University Of California, San Diego

NSF Awards · FY 2025 · 2025-08

Non-Technical Summary: Cells are the smallest component of life. They have been engineered to be useful in areas such as medicine and energy. Cells can be used to produce critical therapies that can combat cancer, or the cells themselves can even be used as the medicine. Biologists are very good at engineering the internal processes that happen within the cell. It is much more difficult to precisely control what happens on the exterior of the cell. This leads to challenges that may limit the production of what the cells were engineered to make. It may also cause cell medicines to target and destroy healthy tissue. This project aims to develop a new way to attach synthetic materials to the surface of cells, This is important for advancing cell-based technologies because it will enable precise control of how cells interact with their external environment. One solution is to add polymers to the cell surface, creating hybrid materials that combine the cell and polymer. However, the tools to do this efficiently are still lacking. This project will focus on a chemical process called Ring-Opening Metathesis Polymerization to create these hybrid materials. The project will develop methods for attaching polymers to cells and create a toolkit for labeling cell surfaces. The project will also study how this labeling affects cell health, label longevity, and potential internal cell changes. The outcomes could benefit fields like healthcare, energy, and sensors. Finally, the project will provide undergraduate transfer students access to research activities, helping improve their academic and career outcomes. Technical Summary: The objective of this project is to develop grafting-from synthetic techniques from the surface of cells using ring-opening metathesis polymerization (ROMP). Cell-based biotechnology is an exploding field with impact in medicine, biosynthesis, sensor design, among many others. However, several limitations remain for cellular technology to be fully maximized. One critical challenge is manipulating the cell-surface to improve on various functional aspects such as diminishing biofouling, improving upon cell targeting in therapeutics, and immobilizing cells for continuous biosynthesis. One way to enable these capabilities is the introduction of polymers onto the cell surface to generate cell/polymer hybrid materials (CPHs). In the CPH realm, very little work has been done to develop the synthetic toolkit to enable the complex polymer chemistry necessary to enhance these capabilities. The work in this project will enable ROMP chemistry directly from the surface of a cell. This project will develop a basic framework to graft norbornene and oxanorbornene monomers directly from cell surfaces that will be broadly applicable to all CPH materials. The project will study macroinitiator composition and catalyst complexes to synthesize complex CPHs that are narrowly dispersed and living. Once catalysts are optimized, the project will develop a toolkit for labeling any cell by performing covalent modification of proteins, membrane insertion, and glycol-anchoring. Finally, the project will evaluate the long-term health, labeling longevity, and potential biochemical pathways associated with labeling. Cell-based technologies are an emerging field with uses in nearly every aspect of biotechnology and the nascent field of CPH materials would greatly impact all areas. This technology will have broad reach into all sectors of the public consciousness, including health care, alternative energy, and long-lasting sensors. Furthermore, the project will support training and mentoring of multiple transfer students at varying levels of engagement. We anticipate impacting ~30 transfer students per year in the Polymer Scientist for a Day/Week/Year modules, hereby positively impacting transfer student capital and improving academic outcomes for this often-neglected population. 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

HIV sequence data plays a critical role in the public health strategy of detecting transmission clusters and guiding interventions to contain recent outbreaks across the U.S. However, the use of this data raises legal and operational concerns, particularly regarding perceptions of risk associated with HIV transmission or non-disclosure. Practical solutions are needed to address these concerns while supporting health departments in optimizing allocation of prevention resources based on transmission data. This project aims to integrate de-identified and aggregated HIV sequence data with publicly available national HIV prevention and treatment data hosted on the AIDSVu platform. The result will be an interactive online dashboard that enables identification of geographic areas with elevated HIV transmission rates and corresponding variations in HIV treatment coverage in the HIV Care Continuum in Florida. The dashboard will be designed using an iterative usability testing process to ensure that its interface is intuitive and aligned with public health priorities. The effort is supported by a coordinated team of technical experts, public health officials, academic institutions (Emory University, UC San Diego, Johns Hopkins University), and the Florida Department of Health (FDOH). The overarching goal is to integrate HIV sequence and AIDSVu data into a regional monitoring tool that identifies transmission patterns and links them to targeted prevention strategies. The dashboard will use regional heatmaps—excluding individual-level data—to highlight clustering patterns, without use of individual or demographic identifiers, and incorporate national prevention metrics to support timely response. Evaluation of the tool will include assessments of system performance and utility in operational settings, guiding refinements throughout development. Specific Aims include Aim 1) Identify Design Requirements for the Dashboard – Conduct structured discussions with FDOH personnel and subject matter experts to define key functionalities, benefits, and limitations; Aim 2) Develop the HIV ME Dashboard – Integrate de-identified molecular epidemiology data with related metrics (e.g., STI incidence, AIDSVu data, and regional health indicators); and Aim 3) Pilot and Evaluate the Dashboard – Deploy a prototype in select Florida regions for real-world testing by FDOH staff. By aligning data science with public health operations, this project offers a scalable model for enhanced outbreak detection and response. Lessons learned may support similar tools in additional jurisdictions.

NSF Awards · FY 2025 · 2025-08

The rapid advancements in neuroscience, robotics, and computer systems have underscored the vital interactions between mechanical and computational systems in shaping behavior. In natural systems, such as those found in animals, the brain and body must collaborate effectively for the successful navigation of a complex environment. The brain contributes computational intelligence, while the body provides mechanical intelligence. Integrating these elements—computational and mechanical intelligence—into the concept of mechano-computation represents a frontier in both robotics and neuroscience research. Progress in this field necessitates interdisciplinary communication and collaboration across various scientific domains. To propel this promising field forward, the Mechano-computation for Expanding Scientific Horizons (MESH) Network aims to unite diverse researchers from robotics, mechanics, materials science, neuroscience, information theory, biology, engineering design, and applied mathematics. Through workshops, travel grants, and the facilitation of collaborative projects, this network seeks to stimulate interdisciplinary dialogue, develop rigorous metrics for assessing autonomous systems, train the next generation of researchers, and push the boundaries of research in all areas of mechano-computation. By establishing a centralized resource for sharing findings, benchmarks, and methodologies, this network of researchers can accelerate innovation and position the United States as a leader in this transformative field, laying the groundwork for enhanced robotic systems in healthcare, agriculture, forestry, national security, and beyond. It may be argued that the full potential of robotics will not be realized until an intelligent physical body is purposefully designed from the outset, with careful consideration of both the available computational intelligence and the affordances the body can provide—affordances that, if appropriately leveraged, can offload and simplify computational demands by enabling efficient, embodied solutions to complex tasks. The Mechano-computation for Expanding Scientific Horizons (MESH) Network will bring together leading experts to tackle these critical challenges in autonomous systems through the integration of mechanical and computational intelligence. Creating intentional mechano-computation will enhance the design and control of autonomous systems, making them more efficient and explainable, and it will contribute to the development of innovative materials, mechanisms, and control strategies, pushing the boundaries of current research. We anticipate five key outcomes as a result of the formation of the MESH Network: (1) A comprehensive theoretical framework and standardized metrics for mechano-computation; (2) Improved interdisciplinary collaboration and communication among researchers; (3) Long-term interactions among network members and early-career researchers, including nurturing graduate students trained at the intersection of disciplines; (4) Sharing of innovative materials, mechanisms, and control strategies; (5) Practical demonstrations by network participants of mechano-computation systems addressing societal and environmental challenges. The network will accomplish these outcomes through tasks that build online repositories of network critical technical and organizational information, in-person events to broaden discussion and collaboration, online communities, and targeted support for bringing in new collaborative research areas. This project is supported by the Dynamics, Control, and System Diagnostics (DCSD), the Engineering Design and Systems Engineering (EDSE) and the Mechanics of Materials (MoMs) programs of the Division of Civil, Mechanical, and Manufacturing Innovation (CMMI) in the Directorate for Engineering. 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 · 2025-08

Hardware resource disaggregation separates individual hardware components from traditional, monolithic servers and connects them via a network. Disaggregation has been used in the context of compute, memory, and storage resources to bring greater flexibility, decrease energy consumption, and reduce costs. This project extends the concept of disaggregation to data center networks with a key research question: Can data centers and data-center applications benefit from disaggregation by moving network functionalities out of end hosts and pooling them together in another system layer? This project explores this question by introducing a rack-level disaggregated network solution called NetFusion, which consists of a pool of programmable Network Interface Cards (NICs) or SmartNICs, each of which can execute network tasks on behalf of end-host applications. NetFusion allows for the consolidation of networking demands associated with both packet processing and network-function processing, enabling statistical multiplexing of networking tasks and bringing disaggregation benefits to data centers and data-center applications. The project addresses a number of challenges in realizing this vision: How to support the safe and fair sharing of NetFusion? How can the system address both the long-term traffic needs and the short-term bursts of applications? How to allocate resources across the pool of SmartNICs? How to support different SmartNICs with varying resources? How can the system provide fault tolerance and react in a timely manner to workload changes? How can applications benefit from network disaggregation? This collaborative project brings together investigators from University of California at San Diego and University of Washington to optimize the network-intensive datacenter applications used by billions of people around the globe on a daily basis. By improving the efficiency of network operations, one can dramatically reduce the cost of provisioning existing datacenter infrastructure as well as make it much cheaper to deploy new public services. The project integrates industry collaborators who will provide access to cutting-edge network technologies and assist in technology transfer to the industry. For the broader community of users and society at large, the project’s artifacts will be made publicly available at https://sites.google.com/cs.washington.edu/netfusion/home, enabling the development of high-performance data center 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 · 2025-08

Metal ions are important components of biomolecules in cells and help those molecules perform chemical reactions for cell survival. In excess, however, metals can be toxic to cells. Organisms evolved ways to regulate metal ion quantity to keep it at a healthy level. This is achieved by controlling metal ion import and export based on its current amount within the cell. One of the ways by which bacteria sense the current cellular content of metals is with RNA “switches” that bind the metal and turn production of metal ion transporters ON or OFF. This project aims to understand the details of how the signal from RNA-metal ion interaction is propagated into the part of a messenger RNA from which the transporter protein is produced. The gained knowledge will be useful for engineering new RNA-based biosensors, for sensing metal ions in water, as an example. This project will engage and support community college students as they navigate applying to transfer to a four-year university and getting involved in research once transferred. Multiple activities scheduled around the transfer application cycle will provide students with information, as well as networking and paid research opportunities. Riboswitches are non-coding gene regulatory RNAs, which adopt intricate folds that are “switched” when a ligand in the cell binds to the RNA “aptamer”. Although riboswitches were discovered ~20 years ago, the details of signal transduction from the aptamer to the expression platform, where the gene regulatory decision is made, are still not well understood. This project will expand our understanding of how riboswitches rearrange their structure during transcription in response to a ligand, getting to the heart of how they execute gene regulatory decisions. In Aim 1, we will map the co-transcriptional folding pathway of example manganese (Mn)-sensing riboswitches in E. coli. In Aim 2, we will expand our studies to other members of the large Mn-sensing family of riboswitches, which share some of the key aptamer elements but diverge in other aptamer components and the expression platform. This analysis will uncover general principles as well as distinct features of how these riboswitches regulate genes upon binding a metal ion ligand within their native environments. To accomplish these goals, we will employ a multidisciplinary suite of experimental tools from in vitro probing of RNA structure during transcription to reading out gene expression outputs in bacterial cells. 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 · 2025-08

Semiconductor chips are at the heart of nearly all modern technology, from smartphones to medical devices. However, designing these chips is complex, expensive, and dependent on proprietary software, making it difficult for students, researchers, and small companies to innovate. OpenROAD, a free, open-source electronic design automation (EDA) tool, makes chip design faster, cheaper, and more accessible to a wider community of companies, researchers, and students. Open-source EDA tools such as OpenROAD lower barriers to innovation of new hardware systems that are vital for the long-term economic health and national security of the U.S. OpenROAD has been used successfully to design hundreds of chips across a wide range of technologies, and is widely used in education and research. By creating a strong, sustainable open-source ecosystem (OSE) around OpenROAD, this project helps to ensure that the U.S. maintains its leadership in semiconductor design and system innovation. The project creates new opportunities and pathways for education and workforce training, preparing more people for careers in chip design and supporting local semiconductor manufacturing efforts. With funding from the Pathways to Enable Open-Source Ecosystems program (POSE), the OpenROAD Initiative provides the vehicle for building a managing organization and governance structure for a self-sustaining and robust OpenROAD open-source ecosystem. Project goals include the support of open-source EDA tool integration for flexible design flows and the deployment of software distribution infrastructure to improve chip design efficiency. The project will also promote knowledge transfer and enable training at scale. The project seeks to provide pathways for developer onboarding and to foster growth of open-source EDA in adjacent domains including analog/mixed-signal design and next generation data-driven chip design flows using AI-assisted EDA. Additional project goals include developing robust security protocols, benchmarking via widely accessible open-source data, and assessing enterprise readiness to ensure OpenROAD’s wider adoption in both academic and commercial settings. The project broadens the nation’s chip design education and workforce development resources through planned partnerships with universities and industry leaders, and by aligning with government initiatives to train the next generation of chip designers and EDA innovators. 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

The proposed K23 will support Dr. Alena Stasenko’s goal of becoming a leading researcher in risk and resilience models of cognitive aging in epilepsy and developing novel, tech-based interventions to improve brain health. This proposal has significant

NSF Awards · FY 2025 · 2025-08

The cells of our body store information about their identity, such as blood, lung or brain, by locking gene expression through the chromatin state. Although common knowledge indicates that the chromatin state locks genes only “on” or “off”, we propose that it can instead lock genes at a wide range of expression levels, thereby enabling analog information storage. The possibility of encoding analog memory in the chromatin state opens a wide range of opportunities, including the possibility of differentiating pluripotent stem cells into sophisticated tissues with gradients of cell types. This could unlock the ability to create organoids that were not possible to create with previous binary memory paradigms as well as new tissues for regenerative medicine. Through the activities of this project, graduate and undergraduate students will be trained in mammalian synthetic biology, chromatin regulation, and mathematical modeling. We will develop new modules for courses taught at MIT and UCSD, use the research material to enrich our mammalian synthetic biology boot camp at MIT, and disseminate our findings broadly to technical and non-technical audiences through local community events. In this project, we propose a model-driven built-to-understand approach to dissect the molecular mechanisms that dictate analog versus binary memory of gene expression. Our project is grounded on the hypothesis that the strength of the positive feedback loop between DNA methylation and histone H3 lysine 9 trimethylation (H3K9me3) determines whether memory is binary or analog. Since the strength of this positive feedback depends on the cellular context, we propose to vary the context by considering different cell lines and promoters and to verify that memory is analog in those instances where the positive feedback is broken. We further propose to engineer analog memory in a cell line where memory is binary by artificially breaking the positive feedback loop through chromatin regulation. This will demonstrate our understanding of the biological rules that make memory analog. We will finally differentiate hiPSCs cell lines engineered with our reporter system to neural stem cells (NSCs) first and then to radial glial cells (RGCs) and monitor gene expression to determine whether and when analog memory emerges. This will validate whether analog memory naturally develops in the neural lineage, where gradients of cell types reminiscent of analog memory have been recently reported. This project is supported by the Systems and Synthetic Biology Cluster of the Division of Molecular and Cellular Biosciences. 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

ABSTRACT Age-related macular degeneration (AMD) is a major cause of blindness in developed nations. This debilitating condition currently impacts 196 million people worldwide, with projections indicating a rise to 288 million by 2050. The majority of affected individuals experience the early and intermediate stages of "dry" AMD, for which no treatments are available due to an incomplete understanding of the disease mechanisms. In these stages, extensive lipoprotein-rich deposits, known as drusen, accumulate in the macula, impairing vision. Although drusen are a hallmark of AMD, the exact mechanism of their formation remains unclear. Drusen develop in the extracellular matrix (ECM) between the basal lamina of the retinal pigment epithelium and the inner collagenous layer of Bruch’s membrane (BrM). Our lab has shown that the glycosaminoglycan, heparan sulfate (HS), is elevated in patients with early and intermediate AMD and regulates lipoprotein retention. Alterations in glycosaminoglycans are observed with aging and in various diseases, including atherosclerosis. These changes have been shown to regulate the retention of lipoproteins in the ECM, leading to the aggregation of lipoproteins and the formation of atheromas. Alteration of the retention of lipoproteins in BrM has the potential to reveal novel therapeutics that could remove drusen in the early stages of AMD. Nevertheless, our progress had been hindered by the lack of meaningful model systems allowing for quantitative analysis of BrM binding dynamics in the context of AMD. To investigate this chemistry, our lab developed a novel Quartz Crystal Microbalance assay specific to human BrM tissue (QCM-BrM), enabling precise binding kinetics studies under more natural conditions than previously possible. In this exploratory research proposal using QCM-BrM, we aim to investigate the determinants of lipoprotein retention in BrM, including apolipoprotein composition (SA1) and BrM HS content (SA2), and explore the pharmacologic potential of novel therapeutics (SA3). The QCM-BrM technology represents a significant advancement in the study of ECM biology, particularly within the context of AMD. The purpose of this application is to investigate the utility and versatility of the QCM- BrM technology using lipoprotein and HS binding in BrM as a proof of principle for investigating natural ECM-on-a-chip. Future studies will explore the impact of AMD-risk alleles and protease activity on BrM ECM kinetics and investigate binding kinetics of other drusen associated proteins and extracellular vesicles in BrM aggregation. In addition, we plan to collaborate with ECM biology researchers to extend our BrM-on-a-chip technology to additional ECM systems, such as the arterial vessel wall in atherosclerosis.

NIH Research Projects · FY 2025 · 2025-08

SUMMARY/ABSTRACT A 2023 report among UN agencies and partners found that preterm birth represents “a silent emergency” with 13.4 million babies born preterm worldwide in 2020. Preterm birth is the leading cause of infant mortality, the most important predictor of long-term morbidity, and at least 40% of preterm birth may be caused by infection. Chlamydia trachomatis (CT) is the most common curable sexually transmitted infection (STI) worldwide. Antenatal CT infection increases the risk of preterm birth, low birth weight, and vertical transmission of HIV. In low- and middle-income countries (LMIC), most CT infections persist untreated because of a lack of asymptomatic screening. Routine screening for asymptomatic antenatal CT is not recommended by the World Health Organization (WHO) because of high test costs and a paucity of data on the effectiveness of screening and treatment to prevent adverse birth outcomes. Most countries treat based on the presence of symptoms. Our previous work in Botswana identified a high prevalence of asymptomatic CT infection (23%), found that CT screening was feasible, acceptable, and contributed to a reduced post-birth CT prevalence. We found that CT screening and treatment may have reduced preterm birth compared to the standard-of-care; however, this study was not powered to find an effect on birth outcomes. We also found differential impacts by sub-groups (e.g. nulliparous women). Larger trials are urgently needed to determine the impact of asymptomatic CT screening and treatment to prevent preterm birth. This project would conduct an individually randomized- controlled trial to evaluate the impact of point-of-care screening and treatment for CT infection to prevent preterm birth among asymptomatic pregnant women in Botswana. We would also assess differential impacts among sub-groups that could be prioritized for screening. Further, we would estimate the costs of screening and treatment compared to the standard of care (syndromic management), model the budget impact of national scale-up, and examine the cost-effectiveness of screening and treating all asymptomatic pregnant women and sub-groups, compared to the standard of care.

NSF Awards · FY 2025 · 2025-08

This project researches the translation of scientific research, specifically human genomic analysis, into a medical tool, newborn genomic screening. It investigates why this development is occurring, including scientific research, biotechnology actors, and other interested parties, and its effects on patients, healthcare systems, and society. Results of this study inform the understanding of scholars, stakeholders, decisionmakers, and the public and contextualize how new areas of modern medical science and biotechnology may be developed and translated into medical tools. This project uses mixed methods to study the grants and publications that pushed the field forward, the roles of biotech actors, and media coverage and their scenarios of the future of DNA testing. The study involves analysis of research documents and interviews with participants in all aspects of the genomic research, and investigates different aspects of the ethical and societal context of this development. 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/ABSTRACT Research Plan: Acute respiratory distress syndrome (ARDS) is a severe and common condition that affects 10% of patients in the intensive care unit (ICU), and was a major cause of morbidity and mortality during the COVID-19 pandemic. While mechanical ventilation is often necessary for ARDS, it can also induce additional lung injury known as ventilator induced lung injury (VILI). VILI may be minimized by using low tidal volumes/driving pressure and with positive end expiratory pressure (PEEP). Some patients with severe and refractory ARDS require veno-venous extracorporeal membrane oxygenation (V-V ECMO), the highest level of life support which provides oxygen and removes carbon dioxide from the blood using an external device. A major benefit of ECMO is thought to be the ability to minimize VILI; however, the optimal ventilator settings for patients with ARDS on ECMO are not known. Current guidelines use a one-size-fits-all approach. Our central hypothesis is that personalized PEEP adjusted by measuring intrathoracic pressures via esophageal manometry (Pes) will decease VILI as assessed by biomarkers of inflammation (main outcomes IL-6 and sRAGE). To carry out these aims, we plan to prospectively randomize 62 patients with ARDS on V-V ECMO and neuromuscular blockade and perform serial biomarker measurements with PEEP of 10 cmH2O (ECMO guidelines) vs. PEEP guided by esophageal manometry. In addition to biomarkers of VILI, we will assess differences in other physiological outcomes including pulmonary mechanics and gas exchange. Although this proposal focuses on patients on ECMO, we believe the knowledge gained will have relevance for all patients with ARDS. Career Development Plan: The goal of the PI, Dr. Mazen Odish, is to personalize ARDS and ventilator strategies for those on ECMO based on physiology and biomarkers. The PI has an interest in applied physiology and critical care, this award will help him refine these skills and develop new skills in clinical trials, statistics, and patient-oriented research, to test rigorously methods to care for critically ill patients with ARDS with or without ECMO. To obtain these new skills Dr. Odish and his excellent and multi-disciplinary mentoring/advisory team (led by Drs. Owens and Malhotra, plus outstanding statistical and methodologic support) has three main training goals. 1) Pulmonary mechanics and biomarkers during ARDS, 2) control of breathing and measurement of work of breathing during ARDS/mechanical ventilation, and 3) clinical trial design and statistical training. These training activities are tailored for the PI to achieve his goals and maximize career development towards becoming an independent physician scientist. Furthermore, his structured course work will lead to a Masters of Advanced Studies in Clinical Research. Dr. Odish is at the right place and time in his career to align his clinical expertise in ECMO and ARDS with his research goals to understand optimal ventilator settings and therapies. Eventually his work and new skill set may improve the lives of all people suffering from respiratory illness.

NIH Research Projects · FY 2026 · 2025-08

The Altman Clinical and Translational Research Institute (ACTRI) at the University of California San Diego (UCSD) dynamically and rapidly translates scientific discoveries into innovative health solutions. Given the significant growth of our biomedical research portfolio during the last funding cycle, we are positioned to grow our profound impact on advancing translational science and public health within our region and beyond. To amplify our efforts, we will leverage our commitment to scientific collaboration to discover, develop, and catalyze clinical and translational science (CTS) innovations, determine their efficacy and effectiveness, and disseminate and implement these inventions to address challenges in translation. Examples of innovative activities that we are excited about include: An online Business and Finance Platform to streamline hub utilization tracking (Element B), a robust workforce development portfolio that supports CTS researchers across the continuum of their careers, including leadership preparation for early-career investigators with our Leadership Academy (Module C1 and K12); the use of an outreach-driven approach to enhance engagement and expand the reach of our research (Module C2); the use of artificial intelligence in CTS research and a new Next-Gen Trial team to help investigators design and execute decentralized, platform, and adaptive trials (Modules D1, D3); the development of a What’s Next? program to assist early-stage investigators who receive pilot project grants and other ACTRI services in their career planning (Module D2); and new methods for sampling the immune milieu in the upper respiratory tract, use of serious games for developing collaborative science and systems thinking, and finding best ways to provide naloxone to stop overdose deaths in rural San Diego areas (Element E). To leverage our expertise and avoid over-extending our resources, we have strategically established partnerships. Our biomedical science partners (i.e., Salk Institute, Sanford Burnham Prebys, and La Jolla Institute for Immunology) provide considerable depth in basic science discoveries that require further translation to improve health. Our clinical partners serve in rural areas and regions near the border to improve access to care (i.e., El Centro Regional Medical Center, Eisenhower Health), children and adolescents (i.e., Rady Children’s Hospital), and military veterans (i.e., Veterans Affairs San Diego Healthcare System). Our new higher education partner, Mesa College of the San Diego Community College District, has a superb track record of advancing student success through well-supported programs and services. Through these strategic alliances and a focus on collaborative innovation, the ACTRI is not just advancing CTS, it is delivering measurable impact, and building a highly-skilled, sustainable workforce that will drive groundbreaking health solutions to address evolving health priorities.

NSF Awards · FY 2025 · 2025-08

Powerful generative artificial intelligence (AI) models have emerged in recent years, with applications extending beyond language and images to fields such as drug design and beyond. One fast-growing branch of generative AI models, called diffusion models, is an especially efficient and effective mathematical framework for generative AI. However, despite the strong empirical performance of diffusion models, the fundamental mechanisms that let them generate novel samples remain poorly understood. This Mathematical Foundations of Artificial Intelligence (MFAI) award enables research to develop new theoretical tools to both elucidate how flow-based generative models—a broad framework that includes diffusion models—produce novel outputs and enhance that capability, while also extending these models to handle complex data such as graphs and sets. The resulting theory will strengthen the mathematical foundations of AI and help make the technology safer for real-world use by reducing risks, such as unintentionally copying private training data into public outputs. The project will also nurture the next generation of researchers through student training at the intersection of mathematics and AI. Research enabled by this award investigates two central challenges in flow-based generative modeling: (1) how to achieve controlled generalization to produce diverse and novel in-distribution samples, and (2) how to extend these models to complex data types beyond the Euclidean setting, such as graphs, point clouds, or sets. The first thrust focuses on understanding why trained flow models often generalize better than the theoretically optimal solution suggests, using tools from geometry, ODE, manifold learning, and deep learning theory. The second thrust takes a metric space perspective, formulating a general-purpose meta framework for generative modeling of structured data via geometric tools and optimal transport. New scientific findings are expected to lead to both theoretical insights and new modeling strategies, potentially improving the safety and applicability of generative AI. 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

Summary GABAA receptors are pentameric ligand-gated ion channels that mediate most fast inhibitory neurotransmission in the brain. These receptors are essential in the regulation of excitatory signals and their dysfunction can lead to neurological disorders and mental illnesses. Their crucial roles in human health have made GABAA receptors popular targets for a variety of drugs and therapeutics such as general anesthetics. The most widely used intravenous (IV) general anesthetic is propofol, which acts as a positive allosteric modulator (PAM) of GABAA receptors. In patients with risks of cardiovascular or respiratory depression, another PAM called etomidate is often used instead. Although these IV general anesthetics work well, they often cause adverse drug reactions such as airway obstruction and vasodilation induced hypothermia. These adverse reactions can be resolved in the operating room through intubation and patient pre-warming, respectively. Such interventions are inefficient and not practical outside the operating room, for example, in emergency conditions. Therefore, this project aims to discover and characterize novel general anesthetics that are not limited to use in controlled operating room environments. Specifically, I aim to discover GABAA receptor modulators through functional studies, structurally characterize GABAA receptor modulator binding sites, and interrogate mechanisms of potentiation. My proposed functional studies will utilize electrophysiology and leverage drug leads identified through screens performed by collaborators. Concurrently, I aim to determine high resolution structures of GABAA receptors bound to allosteric modulators via single particle cryo-EM. Once modulator binding sites are identified, I plan to define mechanisms of potentiation with functional studies. This work will directly result in modulators with novel mechanisms of general anesthesia that could potentially improve the current anesthetic administration and monitoring protocols. Furthermore, this work will enhance our knowledge of GABAA receptor pharmacology and provide a framework for future drug discovery pipelines.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT Ischemic heart disease, the most common cause of death in the world, is a spatially heterogeneous injury. Between areas of cell death and distant normal cells lies the borderzone (BZ), a complex and dynamic region of cells that plays a critical role in infarct expansion and pathologic remodeling. Historically, it was challenging to study the BZ because of reliance on bulk measurement techniques that combine it with infarct and remote zones in uncontrolled proportions. However, our recently published work shows that the BZ can be redefined based on gene expression using single cell/nuclei, spatial transcriptomics, and multiplexed FISH. This led to the Loss of Neighbor Hypothesis, which proposes that the biology of the BZ is mechanically induced as a result of destabilizing forces resulting from large areas of ischemic cell death. We propose that this secondary mechanical injury is central to infarct expansion and precipitates nuclear envelope rupture and repair, which underlies infarct expansion, pathologic remodeling, and development of heart failure. Aim 1 will investigate the relationship between nuclear rupture, DNA damage, and cell fate at the infarct BZ. Aim 2 will delineate cell-type-specific roles in initiation and propagation of the BZ during infarct expansion. Aim 3 will develop a therapeutic strategy to modulate borderzone biology and limit infarct expansion. Success in this project will advance our understanding of multiscale mechanisms in the BZ and reveal new opportunities for therapy to break the links between myocardial infarction and development of chronic progressive heart failure.

NIH Research Projects · FY 2025 · 2025-08

7. Abstract Knee osteoarthritis (OA) affects >14 million Americans. It is important to develop techniques to assess early OA for timely intervention. MRI provides excellent soft tissue contrast, but clinical MRI is insensitive to early OA. There are four major barriers: First, OA is a "whole organ disease" that involves all major joint tissues, but many joint tissues (e.g., the deep cartilage, menisci, ligaments, tendons, and bone) have short T2s and show little or no signal with clinical MRI. Second, early OA is associated with proteoglycan (PG) loss and collagen disruption, which are difficult to evaluate especially for short-T2 tissues. Third, most research has focused on T2 (biomarker of collagen disruption) and continuous wave T1 (CW-T1) (biomarker of PG depletion). However, T2 and CW-T1 are sensitive to the magic angle effect with >100% increase when tissue fibers are reoriented from 0 to ~54 to B0 (exceeding the 10-30% change produced by OA). Fourth, MRI is slow and expensive, requiring fast imaging to reduce cost and automated processing to facilitate clinical applications. There is an urgent need for fast automated angular-independent biomarkers to map PG and collagen in both short- and long-T2 tissues in the knee joint to diagnose early OA accurately. Ultrashort echo time (UTE) sequences can image "MR invisible" tissues. UTE adiabatic T1 (UTE- Adiabatic-T1) and magnetization transfer modeling of macromolecular fraction (UTE-MT-MMF) allow magic angle insensitive mapping of PG and collagen in all major knee joint tissues. Fat is a major confounding factor. It has significantly shorter T1 and higher proton density than most short-T2 tissues, leading to high fat signal and low short-T2 contrast in UTE imaging. Fat also produces strong chemical shift artifacts manifest as spatial blurring and ringing artifacts in non-Cartesian UTE imaging, leading to inaccurate quantitation. Fat saturation (FatSat) can reduce fat signal and chemical shift artifacts. However, FatSat pulses may significantly suppress short-T2 signals directly due to their broad spectra or indirectly due to the MT effect. UTE with a soft-hard composite pulse allows water excitation with little chemical shift artifact. Single point Dixon technique allows robust fat water separation without short-T2 signal attenuation. These techniques can be combined with UTE- Adiabatic-T1 and UTE-MT-MMF to improve PG and collagen mapping. Furthermore, quantitative UTE imaging is time-consuming and involves complicated data processing and signal modeling. Deep learning (DL) allows automatic segmentation and accelerated quantitative mapping. This proposal aims to optimize and validate UTE-Adiabatic-T1 and UTE-MT-MMF techniques on knee specimens for early OA (Aim 1), develop a multi- tissue segmentation with multi-parameter quantification net (MSMQ-Net) for simultaneous segmentation and multi-parameter mapping (Aim 2), and evaluate knee changes before and post (6, 12, and 24 months) meniscectomy for proof of principle (Aim 3). The goal is to deliver a validated postprocessing pipeline from image acquisition to automated segmentation and UTE mapping of all major knee tissues for early OA.

NIH Research Projects · FY 2025 · 2025-08

Project Summary Sarcomeres are the fundamental functional unit of contractility in cardiomyocytes (and the heart) and consist of two major contractile myofilament protein complexes: thick myosin and thin actin filaments. Myosin heavy chain (MYH) proteins function as the molecular motors that produce sliding between these thick and thin myofilaments, resulting in sarcomere contractility. MYH6 and MYH7 serve as the primary myosin heavy chain proteins and are antithetically expressed at significantly different ratios according to cardiomyocyte cell type and state (developmental and disease). Under cardiac stress and pathophysiological conditions including heart failure, adult ventricular cardiomyocytes respond by decreasing MYH6 while increasing MYH7. Because MYH6 displays greater ATPase activity and actin sliding velocity than MYH7, these changes in the ratio of MYH6 to MYH7 expression can have significant effects on cardiac contractility and correlate with a decline in cardiac performance. However, hearts expressing higher levels of MYH6 to such heart failure/cardiac stress conditions exhibit improved responses. Thus, altering the levels of these cardiac MYH proteins can result in significant contractility changes that can profoundly impact overall heart function. Consequently, we propose to investigate and discover the underlying gene regulatory mechanisms that control the antithetical expression of MYH6 and MYH7 and their isoform switching. Toward this end, a multi-disciplinary approach will be used to: (1) investigate key cis-regulatory sequences that regulate MYH6-MYH7 promoter competition for a cardiac MYH locus control region, (2) identify trans-acting factors that may regulate MYH6-MYH7 promoter competition for a cardiac MYH locus control region, and (3) investigate whether altering MYH6-MYH7 gene expression can be used to modify cardiac disease in hPSC-cardiomyopathy models.

NIH Research Projects · FY 2025 · 2025-08

Project Summary/Abstract Preeclampsia (PE) is a severe pregnancy complication that affects 8% of pregnancies globally, contributing to over 50,000 maternal and 500,000 fetal deaths annually1. Characterized by hypertension, PE arises from poor placental development, partially due to impaired extravillous trophoblast (EVT) differentiation and invasion. Transforming growth factor-beta (TGFβ) signaling is essential for trophoblast differentiation and function, regulating cell migration and extracellular matrix (ECM) remodeling4. Dysregulated TGFβ signaling, including elevated TGFβ levels in preeclamptic placentas, disrupts these processes, leading to poor placental function and adverse outcomes1. Our research focuses on rare damaging mutations in key TGFβ latent complex proteins, including Fibronectin 1 (FN1) and Latent Transforming Growth Factor Beta Binding Protein 1 (LTBP1), that we identified in placentas and umbilical cord blood mesenchymal stem cells (MSCs) from PE-affected pregnancies. We hypothesize that these mutations impair TGFβ latency, enhancing active TGFβ signaling, and disrupting ECM integrity which could ultimately affect EVT migration, invasion, and differentiation. Using patient-derived cells and CRISPR-engineered models, we aim to investigate the functional consequences of these mutations on TGFβ production, signaling, and downstream molecular pathways. In Aim 1, we will study the effects of TGFβ activation and signaling in UC-MSC and iPSC-derived trophoblast stem cells (TSCs) from PE-affected and healthy placentas. We will analyze TGFβ levels, TGFβ down stream signaling, EVT differentiation, and perform functional assays to measure migration and invasion. Bulk RNA sequencing will uncover dysregulated pathways contributing to PE. In Aim 2, we will use CRISPR/Cas9 technology to introduce specific mutations into iPSCs, differentiate them into TSCs and EVTs, and test their effects on ECM integrity, TGFβ latency, and EVT function. RNA sequencing will further identify mutation-specific molecular disruptions. The results have the potential to inform new diagnostic tools, therapeutic targets, and preventive strategies for PE, ultimately improving maternal and fetal health outcomes. Additionally, this research may extend to other placental disorders involving TGFβ signaling and ECM dysfunction, contributing to a broader understanding of placental development and disease.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY Transgenic animal models have been transformative tools for biomedical research. These models have been central to efforts to disentangle causal mechanisms of development, and for uncovering the early life origins of disease. Centralized Resource Centers play a key role in efficient generation, maintenance, and dissemination of these transgenic animals. The goal of this proposal, targeted to the Office of Research Infrastructure Programs (ORIP), is to build a national Resource Center for the sea urchin community that will dramatically improve the reproducibility, utility, and efficiency of research in sea urchins; a classic developmental model used for more than century and studied across hundreds of NIH-supported projects since 1966. This resource will provide a consistent supply of high-quality research animals and transgenic tools, including foundational transgenic lines, and platforms for efficient, low-cost knock-in by end users. The proposal uses innovative approaches to transition the sea urchin community away from dependence on wild caught animals and transient genetics. This work will have transformative impact on research across the mandates of NIH, including studies on reproduction, morphogenesis, membrane transport, and gene regulation.

NIH Research Projects · FY 2026 · 2025-08

ABSTRACT This proposal focuses on identifying viremic and/or people with substance use disorder (SUD), to engage for early intervention, as these often-overlapping populations are key drivers of the remaining HIV epidemic in the U.S. An estimated 80% of new HIV transmissions result from persons with diagnosed infection who are not receiving regular care (43%) or do not know they have HIV infection (37%).1 HIV incidence in the U.S. remains the highest among sexual and gender minorities of color (SGMC).2 Substance use is common among SGM,3,4 and impacts HIV transmission. Viral suppression is 20% lower among people with SUD,25 yet screening for SUD is not integrated in most federally qualified health centers (FQHC)s.26,27 In Chicago, viral suppression among SGMC is ~60%.28 Interventions to identify and treat SUD among SGMC can significantly reduce population level HIV incidence,29 but strategies to ensure universal identification of SUD must be improved. Proposed Solution. We propose a two-prong Hybrid Type I trial34 at a large FQHC network that primarily serves SGM in Chicago, IL. The first-prong is implementing routine screening for SUD (using the NIDA Quick Screen 1.038); and the second is a social network intervention (SNI) to identify individuals who are viremic, have SUD, or both and link them to harm reduction and HIV continuum of care services. Although social network methods have been successful at finding people unaware of their serostatus, and have demonstrated effectiveness in finding viremic SGMC through simulation studies,36 they have not been adapted as an intervention for finding PLWH who are viremic or people with SUD to support HIV elimination.35,37 The present study will test the system-wide implementation of a SUD screener and SNI for finding SGMC who are viremic and/or have SUD. To study implementation, we will conduct a rigorous mixed-methods evaluation across all study years guided by EPIS (Exploration, Preparation, Implementation, Sustainment)38 as the determinants framework and the Proctor Implementation Outcomes Framework (IOF)39 as the evaluation framework. The specific aims are: Aim 1: Evaluate the effectiveness of the SUD Screening and SNI implemented at a large FQHC. Aim 1a: Estimate the increased rate of SUD detection with the SUD screener vs. EMR documentation. Aim 1b: Evaluate whether the SNI is effective at identifying people who are viremic and/or have SUD compared a functional control (new or re-engaged FQHC patients seen during the same period). Aim 2: Develop a multifaceted implementation strategy package to support the adoption and sustainment of SUD screening + SNI in organizations serving SGMC. Aim 3: Evaluate the potential population-level reduction in (i) new HIV infections, (ii) individuals out-of-care, and (iii) individuals virally unsuppressed over 10-years if SU screening and SNI are implemented across Chicago.

NIH Research Projects · FY 2025 · 2025-08

Project Summary: Microtubule (MT) dysfunction is linked to various developmental and neurological disorders. While significant advances have been made in understanding MT dynamics in the cytoplasm, their regulation at cellular membranes remains poorly understood. The primary objective of this proposal is to investigate how MT dynamics is regulated at the interface of the plasma membrane and the cytoskeleton, known as the cortex. My recent postdoctoral research suggests that phase separation-dependent condensation, a process of protein de-mixing, may serve as a cellular mechanism to compartmentalize cortical MT regulators, such as EFA-6, and modulate MT dynamics locally. The proposed study aims to uncover the mechanisms governing EFA-6 phase separation at the cortex and its effect on EFA-6's MT regulatory activity. This study will identify novel factors that regulate MT dynamics at the cortex, elucidate their mechanisms of action, and characterize their roles in MT-membrane interactions dependent cellular functions. Unraveling the MTs regulations at this interface will offer new insights into the fundamentals of MT homeostasis and could inform the treatment of diseases associated with MT dysfunction, such as microcephaly, amyotrophic lateral sclerosis, and Parkinson’s disease. C. elegans will be used as the model organism due to its well-characterized MT dynamics, genetic tractability, and transparency for live-cell imaging. The project will focus on two specific aims: 1) Investigating the mechanisms by which EFA-6 undergoes phase separation and modulates MT dynamics, using proximity labeling, in vitro assays, and genetic analyses (K99 phase). 2) Identifying and characterizing novel cortical MT regulators and investigating their roles in regulating membrane functions through genetic, microscopic, and biochemical approaches (R00 phase). This proposal will deepen our understanding of how cells regulate MT dynamics at the cortex to achieve specific membrane morphologies and functions. Furthermore, this study will uncover novel regulators of MTs, shedding light on MT homeostasis under both normal and stress conditions. Overall, the proposed research will broaden our knowledge of MT dynamics and organization and provide insights into management or treatment of MT dysfunction associated diseases. The mentored phase will be conducted at UC San Diego under the guidance of Professors Yishi Jin and Andrew Chisholm, renowned experts in genetics and neurobiology. UCSD and neuroscience faculties provide an excellent environment for the proposed research. I will receive hands-on training in in vitro phase separation and in vitro MT analysis from Prof. Lizhen Chen and Prof. Arshad Desai, respectively. Mentorship from additional experts, including Professors Nicholas Spitzer and Sreekanth Chalasani, will help me transition to an independent research career. Altogether, this research will deepen our understanding of how cells regulate MT dynamics at the cortex, advancing knowledge of cellular morphogenesis and membrane functions, which are critical for understanding and treating diseases such as Alzheimer’s, microcephaly, and ALS.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive cancer, where most patients (~80%) are diagnosed after metastatic spreading has already occurred, coupled with a dismal overall 5-year survival rate of 13%. Novel therapeutic treatments often show promise in preclinical models then fail when advanced to human clinical trials. This naturally leads one to ask how these preclinical models differ from the clinical disease. PDAC tumors are characterized by a complex tumor microenvironment (TME). Its dense fibrotic stroma is known to contain rich amounts of fibrillar type I collagen, known to be a major driver of metastasis and treatment resistance. Interestingly, most preclinical models used to study the PDAC TME or test promising treatment modalities rely on the injection of tumor cells mixed in basement membrane extract (BME, e.g. Matrigel®) to establish primary tumors. However, BME is composed primarily of laminin and collagen IV while containing no collagen I. Our preliminary results show the importance of incorporating collagen I into PDAC preclinical models. Injecting PDAC cells with 3D high density type I collagen (HDC) generates tumors with significantly more collagen content and extensive metastasis, even in PDAC cells lines that do not normally metastasize in mice. We developed the first successful orthotopic PDAC tumor using 3D HDC in a mouse model, which we utilized to discover a stark contrast in survival between mice in the HDC group versus the BME group. These findings together support our hypothesis that PDAC cells grown in 3D HDC recapitulate the metastatic behavior of human PDAC tumors better than existing models. By accomplishing our aims, we will better understand how the collagen-rich PDAC TME drives metastasis and resistance and engineer a synthetic alternative to better study PDAC preclinical models. Leveraging in vitro and in vivo studies through a multidisciplinary approach, the goals of our proposed project are to (1) demonstrate that HDC co-injection models recapitulate aggressive human PDAC better than traditional BME models; (2) identify how HDC drives collective invasion and metastasis. Because natural matrices contribute to experimental variability, we will (3) develop a synthetic hydrogel substitute comparable to HDC to enable broader implementation in PDAC preclinical research. Our multidisciplinary team, led by a female surgeon and female engineer, will produce a better method of modeling PDAC that more accurately recapitulates metastatic progression and therapeutic resistance. Our approach will provide a more realistic preclinical setting to test new therapeutic strategies and the potential to reveal novel treatment strategies for PDAC.

NSF Awards · FY 2025 · 2025-08

CloudBank 2 is a service-based resource that brokers access to commercial cloud resources and builds upon the infrastructure developed by CloudBank. Its flexible multi-cloud infrastructure has been in operation since August 2020, supporting Amazon Web Services, Google Cloud Platform, IBM Cloud, and Microsoft Azure. CloudBank 2 empowers researchers to explore and access a wealth of these rapidly evolving commercial cloud resources. Commercial clouds play an important role in AI research, development, and education, as well as supporting high-performance computing, networking research, edge computing, quantum computing, and a wide variety of other scientific, engineering, medical, and business applications. Through its Education Hub and outreach activities, CloudBank 2 aims to provide access to advanced computing resources and contribute to the continuing U.S. national leadership in "Science, Technology, Engineering, and Mathematics" (STEM) education, training, and preparation of the U.S. workforce. This mission is fully consistent with U.S. national goals towards "increasing the economic competitiveness of the United States," "advancing the health and welfare of the American public," "supporting the national defense of the United States," and "developing an American STEM workforce that is globally competitive," pursuant to 42 U.S.C. §1862. CloudBank 2 builds upon and enhances CloudBank's three core research and education services: a CloudBank Portal that makes it easy for researchers to access and manage their cloud accounts, share access with collaborators, and monitor their spending; Financial Operations that pay monthly cloud vendor bills and relieve users of the burden to manage financial accounts or use their own credit cards; and an Education Hub based on an open-source stack for teaching on the commercial cloud, which has facilitated interactive computing for students and educators by offering an easy on-ramp for data science education. In addition, CloudBank 2: 1) supports projects that require access to regulated data; 2) supports AI educators with an enhanced Education Hub; 3) provides portal tools to support communities and science gateways; 4) facilitates data transfer and interoperability with other ACCESS resources; 5) integrates new commercial cloud vendors to provide innovative capabilities and potential additional cost savings to the science and engineering community; and 6) facilitates cost and security compliance management of commercial cloud resources. A team of experts assists researchers in harnessing the full potential of commercial cloud services to advance multiple research domains through the business hour help desk, cloud clinics, training, user documentation, curated research workflows, and application 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 2025 · 2025-08

PROJECT SUMMARY Changes in placental structure and function not only cause serious pregnancy complications but also determine life-long health by programming the fetus for future metabolic and cardiovascular disease. Unfortunately, the mechanisms linking altered placental function to poor short- and long-term outcomes are complex and remain largely unknown. To better understand placental biology and pathophysiology, a multidisciplinary approach utilizing a wide array of cutting edge technologies is required. Progress in this area is hampered by the paucity of scientific meetings focused on placental biology. The primary objective of this R13 grant proposal is to meet the urgent need of a multidisciplinary, interactive forum for dissemination of novel concepts and exchange of ideas in placental research by featuring exceptional speakers working in cutting-edge areas of research. The secondary objective is to provide a low cost, high-quality learning environment, in the area of placental biology, which will encourage attendance and active participation by a diverse group of in training and early investigators. In our conference plan we seek support for an annual one- day conference as a satellite meeting the day before the Annual Scientific Meeting of the Society of Reproductive Investigation (SRI). By this design we will maximize the impact of the meeting and will allow for attendance of a diverse group of basic scientists and clinical investigators ranging from graduate students to well established researchers. The meeting will allow ample time for interaction, informal discussion and networking and is anticipated to attract 130-150 attendees each year. The program will have a balanced mix of “state of the art” lectures presented by the leaders in the field, emerging concept presentations, and shorter talks by trainees. All speakers will be mandated to provide ample time for questions and discussion. This proposal is significant because the meeting is timely and will promote novel scientific inquiry into placental biology, which is expected to pave the way for future innovation to develop approaches to monitor placental function in vivo and to target the placenta for intervention. The proposal includes numerous innovative aspects. For example, we propose to facilitate the utilization and adaptation of emerging concepts from other research fields by inviting one speaker each year that works in a research area other than placental biology. To provide ample opportunities for early career investigators to connect, discuss, and interact with the speakers we propose to organize the conference lunch so that in-training investigators will have direct access to speakers in a small group. The proposed meeting is expected to have significant and sustained impact on the field because it is unique in bringing together world-leading investigators representing diverse but complementary expertise in a creative and interactive forum, which is necessary to address the complex scientific questions pertaining to the role of placenta in determining health and disease from fetal life to adulthood.