George Washington University

NSF Awards · FY 2024 · 2024-09

4D printing is a new and exciting manufacturing process that creates structures designed to change shape or function over time when exposed to specific stimuli. Compared to traditional 3D bioprinting, incorporating a time dimension in bioprinting is intriguing, as the dynamic 4D effect can more accurately mimic natural tissue development and better regulate cell behaviors. However, the fundamental knowledge of the relationship between living biosystems and dynamic manufacturing is still lacking and needs to be explored to uncover its full potential. This project aims to use this innovative 4D printing technology to develop soft robotic systems and establish the foundational knowledge for targeted stem cell delivery. For this purpose, a versatile 4D bioprinting approach will be created to produce custom living biosystems, expanding therapeutic options and meeting the complex demands of various medical fields. In addition, the project outlines convergent research, educational, and outreach activities, which will address the critical challenges in advanced biomanufacturing for biomedical studies. This project will investigate the manufacturing science underlying the design of reprogrammable soft robotic systems for targeted stem cell delivery within a biomimetic environment. These 4D printed soft robots will be capable of reshaping in response to stimuli, enabling cargo loading and release. Additionally, their magnetic controllability will allow precise guidance to the intended delivery site. To achieve this goal, the project will pursue two aims: Aim 1 focuses on synthesizing a multi-responsive and magnetically controllable 4D ink material for bioprinting structures. Various ink formulations will be explored to optimize printability and achieve desired properties such as stimuli-responsiveness and mechanical strength. Aim 2 involves fabricating soft robots and evaluating their performance in loading, docking, and delivering neural stem cell spheroids (neurospheres) on demand. Furthermore, the ability of these spheroids to integrate into neural networks will be assessed in vitro. The successful completion of this project will build the foundation to enable a novel biomanufacturing platform and push the boundaries of living biosystem manufacturing. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

This project aims to develop a new data platform and analytical toolset for modeling PBI across all 381 US metropolitan statistical areas (MSAs). Our research addresses state-of-the-art topics related to both “what” (configurations) and “why” (trajectories) questions concerning the dynamics of entrepreneurial ecosystems. We analyze both the static conditions of ecosystems to develop a typology with unique configurations and characteristics of successful ecosystems as well as the dynamic movements of ecosystems over time. The results of this analysis are expected to make novel contributions that are highly relevant to policymakers looking to support innovation through place-based policy, especially as the current policy push is exploring ways to invest in regions outside of highly successful hubs such as Silicon Valley to broaden the scope of US competitiveness, supporting the development of nascent regions, and fostering new advanced industry hubs. We will first conduct a configuration analysis to categorize different types of ecosystems, recognizing that ecosystems are heterogenous. To do so, we will accumulate data tracking diverse and multifaceted characteristics of an ecosystem, including metrics and indicators on aspects of innovation, human capital, industry, infrastructure, and culture. We will employ fuzzy-set qualitative comparative analysis (fsQCA) to analyze this dataset which will delineate the different configurations of entrepreneurial ecosystems. Second, we conduct a pioneering study to identify different models and pathways that a region may follow as it develops into an entrepreneurial ecosystem. The study will use the historical trajectories, spatial topologies, and sector orientations of regions to understand how economies transform. Together, these analytical steps will allow not only understanding the current state of affairs in ecosystems, but also how they evolved over time and what are their future trends in both technological and socioeconomic perspectives. A multi-disciplinary research design will combine classical economic theory with modern methods of analysis (fsQCA) and case studies from multiple places. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-08

Abstract: Commercial minibus drivers constitute a large social network of highly mobile men who work long and demanding hours, are at increased risk for HIV, and have limited time to seek health services for HIV. In our preliminary work, our team found a high HIV seropositivity rate of 12.5% among 407 commercial minibus drivers in Nigeria, a prevalence that is nine times higher than the national HIV average. Despite the high willingness to test for HIV among the drivers, the mobile nature of their work poses substantial barriers for those living with HIV to initiate and adhere to antiretroviral therapy (ART) and for those who are HIV-negative and are at risk for HIV to obtain pre-exposure prophylaxis (PrEP). Therefore, innovative strategies such as HIV self-testing (HIVST), which allows individuals to test at home or in private, and long-acting- injectable ART (LAI ART) or LAI PrEP may work better to address the barriers that impede commercial drivers from accessing HIV testing, prevention, and treatment services. Our team has recently evaluated a youth-friendly HIVST intervention combined with linkage to PrEP in Nigeria as part of an NIH-funded project called ITEST: Innovative Tools to Expand Youth- friendly HIV Self-Testing (UH3HD096929). We propose to leverage our established research program in Nigeria in collaboration with the National Institute of Medical Research to implement a tailored ITEST intervention for commercial minibus drivers (ITEST LAIs), which will include male peer-led distribution of HIV self-testing kits combined with demand creation for both oral and LAI modalities of ART and PrEP. Our multi-disciplinary research team proposes a hybrid type I effectiveness-implementation study to assess clinical and implementation determinants outcomes simultaneously. Our specific aims are: Aim 1: Determine the comparative effectiveness of the I-TEST LAI intervention compared to SoC on LAI PrEP uptake and HIV prevention among minibus drivers in Nigeria. In addition, explore the impact of mediating and moderating factors on influencing primary and secondary outcomes. Aim 2: D etermine the effectiveness of the I-TEST LAI intervention compared to SoC on LAI ART uptake, retention in care, and viral suppression among minibus drivers living with HIV with viral suppression (VL below 1000 HIV RNA copies/ml). In addition, explore the impact of mediating and moderating factors on influencing primary and secondary outcomes. Aim 3: As part of our type 1 hybrid implementation-effectiveness design, assess determinants of implementation, and estimate cost-effectiveness to inform scale-up and dissemination.

NSF Awards · FY 2024 · 2024-08

Collaborative Research: Designing Intelligent Industrial Robots for STEM Inclusion by Leveraging Self-Determination Theory to Foster Autistic Talent in Manufacturing Work Workforce diversity is crucial in today's rapidly changing world. Autistic adults, with their unique perspectives and skills, can significantly contribute to workplace diversity. However, compared to similarly qualified peers, they often struggle to find and retain jobs, including in STEM fields where the U.S. faces an increasing skills gap. Autistic adults comprise at least 2% of the U.S. population, so increasing their employment rate could meaningfully expand and enhance the U.S. manufacturing and STEM workforce. This project aims to address this issue by developing smart industrial robots that provide personalized support for autistic employees in manufacturing and STEM work environments. By creating more supportive and inclusive workplaces, we seek to improve job retention, income, and independence for autistic employees. Furthermore, this initiative will help bridge the skills gap in manufacturing and boost economic growth. The advancements from this project will also enhance educational opportunities and improve employment prospects for autistic adults, fostering more neurodiverse and productive work environments that drive innovation in the U.S. manufacturing sector. This project focuses on developing smart industrial robots that offer personalized support for autistic employees in STEM and manufacturing jobs. Our approach combines the co-design framework of mutual shaping with the principles of Self-Determination Theory (SDT). We will engage key stakeholders, including autistic adults and industry experts, throughout all development cycles in an iterative design process to advance industrial robot intelligence. The primary objectives of this project are twofold: (1) to co-create support approaches based on SDT that address fundamental psychological needs (i.e., autonomy, competence, and relatedness) through interviews, focus groups, and human-in-the-loop simulations, and (2) to enhance robot intelligence for accurately identifying and meeting workers' psychological needs in manufacturing settings, resulting in adaptive and personalized support. By integrating SDT-based support into industrial robot design, we anticipate increased motivation, work quality, and job satisfaction for all employees. This neuro-affirming work environment will, in turn, promote inclusion, productivity, and innovation in the STEM workforce. This award has been made in response to the NSF solicitation “Workplace Equity for Persons with Disabilities in STEM and STEM Education” (NSF 23-593). This project is funded by the Advancing Informal STEM Learning (AISL) Program in the Division of Research on Learning in Formal and Informal Settings (DRL) in the Directorate for STEM Education. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

This research studies how decisions in industry influence the movement of people, animals, and resources into rural America. The specific research questions pursued are: (1) How are multinational companies in the food sector shaping land use in rural areas of the US? (2) What are the stated and tacit reasons why such multinational companies open facilities in sparsely populated rural areas? (3) How are federal-and state-specific decisions related to this industry’s labor needs? (4) What measures have public officeholders taken to shape location and labor supply decisions for these facilities? and (5) How do the strategies used at different rural industry sites help us understand the human, non-human, and ecological advantages and disadvantages of the contemporary protein industry and supply chain? Methodologically, the project focuses on roughly 54 facilities, nested within 20 counties between two US states. These two distinctive regions allow for a comparison between states where relevant rules differ. Data collection includes two years of participant observation at industry meetings; ethnographic interviews with industry representatives; ethnographic interviews with community groups, public officials, and community members; analysis of descriptive statistics; and critical analysis of public documents. Though qualitative in focus, the research is triangulated with quantitative secondary data from governmental and publicly available sources. Conducting research in these two regions allows for the comparison of industry strategies in a manner that accounts for both hyperlocal impacts and transnational industry trends, while offering practical and translatable findings for local constituencies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

The origin and development of the human hand has been a focus of anthropological study as scientists try to understand the reasons why our hands look the way they do. One hypothesis is that making and using stone tools influenced the shape of our hands over millions of years. This doctoral research project explores how changes in the human wrist might have helped early humans make tools to modify their environment and diet for their survival. The study provides an in-depth experimental examination of the co-evolution of technology and human anatomy over millions of years. The project supports student training, international research collaborations, and science education outreach. The project considers whether the production of stone tools was a significant manipulative behavior that catalyzed evolutionary changes in the structure of the human hand through time. The investigator conducts a series of experiments on the production of stone tools with both a flexible wrist (similar to a modern human) and a braced wrist which may be more similar to the wrist of early human ancestors. In addition, specific stone tool sites associated with specific human fossils are examined for associations between stone tool and hominin wrist morphology. Finally, the investigator compares previously documented anatomical changes in the hand with coincident variation in stone tools. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-08

Project Summary/Abstract The goal of this R01 is to build upon our sponsored Positive Deviance research by identifying how durably virally suppressed Black sexual minority men living with HIV (BSMM LWH) overcome racism and intersectional stigma on multiple socioecological levels. Only 62% of the 58% of BSMM LWH who adhere to treatment are virally suppressed and HIV care disparities have persisted for the past 15 years. Our preliminary studies suggest that the small proportion of virally suppressed BSMM LWH are “positive deviants” who consciously or unconsciously maintain their health despite adversity and could offer researchers effective solutions for the community. Identifying how exemplar men with successful HIV care outcomes overcome or withstand racism and intersectional stigma in high barrier contexts is significant and novel for intervention design because it shifts the HIV care research paradigm towards community-driven, strengths-based solutions. Therefore, the goal of this R01 is to identify novel strategies and multilevel facilitators that help BSMM LWH sustain durable viral suppression. Guided by Positive Deviance, this study will identify how BSMM LWH navigate racism and stigma to retain in care, adhere to treatment, and sustain viral suppression in two understudied, high-barrier contexts: Shelby County, TN and Prince George’s County, MD. Studying positive deviants in Shelby and Prince George’s Counties is significant because they are two of the largest majority- Black counties in the U.S. with well-documented inequities that could provide unidentified solutions for others who experience substantial barriers. We will begin by building upon our preliminary data using in-depth 60 qualitative interviews (Aim 1), then conduct ethnographic go-alongs to identify unconscious facilitators in their neighborhood and clinical contexts (Aim 2). Specifically, we will interview them in their neighborhoods and audio-record their follow-up HIV care visits to study how they overcome communication challenges with clinicians. Findings will be combined with publicly available data about neighborhood characteristics and clinic policies to design novel multi-dimensional figures called glyphs on county-wide maps. Glyphs will help us visualize and identify the key components needed in an intervention to support other BSMM LWH (Aim 3). Using Positive Deviance in HIV care research to identify existing community strengths for intervention design is highly significant and novel. This study aligns with NIH priorities to understand multilevel factors and design novel interventions to improve HIV care outcomes and is the next step needed in our work to support BSMM LWH. This study uses an innovative and significant strengths-based framework to discover, evaluate, and subsequently diffuse effective interventions for HIV outcomes, leading to high public health impact. Findings will allow us to design, refine, and implement at least one intervention in a subsequent R34 proposal that already exists in real-world contexts but remains unknown to researchers.

NSF Awards · FY 2024 · 2024-08

The US and Japan have a >10-year collaboration on the Japan-US Networking Opportunity (JUNO) Program. This project will support a joint US-Japan workshop to elucidate current challenges in networking research. The workshop will be open to the community and the workshop output will be captured in a publicly-available report. Workshop themes under consideration include: 1) Augmented Network Architectures (Network + X Architecture): The goal of this thematic area is to explore the integration of advanced capabilities, such as computing and artificial intelligence (AI),into the current architecture of wireless and wired networks. 2) Extremely Advanced Networks for Wired and Wireless Communications: The goal of this thematic area is to investigate advanced networking capabilities for enabling wired and wireless communications at scale and with maximum efficiency. 3) Use Cases and Associated Networks: The goal of this thematic area is to exploit emerging use cases that can leverage the capabilities of the first two thematic areas. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-07

Obesity hypoventilation syndrome (OHS) is a severe form of sleep disordered breathing (SDB) characterized by daytime hypercapnia and hypoventilation during sleep. OHS is driven by chronically decreased CO2 sensitivity and depressed ventilatory responses to CO2 (hypercapnic ventilatory response, HCVR). Non-invasive ventilation restores CO2 sensitivity and treats OHS. However, adherence to this treatment is poor. There is no effective pharmacotherapy for OHS. Leptin increases HCVR and treats hypoventilation in leptin deficient ob/ob mice. Diet-induced obese (DIO) mice emulate all features of human OHS, including awake hypercapnia, upper airway obstruction during sleep and sleep hypoventilation. However human and mouse DIO become resistant to leptin limiting leptin as a pharmacotherapy. This proposal is focused on identifying pharmacological targets downstream of the leptin network to treat OHS. Leptin upregulates pro-opiomelanocortin, which is a pre- hormone post-transcriptionally processed into several peptides, including α melanocyte stimulating hormone, a ligand for the melanocortin 4 receptor (MC4R) promoting energy expenditure. The MC4R agonist setmelanotide has been approved for treatment of genetic forms of obesity linked to mutations in the POMC/MC4R/leptin pathways. The role of MC4R in control of breathing remains unknown. Our exciting preliminary data shows that setmelanotide augments the HCVR and treats SDB in DIO mice, that chemogenetic activation of MC4R (+) neurons in the parafacial region containing the chemosensitive retrotrapezoid nucleus (RTN) increases baseline ventilation and HCVR without any effect on metabolism; and that MC4R (+) parafacial neurons project to brainstem respiratory premotor neurons, that, in turn, project to the phrenic motor nucleus. Our overarching hypothesis is that MC4R agonists treat OHS by augmenting hypercapnic sensitivity in MC4R+ neurons in the parafacial region, which is a major center of CO2 sensitivity. In Specific Aim 1, we will determine the therapeutic benefits of the MC4R agonist setmelanotide in OHS in DIO mice. We hypothesize that (A) a single dose will acutely; and (B) a three-month course of setmelanotide will chronically augment HCVR and abolish SDB in randomized placebo-controlled trials; and that (C) the effect of setmelanotide on ventilation will be prevented by the MC4R blocker SHU9119. In Specific Aim 2, we will use DIO Mc4r-Cre mice to examine if the respiratory effects of MC4R activation by setmelanotide can be mimicked by chemogenetic activation and attenuated by chemogenetic inhibition of MC4R+ parafacial neurons. In in vitro Specific Aim 3, we will examine the synaptic neurotransmission from MC4R (+) neurons in the parafacial region to the rostral ventral respiratory group (rVRG) neurons that project to the phrenic motor nucleus using selective expression of ChR2 in Mc4r-Cre parafacial neurons, retrograde identification of spinally projecting rVRG neurons and patch clamp electrophysiology. CO2/pH chemosensitivity markers of RTN will be detected in MC4R(+) neurons projecting to rVRG. The proposal will provide a rationale for the therapeutic development of MCR4 agonists in OHS.

NIH Research Projects · FY 2026 · 2024-07

It is increasingly recognized that the future of nursing and healthcare research must incorporate a clear understanding of non-medical risk factors—such as economic conditions, environmental exposures, housing, education, and other structural conditions—that significantly influence health outcomes. To address persistent health differences and improve population health, there is a critical need to develop educational and research strategies that extend beyond clinical care to encompass these broader influences. Although frameworks and best practices exist for training clinicians, there remains a substantial gap in preparing researchers—particularly nurse scientists—to study and intervene on nonmedical risk factors. Current curricula have largely focused on clinical practice, leaving the research domain underdeveloped. Actionable research is urgently needed to address upstream and downstream influences, life course processes, biological mechanisms, and global data limitations. The nursing profession is well-positioned to lead this work, given its longstanding focus on population health and its deep engagement in care delivery and communities. To build research capacity in this area, we propose a short course to prepare nurse scientists and other health professional researchers to plan and conduct community-based participatory research (CBPR) studies focused on non-medical risk factors. The course will equip participants to identify, measure, and address these factors across all populations. This evidence-based, scalable training model supports rapid capacity-building and knowledge translation—key priorities for NIH and NINR. The initiative addresses workforce development needs in implementation science and advances research that informs policy, strengthens interventions, and accelerates real-world impact.

NSF Awards · FY 2024 · 2024-07

This award provides support to U.S. researchers participating in a project competitively selected by a 55-country initiative on global change research through the Belmont Forum. The Belmont Forum is a consortium of research funding organizations focused on support for transdisciplinary approaches to global environmental change challenges and opportunities. It aims to accelerate delivery of the international research most urgently needed to remove critical barriers to sustainability by aligning and mobilizing international resources. Each partner country provides funding for their researchers within a consortium to alleviate the need for funds to cross international borders. This approach facilitates effective leveraging of national resources to support excellent research on topics of global relevance best tackled through a multinational approach, recognizing that global challenges need global solutions. This award provides support for the U.S. researchers to cooperate in consortia that consist of partners from at least three of the participating countries. The teams will develop transdisciplinary and convergent research approaches on cultural heritage and climate change, foster collaboration among the research community across several regions, and contribute to knowledge advances at the global level. The project focuses on the concept of bicultural heritage which combines elements of the natural environment and cultural heritage, including language, cultural memory, and traditional ecological knowledge to investigate the complex interactions between natural and social systems and the ability of Arctic urban communities to adapt to climate-induced changes. The project team will work with local and indigenous communities to evaluate climate and environmental changes affecting natural components of biocultural heritage and to assess transformations in local and Indigenous perspectives on elements of biocultural heritage such as, traditional ecological knowledge, environmental ethics, and human-animal relations in response to climate and environmental changes. The project will investigate role the arts and culture in representing and imagining biocultural heritage by reflecting environmental change and social transformations and analyze community specific interactions between nature, culture, and urban life in Arctic cities that constitute biocultural heritage and examine its role in climate change adaptation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-07

PROJECT SUMMARY Human immunodeficiency virus-1 (HIV-1) can be managed with anti-retroviral therapies (ART), but a cure remains elusive. This is due to a reservoir of latently infected cells, which are established early in infection. Elimination of these reservoirs is crucial for curing HIV. Several strategies to deplete the viral reservoirs are under investigation, such as the shock and kill strategy, which stimulates latently infected cells into active viral production using a latency reversal agent (LRA). This strategy allows cytotoxic lymphocytes, such as such as CD8T cells and natural killer (NK) cells, to kill HIV infected cells, to kill HIV-infected cells. Unfortunately, these cytotoxic cells are insufficient to clear the infection due to immune exhaustion as a result of chronic inflammation. As a result, current research is focusing on determining molecules and signaling pathways that can boost the cytotoxicity of effector lymphocytes. NK cells have been shown to be important in the control of SIV and HIV infection. However, chronic HIV- 1 infection leads to pathologic changes in NK cells, including defective functionality, and control of viremia with antiretrovirals has been reported to restore some but not all NK cells activity. Interleukin-15 (IL15) is a critical cytokine that trigger the Janus Kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway signaling cascade, which plays a vital role in NK cell function. IL15 is particularly important for NK cell development, differentiation, maturation, cytotoxicity, cytokine production, proliferation, and survival. Nonreceptor tyrosine phosphatases (NTPs) protein tyrosine phosphatase nonreceptor type 1 (PTPN1) and type 2 (PTPN2) can downregulate STAT signaling pathway by dephosphorylating JAKs, STATs, and other proteins through their catalytic domain. Previous studies in the lab have shown that targeting PTPN1 and PTPN2 with the small molecule 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt), enhances the effector function of CD8+ T and NK cells. In Aim 1, I will assess the role of both phosphatases controlling the activation and expression of cytotoxic proteins in NK cells by using a newly identified double inhibitor ABBV-CLS-484 (Osunprotafib or AC- 484) and by generating CRISPR-knockouts of PTPN1 and/or PTPN2. Using a primary HIV-infected CD4 T cell model, I will test the cytolytic activity of autologous NK cells either treated with AC-484 or CRISPR-knockouts against a viral HIV-1 panel including subtype A, B, C, and D. In Aim 2, I will use NSG-Tg (IL15) mice to evaluate HIV control in vivo. By understanding the critical importance of PTPN1 and PTPN2 phosphatases in NK cell cytolytic function, we can better develop more effective cure strategies against HIV. Completion of the proposed project will also help me to develop the necessary research and professional skills that are essential for my career as an HIV investigator.

NIH Research Projects · FY 2025 · 2024-06

There is a need for self-testers in Sub-Saharan Africa (SSA) for follow-up HIV care initiation, including antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP), following HIV self-testing (HIVST). We piloted the Self-Testing Education and Promotion (STEP) intervention, which included peer education and demand creation for HIVST combined with nurse-led distribution of HIVST kits in a community setting, and found low linkage to facility-up services following HIVST. Based on these findings, we have added the community-based Nurse-Initiated Management of ART (cbNIMART) component to include ART or PrEP initiation following HIVST. There are three aims to this study. Aim 1.) Tailor the STEP+cbNIMART intervention using the ADAPT-ITT model. In Aim 1, the intervention will be further tailored through a “theater test” and feedback from key stakeholders and topical experts, and later utilized for training peer educators and nurses who will help deliver the intervention. Aim 2.) Test the effectiveness of the STEP+cbNIMART intervention on ART or PrEP initiation and retention for self-testers. We will conduct a cluster randomized controlled trial using a hybrid type I implementation-effectiveness study design to assess the effectiveness of the intervention. The trial will include an intervention and control arm, with intervention participants receiving nurse-led community-based ART and PrEP initiation, and control arm participants receiving the standard of care. ART and PrEP adherence will be measured through a baseline survey and subsequent follow-ups of participants in both arms. Aim 3.) Evaluate the facilitators and barriers of implementing the STEP+cbNIMART intervention to refine the intervention for adoption in other settings.

NIH Research Projects · FY 2025 · 2024-06

Project summary/abstract Myasthenia gravis (MG) is caused by an antibody-mediated autoimmune response to muscle acetylcholine receptors (AChRs) that impairs neuromuscular transmission. There is no cure for MG or therapy specifically suppressing only the pathological autoimmune response to AChRs. We wish to develop an antigen-specific cell therapy for MG by engineering regulatory T cells (Tregs) with AChR-specific chimeric antigen receptors (CARs) to specifically suppress autoreactive T/B cells. Pathological mechanisms impairing neuromuscular transmission in MG and chronic experimental autoimmune MG (EAMG) are similar. The dysfunction of Tregs to suppress T effector cells and the decrease of Treg population are found in both untreated MG patients and EAMG rats. These suggest that rodent EAMG is a suitable model for evaluating the effectiveness of cell therapies. Adoptive transfer of polyclonal expanded non-specific Tregs reduces EAMG in rats. We hypothesize that AChR-specific CAR-engineered Tregs have greater efficacy and specificity than non-specific Tregs in suppressing the pathological autoimmune response to AChRs in EAMG. To address this hypothesis, we will optimize the transduction efficiency in rat T cells and characterize cellular phenotypes, cytokine profiles, and suppressive function of CAR Tregs in vitro (Aim 1). We have constructed AChR-specific CARs from single chain variable fragments derived from the parental anti-AChR rat hybridoma cell lines. Rat Tregs transduced with an AChR- specific CAR were activated and expanded in vitro in response to antigen-specific stimulation and suppressed T cell proliferation in response to polyclonal stimulation in a dose-dependent manner. We will enhance CAR transduction in rat T cells by producing high-titer retroviral particles using packaging cell lines. Alternatively, we will purify CAR-positive Tregs using the QBend-10 epitope incorporated into the CARs within the CD8 hinge. We will try to increase the yield of CAR-Treg by converting rat conventional T cells into Tregs by enforcing the expression of FoxP3. We will investigate transduced cells for cellular phenotypes, cytokine profiles, and in vitro suppressive function in an antigen-specific manner. Aim 2 is to investigate the safety and efficacy of AChR- specific CAR-transduced Tregs as a potential treatment for MG in EAMG rats. We have developed a novel EAMG model in which the autoimmune response is driven by a feed-forward cycle of autoimmune stimulation to endogenous AChRs released from damaged muscle in the autoimmune assault, allowing to investigate the impact of our CAR-Treg therapy on the self-sustaining autoimmune response to AChRs. Using this novel model, we will investigate prevention of EAMG by administering CAR-transduced Tregs immediately after the induction of EAMG and treatment of ongoing EAMG by administering CAR-transduced Tregs after the onset of chronic EAMG. The latter is the clinically relevant model for treating MG. We will investigate whether and how the epitope specificities of the CARs influence the efficacy and safety profiles of the CAR-Tregs. This work will provide the basis and rationale to investigate the mechanisms by which the CAR Tregs act and create CARs for human use.

NSF Awards · FY 2024 · 2024-06

The need to develop high-expertise graduates for the US government's cybersecurity workforce is critical to the nation’s security and prosperity. The George Washington University (GW) is a Center of Academic Excellence in Cyber Research (CAE-R), designated by the National Centers of Academic Excellence in Cybersecurity (NCAE-C) program with over twenty years of experience training CyberCorps students for government employment. This renewal project, entitled the GW PISCES program, aims to recruit and place highly trained cybersecurity professionals into the public service. The project will support scholarships for students as well as expand opportunities for cybersecurity students beyond those directly supported by scholarships. The scholars will be equipped with knowledge of cybersecurity mechanisms, tools, policies, and available resources before entering the federal workforce. This project will be built on the successful and solid foundation established by PISCES over the past two decades. The project will train four cohorts of students for employment in the cybersecurity mission of the federal government. The key enabler is an interdisciplinary approach to cybersecurity education, which will provide students with hands-on experiences, personal connections, and an understanding of the cybersecurity landscape in the federal government. The project’s goals include: (1) enhancing interdisciplinary education by collaborating with initiatives focused on trustworthy artificial intelligence (AI) and quantum computing; (2) increasing research opportunities available to SFS students through partnerships with the cybersecurity labs and research groups on the GW campus; (3) making portions of the exclusive SFS Seminar Course available to broader range of students to raise awareness of cybersecurity careers in government through invited talks and recruiting events; (4) enlarging the pool of prospective students by promoting a new bridge-to-cyber program to attract students from non-technical backgrounds to pursue degrees in cybersecurity. This project is supported by the CyberCorps® Scholarship for Service (SFS) program, which funds proposals establishing or continuing scholarship programs in cybersecurity and aligns with the U.S. National Cyber Strategy to develop a superior cybersecurity workforce. Following graduation, scholarship recipients are required to work in cybersecurity for a federal, state, local, or tribal Government organization for the same duration as their scholarship support. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2024-06

PROJECT SUMMARY/ABSTRACT Preterm birth is well established as the leading cause of perinatal mortality and a significant contributor to both chronic medical conditions and learning/societal challenges amongst those born too soon. Though complex in its origins, preterm birth is predominantly the result of spontaneous preterm birth and ischemic placental diseases (preeclampsia, fetal growth restriction and abruption). Beginning in the 1980's low dose aspirin (LDA) was trialed as a therapy for the prevention of preeclampsia. Subsequent meta-analyses of randomized controlled trials of LDA have demonstrated its efficacy in preventing both preterm birth and other components of ischemic placental diseases. Limited data suggest that the effect of LDA in preventing both preterm birth and preeclampsia may be greater if therapy is begun before 16 weeks and utilizing doses >100 mg. Recently the ASPIRIN trial randomized 11,976 nulliparous women with a singleton gestation in low-middle income countries to either aspirin 81 mg orally or an identical appearing placebo between 60/7 weeks and 136/7 weeks. This trial demonstrated a 11% decrease in preterm birth, 25% decrease in early preterm birth <34 weeks, 11% decrease in hypertensive disorders of pregnancy and 62% decrease in preterm delivery at <34 weeks with hypertension. Though promising, Aspirin has yet to be fully accepted as a preventive strategy for preterm birth, whether aspirin portends efficacy in a dose-response fashion remains unexplored, and mechanistic studies of the pathways by which LDA prevents both preterm birth and ischemic placental disease are lacking. The proposed project is designed to overcome these limitations. The goal is to enroll 1,300 women with a prior preterm birth due to either spontaneous birth or indicated preterm birth and a current singleton pregnancy between 100/7 weeks to 166/7 to a randomized clinical trial of Aspirin 81 mg orally daily and a sham (n = 650) or 162 mg orally daily (n = 650). We will test three overarching hypotheses: (i) Women with a prior preterm birth randomized to 162 mg of Aspirin daily compared to 81 mg of Aspirin daily will have lower rates of preterm birth; (ii) Women with a prior preterm birth randomized to 162 mg of aspirin daily compared to 81 mg of Aspirin daily will have lower rates of ischemic placental diseases; and (iii) Biochemical markers (Thromboxane B2, Specialized pro-resolving mediators, etc.) will correlate with clinical outcomes. Our research group will draw upon the collective experience and leadership of the Perinatal Research Consortium (10 academic centers), an experienced data management and statistical analysis core and a strong biospecimen analytic core. This innovative project by combining a rigorously conducted RCT with appropriate biospecimen analysis will both address a pressing question about one of the few therapies shown to improve the obstetrical outcomes of preterm birth and ischemic placental diseases and provide insight to the mechanisms of how aspirin improves outcomes.

NIH Research Projects · FY 2026 · 2024-06

Abstract In 2021, the US Surgeon General issued an advisory warning of a youth mental health crisis. Latino/a youth have exceedingly high rates of internalizing symptoms such as depression and anxiety. Ecosocial theory posits that historical, societal, and ecological conditions over the life course have critical impacts on later mental health. This research will examine how distal and proximal stressors influence mental health trajectories for US Latino/a youth followed from early childhood into young adulthood. Distal stressors, such as economic stress, may increase Latino/a youth’s internalizing symptoms directly and indirectly through proximal societal stressors, such as families’ economic, health, and social problems. These kinds of stressors also may have direct and indirect effects on increased internalizing symptoms through family stress processes, including maternal depression and harsh parenting. The nature of youth’s exposure to these stressors (for how long, when in history and development) and the presence of protective adaptive factors (e.g., family socialization practices, youth self-regulation) can moderate stressor impacts on internalizing symptoms. This research will leverage advances in Integrated Data Analysis (IDA) to pool data from five longitudinal Latino/a cohort studies to obtain a single, aggregated data set with 2,515 Latina mother-youth dyads following youth from age 2 to 22 (2010-26). IDA increases statistical power, sample heterogeneity and generalizability, and measurement breadth and depth in ways not possible with a single data set. The application will support 1) collecting cross-sectional data for 500 Latino/a individuals to establish standard measurement scaling across the five studies; 2) integrating data across all five studies; and 3) extracting data from Twitter and the US Census to assess economic stress and neighborhood factors, respectively. Analyses will utilize a general latent variable modeling framework that includes multilevel modeling, structural equation modeling, item response modeling, and finite mixture modeling. We hypothesize a cascade of effects from distal stressors to increased internalizing symptoms through greater proximal stressors and increased family stress processes. We expect that pathways linking societal stressors to youth’s internalizing symptoms will vary depending upon the presence of adaptive factors, the developmental timing and cumulative effects of youth experiences, and sociodemographic characteristics (e.g., youth biological sex). This study offers an unparalleled opportunity to understand Latino/a youth mental health in relationship to multi-level stressors, adaptive factors, and sensitive periods of development. As Latino/a youth comprise more than one-in-four US youth, findings from this research will help identify solutions and guide new preventive interventions and refine existing ones for a large and growing segment of the US population.

NSF Awards · FY 2024 · 2024-06

This project is focused on developing and demonstrating applications for a standoff, laser-based, fire radiometer. Instruments developed will address data deficiencies for two challenging problems associated with climate change. Wildfires, as a response to and a cause of climate warming, are an increasing global threat. The total burned area during “fire seasons” has gone from approximately 1000 square miles prior to 2000 to over about 2500 square miles in the last 20 years. NASA’s FireSense program emphasizes real-time observation and characterization of wildfires as a priority focus. However, satellite characterization of fires is limited by daylight, clouds, spectral, spatial, and temporal resolution. Thus, a clear need for terrestrial based data gathering that can fill in data voids and provide real-time data to first responders. A second “use case” for this technology is in the characterization of industrial flares. The project plan involves the construction of two laser heterodyne radiometers for laboratory demonstrations as well as simple “field-scale” demonstrations. The first system will operate in the near infrared and will focus on potassium emission detection, which is a characteristic of only intense fires of plant materials and not fossil combustion. Because of the close technological connection with the PI's prior work and the ready availability of optoelectronics for this spectral region, this system will be the first constructed. The second system will proceed in two generations. In the first instance, a free space heterodyne unit will be constructed for operation at about 2200 1/cm and will focus on detection of both carbon monoxide and carbon dioxide radiative emissions. This sensor is expected to provide directly flame temperature as well as a measure of combustion efficiency. In the second iteration, a source close to 2780 1/cm will be used to explore radiative emissions from methane. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-05

PROJECT SUMMARY Liver cancer incidence and mortality continue to rise, and new therapeutic targets are needed. This fellowship application will explore how the enzyme histone deacetylase eleven (HDAC11) drives liver cancer, and tests HDAC11 as a potential new target for therapy. HDAC11 acts primarily as a lysine fatty acid (KFA) hydrolase, an enzyme that removes fatty acids from proteins (de-KFA). HDAC11 is expressed at low levels in most healthy tissues, but is increased in liver cancer, and high levels are significantly correlated with poor patient outcomes. Proteomic studies have implicated HDAC11 in alternative mRNA splicing, which is prevalent in most cancers. The overall goal of this application is to understand the role of HDAC11 in liver cancer and assess the potential of new, highly specific HDAC11 small molecule inhibitors. In two aims, this application will test the hypothesis that HDAC11 promotes hepatocellular carcinoma through de-KFA of the splicing factor SF3B2, and that inhibiting HDAC11 will block hepatocellular carcinoma progression. In Aim 1, SF3B2 will be authenticated as an HDAC11 substrate in established hepatocellular carcinoma cell lines using a click chemistry-based approach. Preliminary data confirms the feasibility of this technique and establishes that SF3B2 can be lysine fatty acylated. Proposed studies will test if HDAC11-mediated de-KFA of SF3B2 changes its nuclear localization, thereby changing its ability to regulate RNA splicing in the nucleus and resulting in alternative mRNA expression. To detail the alternative splicing outcomes driven by HDAC11, mRNA isoform specific long read sequencing will be conducted. The abundance of isoform specific alternative mRNAs in HDAC11 wild type versus knockout and inhibitor-treated liver cancer will be quantified. In Aim 2, HDAC11 specific small molecule inhibitors will be tested to establish HDAC11 inhibition as a potential cancer treatment approach. Preliminary data show that HDAC11 inhibition specifically decreases colony formation and increases drug sensitivity, leading to the inference that HDAC11 may promote cancer cell stemness characteristics such as self-renewal and drug resistance. Oncogenesis in vivo will be tested following wildtype, knockout, and inhibitor treatments with disease progression monitored by luminescence imaging. This study will provide new knowledge on the molecular functions of HDAC11 in alternative mRNA splicing and liver cancer progression, and evaluate clinically-relevant small molecule inhibitors for potential liver cancer treatment. Completion of the proposed project will develop necessary research and professional skills that are essential for a career as a cancer investigator.

NIH Research Projects · FY 2026 · 2024-05

A dual 3D bioprinting platform for engineering a thick anisotropic myocardial tissue with geometric vasculature Project summary Cardiovascular disease associated with myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Adult cardiac muscle is thought to lack the ability to repair and regenerate after MI. Additionally, the death of cardiomyocytes stemming from MI activates an irreversible cascade of events leading to heart failure. Stem cell technologies, biomaterials, and various bioengineering approaches have been used to develop functional human-engineered tissue, which ultimately can serve to revolutionize the treatment of the damaged heart. The heart is a complicated, multicellular tissue with hierarchical, structural, and multifunctional characteristics. As such, this tissue presents a huge challenge to replicate through traditional tissue engineering approaches. Based on an anatomical and physiological understanding of cardiac tissue, one crucial challenge in cardiac tissue engineering is replicating the complex architecture (anisotropic myocardial fibers and geometric vasculature) within a cardiac tissue construct and improving its functional maturation. Thus, the objective of this project is to develop a novel advanced dual 3D bioprinting platform and multiple biomechanical stimulation strategies for engineering a novel thick, functional myocardial tissue with anisotropic myocardial fibers and geometric vasculature. Three specific aims of this project are: (1) to fabricate anisotropic myocardial constructs with geometric vasculature via dual 3D bioprinting, (2) to conduct a systemic investigation of hemodynamic behaviors and cell responses for the vascularized myocardial construct under rhythmic mechanical stimulation, and (3) to perform a functional evaluation with an in vivo pig MI model. We expect that innovatively integrating a dual 3D bioprinting platform with biomechanical stimulation will create a functional cardiac tissue with myocardial beating and mature microcirculation for MI treatment. If successful, it will contribute to the prevention of post-infarction ventricular remodeling and the restoration of normal cardiac function. Furthermore, it will not only help patients who are suffering from extensive physical and emotional pain to fight and win the battle against heart failure, but will revolutionize current bioengineering research, leading to a long-term solution for advanced clinical therapeutics.

NIH Research Projects · FY 2025 · 2024-04

PROJECT SUMMARY/ABSTRACT Cannabis is the most commonly used federally illicit drug in the US, with rates increasing, particularly in young adults. Since 2012, 22 states legalized cannabis for non-medical (i.e., recreational) use and have established regulatory oversight for product safety. Meanwhile, derived psychoactive cannabis products (DPCPs; e.g., Delta- 8 THC) entered the US market as a result of the 2018 US Farm Bill, which classified cannabis products with <0.3% Delta-9 tetrahydrocannabinol (THC) by dry weight as hemp, making DPCPs federally legal, but unregulated. Although some states have prohibited or regulated DPCPs, others have not addressed DPCP legality. As a result of this complex and/or ambiguous regulatory context, DPCPs introduce new public health concerns (e.g., use in young people, contaminants, poisonings). This line of research aims to advance evidence- based policy and practice to reduce cannabis and DPCP use, its consequences, and related inequities. Guided by a multilevel Social Determinants of Health lens, we will examine legal, commercial, and individual determinants of cannabis and DPCP use outcomes. While research on the impact of legalizing non-medical cannabis on cannabis use has yielded mixed results, cannabis marketing/retail are well-documented determinants of cannabis perceptions (e.g., risk, social norms), use motives, and use outcomes. Limited research has focused on DPCPs given their recent emergence. There may be similarities in determinants of DPCP vs. cannabis use (e.g., sociodemographic correlates). However, there may be key legal and commercial determinants that differ; for example, DPCPs may be more popular in states without legal non-medical cannabis, and DPCPs may use distinct marketing strategies. Given the complex federal vs. state policy/regulatory context of cannabis and DPCPs, it is crucial to understand determinants and their impact on individual cannabis and DPCP use outcomes in order to inform laws/regulations and interventions to address use and related inequities. Our specific aims are to: 1) examine cannabis and DPCP marketing characteristics over time (2018-2024) with regard to regulatory context and potential target consumers, using existing marketing surveillance data; 2) examine associations between cannabis and DPCP state policy, marketing, individual determinants (perceptions, use motives), use, and related consequences (e.g., driving after use), using longitudinal data of 4,000 young adults ages 18-34 in an ongoing R01; and 3) qualitatively assess young adults’ cannabis- and DPCP-specific experiences with, and perceptions of, legal and commercial determinants of cannabis and DPCP use (via semi-structured interviews). Building on Dr. LoParco’s existing knowledge and skills, the training goals focus on: 1) legal and commercial determinants of health; 2) qualitative/mixed methods research and advanced quantitative analysis; and 3) professional development. This study will yield novel, high-impact, policy-relevant findings and uses rigorous methods to address NIDA research priorities and will facilitate the successful launch of Dr. LoParco’s independent research career focused on cannabis policy, industry, and population impact.

NIH Research Projects · FY 2025 · 2024-04

Project Summary/Abstract The George Washington University Milken Institute School of Public Health (GWSPH) has vast experience in international research ethics education, training, and research in research ethics in Africa. The main aim of the US-Zim RETP project is to establish and implement International Research Ethics (IRE) education, training, and research in Zimbabwe at the University of Zimbabwe Faculty of Medicine and Health Sciences (UZFMHS). UZFMHS is the premier health professionals education and training institution in Zimbabwe and is the major centre for health research in Zimbabwe. There is inadequate research ethics training, education, and capacity in ethics research to support the growing robust research agenda to provide the evidence base to address the most pressing health needs of the country. The overall goal of US-Zimbabwe Research Ethics Training Program (US-Zim RETP) project is to develop the capacity for research ethics education, training, and ethics research in Zimbabwe. The aims of the program are to; Aim 1: Enhance the pedagogical and curricular strengths of key UZFHMS faculty to deliver research ethics courses and mentoring in Zimbabwe. Aim 2: Develop and implement a two-year Master’s level degree in Research Ethics at UZFMHS. Aim 3: Promote research around key priorities for research ethics in Zimbabwe. The US-Zim RETP program will be implemented by GWSPH faculty in collaboration with UZFMHS faculty and other experts in the region. The ethics research will be in line with the priority national research agenda, infectious diseases, and non-communicable diseases. The Master’s program will consist of mentorship/multiple mentorships, coursework, mentored research projects, attachments to research ethics committees, and training in grant and scientific writing and presentation skills. The degree program is designed to run for 2 years. Three cohorts of 5 students each will be recruited over the 5-year grant period. The short courses will be run 3 to 4 times per year, while the faculty development programs will have health ethics components embedded in them.

NIH Research Projects · FY 2026 · 2024-04

Project Summary Approximately 200,000 new cases of ovarian cancer (OC) occur per year, but overall survival has not significantly changed for decades and novel therapies are urgently needed. High grade serous OC makes up about 70% of cases. It is most commonly derived from the fallopian tube epithelium and is characterized by nearly 100% mutant TP53 and high expression of transposable elements (TEs). Nearly half of our genome is composed of TEs, and their transcription is tightly regulated during development. Select TEs are expressed at high levels in embryonic stem cells, but most are silenced by DNA methylation and repressive histone modifications in differentiated cells. As part of the global epigenetic dysregulation that cells undergo during transformation from normal to cancer, TE silencing is compromised and TEs become transcribed. Recent studies from our group and others have implicated TEs in control of innate immune signaling in OC. Our studies in a cancer progression model show that LINE-1 elements lose methylation and are transcribed specifically during cellular transformation rather than immortalization. LINE-1 is the only protein-coding TE known to be able to retrotranspose, and LINE-1 is significantly overexpressed in OC. We showed that LINE-1 is expressed after P53 mutation in OC precursor lesions and that wild type and mutant P53 transcriptionally regulate LINE-1 in OC cell lines. Finally, LINE-1 activation in the absence of P53 interferes with DNA replication to activate the DNA damage response in cancer cells. We know that LINE-1 and other TEs become activated during cancer progression but we do not understand how this occurs or the immune effects of this activation. The objective of this application is thus to uncover the biological mechanisms by which epigenetic dysregulation of LINE-1 changes the OC tumor microenvironment. We hypothesize that by loss of epigenetic regulation, LINE-1 contributes to OC immune evasion. We will test this hypothesis with the following Aims: 1) Determine effects of LINE-1 expression on innate immune signaling, 2) Determine effects of LINE-1 retrotransposition on innate immune signaling, and 3) Determine how LINE-1 expression affects the OC immune microenvironment. Using existing immortalized fallopian tube lines with wild type, mutant, and null P53, we will transform the lines with the C-Myc oncogene. We will perform genome-wide characterization of LINE elements during transformation and will assess effects of LINE-1 expression on the DNA damage response and the tumor immune microenvironment. Taken together, the experiments described in this proposal will add to our knowledge of epigenetic regulation and immune activity of an understudied 20% of our genome, LINE-1 elements. These experiments will enable us to identify potential OC driving alterations and vulnerabilities to novel immunotherapies.

NIH Research Projects · FY 2026 · 2024-04

ABSTRACT Programmed death-ligand 1 (PD-L1) and its receptor, programmed cell death protein 1 (PD-1), modulate anti-tumor immunity and are major targets of current checkpoint blockade immunotherapies. However, clinical trials of αPD-L1/αPD-1 antibodies in breast cancer to date have demonstrated only limited efficacy. The importance of a breast-specific tumor microenvironment (TME) in regulating anti-tumor immunity is vastly under- explored. Given the abundance of adipocytes in breast tissue, the well-documented association between adiposity and breast cancer-related mortality, and the emerging obesity paradox in anticancer immunotherapy, it is imperative to investigate the molecular underpinnings of the complex adipose-immune-tumor network within the adipocyte-rich breast TME. We recently identified a previously unappreciated, functionally significant source of PD-L1 in white adipocytes. Adipocyte PD-L1 is markedly induced during adipogenesis and obesity-related chronic inflammation. Using an adipocyte-specific knockout mouse model, we demonstrate an important role of adipocyte PD-L1 in promotion of tumor growth and attenuation of anti-tumor immunity. Furthermore, our preliminary data indicate physical and functional interactions between PD-L1 and lipid metabolism-related proteins and pathways in adipocytes, which suggests an adipocyte-intrinsic function of PD-L1. Based on our preliminary data, we hypothesize that adipocyte PD-L1 impedes anti-tumor lymphocytes and/or abets tumor cells through a lipid metabolism-related mechanism. We further propose that this action of adipocyte PD-L1 is particularly important at the tumor margin of immune-excluded tumors, where adipocytes are in proximity with both tumor and immune cells. We will combine our established tools and expertise in cancer biology, tumor immunology, and transcriptional regulation to validate this novel hypothesis through the following Aims: (1) Delineate how adipocyte PD-L1 mediates adipose-immune-tumor crosstalk, (2) Determine how adipocyte PD-L1 expression is regulated, and (3) Determine how adipocyte PD-L1 impacts immunotherapy in obese vs non-obese hosts. Our studies on adipocyte PD-L1 signaling in lipid metabolism will provide new molecular explanations for PD-L1 action in tumor immunology, a clear departure from the prevailing paradigm regarding tumor/immune PD-L1 actions. This proposed work represents a conceptual advance toward understanding the spatial landscape of the breast TME in immune regulation and tumorigenesis – a clinically relevant yet mechanistically under-explored problem. Our results could lay a solid foundation for developing new tools that predict and enhance therapeutic response to aPD-1/aPD-L1 immunotherapy for breast cancer patients, especially those with obesity.

NIH Research Projects · FY 2026 · 2024-04

ABSTRACT We propose a large randomized clinical trial within the MFMU Network designed to evaluate the benefits and safety of azithromycin-based prophylaxis (azithromycin plus standard cephalosporin) relative to standard cephalosporin alone prior to surgical incision to prevent post-cesarean (CD) infection. In contrast to cephalosporin, azithromycin is effective against additional pathogens encountered in polymicrobial post-CD infections. We demonstrated adjunctive azithromycin, compared to standard prophylaxis, reduced maternal infections by 50% with remarkable cost-savings in unscheduled CDs. The American College of Obstetricians and Gynecologists (ACOG) now recommends routine use in unscheduled CDs. Our preliminary studies suggest azithromycin may also lower infection risk in the 40-50% that are scheduled/pre-labor CDs, but there are safety concerns regarding the adverse neonatal and long-term microbiome-mediated effects of perinatal exposure. During the project period of 5 years, we will randomize up to 8000 women undergoing scheduled/pre-labor CD to either 500mg of intravenous azithromycin or identical placebo initiated prior to surgery. Both groups will also receive standard single-dose cefazolin prophylaxis (or alternative in the 5% allergic to cephalosporin). Women will be followed for 6 weeks according to adapted Centers for Disease Control and Prevention (CDC) recommendations for ascertaining surgical site infections. The following specific aims will be addressed: Primary Aim (Efficacy): Test in patients undergoing scheduled/prelabor CD if pre-incision adjunctive azithromycin prophylaxis reduces the risk of post-CD infections compared to placebo. Primary Hypothesis: Compared to standard prophylaxis (i.e. placebo + cefazolin alone), azithromycin (+ cefazolin) reduces the incidence of post-CD infections (primary composite outcome of endometritis, wound and other severe infections). Secondary Aim 1 (Safety): Assess the perinatal and maternal safety of pre-incision adjunctive azithromycin. Hypothesis: Compared to standard prophylaxis (cefazolin alone), the use of azithromycin for scheduled CD does not increase adverse perinatal outcomes including a perinatal composite of death, neonatal morbidities, cardiac resuscitation, and hypertrophic pyloric stenosis. We will also examine maternal and neonatal adverse events. Secondary Aim 2 (Resource use): Test the hypothesis that compared to standard cefazolin prophylaxis alone, adjunctive azithromycin reduces a secondary maternal composite outcome (postpartum readmission or ER or unscheduled clinic visits), maternal hospital stay, neonatal ICU admission and neonatal hospital stay. We will collect and store biological specimens including maternal and umbilical cord blood for future mechanistic and biomarker studies. We also plan a separate microbiome sub-study proposal. Completion of this trial, ranked #1/28 by MFMU, will likely change policy, extending the benefits of azithromycin prophylaxis to scheduled CDs faster than the 20 years it took to for standard prophylaxis.