often struggle to write successful funding proposals. This workshop offers junior researchers without prior SaTC funding training and experience in proposal development. The workshop’s novelties include providing not just lectures, but hands-on experience such as writing a short mock proposal and participating in a peer-review session modeled on real NSF review panels. This provides participants with direct knowledge of the process as well as peer feedback on their proposed ideas. The workshop’s broader significance and importance lie in allowing junior researchers, especially those without pre-existing networks of successful SaTC researchers, to access implicit knowledge they may not otherwise have access to, enabling them to present their ideas in the best light. This helps ensure that promising ideas for new SaTC research will contribute to our overall understanding of cybersecurity. The 1.5-day workshop includes panel discussions and small-group mentoring from established SaTC researcher “coaches,” as well as mock panel review led by these coaches. Participants write mock proposals before arriving, edit them on day 1 after learning more about proposal writing, and review each others’ proposals on day 2. Participants leave the workshop with an increased understanding of the panel review process, explicit instruction in how to structure and format proposals to meet SaTC expectations, and an expanded peer and mentoring network. The workshop will help new investigators establish themselves within the security and privacy research community so that they can continue to contribute valuable research over the course of their careers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-07

This project investigates users in an enclave community to understand how they achieve and set standards for security and privacy, and the technologies specifically designed and deployed by these communities. The proposed work begins with a focus on ultra-Orthodox Jewish communities worldwide that have developed tailored technologies of specialized phones and network infrastructure that enables internet access with community-defined interventions. The project aims to fulfill two main goals: to provide scientific insight into the dynamics between modern technological and restriction and its impact on security and privacy, and to understand the technical and social mechanisms by which the technological infrastructure affects access and the kind of content that is accessible. To achieve these goals, this project leverages an international collaboration to study these communities and the technologies they produce. The project will investigate how community members and IT staff interact with technology, their perceived risks and concerns, and how those beliefs and attitudes form their mental models of security and privacy. The project will also investigate the advice and guidance provided by IT staff and the community, the mechanisms by which the community evaluates and influences access, and the kind of content that is accessible to members. As an outcome of this research, the project seeks to expand a broader understanding of security and privacy for previously unstudied communities with potential to improve security and privacy for all. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-07

The Traveling Gallery of Fluid Motion (TGFM) is an art exhibition inspired by fluid dynamics, a discipline that describes the flow of liquids and gases. The TFGM exhibition will be open to the public from October 2025 through February 2026 at the Houston Museum of Natural Science (HMNS), one of the most visited museums in the U.S., attracting nearly 2,000,000 visitors annually in Houston, TX. This unique exhibition draws from past submissions to the Gallery of Fluid Motion (GFM), a program founded in 1987 as part of the American Physical Society (APS) Division of Fluid Dynamics (DFD) conference, to highlight unique images and videos of the aesthetics and science of contemporary fluid dynamics. The TGFM expands this stimulating experience by teaming with curators and museums to expose science and art to the general public audience. For the third consecutive year, a selection of past GFM submissions have been transformed into an educational art exhibition designed to engage the senses and inspire a broader audience. The creators of the artworks on exhibit, ranging from photography and video to sculpture and sound, are created by scientists and artists and often combined with music. Their work enables us to “see the invisible” and understand the ever-moving elements surrounding and affecting us in fluid flows. Several of the artworks are specifically connected to the Houston region’s deep ties to the oil and energy sectors, highlighting fluid motion in contexts such as drilling, refining, and atmospheric flow. Gases and liquids are in constant motion, advancing in seemingly chaotic ways, yet the flow images and videos in this exhibition offer a closer look, revealing elegant and poetic patterns amidst atmospheric turbulence. The first TGFM exhibit, Chaosmosis: Assigning Rhythm to the Turbulent, premiered in 2023 at the National Academy of Sciences (NAS) in Washington, DC. The second exhibit, Spiraling Upwards, was showcased at The Leonardo Museum in Salt Lake City, UT, in 2024, and focused on the intersection of Leonardo da Vinci's studies on fluid dynamics and flight. The TGFM program will also include STEM enrichment events, panel discussions with artists and scientists, a website with extra educational resources such as articles, interviews, do it yourself (DIY) guidelines, and a HMNS reception at the conference in November 2025 to create opportunities for interdisciplinary dialogue and local community engagement. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-07

ABSTRACT Hypertensive disorders of pregnancy (HDP) affect up to 1 in 8 pregnancies and lead to significant short and long- term morbidity and mortality for mothers and neonates. HDPs are classified as non-severe and severe. In non-severe forms of HDP, specifically gestational hypertension or preeclampsia without severe features, pregnant individuals have elevated systolic blood pressure (BP) between 140 – 159 mmHg and/or elevated diastolic BP 90 – 109 mmHg without evidence of end-organ dysfunction. In contrast, severe HDP, including preeclampsia with severe features and eclampsia, is characterized by severe hypertension defined as BP ≥160/110 mmHg or evidence of end-organ damage such as liver or kidney dysfunction or seizures. Although delivery minimizes risks to the mother, depending on the gestational age, delivery may lead to increased risks for the neonate, particularly adverse outcomes associated with prematurity. Five percent or more of all pregnancies are affected by non-severe HDP at <370 weeks. The standard of care is to expectantly manage patients with non-severe HDP with close observation and serial surveillance until 370 weeks gestation or when severe disease develops, whichever occurs first, at which time delivery is indicated. Unfortunately, non-severe HDP progresses to severe HDP in 30 - 50% of cases <370 weeks gestation. As such, it is critical to identify interventions to safely reduce the progression from non-severe to severe HDP. A recent trial in pregnant women with chronic hypertension demonstrated that treatment of BP to a goal of <140/90 decreases the risk of preeclampsia and improves outcomes for mother and baby. Based on this, clinical guidelines were changed and now recommend a BP goal <140/90 for all pregnant individuals with chronic hypertension. However, no definitive trial has been performed demonstrating that BP goals <140/90 in non-severe HDP are beneficial and safe, leaving the clinical question: Does starting oral antihypertensive medication when a patient develops a non- severe HDP prolong gestation and benefit the mother and infant without increasing maternal or fetal risks? Therefore, we propose The GOALPOST Trial, a phase III, open-label randomized control trial (N=4,120) of antihypertensive treatment in pregnant individuals with non-severe HDP conducted through the NICHD Maternal- Fetal Medicine Units Network. Participants will be randomized 1:1 to 1) intervention – oral antihypertensive therapy to targeted BP goals <140/90 mmHg or 2) usual care – no antihypertensive therapy unless BP ≥160/110 mmHg. We will evaluate whether the intervention reduces adverse pregnancy (Primary Aim) and neonatal outcomes (Secondary Aim). A comprehensive safety plan will ensure close clinical monitoring of mother and fetus to enhance safety. The GOALPOST Trial has the potential to change management guidelines for the treatment of non-severe hypertensive disorders of pregnancy in the US and worldwide and to improve outcomes for countless women and children.

NSF Awards · FY 2025 · 2025-07

This I-Corps project is based on the development of medical device designed to prevent guidewire retention incidents during catheterization of blood vessels. In vascular procedures, a guidewire serves as a support to help guide a catheter into blood vessels, ensuring accurate and secure placement. A guidewire is used in central venous catheterization, which is a common medical procedure performed over 5 million times annually in the United States for critically ill patients. Despite clinicians’ best efforts, the procedure carries a complication rate of 12–15%, including the rare but serious event of complete guidewire retention in the body, which can lead to serious medical complications and even death in up to 20% of cases. This technology addresses this issue with a fail-safe design that reduces reliance on human vigilance. It features a P-shaped tail that externally anchors the guidewire, preventing it from unintentionally slipping into the body. This design enhances procedural safety without increasing complexity or training burden. Use of this guidewire may improve patient safety, reduce liability risks for hospitals, and result in savings in healthcare costs. This I-Corps project utilizes experiential learning coupled with first-hand investigation of the industry ecosystem to assess the translation potential of a modified guidewire designed to prevent retention incidents during central venous catheterization (CVC). CVC is a common medical procedure performed over 5 million times annually in the United States across emergency departments, intensive care units, and operating rooms for critically ill patients requiring parenteral nutrition, dialysis, and medication administration. The guidewire is designed with a rear loop in the shape of a P that acts as a physical barrier against accidental intravascular retention. The technology builds on the widely used Seldinger technique but incorporates a structural safeguard that functions independently of user behavior. Currently, guidewires do not include a built-in mechanical feature to prevent retention and rely on manual techniques that are vulnerable to human error. This technology may be integrated into existing central-line kits, creating value for medical device manufacturers, reducing liability risks for hospitals, and improving patient safety. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-07

This award supports student travel for about 15 U.S.-based students to attend the 2025 Privacy Enhancing Technology Symposium (PETS) in July 2025. PETS is a leading venue for cutting-edge research that addresses the design and development of privacy services for the Internet, as well as other data systems and communication networks. The symposium brings together anonymity and privacy experts from around the world to discuss new perspectives and recent advances around privacy. This travel award will enable a number of students with financial need to attend the conference, providing them the opportunity to discuss leading edge research with world-class computer researchers in privacy, and establish professional connections and mentoring relationships that will serve them well during their research careers. This grant provides travel support to encourage participation in the 2025 PETS conference by students who would normally find it difficult to attend. The organizers will widely advertise the availability of funding and encourage applications by students from groups under-represented in computer security. Criteria for selection include evidence of a serious interest in the field, as demonstrated by research output, coursework and/or project experience; financial need; and, among qualified candidates, a breadth of institutional, disciplinary, topical, and personal backgrounds. Selected students will be invited to volunteer at the conference; student volunteering provides additional opportunities to meet other volunteers in their cohort as well as senior researchers in the field. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-07

Opioid addiction and misuse is a serious national crisis that affects public health, as well as social and economic welfare. The opioid crisis has been greatly exacerbated by the increased availability of synthetic opioids, such as fentanyl, and by the increased prescribing of opioid pain relievers. Opioid overdose kills 130 people in the United States every day. The primary cause of death associated with opioids is opioid-induced respiratory depression (OIRD). Naloxone, a competitive antagonist of mu-opioid receptors (MORs), has a rapid onset and helps reverse OIRD but is short acting and re-dosing is often necessary. A recently approved MOR antagonist, nalmefene, is long-acting, however both naloxone and nalmefene reverse opioid mediated analgesia and induce acute withdrawal leading to low adherence that limit their use for OIRD prevention particularly in highly vulnerable populations such as patients chronically receiving high doses of opioids for pain. In addition, naloxone does not reverse opioid induced muscle rigidity, upper airway obstruction in patients with underlying obstructive sleep apnea, and may cause pulmonary edema. Alternative, non-opioid receptor antagonist-based approaches for both OIRD treatment and prevention are needed. Our approach targets Oxytocin (OXT), as our work has shown OXT is effective for treatment of sleep disordered breathing by increasing respiratory rate and decreasing the duration of the apneic/hypopneic events and severity of hypoxemia in patients with obstructive sleep apnea. OXT is FDA approved for other uses. Our overarching hypothesis, based on our exciting Preliminary Data, is that OXT prevents fentanyl associated mortality, and reduces fentanyl evoked respiratory depression and increased incidence of apneas. In response to PAR-22-200, we propose to conduct studies that will evaluate the potency, efficacy, and duration of action of OXT in reversing OIRD and reducing opioid lethality. In Specific Aim 1: we will identify, validate and optimize OXT dose, routes of administration (intranasal (IN), subcutaneous (sub- Q), and intravenous (IV)), and need for redosing, to reverse acute OIRD induced by fentanyl. In Specific Aim 2: we will use an animal model of chronic pain and daily ED50 administration of fentanyl to test if OXT provides additional analgesia and helps prevent the risk of overdose lethality and OIRD that occurs with chronic opioid use and opioid tolerance. In Specific Aim 3: we will test the hypothesis that selective chemogenetic activation of OXT neurons in the paraventricular nucleus of the hypothalamus will prevent and treat OIRD. In Specific Aim 4: we will obtain the approvals required for two clinical trials. In Specific Aim 5: we will quantify, in a double blinded, placebo-controlled phase 2 clinical trial, the therapeutic efficacy of OXT in decreasing apneas, respiratory depression and oxygen desaturations in patients given opioids upon in-hospital recovery from laparoscopic bariatric surgery. In Specific Aim 6: we will test in a double blinded, placebo-controlled phase 2 clinical trial, the therapeutic efficacy of OXT in decreasing A) the severity of sleep disordered breathing; B) pain perception, C) opioid dose and D) drug liking in patients on chronic opioid therapy for chronic pain.

NSF Awards · FY 2025 · 2025-07

This project explores questions in ergodic geometry, an interdisciplinary field connecting ergodic theory and geometry. Ergodic theory, a branch of dynamical systems, investigates systems that evolve over time, often exhibiting unpredictable and chaotic behaviors. Examples of such systems include planetary motion, weather patterns, and stock markets. Geometry, on the other hand, studies the shape and structure of objects. Ergodic geometry combines these perspectives, using tools from dynamical systems to address geometric problems. For instance, the shape of an object can influence the complexity of certain dynamical systems occurring on that object. This project aims to deepen our understanding of the relationship between an object’s shape and key dynamical quantities associated with it, such as entropic quantities, which serve as indices of complexity. In addition to advancing mathematical knowledge, the PI will establish the GW Experimental Mathematics Lab, creating a collaborative and vertically integrated research environment for students at George Washington University. This lab will foster hands-on learning and mentorship, preparing students to engage in cutting-edge mathematical research. In ergodic geometry, significant milestones have been achieved when the underlying dynamical systems are compact and uniformly hyperbolic. This project aims to extend these findings to geometric systems that are non-compact, nonuniformly hyperbolic, or both, using thermodynamic formalism. The research focuses on three objectives: studying correlations in higher-rank cusped geometric structures through orbital distribution analysis; examining the metric geometry of deformation spaces of these structures via Thurston’s asymmetric metric; and analyzing orbital correlations in nonuniformly hyperbolic geometric structures. Progress in these areas will involve developing new tools in thermodynamic formalism combined with geometric insights, potentially advancing our understanding of the interplay between geometry and dynamics in more general settings. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-06

Project Summary/Abstract This R34 grant proposal is to plan a clinical trial that will test the proof-of-concept that the lead candidate hookworm vaccine antigen, Na-GST-1, can have a meaningful biological impact on hookworm infection. This trial will utilize an innovative paradigm for early assessment of investigational vaccine antigens by challenging human volunteers using a controlled human infection model (CHIM) after vaccination. Hookworm is one of the most important parasitic infections, with over 400 million people infected worldwide, most with the Necator americanus species. The clinical hallmark of hookworm infection is iron deficiency anemia resulting from intestinal blood loss. Na-GST-1 is a critical component of the blood-feeding pathway of N. americanus and was selected for clinical development based on its protective efficacy in animal trials. Recombinant Na-GST-1, formulated on Alhydrogel, has been shown to be safe when administered to healthy adults and children in Phase 1 trials. In a small pilot Phase 2a CHIM proof-of-concept study conducted in hookworm-naïve volunteers, Na-GST-1/Alhydrogel administered in combination with the CpG 10104 immunostimulant, provided significant protection against a single challenge with NaL3 larvae. In the proposed study, healthy hookworm‐naïve adult volunteers will be vaccinated with Na-GST-1/Alhydrogel/CpG 10104 according to different doses followed by challenging them with repeated doses of infective N. americanus larvae to assess the effect of vaccination on infection, as assessed by parasitologic, immunologic and hematologic parameters. Repeated challenges will more faithfully mimic exposure conditions in endemic areas, and will also provide more insight into the duration of protection afforded by the vaccine. Traditionally, proof-of-concept for novel investigational vaccines is tested in large field trials in endemic areas. These can take considerable time depending on the incidence of infection in the control arm of the study. The objective of this R34 proposal is to plan a study in which proof-of-concept is tested early in the clinical development of new vaccines for hookworm, one of the most prevalent and important of the Neglected Tropical Diseases. The results of this trial will permit critical Go/No-Go decisions to be made on further development of the Na-GST-1 hookworm vaccine, prior to conducting larger, more costly Phase 2 and 3 trials.

NIH Research Projects · FY 2025 · 2025-06

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units (MFMU) Network was set up in 1986 and continues to conduct major practice-changing clinical trials in maternal and fetal medicine. Primary results of the MFMU Network’s trials have amassed over 7,400 citations (average 320 citations per primary manuscript) and are frequently referenced in the American College of Obstetricians and Gynecologists Practice Bulletins. The NICHD also supported the Management of Myelomeningocele Study (MOMS), a groundbreaking trial of surgical repair of the spina bifida defect before the baby is born versus the usual postnatal surgical repair and the follow-up study of the children (MOMS2). Results from obstetrical clinical trials can be challenging to understand and inform clinical practice since the effects of an intervention on the outcomes of the birthing individual and their perinate may be discordant. For example, for any individual trial participant and their perinate (dyad), an obstetrical intervention may improve a perinatal outcome but worsen a maternal outcome. In practice, this imbalance of benefit may increase the complexity of decision-making and back-and-forth discussions between clinical provider and patient due to various understandings and perceptions of treatment strategies and outcomes for the pregnant person or perinate. The Desirability Of Outcome Ranking (DOOR) is a paradigm shift for the design and analysis of clinical trials that can consider both maternal and perinatal outcomes concurrently to comprehensively and objectively evaluate the effects of interventions on the overall success of the pregnancy. The partial credit strategy, part of the DOOR analysis, assesses the robustness of trial results which further allow any individual to evaluate results with respect to their own perspective on outcomes. The primary goal of this research project is to utilize the DOOR methodology to generate and disseminate clearer and more meaningful interpretations of trial results to advance understanding from these NICHD funded studies (MFMU and MOMS) that have informed clinical practice. Providing more interpretable results is the fundamental basis for understanding how interventions lead to healthier pregnancy and infant outcomes, both of which are topics directly related to the NICHD’s mission. Results from these DOOR analyses of existing high-impact studies will enhance the global understanding of how obstetrical interventions lead both the birthing individual and their perinate towards healthier and desirable outcomes and will provide the foundational education and knowledge for future obstetrical trials.

NSF Awards · FY 2025 · 2025-06

The Department of Statistics at George Washington University will host the conference “The Past, Present, and Future of Statistics in the Era of AI” from May 8-10, 2025, in Washington, DC. This event will explore the evolving relationship between statistics and artificial intelligence (AI), examining its growing impact on scientific research, education, and society. The conference will explore AI’s influence on statistical research and its role in shaping the future of data-driven decision-making. The program will feature technical sessions, short courses, panel discussions, and poster presentations, providing a platform for knowledge exchange and interdisciplinary collaboration. The event will also include plenary talks from leading experts in the field, offering insights into cutting-edge developments and future directions. Additionally, we have invited practitioners from both academia and industry to attend and participate in panel discussions, ensuring a broad range of perspectives. A key priority of the conference is to promote the active participation of junior scholars, including as speakers and presenters, providing them with opportunities to engage with experts and showcase their work. The conference contributes to statistical science by facilitating dialogues among experts, inspiring new research directions, and promoting advancements in statistical methodologies and AI applications. In particular, discussions will focus on scalable data analysis, model interpretability, causal inference, and responsible AI. Key topics include uncertainty quantification through probabilistic modeling, Bayesian methods for AI-driven decision-making, and fairness and bias correction in machine learning. The program will also address reinforcement learning for dynamic treatment regimes and privacy-preserving statistical methods for large-scale datasets. The conference will serve as a hub for knowledge sharing, highlighting the evolving role of AI in statistical research and its broader implications for innovation and societal progress. More details about the event, including registration and program updates, can be found at https://statistics.columbian.gwu.edu/GW-STAT-90. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-06

This I-Corps project focuses on the development of advanced membrane materials for water treatment systems that are more durable, cost-effective, and efficient. Reverse osmosis membrane technologies are widely used in industries such as food and beverage processing, wastewater reclamation, chemical processing, power plants, and resource recovery, but they suffer from severe challenges due to the accumulation of mineral scale and organic foulants. These issues lead to frequent cleaning cycles, high energy consumption, and premature membrane failure. The solution under investigation offers a novel approach to reducing these maintenance costs while improving overall performance and lifespan. By improving operational reliability and decreasing dependence on chemical cleaning agents, the technology supports sustainability, industrial efficiency, and public health through improved water treatment practices. Implementation of this technology could significantly lower the cost and chemical footprint of industrial water purification processes, contributing to economic prosperity and resource conservation. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of ultra-thin polyamide reverse osmosis membranes fabricated via a rinse-free, molecular layer-by-layer deposition process. Unlike conventional interfacial polymerization methods that produce rough, heterogeneous surfaces prone to fouling and scaling, this technique yields smooth membranes with tunable thickness and surface chemistry. By optimizing monomer concentration and eliminating intermediate rinsing steps, the fabrication process is significantly faster and more sustainable. The membranes can be functionalized with antifouling or scale-resistant coatings without compromising salt rejection or water permeability. Early tests indicate exceptional resistance to mineral scaling and organic fouling, potentially extending cleaning intervals by a factor of three or more. This innovation offers a scalable path toward next-generation membranes that address longstanding performance and cost barriers in industrial water purification. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-05

Asgard archaea are a group of microbes that hold keys to understanding the diversification of life on Earth, including the origin of eukaryotes. They likely originated in thermal environments such as deep-sea hydrothermal vents or terrestrial hot springs. There is limited documentation of diversity and ecology of Asgard archaea from hot springs in particular. This project will collect samples of microbes from understudied hot springs in the western U.S. and analyze their genomes. New species of Asgard archaea will be identified and characterized. Data from hot spring samples will be compared with those from other habitats to answer questions of origins. Researchers will also study the evolutionary history of eukaryotic signature genes in archaea. This project will train a postdoctoral researcher, graduate and undergraduate students, and high school interns from local schools. A new undergraduate course will provide students with hands-on research experience in microbial ecology and evolution. YouTube videos of the field and laboratory research will be developed as part of outreach to the broader public on diversity of Asgard archaea. This project will collect hot spring sediment samples from the western U.S. to recover and identify novel Asgard archaeal lineages. A combination of amplicon, metagenomic, and metatranscriptomic sequencing will be performed from DNA and RNA extracted from these samples. Amplicon sequencing will be done using archaeal primers that capture most of Asgard archaeal diversity. Near full-length sequencing of amplicons will result in phylogenetically useful information enabling assessment of diversity and abundance in the hot springs. Metagenomic sequencing using both short and long reads of the most abundant archaeal samples will enable reconstruction of near-complete genomes. Metatranscriptomic sequencing will reveal novel lineages that may have been missed due to PCR bias. Phylogenomic and ancestral state reconstructions with the improved representation of lineages from hot spring habitats will shed light on the origins of Asgard archaea in terrestrial or marine geothermal features. Phylogenetic analysis of the eukaryotic signature proteins found in these archaea will also reveal where the genes encoding these proteins first appeared during geologic time. This research will advance our knowledge of diversity and deep evolutionary relationships of Asgard archaea. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-05

ABSTRACT Early life experience is critical in shaping the circuits that underlie adult behavior, and adversity or deprivation early in life robustly increases the risk for development of numerous neuropsychiatric disorders. In this project, we will investigate the role of serotonergic neurons in alterations in adult social behavior following early life adversity. Here, we will use the limited bedding and nesting model of early life adversity in mice to understand links between early experience, the serotonergic system, and social competition in dominance tasks. We will take a multidisciplinary approach, utilizing electrophysiology, behavioral assays, and fiber photometry to address the hypothesis that early life adversity leads to reduced excitability of serotonergic neurons and alterations in social dominance processing. In the first aim, we will examine the effect of bidirectionally modulating the activity of serotonergic neurons on social competition in adult mice who experienced early life stress. In the second, we will use fiber photometry to investigate early life adversity-induced alterations in serotonergic dynamics during competitive social behavior. These studies hold the potential to contribute significantly to our understanding of how the serotonergic system is altered by early life experience and may lead to novel avenues for the development of therapeutics for social symptoms of neuropsychiatric illnesses.

NIH Research Projects · FY 2026 · 2025-04

SUMMARY/ABSTRACT The burden of tobacco-related diseases is well-documented, with differential impact among certain high-risk populations (e.g., Black or Hispanic individuals, low socioeconomic status groups, rural populations). However, the literature is limited by insufficient examination of: 1) differences across subpopulations in tobacco use, particularly use of the various tobacco products in the current tobacco market; 2) mechanisms (e.g., marketing exposure, differing product perceptions) underlying such differences; and 3) longitudinal associations, particularly using nationally-representative data. Regarding the former, groups particularly impacted are typically described by social identifiers that are visible and relatively static, like race. However, certain determinants (e.g., industry marketing) may especially impact high-risk subpopulations, thus requiring a more nuanced understanding of the mechanisms by which these subpopulations are impacted. This study’s objective is to test our central hypothesis that US adults and youth representing certain high-risk subpopulations will demonstrate distinct tobacco use behaviors (e.g., likelihood of use vs. no use of distinct products, polyproduct use profiles) and related mechanisms (e.g., marketing exposure and perceptions) over time. The rationale is that certain products may have specific characteristics (e.g., novelty, technology, flavors) that appeal to and/or are marketed toward different high-risk subgroups and thus shape their perceptions (e.g., risk, social norms) and use behaviors. We will use the Population Assessment of Tobacco and Health (PATH) study (both adult and youth survey data) – a nationally-representative longitudinal cohort study – to examine: 1) differences in tobacco use behaviors over time (i.e., trajectories in use of different products, any product, or multiple products; use of flavored products) among adults, including those representing high-risk populations; 2) pathways underlying differential tobacco use behaviors over time, including tobacco marketing exposure and product perceptions (i.e., risks, social norms); and 3) differences in marketing exposure and product perceptions over time as outcomes – and as mechanisms of use to the extent possible (due to lower youth use prevalence) – in youth, including those representing high-risk subpopulations. This proposal will advance our long-term goal of informing research, interventions, and regulations (such as restrictions on marketing that targets high-risk subpopulations), to ultimately catalyze the reduction of the burden of tobacco-related diseases and its population impact in the US.

NSF Awards · FY 2025 · 2025-04

The significance of this I-Corps project is based on the translation from lab to market of an artificial intelligence (AI)-powered microbial profiling platform that analyzes DNA sequencing data with enhanced speed, accuracy, and scalability. The benefits of this approach include increased scalability, reduced processing time, and improved sensitivity for detecting rare microbial species. Microbial profiling is crucial for applications in public health, infectious disease and environmental monitoring, precision medicine, and pharmaceutical development. For example, in the U.S. alone, healthcare-associated infections affect over 1.7 million patients annually and current sequence analysis workflows are too resource-intensive to scale effectively, creating a significant barrier to timely and cost-efficient microbial detection. By reducing the computational burden and expertise required for sequencing analysis, this innovation may expand access to genomic insights, facilitating advances in healthcare, biotechnology, and biosecurity while reducing costs for clinical and research institutions. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of a microbial profiling platform powered by large language models (LLMs). This approach processes DNA sequencing data as a structured language, applying deep learning techniques to recognize taxonomic patterns, host-microbe interactions, plasmid differentiation, and antibiotic resistance markers. This new solution consists of a two-step artificial intelligence (AI) framework: (1) foundational LLMs pre-trained on extensive sequencing datasets to learn genomic patterns and (2) a fine-tuning mechanism that customizes model predictions for domain-specific microbial profiling. Unlike conventional alignment-based sequencing analysis which requires extensive computational resources and bioinformatics expertise, this method rapidly extracts meaningful biological insights with minimal manual intervention and further automates data interpretation, optimizing results for clinical and research applications. The ability to rapidly analyze microbial communities with high accuracy has significant implications for infectious disease management, antimicrobial resistance tracking, and precision medicine applications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

In nature, populations of plants and animals occasionally explode in numbers, providing a temporary surplus of nutritious food for consumers. When these nutritional ‘pulses’ occur, they can initiate chain reactions in food webs, as consumers switch from their normal diets to feast instead on the abundant new food items. Understanding the consequences of these food pulses for natural communities – which organisms are affected, for how long, and if they stop performing their normal “jobs” to take advantage of the new resource – can provide insights into how ecological systems function and respond to change. The synchronized emergence of billions of periodical cicadas every 13 or 17 years in the eastern U.S. provides an enormous pulse of insect food for a variety of generalist consumers. The assembled research team will be the first to document the impacts of cicada pulses on the foraging behaviors and population dynamics of one of the most abundant animals on the planet: ants. Results of the study will advance our understanding of how nutrient pulses alter the varied ecosystem services that ants routinely provide, many of which are relevant for both the forestry and agriculture sectors. In addition to training undergraduate researchers in field biology, the research team has created a free digital education program, “Friend to Cicadas,” the goal of which is to train and empower teachers throughout the entire range of periodical cicadas to provide activities that spark wonder and curiosity in their students. In this study, the researchers test the hypothesis that most ants will opportunistically adjust their foraging to capitalize on abundant cicada prey, both during the dramatic spring emergence and again when the next generation of cicadas hatches later in the summer. Further, they predict that changes in ant foraging will alter the strength of their competitive and mutualistic interactions, initiating chains of indirect effects in the forest community. Using a combination of direct foraging observations, nutrient baiting, ant exclusion experiments, pitfall trapping, and isotopic analyses, the researchers will quantify the impacts of these biomass pulses on ant foraging at both the population and community levels. Within- and between-years comparisons will enable the team to gauge the impacts of cicada pulses on ant-mediated ecosystem functions, foraging dynamics, and ant-ant interactions. Specifically, the team will document the indirect effects that are likely to occur if shifts in foraging alter seed dispersal, scavenging, and protective services provided to aphids. Using stable isotopes to quantify the trophic position of ant foragers in both emergence and non-emergence years will allow the team to test whether ants initially occupying a range of trophic positions converge when fed a common diet. Moreover, these biomass pulses present a unique opportunity to examine the context-dependency of species interactions in both mutualistic and competitive settings. Taken together, these findings will contribute to the very limited literature describing the impacts of resource pulses on terrestrial invertebrates and provide important insights into how trophic ecology is altered during, and subsequent to, nutrient pulses. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

Social loss, or the death of a member of the group, is usually a stressful experience for partners, to which humans respond by increasing social efforts that strengthen social bonds. These responses are compensatory socialization mechanisms that attenuate stress, thus mitigating the negative effects of loss. This dissertation research project provides broader comparative and evolutionary context to advance our understanding of responses to social loss. The PI assesses the behavioral and physiological responses that follow the loss of social partners in a social non-human primate species, evaluating whether social loss leads to long term consequences and comparing the physiological and behavioral responses of the study species with those observed in humans. The study provides research, mentoring, and educational opportunities to students and the general public. This study assesses how the loss of individuals from a community may differentially affect surviving bond and non-bond partners in a wild non-human primate species. To this end, the study integrates historic, behavioral, and physiological data. Longitudinal and newly collected social data are used to map social networks. Behavioral data is evaluated to determine whether compensatory socialization mechanisms follow conspecific loss in this species. Ultimately, analyses address how individuals that live in fission-fusion groups behaviorally compensate for the death of a social partner, and how loss affects their social networks. The longitudinal analyses assess whether loss has a long-term impact on health and well being. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

This Faculty Early Career Development (CAREER) award supports research that will target and innovate system design and operational problems involved in the last segment of urban delivery, known as the “final 50 feet.” This segment, driven by the rapid growth of urban delivery, places new and significant demands on already crowded urban city streets and curbs, causing spillover effects such as extensive cruising, illegal parking, and street blockages in busy urban neighborhoods. The project will conduct economic and system-level analyses to characterize the “final 50 feet” problem in urban environments, identify the key drivers of critical issues, and evaluate the effectiveness of new policies, designs, and operations intended to address these challenges. The research activities will be well integrated into teaching and outreach plans, to further disseminate the impacts. The project will engage public agencies to share findings and develop and complete practice-oriented discussions. Educational activities are planned to increase public scientific literacy on relevant topics and facilitate broader engagement through lab open houses, engineering student professional chapter engagement, social media channels, and research showcases. The project will also introduce innovative course designs featuring out-of-classroom exercises aimed at enhancing both undergraduate and graduate students' ability to apply textbook methods to address newly arising problems and contexts related to the “final 50 feet.” The project will devise a suite of analytical, numerical, and empirical tools to investigate the “final 50 feet” problem through three interconnected research axes. The first axis focuses on deliverers’ common “final 50 feet” problem by capturing their interaction with the system environment. Emphasis is placed on examining how the multiple stages composing the “final 50 feet” are interlinked and how these linkages further influence system performance and externalities. The second axis explores the potential of non-traditional means to enhance deliverers’ work efficiency in the “final 50 feet.” This includes identifying optimal paradigms for operationalizing various non-autonomous and autonomous delivery means and determining the system conditions under which the solutions are most competitive. The third axis investigates the infrastructural and environmental contexts in which the “final 50 feet” occurs. Prevalent and emerging infrastructural configurations, developments, and management schemes will be analyzed to assess whether and how they transform operations in the “final 50 feet” and influence multi-modal curb dynamics. Together, these three research axes connect crucial stakeholders, influencers, and game-changers involved in the “final 50 feet” in urban neighborhoods and address critical considerations for both current practices and future developments in urban mobility. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-01

Black, Latin American, and Multiracial individuals are disproportionately impacted by HIV. One impact is access to health resources, including HIV knowledge. Knowledge about Undetectable=Untransmittable (U=U), the scientific conclusion that people living with HIV who have a sustained undetectable viral load cannot sexually transmit HIV to their sexual partners, has been associated with reduced HIV stigma and increased HIV testing. However, many people remain skeptical of U=U, in part due to unclear and inaccurate messaging about U=U from trusted sources. Ensuring that messaging about HIV transmission risk is accurate, acceptable, and credible may prove to be a recurrent challenge as knowledge about transmission risk continues to evolve. A 2023 review of evidence indicated that people living with HIV who have a suppressed but detectable viral load (200-1000 copies/mL) have “almost zero” risk of transmitting HIV to their sexual partners (“Almost U=Almost U”; aU=aU), prompting the World Health Organization (WHO) to recommend disseminating this new information. Integrating aU=aU into HIV transmission risk messaging may complicate understanding of U=U and undermine U=U belief. Despite the WHO’s call to disseminate the aU=aU message, no research to date has examined its potential impact. This proposed cross-sectional survey-based study aims to evaluate the effect of messaging about aU=aU on HIV transmission beliefs using a pre/post design with 2,000 Black, Latin American, and Multiracial individuals. A second aim is to examine associations between various demographic and psychosocial factors with (a) perceptions of the message (e.g., acceptability, credibility) and (b) the anticipated impact of the message on psychosocial health (e.g., HIV stigma) and health behavior (e.g., HIV testing intentions). A final aim is to qualitatively assess perceived benefits, concerns, and recommendations related to aU=aU messaging. The proposed training plan in this F31 application will provide the essential knowledge and skills that I need to help reach my goal of becoming an independent scholar. The training I will acquire through this timely and innovative research project, in combination with formal coursework, one-on-one mentorship, focused workshops, academic conferences, manuscript preparation, grant-writing, and other training activities, will target three training objectives: (1) to enhance skills in conducting advanced research methodology, (2) to gain mastery on the topic of health communication, and (3) to gain experience with the dissemination of research and to gain skills in grant writing. I will be mentored by Dr. Sarah K. Calabrese (Sponsor), Co-sponsors: Drs. David Huebner, Jonathon Rendina, and Tamara Taggart, and Scientific advisor: Dr. Ana María del Río González.