Dartmouth College

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT Perioperative organ injury (POI) is a major contributor to morbidity and mortality in surgical patients, impacting multiple organs, including the heart, lungs, kidneys, liver, and gastrointestinal system. Perioperative acute kidney injury (AKI), for instance, occurs in 2% – 18% of patients and 22% – 57% of intensive care patients, accounts for 30% – 40% of total AKI cases in the United States, and increases hospitalization costs by up to 70%. Despite substantial advances in anesthesiology, POI remains largely unpredictable, with treatment still limited to organ- supportive care. While hypoperfusion and inflammation are recognized as the pathophysiological hallmarks of POI, current understandings are still broad and inadequate. In particular, anesthesia is a crucial factor in the pathophysiology of POI, but its specific roles remain to be clarified. Suboptimal anesthesia is known to impair organ function, but certain anesthetics, via preconditioning and postconditioning procedures, have been reported to offer protective effects against ischemia-reperfusion injury, a leading cause of POI. This ambiguity is largely due to the lack of advanced monitoring techniques capable of continuously and comprehensively tracking the pathogenic processes of POI to yield robust interpretations. The overall vision of this research program is to elucidate the pathophysiology of POI and the role of anesthesia therein by pioneering the development of a wireless, soft implant for continuous and comprehensive tracking of organ physiology and biochemistry. The goals for the next five years include: 1) Develop a wireless, battery-free soft implant with a protruding micronee- dle sensor array for spatiotemporal probing of organs, using a 3D-printing based manufacturing process to achieve 3D sensor configuration and fully biocompatible materials to minimize immune response. 2) Develop sensors on microneedle tips for monitoring hypoperfusion (oxygen and lactate), inflammation (interleukin-1β, interleukin-6, and tumor necrosis factor-α), and organ injury (neutrophil gelatinase-associated lipocalin), with a focus on achieving direct in vivo electrochemical detection of biomarkers and stable chronic recordings for at least 7 days post-operation. 3) Use the integrated implant to investigate the harmful effects of anesthetics at various dosages and the protective effects of different anesthetic preconditioning and postconditioning protocols in rat models. This project is significant because it seeks to decode the role of anesthesia in the complex patho- physiology of POI, offering potential insights that could inform clinical anesthesiology practices. This project is innovative because it pioneers the development of a wireless, soft implant capable of spatiotemporally tracking important organ biochemical markers over extended periods.

NSF Awards · FY 2025 · 2025-09

This NSF CAREER project aims to enhance electric power grid operators' situational awareness, improve dynamic model quality, and enable online controls to ensure secure power system operation with high penetration of inverter-based resources (IBRs). The project will bring transformative changes to the use of measurements for dynamic state estimation, model deficiency diagnosis and calibration, and measurement configuration, thereby enhancing system reliability and security. This will be achieved through innovative dynamic estimation theories and algorithms that leverage the increasing diversity of sensors and communication infrastructure, as well as advancements in robust estimation, uncertainty quantification, optimization, and data analytics. The intellectual merits of the project include i) a generalized, computationally efficient derivative-free observability theory, with observability indices tailored for dynamic systems with black-box models, ii) integration of Bayesian inference with robust estimation to develop novel nonlinear dynamic estimation methods and iii) a scalable Bayesian framework for dynamic parameter estimation and uncertainty quantification. The broader impacts of the project include developing the next generation of robust dynamic estimation paradigms for IBR-dominated power systems, and industry-academia collaborative initiatives to promote industry-driven research, course renovation, and training to equip students (including K-12 students, and those from underrepresented groups across different disciplines and diverse backgrounds) with unique experiences in renewable energy technologies, data analytics and power engineering. The rapid deployment of IBRs, such as solar and wind farms, and battery energy storage is changing the dynamic landscape of electric power grids. Traditional steady-state-based static state estimation, used in current energy management systems, is insufficient for capturing these dynamics in real-time operations. This project addresses the critical need for improved dynamic observability and reliable models for system reliability analysis and decision-making. The research objectives include i) developing a generalized derivative-free state and parameter observability theory for black-box and hybrid dynamic systems, overcoming limitations of linearization-based and Lie-derivative-based theories for IBR-dominated systems, ii) fusing robust statistics with estimation and optimization to create nonlinear dynamic estimation methods capable of addressing black-box IBR models, control mode switches, current limiters, anti-windup constraints, unknown controls, and multi-timescale dynamics and iii) designing observability-informed, scalable parameter estimation and uncertainty quantification algorithms to continuously refine power system dynamic models. 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 · 2025-09

Sea-level changes are actively damaging coastal communities, ecosystems, and infrastructure. Glacier mass loss is a key uncertainty in determining how much sea-level rise will occur in the near future. Among the key unknowns in glacier science is how fast does ice slide across the land. The presence and pressure of water at the base of glaciers influences their sliding speed, which affects the resulting sea-level rise. This project will improve our understanding of how water moves beneath glaciers and ice sheets. Current models do not accurately represent subglacial water flow. By improving these models, this project will provide more reliable projections that are essential for informing policymakers and communities about the risks of changing sea levels. At the same time, through lectures and laboratory experiments about snow, ice, and sea-level, this project will ignite interest and improve scientific literacy among elementary and undergraduate students. This project aims to resolve discrepancies between observations and existing subglacial hydrology models through incorporating subglacial thermomechanics, particularly the process of ice infiltration into sediments, forming what is known as a ‘frozen fringe’. This project involves compiling a comprehensive catalog of subglacial water pressure observations to inform model development. This project has three main research aims: first, to characterize subglacial effective pressures and frozen fringe thicknesses; second, to model the impact of frozen fringe growth and sediment erosion on channelized water flow beneath glaciers; and third, to integrate these thermomechanical processes into the Subglacial Hydrology And Kinetic, Transient Interactions (SHAKTI) model to improve its accuracy. This research combines theoretical modeling, laboratory experiments, and field data to develop a model consistent with observed pressures. The resulting model will be implemented into the Ice-sheet and Sea-level System Model (ISSM) to reduce uncertainty in sea-level change predictions. Concurrently, this project fosters education through hands-on glacier and snow science activities for schools as well as an interdisciplinary undergraduate course. 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 · 2025-09

This doctoral dissertation award investigates human settlement and agricultural practices at a site that has largely characterized the region as dominated by hunter-gatherers with low population density, who moved seasonally to different environmental settings, and practiced limited, if any, domestic agriculture. New evidence suggests the possible presence of widespread maize cultivation and nucleated permanent villages. Resolution of questions surrounding past settlement and subsistence practices has broad implications for understanding of the relationships among sedentism, emergent social complexity, and agricultural intensification, as well as the anthropogenic impact on the natural environment prior to population expansion. The study’s use of phytolith analysis advances administrative priorities for investments in understanding the adoption of biotechnological innovations in scientific research. The researcher also makes use of remote sensing methods (LiDAR) and ground-penetrating radar systems (GSST), which enhance the integration of artificial intelligence in scientific research. The project also provides training for graduate students in these analytical and other archaeological methods. This project locates, documents, and analyzes archaeological remains through a multi-scalar research strategy. The region where the research is focused is ideal because of the minimal development that has occurred compared to other parts of New England, coupled with an environment well-suited for agriculture and a rich ethnohistoric tradition. The project integrates regional remote sensing, landscape-scale geophysical prospection using ground penetrating radar and other methods, as well as targeted excavations to secure dating, artifactual, and paleoethnobotanical samples. Soil samples are processed for phytoliths to understand the ecological composition of the region and recover evidence of domesticated crops. Collectively, the results reshape understanding of agriculture, the social organization of the communities who resided in these regions, and their potential impacts on the region’s ecology. Likewise, innovative methods developed by the project form a blueprint for archaeological investigations broadly. 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 · 2025-09

Project Summary/Abstract: Membrane proteins are critical for organelle identity and function. Among these, tail-anchored (TA) proteins represent a special class of membrane proteins that are post-translationally inserted into their respective membrane via a single C-terminal transmembrane (TM) domain. TA proteins are prone to mislocalization, which can disrupt cellular function and initiate proteostatic collapse, a hallmark of age-related disease. While initial TA protein studies focused on yeast, mammalian systems represent a richer diversity of TA proteins and, in tandem, regulatory mechanisms. In this proposal, I will explore how mammalian TA quality control systems function, using the TA protein BNIP3 as a model. BNIP3 dually localizes to the ER membrane and outer mitochondrial membrane (OMM) and has been broadly implicated in organismal health span and aging. BNIP3 function and stability are regulated by the homodimerization of its transmembrane domain. By generating BNIP3 variants that localize exclusively to either the ER or OMM, this project aims to dissect 1) the specific signals used to identify orphan TA proteins, 2) the cellular machinery that recognizes them, and 3) how this dictates BNIP3 fate across organelles. The project will be pursued through two main objectives: In Aim 1, I will utilize a fluorescent reporter for ER-localized BNIP3 to pinpoint the critical signals within BNIP3 necessary for its recognition and proteasomal processing from the ER membrane. In addition, I will perform an unbiased genome wide CRISPR knockout screen to identify the cellular factors mediating TA quality control at the ER. In Aim 2, I will utilize a fluorescent reporter for OMM-localized BNIP3 to identify the signals within BNIP3 necessary for its turnover from the OMM, as well as investigate the factors mediating TA quality control from the OMM, parallel to the approaches used in Aim 1. This research promises to reveal the sophisticated mechanisms cells use to control the quality of TA proteins like BNIP3, potentially highlighting novel ways in which the ER and mitochondria maintain proteostasis through additional coordination. The findings from this work could subsequently open new avenues for understanding mechanisms of age-associated proteostatic collapse.

NSF Awards · FY 2025 · 2025-09

With this award, the Chemistry of Life Processes program in the Division of Chemistry supports Drs. Harish Vashisth from the University of New Hampshire and Esteban A Orellana Vinueza from Dartmouth College to study how modifications to nucleic acid bases affects the structure of tRNAs and their functions in the biosynthesis of proteins. Transfer RNA (tRNA) delivers amino acids to ribosomes for the construction of proteins, with the three-base anticodon of tRNA specifying which amino acid is brought to the ribosome. The sequence of nucleotides outside of the anticodon can vary to create what are known as isodecoders of the tRNA. The nucleotide bases of isodecoders are chemically modified by cells under environmental changes, at different stages of cellular development developmental stages, and between cell types. This project applies approaches from the disciplines of biological chemistry as well as theoretical and computational chemistry to enhance the understanding of how these modifications affect the structures, dynamics, and folding/misfolding mechanics of the tRNA isodecoders, and reveals their potential roles as therapeutic targets and diagnostic biomarkers. This project is integrated into outreach and broader impact activities that visually teaches spatial thinking skills about RNA structure and function to STEM learners. The result is to increase the national talent pool for the STEM workforce in the emerging areas of RNA-based chemical tools and technologies. This research project addresses fundamental questions about the structures of tRNA isodecoder molecules and studies the impact of chemical modifications to uniquely alter tRNA structures and folding mechanisms. A combination of experimental techniques (spectroscopic methods, CRISPR technology, translation assays, and proteomics) and computational techniques (molecular dynamics simulations and thermodynamic property calculations) are used to resolve the functional, conformational, and energetic effects of chemical modifications in tRNA isodecoders. The project also establishes approaches, including new protocols for computing circular dichroism spectra of RNA molecules based on conformational ensembles from atomistic simulations, that are broadly applicable to other RNA molecules. Moreover, the conformational and thermodynamic property datasets emerging from simulations are highly useful in training of data-driven learning models. The education and outreach broader impact activities contribute to implementation of the next-generation science standards, increase in national talent pool, and enhanced education about RNA based technologies through summer research programs, 3D printing based and software generated molecular models, seminar series, journal clubs, and course teachings. 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 · 2025-09

The early Paleogene (~66-48 million years ago) was an important time in Earth’s history: It immediately followed the mass extinction of all dinosaurs (except birds), many modern groups of mammals first appeared, and the Paleocene-Eocene Thermal Maximum (a significant climate event) occurred. Knowledge of these events is mostly based on a well-dated and characterized North American stratigraphic record; a global perspective on these events is missing. This project will apply modern, high-precision, age-dating techniques to the sedimentological and mammal fossil records of Mongolia. These methods will allow the building of a critical framework for comparing the North American and Asian fossil records across this important time interval. New physical and digital collections of fossils and a pop-up traveling exhibition on Paleogene mammal evolution and climate will be created. Developing a modern chronostratigraphy and paleoenvironment reconstruction for the highly fossiliferous Naran Bulak and Gashato Formations in Mongolia is the goal of this project. Four geochronological methods will be used, including magneto- and chemo-stratigraphy and Ar/Ar and U-Pb geochronology. Age and correlation data will be combined with careful sedimentological and paleoenvironmental analysis. These methods will be used to precisely constrain this important fauna and permit precise correlations with other parts of Asia and with the North America record. This geochronologic focus will be coupled with detailed sedimentologic analysis and stable isotope analysis of ancient soil and lake deposits to identify the PETM boundary by its signature global negative carbon isotope excursion. 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 · 2025-09

PROJECT SUMMARY (See instructions): Human cytomegalovirus (HCMV) establishes a latent infection in hematopoietic progenitor cells (HPCs) and cells of the myeloid lineage and its reactivation is exquisitely linked to hematopoietic differentiation and stress. Latency is poorly defined for HCMV at the molecular and cellular level. The long-term goal of our work has been to define the mechanisms by which HCMV enters and exits the latent infection. The UL 133-UL 138 locus coordinates the expression of four genes, UL 133, UL 135, UL 136, and UL 138 with pro-latency and pro-reactivation functions. We have defined the cellular pathways modulated by these viral proteins to define mechanisms of latency and reactivation. Our work has shown that accumulation of the reactivation determinant, UL 136p33, is controlled by the host E3 ubiquitin ligase IDOL, which is induced by the liver X receptor in response to sterol levels. Maintenance of low levels of UL 136p33 by IDOL is critical for the establishment of latency and downregulation of IDOL with differentiation is important for reactivation. A host target of IDOL is the low-density lipoprotein receptor (LDLR). We determined that HCMV infection downregulates LDLR and prevents the maturation of LDLR through the ER. We show that UL 138 is important in driving ER-associated degradation (ERAD) of immature LDLR forms in infection. UL 138 further is required for the induction of the unfolded protein response and sterols in infection. We have identified UL 138-host interactors important to ERAD and regulation of the unfolded protein response and ER stress. We hypothesize that UL 138 regulates ER stress, proteostasis, and sterol metabolism important for viral latency through its ERAD-related host interactions. We will determine how UL 138 regulates ERAD by defining virus-host interactions (Aim 1), how UL 138-mediated regulation of ERAD impacts ER stress and lipogenesis/sterol synthesis in infection (Aim 2), and how this regulation of host pathways impacts the regulation of latency and reactivation (Aim 3). We anticipate that UL 138 regulation of ERAD impacts the cellular sterol environment sensed by HCMV to control UL 136p33 levels through changes in IDOL concentration for latency. Our work reveals new mechanisms by which HCMV controls UPR/ERAD with implications for the regulation of ER stress and sterol synthesis to regulate HCMV latency and reactivation. Defining these mechanisms elucidates novel host pathways important for HCMV latency and reactivation.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY Cell fate is determined through a complex hierarchy of events that require tight regulation of signaling pathways. Misspecification of cell fate can have detrimental effects on downstream developmental events, leading to tissue mispatterning and disease. Key principles of cell fate specification remain unknown. Defining the mechanisms that provide spatial and temporal precision to gene regulatory networks is crucial for understanding how cell identity is established and can be leveraged to generate desired cell types for the repair of damaged or diseased tissues. In previous work, the PI has identified protein glycosylation as an unexplored mechanism that regulates cell fate. The long-term goal of the PI’s research program is to exploit the intrinsic plasticity of endothelial cells to define the fundamental principles by which glycosylation determines the identities of differentiated cells. The proposed R35 project will investigate two parallel cell fate decisions, representing four distinct cell types: artery, vein, lymphatic, and hematopoietic stem/progenitor cells. It will harness the optical transparency of zebrafish embryos to make highly quantitative measurements of these processes as they unfold naturally in vivo. It will also leverage a first-of-its-kind list of glycoprotein candidates and its glycosylation sites that are misglycosylated in a cell fate mutant. The overall objectives of this study are: 1) To decipher how glycosylation regulates the functions of cell fate regulators; and 2) To determine how glycan composition dictates the choice of cell identities. In Project 1, loss-of-function studies in zebrafish will reveal how five N-glycoproteins regulate the cell fate transformation of arterial endothelial cells into hematopoietic stem/progenitor cells. Additionally, missense mutations that prevent glycan attachment to these candidate proteins will be generated to assess the requirement for glycosylation in their fate-determining functions. Project 2 will use a cell fate mutant as a tool to test how glycosylation regulates the transformation of venous endothelial cells into lymphatic endothelial cell progenitors. The experimental approaches will identify the glycosylation enzymes and glycan repertoire required for this important fate decision, ultimately demonstrating that discrete glycans repertoires instruct endothelial cell identity. This research is innovative in that it seeks to apply state-of-the art microscopy, genetic, and glycomic technologies to characterize glycosylation-dependent mechanisms of specification for multiple clinically relevant cell types in vivo. Using this process to compare cell fate decisions from a common lineage provides a rare opportunity to define the universal and cell-specific mechanisms of glycosylation in cell fate regulation. The proposed work is highly significant as the results have the potential to reveal new design principles of cell fate specification, and thereby inform new strategies of cellular reprogramming, via glycoengineering, for therapeutic interventions.

NSF Awards · FY 2025 · 2025-09

Many solar energy projects are installed in agricultural lands, creating land competition with crops, orchards, vineyards, and pastures. However, relatively little is known about how these solar installations affect surrounding communities, landscapes, and agriculture. Moreover, careful design and siting of these installations can yield a variety of benefits, including increasing farm income, enhancing water resources, improving plant and animal habitat, and enriching soil. To address these issues, this project will bring together an interdisciplinary team of scientists and engineers with agricultural extension specialists, landscape designers, community members, and industry and nonprofit partners. The project will focus on two questions: 1) how is solar energy affecting the landscape and surrounding communities?; and 2) how can the U.S. build a stronger, more productive, and more resilient agroenergy landscape? The project explores practices that will improve outcomes of solar energy in agricultural landscapes. To do so, the project will collect novel data at existing solar facilities and launch a first-of-its-kind scientific research facility to collect data on how solar installations affect agricultural land and communities. Using these data, the research team will study how solar facilities change soil and habitat conditions, the water cycle, crop production, economic returns, and surrounding communities. Throughout the project, an advisory team of farmers, stakeholders, policymakers, and community members will help shape the research and focus the project’s efforts on the needs of farmers, utilities, and the public. This approach will bring together new forms of biogeophysical data collection, modeling, and life cycle assessment with community co-creation. The project’s findings will be used to create decision-support tools, design new solar installations, conduct workforce training, and develop educational workshops and programs. 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

Algebraic objects such as groups are used to measure symmetry in both mathematics and the natural world. In combinatorial representation theory, one aims to make algebraic structures more accessible by translating them into concrete combinatorial objects such as graphs, tableaux, and partitions. These combinatorial models not only provide intuitive insight but also lead to more efficient computations. A central focus of this project is to study how representations can be combined, especially through operations like the tensor product and composition of group representations. Our goal is to build algorithms that use combinatorial tools to break down the combined representations into basic building blocks, called irreducible representations. This decomposition problem has broad significance across fields like algebraic combinatorics, complexity theory, and statistics, and it finds practical applications in computer vision, quantum physics, chemistry, and even fast matrix multiplication. At its core, it addresses the fundamental challenge of disentangling individual signals from a composite one. In parallel, the PI will continue collaborative work with students on the chromatic symmetric function, a rich yet accessible topic that provides an ideal entry point for introducing students to mathematical research. Three of the most important open problems in combinatorial representation theory are the Kronecker, plethysm, and restriction problems. Each focuses on understanding how representations decompose into irreducibles, and all three are closely connected. The PI and her collaborators have identified the plethysm problem as the key to solving the others. In joint work with Saliola, Schilling, and Zabrocki, the PI developed a new approach to plethysm using the representation theory of diagram algebras. These efforts led to a new algorithm for computing plethysm based on the uniform block permutation algebra. Together with Zabrocki, she also introduced new bases of symmetric functions that have led to progress on the restriction and Kronecker problems. Building on this foundation, the proposed projects will further develop the combinatorial and algebraic frameworks aimed at deeper understanding of the plethysm and related decomposition problems. 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

The Super Dual Auroral Radar Network, or SuperDARN, is an international collaborative experiment for observations of plasma motions in Earth’s upper atmosphere. By observing ionospheric plasma motions, a multitude of geophysical processes are being studied. These processes range from fundamental plasma instabilities to the global-scale plasma response to changes in the solar-terrestrial environment. Each of these areas of study contributes to developing an understanding of the coupling of energy from the Sun into Earth’s upper atmosphere and its effects on humanity and technological systems. This project will support operations and maintenance of the U.S. SuperDARN radars in the northern hemisphere by the consortium of Penn State University, Virginia Tech, Dartmouth College, and the Johns Hopkins University Applied Physics Laboratory. The collaboration operates twelve radars that cover a vast region from Alaska to Iceland at high latitudes, and Oregon to Virginia at middle latitudes. In addition to operation and maintenance activities, the project will support a program of research that exploits new capabilities that have been developed over the last several years. This includes providing improved fidelity in measurements (plasma convection mapping and imaging), extending the area over which measurements are obtained (bistatic observations), and providing new types of measurements (sounding). SuperDARN has a long-standing commitment to including graduate students in all aspects of the program. The SuperDARN observations are also important for space weather applications since HF radio propagation is sensitive to perturbations in the bottomside ionosphere, e.g., solar flares. 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

The research supported by this grant will contribute to the advancement of national prosperity and economic welfare by developing models to engineer delay announcement systems to determine what delay information to announce, as well as when to announce it, to maximize customer satisfaction and/or minimize abandonment. Every day patients needing critical care walk out of the waiting rooms of Emergency Departments (ED) because they are frustrated by long delays, incurring increased risk of returning to the ED, hospitalization, and even mortality. Adding more doctors, nurses, ED rooms and equipment is not always possible given limited budgets. In this work the researchers plan an almost costless approach: sharing waiting-time information in a way that will encourage patients to wait for a provider and will also increase their overall satisfaction with the experience. The approach is to engineer delay announcement systems to optimize both what delay information communicate to patients and when to communicate it. Similar techniques may be used to improve the customer’s experience in other service environments, such as financial services, hospitality (restaurants, hotels), and call centers. Therefore, this work will increase the health of our citizens, the satisfaction of consumers, and the economic welfare of services industries. In general, by designing effective delay announcement systems, this project will have a positive impact on the economy, healthcare and society within the United States. This project will (1) Develop rigorous multidisciplinary analytical and behavioral models rooted in behavioral economics and operations research for understanding and improving customer satisfaction via delay announcements. Methodologies used will include stochastic dynamic programming, queueing theory, prospect theory, and econometrics. (2) Introduce a fundamentally new vision of delay announcement system design. The classic criterion of “forecast accuracy” is enriched to capture relevant features of human reactions to forecasts, including loss aversion and the passage of time. (3) Develop a standard framework to bridge the research in the OR/MS and Medical fields to improve customer/patient satisfaction through the provision of delay information. This research will promote and strengthen the field of behavioral service operations, and the results will be tested and fine-tuned via field experiments within a network of Emergency Departments. In general, the project will use data, optimization and communication technology to engineer customer satisfaction and to trigger additional high-impact research. 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

The domestication of animals has long been established as a critical predictor of human social and economic complexity. Among domesticated animals, the domestication of certain livestock have held an especially significant role in the human development, since livestock management is one critical pathway for establishing food security. Yet the origins of domestication and the broader roles livestock played in shaping human social organization remain poorly understood. This project investigates how livestock domestication shaped key historical shifts in food production and economic organization. In doing so, the project advances understanding of the origins of agriculture and the development of early social structures. The results have use-inspired translational value for public safety and security by modeling a range of outcomes where food security can be established through livestock management. The project involves the use of innovative biotechnological methods, while training students and engaging the public in techniques such as microfossil analysis, dental calculus analysis, and the integration of stable isotope data. The project focuses on two central questions: (1) How did livestock domestication occur in early farming societies? and (2) What role did livestock management play in the emergence of social complexities and early states? The project draws on regional archaeological sites with some of the world’s earliest evidence for livestock domestication and state formation. It analyzes remains spanning 9,000 to 3,500 years ago. Using microfossil analysis of dental calculus and tooth measurements, the research team reconstructs diets, domestication status, and management strategies. By compiling data from nine sites, the study traces how domestication took place, whether production became centralized under emerging political authorities, and whether management contributed to the development of new forms of complexity. This integrative approach offers new insights into social, economic, and ecological dimensions during key periods of societal change. 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 Management of positive surgical margins in the resection of oropharyngeal squamous cell carcinoma (OPSCC) is an imprecise science, yet its results drastically affect patient outcomes. New cancers of the oral cavity and pharynx are diagnosed at 11.4 cases per 100,000 Americans annually, with incidence rising steadily due to HPV- mediated disease. Most patients with early-stage OPSCC are treated surgically; however, positive surgical margins (PSMs) complicate approximately 30% of traditional and 15% of robot-assisted procedures. Re- localization of positive margins is important for both intraoperative management with frozen section guidance, and for postoperative planning of adjuvant radiation therapy. In both cases, inaccurate orientation and localization can lead to incomplete treatment and excessive iatrogenic damage to healthy tissue, resulting in reduced local control and overall survival. We propose a novel, robot-integrated system for intraoperative creation and annotation of digital 3D models of resection specimens and the residual tumor bed. These models will employ visual feature correspondences to warp between the shape of the flattened specimen and the in situ oropharyngeal anatomy. As such, positive margins identified intraoperatively by frozen section or postoperatively by permanent section can be accurately mapped to the specimen and also to the in situ anatomy. We hypothesize that this digital pathology solution will integrate seamlessly into the transoral-robotic surgery (TORS) workflow and provide the care team with qualitative and quantitative margin localization data that will 1) improve clinical communication around specimen orientation and margin context, and 2) enable more precise, patient- specific adjuvant therapies, ultimately reducing recurrence and improving overall survival. In Aim 1, we will develop 1) the necessary workflow from stereovision to 3D specimen models, 2) in-console annotation functionality, and 3) model deformation capabilities. In Aim 2, we will conduct a single-site human subjects feasibility and effectiveness evaluation. At the end of the performance period, we will deliver a robust, robot- integrated specimen orientation and margin visualization system ready for implementation in a multi-site prospective study designed to quantify the effects of the proposed system on local control and survival in TORS.

NIH Research Projects · FY 2025 · 2025-08

SUMMARY The overarching goal of this COBRE is to establish a multidisciplinary research program in implementation science at Dartmouth College and to provide training, expert mentorship and new scientific infrastructure to train and support a critical mass of early-stage investigators as they transition into independent investigators dedicated to advancing the field of implementation science. Implementation science is the study of methods to promote the integration of research findings and evidence into healthcare policy and practice as a critical emerging discipline in biomedical research. This multidisciplinary field combines methods from medical anthropology, healthcare and behavioral economics, intervention effectiveness and process research, improvement science, education and learning, social psychology, organization and management, and marketing. Currently, there is $3 billion annually in federal funding for implementation research. Yet, there is a critical gap in academic development opportunities for junior faculty to be trained and mentored in the implementation sciences or resources to increase their academic trajectory towards independence. Despite the escalation in funding and the unique needs of IDeA states for effective biomedical health interventions, IDeA states continue to lag in implementation research funding. Therefore, we propose to build state-of-the-art infrastructure in implementation science to accelerate biomedical research funding for implementation in the IDeA state of New Hampshire, and create systems and training opportunities for use by other IDeA states regionally and nationwide. Our proposed Center for Implementation Science, supported by Centers of Biomedical Research Excellence (COBRE) mechanism, will support and advance research by junior faculty, building on Dartmouth’s recognized academic and research excellence. The proposed Center will support five research project leaders and will address the following specific aims: Aim 1: To establish a multidisciplinary COBRE Center for Implementation Science; Aim 2: To implement and sustain a vibrant organization and management plan for the Center; and Aim 3: To accelerate the transition of junior faculty into NIH grant- competitive, strong? independent investigators. Impact: The proposed Center for Implementation Science will provide needed funding, new scientific resources, and mentorship to advance junior faculty into independent research careers focused on the study and application of implementation science. The initial research projects will support the development of a self-sustaining, multidisciplinary, research program in implementation science and provide a needed resource for IDeA Centers for Biomedical Research Excellence nationally to foster national collaboration and accelerate NIH funding independence.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT The human gastrointestinal tract is densely colonized by bacteria that are under threat of infection by phages. To combat threats, bacteria commonly form groups, termed biofilms, comprised of bacterial cells and secreted adhesive matrix. Temperate phages differ from virulent phages as they can either lyse their host cell to produce a burst of new virions, or they can integrate into the host genome and propagate vertically, reserving the ability to enter the lytic cycle under specific environmental conditions. Despite the ubiquity of temperate and virulent phages, the fundamental patterns of how these different life strategies fare when in direct competition within a structured community has never been explored on cellular spatial scales. The first aim of this proposal is to determine competition dynamics between temperate and virulent phages within a biofilm context. We will determine how host availability within structured and unstructured microbial communities alters this competition. We will then determine optimal invasion dynamics for temperate phages as a prophage or as an active virion, as well as how temperate phages propagate through biofilms after prophage induction. The second aim of this proposal is to explore the social evolution of temperate phages. In environments where virulent phages are able to successfully infect bacteria lysogenized with temperate phages, the virulent phages always outcompete temperate phages. How then do temperate phages evolve? We will investigate how temperate phages can win in a global population through the evolution of restraint while still being outcompeted in discrete microenvironments. We will investigate this question in both laboratory experiments and theoretical modeling work. This work will provide medically relevant insight into the interplay phages attempting to colonize and infect residing host bacteria in humans. The proposed training plan encompasses the acquisition of various skills, including the mastery of laboratory techniques, enrollment in an off-campus course at Cold Spring Harbor, the development of effective experimental designs, proficient science communication, and the cultivation of active mentorship abilities. Dartmouth College and my mentorship team are highly equipped to assist in the successful execution of my research project and facilitate my advancement to the next stage of my career as a postdoctoral researcher, with the ultimate goal of securing a faculty position at an R1 institution.

NSF Awards · FY 2025 · 2025-08

This is a project jointly funded by the National Science Foundation’s Directorate for Geosciences (NSF/GEO) and the National Environment Research Council (NERC) of the United Kingdom (UK) via the NSF/GEO-NERC Lead Agency Opportunity. This Lead Agency Opportunity allows a single joint US/UK proposal to be submitted and peer-reviewed by the Agency whose investigator has the largest proportion of the budget. Upon successful joint determination of an award recommendation, each Agency funds the proportion of the budget that supports scientists at institutions in their respective countries. Antarctic ice mass loss is linked to the way the ocean interacts with floating ice shelves around the continent, which will play a key role in controlling how fast glaciers flow into the sea. Reproducing historic records of mass loss has proven challenging because ice sheets respond relatively slowly to changes, carrying the imprint of many past events, and because important processes, like how ocean-driven melting affects ice shelves, are not fully captured by current models. This project will address these challenges by combining state-of-the-art satellite observations with advanced glacier modeling and high-resolution ocean simulations to capture interactions and feedbacks between Antarctica’s glaciers and the surrounding ocean. By delivering the most reliable projections yet of Amundsen Sea Sector, Antarctica's most dynamic region, the project will address critical knowledge gaps regarding 21st century ice loss from Antarctica. This project will reduce uncertainty in 21st century ice loss from Antarctica through next-generation assimilation of satellite observations into ice sheet models and advance Earth system downscaling through high-resolution ocean simulations. This will be achieved through the following objectives: 1) improve ice-sheet data assimilation to capture the current dynamic state of Antarctic glaciers and reduce model uncertainty, 2) improve model representation of poorly constrained ice processes by leveraging the results of assimilation, 3) develop an effective modeling treatment for ocean-driven melt through high-resolution simulations, 4) improve projections of 21st century sea-level contributions through coupled modelling of dynamic Antarctic glaciers under different emission scenarios. This collaboration will produce novel 21st century projections of ocean-driven ice loss from Antarctica that are consistent with the full range of satellite observations of ice sheet thinning, ice-stream acceleration, and ice-shelf melt. By focusing on regions in West and East Antarctica with the strongest thinning rates and oceanic forcing, this project will greatly reduce uncertainties in century-scale ice loss and provide step-change improvements in ice-sheet data assimilation and ice-ocean modelling to the Antarctic modeling community. 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

Improving herpes simplex virus (HSV) vaccination efficacy and neonatal outcomes A successful Herpes Simplex Virus (HSV) immunization has remained elusive, despite over 80 years of research. Moving forward in murine studies with HSV immunizations it is imperative to consider overlooked biological factors that impact immune responses to immunization and therefore impact the overall efficacy. Age is a conserved biological variable across species that has been shown to impact both innate and adaptive immune functions. Clinical research has shown that age influences severity and outcomes of HSV infection in humans. Neonatal herpes simplex virus (nHSV) is observed in 1/10,000 live births, causing significant mortality and lifelong neurological morbidity. Early diagnosis and treatment with antiviral therapy ameliorates poor clinical outcomes but a lack of clinical suspicion leads to delayed treatment and so lifelong neurological morbidity remains prevalent, however longitudinal studies following neurological outcomes remain sparce. Our lab has published that neonatal infection with low-doses of HSV-1 leads to increased anxiety-like behaviors in mice. By utilizing a low-dose neonatal infection model, the relationship between viral infection and long-term neurologic morbidity can be studied. My overall goal is to determine if age impacts murine immunization efficacy and characterize the neonatal response to viral challenge. My central hypothesis is, therefore, that the type, and especially the timeline of neonatal, juvenile, adolescent, and maternal vaccinations are critical efficacy determinants of vaccines designed to prevent nHSV. In Aim 1, I will determine the extent of protection afforded to neonates via maternal immunization. I will utilize survival benchmarks during the acute phase of neonatal HSV infection and behavioral assays such as modified Barnes maze (MBM), and different paired associates learning (dPAL) to measure long-term behavioral changes following neonatal HSV infection. In Aim 2, I will establish and characterize murine neonatal, juvenile, and adolescent HSV immunization. I will utilize plaque neutralization assays and flow cytometry to characterize neutralizing and T cell responses following HSV immunization. Completion of these aims will form a foundation for human HSV vaccine clinical trials that take age and serostatus into account and will provide a comprehensive account of the long-term behavioral morbidities due to an early life clinical HSV infection.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT Cystic fibrosis (CF) is characterized by the formation of thick mucus in the respiratory tract contributing to chronic infections of numerous pathogens, including commonly Pseudomonas aeruginosa (Pa). Pa forms robust biofilms, aggregates of bacteria encased in a protective extracellular matrix, in the airways of people with CF (pwCF) and is a major cause of morbidity and mortality for pwCF. Pa harbors a wide repertoire of competitive mechanisms that mediate host-microbe and microbe-microbe interactions. One such defensive mechanism is the type VI secretion system (T6SS) which is known to be expressed during respiratory infection in pwCF. The T6SS apparatus transports diverse effectors, one of which is TseT. The tseT operon consists of a PAAR/tip protein, chaperone proteins, the effector TseT, and its cognate immunity protein TsiT. Preliminary results found that deletion of the tseT operon decreases Pa biofilm growth in association with human CF bronchial epithelial cells and expression of TsiT alone is sufficient to restore biofilm production in the tseT operon mutant. Thus, the T6SS immunity protein TsiT is important for Pa biofilm growth, but the mechanism is unknown. TsiT has sequential and structural homology to a general LysR-type transcriptional regulator (LTTR). LTTRs are known to regulate diverse genes including those involved in virulence, metabolism, and quorum sensing. Homology to LTTRs suggests a secondary, unconventional function for TsiT, in addition to its role as a traditional T6SS immunity protein. This application aims to test the hypothesis that TsiT has a secondary function as a transcription factor that regulates biofilm. As TsiT is conserved across several Gram-negative bacterial pathogens, this work will provide far reaching insights into biofilm regulation and thus clinical treatment. The applicant plans to pursue a career in academia in the area of host-pathogen interactions. Support for this application will enable her to hone skills in bioinformatics and biochemistry, acquire experience mentoring/teaching, experience with manuscript and grant preparation, and experience presenting to diverse audiences. This application will not only provide a broad range of laboratory techniques, but also provide transferrable skills for her long-term goal of becoming an academic researcher.

NSF Awards · FY 2025 · 2025-08

This project explores exciting new interactions between two central areas of mathematics - algebra and geometry - and their unexpected connections through physics. Algebra and geometry are foundational tools in mathematics, widely used in numerous scientific and engineering applications, such as computer science, data analysis, robotics, and theoretical physics. Historically, the interplay between algebraic equations and geometric shapes has led to powerful methods and profound insights, shaping much of modern mathematics and technology. In recent decades, researchers discovered surprising connections linking algebraic geometry, which studies shapes defined by polynomial equations, to symplectic geometry, an area crucial to physics and engineering. This project leverages these emerging connections to develop new mathematical tools that bridge algebra and geometry. Broader impacts of this research include significant training and mentoring activities. The project supports early-career researchers and graduate students, providing extensive professional development through workshops, virtual seminars, public lectures, and the creation of publicly available computational tools. On the technical side, the project aims to advance understanding in multigraded commutative algebra, toric geometry, and symplectic geometry. It addresses long-standing gaps and open questions in commutative algebra and toric geometry by introducing methods inspired by recent advances in homological mirror symmetry into purely algebraic contexts. The P.I.’s will explore new approaches to studying multigraded polynomial rings, aiming to uncover deeper structural properties that parallel classical results for standard graded polynomial rings. The project will develop algebraic analogues of effective symplectic geometry techniques, such as "stop manipulation," adapting these symplectic methods to algebraic settings. The project will also extend foundational results, including Orlov’s Theorem, to multigraded and toric settings, construct novel categorical structures that unify algebraic and geometric perspectives, explore applications to virtual resolutions and other questions involving shortest resolutions, and investigate extensions to broader classes of geometric objects through toric degenerations and natural generalizations from toric varieties. Furthermore, by establishing explicit links between algebraic constructions and Fukaya categories, the project will introduce new computational tools and theoretical approaches in symplectic geometry. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-07

Massive amounts of data are collected or generated in industries such as finance and healthcare; in scientific fields such as genomics and high-energy physics; and in technological applications such as cloud computing and training machine learning models. This has motivated the design and analysis of data stream algorithms, a highly productive research area within computer science. The focus is typically on algorithms with provable guarantees regarding their running time, memory usage, and accuracy. However, the guarantees established in previous work often require explicit and implicit assumptions about how the algorithms will be applied. Many existing algorithms become ineffective when these assumptions do not hold. This project aims to design resilient data stream algorithms that are less dependent on such assumptions and more reliable in practice. It will also support curriculum development and the training of graduate students. The project tackles several key challenges in the theory of data stream algorithms. First, it aims to develop adversarially robust algorithms that remain effective even when inputs are adaptively chosen in response to algorithmic behavior. This situation naturally arises in interactive data analysis. Second, the project investigates parameter-free and non-adaptive algorithms that do not rely on prior knowledge of problem-specific parameters, avoiding the costly, generic technique of multiple instantiations. Third, it examines when the performance of randomized streaming methods can be matched or approximated by pseudo-deterministic or deterministic algorithms. Such algorithms provide reproducibility, which is important in experimental science. Finally, the project seeks data stream algorithms that address fault-tolerance, ensuring correctness amid hardware or communication errors. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-07

PROJECT SUMMARY Myelin has evolved to speed up, finely tune, and increase the metabolic efficiency of electrical signal transmission in the brain. In numerous human diseases, myelin degenerates, ultimately resulting in devastating motor and cognitive impairment. One key reason that this degeneration progresses to functional impairments is the decline in the ability of resident oligodendrocyte precursor cells (OPCs) to generate new myelinating oligodendrocytes and replace the dying cells. To generate new oligodendrocytes, OPCs go through many cellular and molecular checkpoints, coordinating external microenvironmental signals with internal genetic, epigenetic, and metabolic states. Given this complexity, there are still many questions related to how these signals are integrated within the cell to ultimately result in the cell fate decision to transform into a postmitotic myelinating oligodendrocyte or remain a proliferative OPC. Mitochondrial activity has been shown to play important roles in similar fate decisions in other cell types throughout the body in addition to playing major roles in cell death pathways, however, less is known about how these organelles impact OPC fate, oligodendrocyte generation, and oligodendrocyte death in the intact brain. To directly study this, we have developed advanced techniques for high resolution imaging and manipulation of mitochondria throughout the oligodendrocyte lineage. These techniques permit longitudinal analyses of mitochondrial structure, localization, and dynamics in real time all in the live mammalian cerebral cortex. Here we propose to use these approaches to determine how disruptions and alterations in mitochondrial dynamics, characterized by mitochondrial fission, fusion, motility, generation, and degradation, impact OPC fate and oligodendrocyte survival. These experiments will be performed in the context of development, adulthood, aging, and in demyelination models, thus revealing the precise role mitochondria play in oligodendrocyte generation, plasticity, death, and regeneration. Ultimately, these studies will reveal multiple aspects of cell metabolism with a mitochondrial lens providing a critical foundation to understand this multifunctional organelle in oligodendrocyte physiology and pathology.

NIH Research Projects · FY 2026 · 2025-07

PROJECT SUMMARY/ABSTRACT Poor bone quality in the jaw is a significant clinical problem that leads to pain, along with an increased risk of fracture and infection. Multiple clinical conditions may lead to poor jawbone quality, but two of the leading causes are osteoporosis and osteonecrosis as a result of radiation therapy (RT). Osteoporosis affects 200 million people worldwide and while the focus is often on the appendicular skeleton, craniofacial bones, including the jaw, become brittle and diseased. While not as pervasive, head and neck cancer (HNC) is the sixth most common cancer type worldwide with a predicted 30% global increase annually by 2030. RT is the standard treatment for HNC, and osteoradionecrosis (ORN) of the jaw is a frequent and severe complication. Interestingly, the molecular mechanisms underlying the poor bone quality in these two conditions are similar, with cellular senescence and dysregulation of osteoblast to osteoclast management playing a significant role in disease etiology. Senescence is a cellular-level response that restricts aged or damaged cell proliferation and represents a major cause of aging due to genomic instability and telomere damage. Studies have demonstrated an increase in senescent cells as a person ages, contributing to diseases associated with aging (e.g., osteoporosis). Additionally, we have identified a strong correlation between cellular senescence and increased expression of the bone inhibitor sclerostin (SOST). The long-term goal of this project is to tune a novel 3D-printed (3DP) mineral framework infiltrated with cryogel scaffold to resist destructive structural and cellular modulations following radiation in order to improve bone regeneration. We propose the central hypothesis that a combined cryogel scaffold/mineralized 3DP framework will induce osseointegration and bone formation in HNC patients, while modulating senescence caused by radiation. We test this hypothesis through three main aims: i) enhancement of bone formation in the setting of radiation through the fabrication of combined tissue- engineered cryogel/3DP mineral constructs; ii) systematic modulation of in vitro senescence through optimization of scaffold mineralization, with or without the addition of senolytic drugs; and iii) quantification of senescent cells and overall bone healing in an established in vivo osteonecrosis mandible murine model exposed to RT. This approach will allow for the creation of a cost-effective and biologically improved targeted treatment option consisting of uniquely combined mineralized 3DP framework and cryogel technology. The potential to induce osteogenesis and modulate senescence, both in vitro and in vivo, is innovative and impactful mechanistically, where our fabrication expertise and mechanistic knowledge will establish a scaffold capable of stimulating/accelerating bone formation. Further, the innovative impact of the combined scaffolding for modulating senescence has the potential to be highly translational to additional complex bone defects, especially those in aging patients. This will fit a need in the research and clinical community for improved patient-specific treatment options while supporting the NIDCR mission of improving oral, dental, and craniofacial health.

NSF Awards · FY 2025 · 2025-07

Imaging cells deep within living things is challenging because light is scattered as it travels through tissues. Two-photon (2P) microscopy is a technique that uses longer wavelengths which are less prone to scattering to allow for deeper penetration into the tissue while maintaining the ability to visualize single cells. However, the depth of penetration is limited. This project uses an ultra-compact chip-scale device based on optical nanostructures to overcome the depth limits of 2P microscopy. This technology could enable tissue imaging at faster speeds over larger volumes using a chip-scale microscope. This technology will enable new observations of cell behavior to improve our fundamental understanding of biology, leading to improved diagnostics and therapeutics. This project focuses on the development of photonic-integrated-circuit two-photon microscopy (PIC-2P), whereby light is delivered from a minimally-invasive nanophotonic chip with cellular-scale thickness (<50 µm). This technique overcomes the fundamental imaging depth of 2P imaging by delivering light orthogonally with respect to the image collection, obviating the effects of scattering and absorption from superficial layers, and leading to a signal-to-background (SBR) many orders of magnitude higher than traditional 2P imaging. This project aims to demonstrate feasibility of PIC-2P imaging in scattering and absorbing specimens and to characterize the anticipated imaging depth improvements. The team combines expertise in nanophotonic devices and multiphoton label-free tissue microscopy. Goal 1 develops a low-loss, packaged biocompatible fiber-to-chip coupler that can efficiently deliver multiphoton pulses to the PIC using co-design of micro-optics and a PIC coupler. Goal 2 develops a dispersion-compensated, low-loss PIC-2P waveguide platform for 2P pulsed light delivery through fundamental investigations of dispersion and power handling properties of dispersion-engineered waveguide systems. Dispersion management techniques based on waveguide and cladding cross-section optimization and transverse and longitudinal nanostructuring of the waveguide will be used to tune the dispersion throughout the system. Goal 3 integrates the PIC with a free-space 2P microscope to characterize the image depth improvements of PIC-2P vs 2P imaging in phantoms with varying physiologically relevant scattering and absorption properties. 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.