Johns Hopkins University

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT Prostate cancer (PCa) is the most commonly diagnosed type of cancer and the second leading cause of cancer related deaths among US men. The proposed project aims to improve prostate image-guided interventions (IGI) with a novel ultrasound probe and robot developed by our team, ProBot. We propose a Phase 1 clinical trial to evaluate the safety and feasibility of the new device at biopsy. We also propose to improve the technology and expand it to focal therapy of PCa. ProBot is an entirely new concept including a novel ultrasound probe and robot kinematics specifically designed for prostate IGI. A novel feature is that it does not change the deformation of the prostate gland, allowing more accurate MRI-ultrasound co-registration and needle targeting. In addition to accurate MRI targeted biopsy (TB), at systematic biopsy (SB), instead of using the usual template plan, our innovative software optimizes the plan to ensure appropriate biopsy spacing and obtain diagnosis representative of whole gland histology. ProBot will also be uniquely capable of transrectal (TR) and transperineal (TP) biopsy and focal therapies. ProBot is ready for immediate clinical assessment as proposed. It is a refined prototype and has already attained approval by the FDA for clinical trial evaluation. We recently completed 2 TR biopsy cases with ProBot with IRB approval. We propose to extend the approval for TP biopsy and perform the trial for TR and TP biopsies. Focal therapy is a promising, minimally invasive treatment strategy to selectively treat localized PCa while minimizing the side effects associated with whole gland treatment options. Focal therapies aim to deliver ablative energy to PCa lesions sampled at biopsy. Repeatably targeting a lesion between biopsy and therapy may be improved if the same device, such as ProBot, is used to guide both procedures. As a research aim, we also propose to further develop ProBot for percutaneous interstitial ablative treatment, an innovative approach to be integrated with ablative technology and tested in a future trial. ProBot is a small, lightweight (1.3Kg ultrasound probe and robot), inexpensive to manufacture device that could ultimately provide a cost-effective solution for PCa care. The ProBot allows hands-free operation of its ultrasound probe at 3D image scanning and needle targeting. This device could reduce the level of physician training and skill currently needed while minimizing the variability in outcomes among physicians, and ultimately improve the accuracy of biopsy targeting and reliability in the results of biopsy. An early-stage clinical trial is required to evaluate the safety and feasibility of the new device and biopsy approaches.

NSF Awards · FY 2025 · 2025-08

NON-TECHNICAL SUMMARY The defects present in engineering metals and alloys are pivotal in controlling properties such as mechanical strength and toughness. Properties such as these are crucial in fueling advanced technologies. Yet, alloy design principles and frameworks that target specific materials phases seldom treat the defects as objects for design themselves. Extending the fundamental thermodynamic, kinetic, and structural principles widely used to design bulk materials to the defects within these materials would enable more purposeful engineering of new materials with improved properties. To address this goal, this project will synthesize, characterize, and simulate the thermodynamics and kinetics of nanostructured metallic alloys containing a large quantity of interfacial defects known as grain boundaries. By encouraging specific chemical and structural environments at these defects, local phase transitions will be studied with the goal of promoting excellent thermal stability and ultimately mechanical behavior. This research aims to expand the scientific underpinnings of nucleation from nanoscale confined arrangements for bulk metallic systems where classical nucleation theories are not appropriate. A primary goal is to also use the insights gained from this research to advance the emerging paradigm of defect phases and their intentional design, which requires new theories on the thermodynamics and kinetics of small confined systems, as well as new approaches to defect-aware materials design. This project also supports outreach to K-12 populations in the Santa Barbara, CA and Baltimore, MD communities through local school and art museum engagement in addition to engagement with older adults using STEM-based programming to help combat social isolation and loneliness. TECHNICAL SUMMARY Amorphous complexions, also known as defect phases, are analogous to bulk amorphous phases but restricted to a thin nanoscale film along grain boundaries. Such microstructural features are particularly useful interfacial states since they imbue nanocrystalline materials with thermal stability at very high temperatures. Interestingly, these features are considered to be a major weakness of these otherwise promising materials. A fundamental advantage of amorphous complexions as designer interfaces is that their disordered structure is the preferred local equilibrium state upon undergoing a pre-melting event. However, the kinetics of these phase transitions localized to defects are not well understood, since their signatures are challenging to measure and depend strongly on the nature of the abutting crystals that surround the resulting confined structures. The proposed work will use alloy design of nanocrystalline metals to target these pre-melting transitions, produce thermally-stable, nanoscale-confined disordered interfacial states, and quantify the kinetics of these transitions. These regions are the starting point for solidification pathways with microstructures not accessible through conventional alloy synthesis and processing routes. State-of-the-art experimental approaches including ultrafast calorimetry, materials synthesis in both thin film and bulk forms, and in-situ scanning/transmission electron microscopy will be complemented with computations of phase equilibria and kinetics using atomistic and kinetic simulation approaches based on machine-learned interatomic force fields. The insights gained on the kinetics of nanoscale complexions having varying degrees of order are expected to inform frameworks for predicting the behavior of confined interfacial states of matter and guide alloy design strategies with intentional populations of targeted defects. This project also supports outreach to K-12 populations in the Santa Barbara, CA and Baltimore, MD communities through local school and art museum engagement in addition to engagement with older adults using STEM-based programming to help combat social isolation and loneliness. 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 Fibrosis underlies a vast number of cardiac pathological conditions, ranging from genetic cardiomyopathies to ischemic heart failure. Although substantial progress has been made in identifying molecular signals that trigger the characteristic activation of quiescent cardiac fibroblasts (CFs) and their transdifferentiation into myofibroblasts (MyoFBs), far less is known about the mechanisms that govern their long-term fate and persistence, which presents major obstacles to the development of effective anti-fibrotic therapies. This K99/R00 application describes a five-year research training plan that proposes to leverage (i) human induced pluripotent stem cell-derived cardiac fibroblasts (iPSC-CFs), (ii) engineered biomaterials with tunable mechanical properties, and (ii) single-cell multiomics platforms to investigate molecular mechanisms that govern MyoFB fate and plasticity. Given the well-established sensitivity of CFs and MyoFBs to extracellular matrix (ECM) stiffness, the applicant Dr. Sangkyun Cho will test the hypothesis that modulation of ECM-mediated mechanical signaling potentiates the de-differentiation of MyoFBs, by synergizing with soluble factors known to regulate major pathways in fibrogenesis. In Aim 1 (K99), Dr. Cho will use reporter iPSC lines (with fluorescently tagged canonical MyoFB ‘marker’ genes, e.g., CFP-TAGLN) and a novel dynamically softening hydrogel system to characterize in real-time the effects of mechanical unloading on MyoFB fate. In Aim 2 (K99), Dr. Cho will investigate the synergy between ECM softening and the TGF-beta pathway in regulating MyoFB states, (i) by examining stiffness-dependent protein interactions among mechanosensitive transcription factors (e.g., yes- associated protein 1 (YAP)), and (ii) by identifying epigenetic regulators downstream of ECM stiffness with single- cell assay for transposase transposase-accessible chromatin (scATAC-seq). In Aim 3 (R00), Dr. Cho will identify potential druggable targets along the cell’s mechanosensory apparatus, and test candidate compounds in engineered heart tissues and a mouse model of pressure-overload induced hypertrophy and heart failure. The proposed studies build upon PI Dr. Sangkyun Cho’s well-suited prior training in biomaterials, proteomics, and ECM mechanobiology, while providing new training opportunities in (i) reporter iPSC-CFs, (ii) single-cell multiomics platforms, and (iii) animal models. Mentor Dr. Joseph Wu is a pioneer in iPSCs and cardiovascular biology, and co-mentor Dr. Sarah Heilshorn is a leading expert in biomaterials and regenerative medicine, whose mentorship complements that of Dr. Wu. Advisory Committee members Drs. Jeffery Molkentin (cardiac fibrosis), Joseph Hill (heart failure models), and Michal Snyder (single-cell genomics) provide additional expertise and guidance. In Summary, the well-tailored research training plan, exceptional mentoring team, and an outstanding Environment at Stanford University are anticipated to help propel Dr. Cho toward his long-term goal of establishing an independent research program at the intersection of bioengineering and cardiovascular stromal biology.

NIH Research Projects · FY 2025 · 2025-08

Surgeons need expert feedback to improve their skill throughout their career. But expert feedback is not easily available to surgeons after they complete training. Expert feedback typically takes the form of natural language, i.e., surgeons learn from experts’ verbal teachings. Recent advances in artificial intelligence (AI) have created a tremendous potential for technology that can provide surgeons with expert-like language-based (i.e., narrative) feedback on any surgery they perform. This project aims to leverage current AI models and develop new ones that analyze videos of surgical procedures and generate expert-like narrative feedback. The AI models will include those that analyze language (i.e., large language models) and videos plus language (vision language models). This project will focus on cataract surgery as a prototype procedure to develop the AI models and evaluate them in additional procedures including surgery of the sinuses around the nose and surgery to remove a lobe in the lung. The overall goal for this project is to develop AI models that provide an expert analysis of a surgical video that includes description, interpretation, and reasoning about what is observed in the surgery and prediction of how the procedure evolves over time. To achieve this goal, this project consists of the following specific aims: (1) To develop a unified framework of vision language and large language AI models to generate expert analyses of surgical videos; (2) To develop methods for the AI models to continuously learn from techniques such as data augmentation, pretraining, and incorporating expert feedback; (3) To develop methods for synthesizing surgical videos from expert analyses to address the challenges in creating sufficiently large datasets needed to train the AI models; and (4) To create a dataset that enables this research. The expected impact of this work is to allow surgeons to learn more skill quickly and reduce variation in patient outcomes resulting from different skill among surgeons.

NIH Research Projects · FY 2025 · 2025-08

While antiretroviral therapy (ART) has significantly reduced HIV-related mortality and increased life expectancy for people living with HIV (PWH), a range of comorbidities (e.g., kidney disease, mental health conditions, cognitive impairment) remain highly prevalent. Depression, the most common mental health comorbidity in PWH, affects 20% to 60% of this population, posing a major challenge to long-term HIV management. Modern combination ART (cART) regimens typically consist of three or more drugs from multiple classes with different mechanisms. Since PWH must remain on cART indefinitely once initiated, and its effects on depression vary across individuals, designing individualized, optimally effective cART regimens with minimal risk of worsening depression is critical in the emerging field of precision medicine for HIV. The availability of large-scale, longitudinal HIV cohort data, such as the MACS/WIHS Combined Cohort Study (MWCCS), spanning over 35 years, presents an unprecedented opportunity to investigate the effects of cART on both viral suppression and depression at an individual level. However, significant scientific challenges remain, including the need to accurately predict individuals' depression and other health outcomes, account for complex drug-drug interactions in estimating cART effects, and develop strategies for planning long-term, patient-tailored regimens that adapt to evolving health conditions. This proposal aims to develop novel statistical and machine learning methods to address these challenges, advancing NIAID's mission by leveraging real-world cohort data and innovative data science approaches to drive precision medicine for people with HIV. Specifically, we propose three aims: (1) Develop novel causal structural discovery models and robust prediction tools to effectively handle distribution shifts resulting from interventions in HIV-related health outcomes; (2) Develop a Bayesian model-based reinforcement learning (RL) framework to optimize personalized cART regimens and improve long-term mental health outcomes in PWH; and (3) Encapsulate the proposed statistical methods and computational algorithms into R and Python packages and develop a web interface for practical application and dissemination. RELEVANCE (See instructions): While antiretroviral therapy (ART) has reduced HIV-related mortality and increased life expectancy for people with HIV, mental health comorbidities, including depression, remain prevalent. Our proposed Bayesian causal discovery and reinforcement learning methods aim to accurately predict depression and other health outcomes while optimizing personalized ART. These advancements have the potential to reduce HIV transmission risk and assist physicians in making personalized treatment decisions.

NSF Awards · FY 2025 · 2025-08

Organoid intelligence (OI) is an emerging field that aims to harness the computational power of brain organoids for biocomputing and biomedical research, seeking to generate computing devices with substantially lower energy requirements than conventional digital electronics. Brain organoids are lab-grown brain tissues, each about the size of a small grain of sand, that can naturally form networks. This project seeks to incorporate reward-based learning mechanisms into brain organoids to enable more complex and adaptive behaviors and increase training efficiency. By connecting the organoids to tiny electronic shells and using chemical signals, the research team will teach them to play simple video games and guide small robots. Throughout the project, bioethicists will monitor every step to ensure responsible and ethical conduct of research and to keep the public informed about both benefits and concerns. The work will train multiple students, create open-source hardware and software, and launch community courses that invite citizen scientists to learn about biological computing. Success of this project could pave the way for computers that use a million times less energy than today’s artificial-intelligence (AI) systems and open fresh paths for studying disorders such as Alzheimer’s disease. This project seeks to advance organoid intelligence through engineering three-tier brain assembloids that couple cortical, dopaminergic, and striatal regions inside self-folded shell micro-electro-fluidic arrays (SMEFAs). These interfaces can deliver millisecond-precision electrical stimulation and micromolar-resolution neuromodulator gradients while recording three-dimensional neural activity. The central hypothesis of this research is that reward-modulated spike-time-dependent plasticity (R-STDP) will enable data-efficient, continual reinforcement learning in biological networks. The goal of Thread 1 is to develop standardized culture protocols and validate long-term SMEFA stability. Under Thread 2, real-time closed-loop software will be created that maps environment observations to stimulation codes and decodes action signals from high-density recordings, benchmarking OI against deep-reinforcement learning baselines on curricula of Atari-like tasks and embodied robot control. In Thread 3, an experimental neuroethics program will be embedded that defines measurable capacities (sentience, agency, evaluative cognition) and implements tiered safeguards in any case of evidence of consciousness. This project will explore the fundamental mechanisms of biological learning and is expected to develop new biocomputing architectures and to create a framework for experimental neuroethics. The work should position OI as a transformative, sustainable architecture for next-generation adaptive systems. 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 expansion rate of the universe, also known at the Hubble constant, is measured both from a distance scale and from the Cosmic Microwave Background. These two methods give different values. It is possible that systematic errors cause these different values, so independent techniques for the measurement of the Hubble constant need to be developed. The infrared tip of the red giant branch method (IR-TRGB) could be a powerful tool to probe large volumes and a wider set of Type Ia supernova galaxy hosts. However, the IR-TRGB method needs proper calibration, which requires new ground-based observations. This project will develop new tools for the IR-TRGP measurement. Ongoing projects, in collaboration with minority serving institutions, that provide research opportunities for undergraduate students will be enhanced with these tools. A sibling robotic optical telescope with time allocated for E/PO efforts will be made accessible to outreach via the creation of supporting materials and a wide range of E/PO education modes for both classrooms and informal settings. This project will provide two anchor points to a distance scale built on the IR-TRGB and seamlessly connect these anchor points to IR-TRGB measurements made with space-based facilities. The IR-TRGB has the intrinsic brightness and efficient application to measure distances for statistical samples of SN Ia hosts. The team will: (1) Complete the implementation a fully-robotic, dual channel optical/infrared facility capable of monitoring bright stars in the infrared and publish design specifications and operational data for the facility. (2) Use this facility to produce photometry of key calibrations for the IR-TRGB in the Milky Way and LMC. (3) With an on-going HST program, derive or predict filter transformations between ground- and space-based filter systems that enable the IR-TRGB. (4) Calibrate the absolute magnitude-color behavior of the IR-TRGB in two anchor objects with high precision geometric distances (Milky Way Field and LMC). 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 (See instructions): Humans and other animals exhibit a critical behavioral phenomenon in the control of movement: they switch between two distinct modes-fast, exploratory "active sensing" and slower, goal-directed "task control." This proposal aims to uncover the computational, behavioral, and neural mechanisms that regulate these two modes. We hypothesize that animals use internal estimates of sensory uncertainty to decide when to switch between modes, with uncertainty thresholds triggering transitions between exploratory and goal-driven behavior. To test this, we will use a uniquely tractable animal model-weakly electric fish performing a refuge tracking task-in which behavior, sensory feedback, and neurophysiology can be measured and manipulated in real time. The project comprises three specific aims: (1) develop computational models and theoretical tools to identify how and why animals switch between active sensing and task control modes; (2) conduct high-throughput behavioral experiments to quantify how sensory salience and feedback influence mode switching and control strategies; and (3) perform neurophysiological recordings to identify neural correlates of locomotor control policies and mode switching in the brain. This multidisciplinary effort integrates control theory, machine learning, and neuroscience to reveal the computational strategies underlying the regulation of active sensing and task control. Our findings have the potential to transform our understanding of biological motor control, identify mechanisms for assessing sensory uncertainty, and advance strategies for movement control in complex environments.

NIH Research Projects · FY 2025 · 2025-07

Enter the text here that is the new abstract information for your application. The Biomedical Engineering (BME) Ph.D. Program at the Johns Hopkins School of Medicine was established in 1961 and has trained more than 500 scientists. JHU BME is engineering the future of medicine, which involves a hybrid approach combining science and medicine, and the program has seen tremendous growth in recent years due to its leadership in applying quantitative methods to life science problems and its unique interdisciplinary nature. We are among the oldest multidisciplinary graduate programs in the country, encompassing nearly 20 departments. More than 100 faculty members are actively involved in research, teaching, and as mentors. In addition to BME, participating departments include Anesthesiology, Biophysics, Cell Biology, Chemical and Biomolecular Engineering, Electrical and Computer Engineering, Imaging, Mechanical Engineering, Medicine, Neuroscience, Oncology, Radiology, Public Health, and Surgery. Our program has seen dramatic growth, and an average (over the last 5 years) of 54 students matriculate each year and obtain their Ph.D. in an average of 6.1 years. The proposed Training Program in BME will support recruitment into our program of students with high research aptitude but who, due to their scientific background, do not neatly fall within the narrow scope of individual BME labs. Our objectives are: (1) to provide a broad and deep curriculum in biology, medicine, and engineering; (2) to provide longitudinal training in rigorous, reproducible, and responsible experimental and/or theoretical research; (3) to provide the students the opportunity to explore multiple research directions before settling on a thesis lab; (4) to provide training in professional skills; (5) to provide activities for trainees to explore career options; and (6) to recruit and support a multidisciplinary student population. These objectives will be met through an extensive, rigorous, and multifaceted curriculum covering the first two years of study, including required courses on BME-specific ethical issues and quantitative methods, electives in both life and quantitative engineering sciences, and up to three research rotations. Students are explicitly guided in selecting personalized cross-disciplinary sets of courses to develop knowledge that crosses the borders of their initial training. Moreover, there are discussion courses on responsible conduct of research and department-based workshops as students advance in their thesis work. Oral and written presentation skills are developed throughout training, targeting different specific tasks. Professional development and career planning are integral to the program, occurring through courses, individual development planning meetings, or internships. Most students publish multiple research papers, and the training concludes with a presentation of a public seminar and submission of the doctoral thesis. BME graduates hold leadership positions at all levels of academia, government, and industry. The success of our students is fostered by an extraordinary level of collaboration and interaction among the faculty and trainees. Here, we request 20 training grant slots to appoint eligible students during their first two years in the program.

NIH Research Projects · FY 2025 · 2025-07

PROJECT SUMMARY/ABSTRACT The role of minimally invasive surgery (MIS) for treatment of ICH is well studied across many individual trials but lacks a joint community approach to harmonize strategies for a definitive trial to potentially bring MIS into practice changing guidelines. The Minimally Invasive Surgery Consensus ICH Conference will bring together a diverse and comprehensive group of field- leading experts as well as the stroke community at large to define the specific discoveries needed to produce level one evidence regarding the possible value of MIS. Specific grant aims are: To assess the evidence requirements to promote practice change in Minimally Invasive Surgery for ICH (MIS-ICH). We will engage the full range of the US scientific community with regards to specific discoveries needed to produce level one evidence regarding the possible value of MIS. To convene a fully representative group of medical professionals caring for ICH patients to develop a categorical classification of data deficiencies requiring mitigation in a test(s) of the value of MIS-ICH. We will engage the full range of the ICH scientific work force across specialties, geography, age, race and ethnicity to develop a prioritized list of discovery targets. To address the range of emergency medical, acute care, urgent surgical, post-surgical care, recovery and rehabilitation requirements for ICH patients who would be subject to MIS-ICH therapy. The participants will address the needs for a national level approach to a large practice changing trial and or a sustained Platform Trial approach to develop clear evidence around the current promising MIS-ICH trial results suggesting functional benefit for an acute surgical intervention. This evidence will be shared publicly via peer reviewed commentary and in discussion forums across interested consortia who support clinical trials in the US. The full day conference will define the unanswered questions in ICH care, the standards in surgical deliverables needed from different surgical techniques, the standards for pre and post- operative care, and answer biological questions across the general population. Expanding both the workforce and the trial outreach is key to bringing health care improvements, drugs and devices to populations with rare intracranial hemorrhagic diseases.

NIH Research Projects · FY 2026 · 2025-07

PROJECT SUMMARY Each year, over two million US youth experience the death of a caregiver before the age of 18 (hereafter referred to as caregiver death). Given the syndemic of COVID-19, the opioid crisis, and gun violence, rates of caregiver death among US children are likely to remain elevated or increase in the next decade. US non-Hispanic Black children are three times more likely to experience parent death than White children. Bereaved youth (i.e., who experienced a caregiver death) are vulnerable to adverse emotional and behavioral health (EBH) outcomes, such as higher risks of depression, anxiety, substance use, and suicidality. The goal of this research is to identify opportunities for improving EBH outcomes among bereaved youth. Three knowledge gaps must be filled to achieve this goal. First, we need to evaluate caregiver death in the context of other co-occurring adverse experiences. Second, we need to understand how the caregiving context mediates the relationship between caregiver death and EBH outcomes. Third, we need to learn from the lived experiences of bereaved young people. In addition to our multidisciplinary investigative team with relevant content and methodological expertise, an Advisory Board of bereaved young adults and grief professionals will be developed to inform this research. Guided by a Life Course Framework and Multidimensional Grief Theory, we will use a convergent mixed-method design to achieve three aims and fill the identified knowledge gaps: 1) Assess associations between caregiver death and EBH outcomes in the context of adverse childhood expereinces among young adults from the Future of Families and Child Wellbeing Study (N = ~2900); 2) Determine the extent to which the caregiving context (i.e., material hardship and parental monitoring) mediates the relationship between caregiver death and EBH outcomes; 3) Identify diverse strategies to support bereaved youth using longitudinal survey data and lived experiences (i.e., life history interviews with 80 young adults and consensus building with our Advisory Board). Achieving these aims will improve our ability develop tailored, family-centered interventions, practices and policies that support bereaved youth across sociodemographic groups. Ultimately, study findings will inform theory-driven and data-informed recommendations for future research, practice, and policies to improve EBH outcomes for the growing number of bereaved young people.

NIH Research Projects · FY 2026 · 2025-07

Project Summary The proposed project aims at developing the next generation of photon counting detectors (PCDs) with multi- energy inter-pixel coincidence counter (MEICC) and digital pulse energy correction (DPEC) for x-ray computed tomography (CT). We believe that MEICC–DPEC design will bring PCDs much closer to ideal devices and brings many clinical dreams surrounding PCD CT into reality. In a prior R21 EB029739 grant, we developed MEICC concept using Monte Carlo simulations and found that MEICC improved the dose efficiency by a factor of 3.9, which is 87% (=3.9/4.5 with respect to dose efficiency) toward the ideal spectral PCD. Simulations showed that DPEC made the PCD performance almost insensitive to the intensity of x-rays. Building upon this foundation, under this BPI project, we propose to translate our theoretical results into the real world, fabricate physical application-specific integrated circuits (ASICs) with MEICC–DPEC functionality, develop algorithms to process MEICC–DPEC data, and evaluate the performance of PCD using a tabletop x-ray CT system. Our goas are to achieve Cramér–Rao lower bound values (i.e., the minimum noise variance with unbiased estimators) that are >75% lower than the current PCD with 2 energy bins for spectral imaging tasks, which corresponds to dose efficiency improvements by a factor of >4. The specific aims are: (SA1) Optimize MEICC– DPEC design parameters and develop algorithms. (SA2) Develop MEICC–DPEC PCD. (SA3) Assess MEICC– DPEC PCD using a tabletop CT system. We will compare results against (a) the same PCDs but with 2 energy bins without MEICC–DPEC, (b) a clinical PCD CT system, and (c) two clinical dual-energy CT systems. Experimental results in SA3 will be compared against computer simulation results in SA1.

NSF Awards · FY 2025 · 2025-07

The principal motivation of this project is to exploit gravitational-wave observations to gain a deeper understanding of gravity and to test the nature of black holes via "black hole spectroscopy." The spinning, deformed black hole formed when two black holes merge rings down like a bell. The idea of black hole spectroscopy is that such a deformed black hole can be treated as a "gravitational atom" (in analogy with atomic spectra), because its damped oscillation frequencies (the "quasinormal modes") carry unique fingerprints of spacetime dynamics. With the expected increase in volume coverage of LIGO-Virgo-KAGRA (LVK) in their fourth and fifth observational runs O4 and O5, and with the ramping up of activity on Cosmic Explorer in the US and the Einstein Telescope in Europe, this work is timely, geared at enhancing the scope of the physics and astrophysics enabled by ground-based interferometers. The project will train students and postdocs in a highly interdisciplinary field that requires expertise in general relativity, astrophysics, data analysis, and high-energy physics. The students and postdocs will benefit from interactions with a large international network of world-leading experts in gravitational physics. Large financial resources have been invested in advanced detector design on the experimental side, and in a community effort to build compact binary detection templates on the theoretical/data analysis side. The first gravitational-wave detections by the LVK collaboration were a major milestone, but for gravitational-wave science to make even more groundbreaking contributions, we must be able to go beyond detections, extracting fundamental physics from the strong-gravity dynamics of the sources. This project on black hole spectroscopy has four main objectives: (1) to build models for the amplitudes of linear and nonlinear quasinormal modes; (2) to understand and alleviate ringdown modeling systematics in real data; (3) to clarify the connection between ringdown and light-ring physics; (4) to search for deviations from general relativity using parametrized ringdown tests. The reduced budget and duration of the award will allow us to complete only about half of the projects listed in the original proposal. 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

Combinations of metabolic deregulation and immunotherapy are gaining prominence for treating immune- tolerant “cold” tumors, such as triple-negative breast cancer (TNBC). Evidence indicates that such treatments can activate the immune system and induce regression of distant untargeted tumors, i.e., an abscopal effect. In pre-clinical and clinical settings, chemotherapy and immunotherapy demonstrated superior treatment efficacy and immune-related progression-free survival. Furthermore, chemotherapy, such as cisplatin and doxorubicin, in combination with immunotherapy, exhibited clinically significant response rates. However, much more research is required to optimize treatment strategies and scheduling to determine how to induce a sustained systemic immune response with clinically meaningful outcomes. In this application, we will leverage the use of a DDX3 inhibitor, RK-33, to alter the metabolic tumor environment. We will combine this treatment with immunotherapy to create a tumor environment that favors an effective response to immunotherapy. We have demonstrated that DDX3 is involved in mitochondrial biogenesis in breast cancer cells and using RK-33 unambiguously generated mitotoxic effects with increased reactive oxygen species production leading to breast cancer cell death, including TNBC. Also, RK-33 converted high glycolytic TNBC tumors to low glycolysis, resulting in decreased extracellular lactate, which has been shown to facilitate an immune permissive microenvironment in TNBC. In addition, using an immunocompetent preclinical model of TNBC, we have demonstrated that RK-33 can alter the immune profile within a 4T1 tumor environment. As reprograming metabolic dependencies favors immune responses, we propose a therapeutic strategy combining RK-33 treatment with immunotherapy (anti-mouse PD-1 mAb). We propose to test this hypothesis with the following specific aims. Aim 1: Determining the effect of targeting DDX3 by RK-33 on metabolic reprogramming to improve cancer immunotherapy. Aim 2: Reprogramming the immune microenvironment by RK-33 to enhance TNBC treatment. Aim 3: Targeting the glycolysis-immune checkpoint axis as a potential treatment for TNBC. The goal is to disrupt the metabolic equilibrium of the tumor environment and generate an increased efficacy of immunotherapy in TNBC.

NIH Research Projects · FY 2025 · 2025-07

For this NIH High-End Instrumentation Award application, we propose to acquire a high-performance small animal SPECT/CT system that utilizes state-of-the-art solid-state cadmium zinc telluride (CZT) detectors. The aim of this system is to support ongoing research projects at Johns Hopkins focused on developing novel alpha-emitter radiopharmaceuticals therapy (αRPT). αRPT is an emerging modality in targeted cancer therapy, directly killing cancer cells via DNA double-strand breaks, making it less susceptible to resistance and highly effective for systemic disease treatment. Image-based distribution is crucial for understanding dose response, toxicity, and dosimetry in preclinical studies. Alpha-emitters decay through a complex scheme involving multiple daughters and are potent enough for effective treatment at sub-GBq activity levels. Therefore, accurate quantification of both alpha-emitters and daughters are essential. Currently available small animal SPECT/CT systems, based on scintillator detectors, offer poor energy resolution. We propose acquiring a Scintica High-Resolution SPECT/CT System with CZT detectors, which includes three components: 1) A stationary SPECT system based on the latest 3-D CZT imaging-spectrometer, offering unprecedented energy resolution (<2.5 keV at 140 keV) over the 50-600 keV range, ultrahigh spatial resolution of 0.25 mm in 3-D, and excellent detection sensitivity (2-3%). This system has the best SPECT specifications on the market, providing quick, straightforward anatomical visualization. It has a SPECT FOV diameter of 6 cm with an axial FOV of 9 cm, allowing whole-body spectral imaging to identify all daughter radionuclides. It also supports dynamic SPECT imaging. 2) A high-resolution CT scanner system with 15 μm resolution, a transaxial FOV of 8 cm, and a fixed axial FOV of 12 cm, expandable to 35 cm with dynamic bed movement. The scan acquisition time can be as fast as 15 seconds. 3) State-of-the-art imaging accessories, including a physiological monitoring system for simultaneous temperature control, cardiac and respiratory gating, and an anesthesia system. The high energy resolution of this system will greatly expand the number of radionuclides suitable for medical imaging, serving broader preclinical research needs in oncology, cardiology, and neurology. The operation of the proposed equipment will be overseen by an Advisory Committee composed of the PI, the Co-I, and major users across Johns Hopkins. This committee will meet twice a year to review the system's operation and set policies and procedures to ensure broad use. Additionally, we will hold an annual showcase at the Department of Radiology’s research day to attract potential new users. .

NIH Research Projects · FY 2026 · 2025-07

PROJECT SUMMARY Over time, our goal-directed behavior become automatic; without deliberation, when driving for example, we will habitually push a gas pedal at a green light and the brake pedal at a red light. More specifically, an initial goal- directed response (R) after a cue (S) yields a desired outcome (O) which then evolves into a habit where the cue elicits the action (S-R) without necessarily having the goal in mind. The automatization of decisions is an efficient way to offload well-learned contingencies to free up resources for more flexible, goal-directed learning, and is thought to rely on a gradual shift in control from the dorsomedial to dorsolateral striatum (DMS and DLS). Yet, an overreliance on habit may contribute to maladaptive behaviors in substance use disorders (SUD) indicating a need to understand precisely when and how habits form. It has been challenging, however, to identify when transitions occur since established methods require discrete test sessions which cannot be performed in ‘real-time’. We recently developed a novel behavioral paradigm, ‘volitional engagement’, that reasons that animals in naturalistic environments seek nourishment intermittently and based on underlying needs (i.e. goal- directed behavior). To mimic this, we trained ‘undermotivated’ animals to respond to one auditory cue (S+) and withhold responding to a second cue (S-). Mice rapidly discriminated between the two cues but exhibited fluctuating response rates to the S+ cue for days to weeks afterwards. Surprisingly, and well after expert discrimination performance, mice abruptly transitioned to high and constant response reliability (i.e. habit). This provides one of the first ‘real-time’ measures of transitions between goal-directed to habitual control providing a unique opportunity to assess the neural dynamics and circuits of habit formation en passant. Our overarching hypothesis is that rather than sequential recruitment of DMS and then DLS, both controllers are engaged in parallel throughout learning and that pre-motor cortical signals serve as a higher-level ‘arbiter’, determining whether the DMS or DLS controls behavior at a given moment. To test this, we will (1) validate our volitional engagement approach using optogenetics, sensory-specific outcome devaluation, and contingency degradation (Aim 1), (2) use neural circuit tools to monitor and manipulate pre-motor cortical and dopaminergic inputs and medium-spiny neuron output in the DLS/DMS across learning (Aim 2), and (3) extend our volitional engagement behavioral approach to a habit-promoting task in rats to test for generalizability (Aim 3). Future work can leverage our approach to study how drugs hasten habit formation in real-time. The proposed studies using natural reward will thus pave the way to better understand and potentially treat SUD.

NIH Research Projects · FY 2025 · 2025-07

Project Summary Uterine fibroids are highly prevalent tumors, even in young reproductive-aged women. They are present in up to 10% of pregnancies, about half a million US births per year. These tumors display substantial inflammatory, hypoxic, angiogenic, and oxidative stress aberrations with conceivable implications during pregnancy on the developing placenta and offspring. However, to date the long-term impacts of uterine fibroids on offspring have not been examined. The overall goal of this proposal is to assess the impact of uterine fibroids on the In- Utero environment and offspring long-term cardiometabolic health by leveraging the existing resources of the Boston Birth Cohort (BBC), an ongoing large longitudinal, predominantly urban African-American birth cohort. Aim 1 will test the hypotheses that 1) the risk of maternal vascular malperfusion of the placenta is increased in the presence of any fibroid, regardless of location, 2) the risk of small-for-gestational age births is increased for women with uterine fibroids, and 3) women with uterine fibroids demonstrate unique metabolomic profiles compared to women without uterine fibroids. Aim 2 will test the hypothesis that that presence of uterine fibroids in utero will be associated with unique offspring metabolomic profiles, increased risk for offspring obesity/overweight status, elevated blood pressure, and increased leptin levels up to offspring up to age 21 years. This study will leverage extensive high-quality epidemiological and clinical data to allow for rich analysis of covariates (including shared risk factors between uterine fibroids and cardiometabolic dysfunction), along with biospecimens already obtained by the BBC. Dr. Cameron has built a nested cohort within the BBC of approximately 7000 mother-infant pairs (including close to 500 pairs with uterine fibroids present at time of delivery). This would be the first large-scale prospective birth cohort study to integrate cutting-edge metabolomics to address critical questions about the impact of uterine fibroids on early-life fetal programming and explore underlying mechanistic pathways. Dr. Cameron is a reproductive endocrinology and infertility specialist trained in clinical epidemiology. The additional training she proposes in molecular epidemiology, advanced statistical modeling including network analysis skills, and the creation and maintenance of multi-generational birth cohorts will help achieve her long- term goal of leading studies to investigate the impact of reproductive conditions on developmental origins of disease in diverse clinical contexts utilizing multiomics techniques with a lifecourse approach. This proposed study will lay a critical foundation for planned future R01 applications.

NSF Awards · FY 2025 · 2025-07

In our increasingly digital world, children are exposed to technology that collects and uses personal data at younger ages than ever before. This makes understanding and protecting personal privacy a crucial life skill. However, teaching young children about privacy is not just about online safety; it's about empowering them to understand their rights, make informed choices, and build healthy relationships with technology. This project focuses on this urgent need and proposes a collaborative approach to privacy education for elementary school children (ages 5 to 10). The project develops a new learning model that builds partnerships among families, schools, and community organizations like libraries and museums. By working together and leveraging the unique strengths of each role, the project will create a supportive network that reinforces privacy concepts, fosters critical thinking about privacy, and helps elementary children navigate the digital landscape with confidence. This collaborative approach will equip our youngest citizens with the essential tools to protect themselves and respect the privacy of others, ensuring a safer digital future for all. The project work is organized around two main thrusts. In the first thrust, inspired by Epstein's Theory of Overlapping Spheres of Influence, the investigator will conduct interviews, focus groups, and co-design sessions with parents, teachers, and community members to identify opportunities and challenges in supporting partnerships. The results will inform the development of privacy education tools designed to foster collaboration and partnerships among stakeholders. In the second thrust, the project team will conduct a three-year field deployment study to examine the long-term impact of partnership-enabled privacy education on children's privacy literacy development. During the field study, the investigator will deploy the materials, methods, and systems developed in the first thrust with families and collect data about children's privacy literacy development progress through learning stories, questionnaires, interviews, and system logs. These data ensure a comprehensive understanding of children's privacy learning trajectories. This research will yield a novel privacy education framework, design guidelines for collaborative tools, insights into the long-term impacts of privacy education, and an annotated dataset of children's privacy literacy 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 · 2025-07

PROJECT SUMMARY Confocal microscopy is an essential tool in biomedical research, imaging structural and dynamic interactions within complex biological systems. The nature of confocal microscopy posed several practical limitations in multiplexing capabilities, imaging volume with sufficient spatial resolution, imaging speed, as well as postprocessing when image stitching and registration is needed. In addition, time-lapsing imaging in dynamic processes requires system automation and stability to accommodate with any motion artifacts and focus drift over time. All these practical limitations, if not addressed adequately, would limit our research capacity. The acquisition of the Olympus FV4000 confocal microscope provides solutions to all above limitations, enabled by new generation of silicone photomultiplier (SiPM), high-speed resonance scanner, as well as advanced software package. In this application, we provided detailed justification and description of the Olympus FV4000 confocal microscope, description of NIH-funded research projects by the major users, as well as necessary technical and institutional support to maximize the utility. We also have a well-developed administrative plan in place to manage the equipment in a shared facility. In summary, the acquisition of Olympus FV4000 confocal microscope will support a wide range of research topic from large number of research labs in Wilmer Eye Institute and Johns Hopkins research community and will boost the important research initiatives in Wilmer and JHU.

NIH Research Projects · FY 2025 · 2025-07

PROJECT SUMMARY The accumulation of the aminoacyl-tRNA synthetase complex interacting multifunctional protein-2 (AIMP2) has been found to be pathogenic in Parkinson's disease (PD) patients. This accumulation has been observed in the brains of Parkin knockout mice and in postmortem brains from both juvenile PD patients with Parkin deletion and sporadic PD patients. The overexpression of AIMP2 results in a selective, progressive, and age-dependent loss of dopamine neurons through the activation of poly (ADP-ribose) polymerase-1 (PARP1). Additionally, our recent discovery shows that AIMP2 has a self-aggregating tendency which results in toxicity. AIMP2 aggregates act as a catalyst for the aggregation and spread of α-synuclein, pointing to a pathological role in PD. Significantly, a recent human genetics study on PD identified rare variants in the AIMP2 gene that are linked to late-onset PD (LOPD). However, there have been no investigations on the pathological effects of AIMP2 variants in mammals, due to the lack of suitable mammal models. Hence, mouse models are required to study the pathogenic mechanisms underlying PD caused by AIMP2 mutations. Our preliminary studies using variants such as wild type (WT), R26Q, R65C, D86E, L165F, L165V, P177L, T203M, and I213T have revealed that the R65C variant is more susceptible to insoluble redistribution, aggregation formation, and cytotoxicity than the WT AIMP2 and other variants. Based on these findings, we propose in aim 1 to create an R65C AIMP2 knock-in (KI) mouse model using CRISPR technology. The motor phenotype and brain pathology of the mouse model will be characterized. Our recent publication has shown that AIMP2 has a tendency to self-aggregate and interact with α-synuclein, leading to an acceleration of coaggregation both in vitro and in vivo. Furthermore, preliminary studies have indicated that the R65 variant causes the rapid formation of α-synuclein aggregates and an increase in toxicity when AIMP2 and α-synuclein are co-expressed in cell cultures. Based on these findings, we hypothesize that the R65C AIMP2 variant contributes to the transmission of pathological α-synuclein induced by α-synuclein preformed fibrils (PFF). To test this, in aim 2, we will examine the impact of the R65C AIMP2 variant on Lewy body pathology caused by α-synuclein PFF. For this purpose, we will inject α-synuclein PFF into the striatum of the R65C AIMP2 knock-in mice. We will prioritize examining Lewy body pathology using these mice. The completion of this study will greatly enhance our understanding of the underlying pathogenesis of AIMP2- related PD and provide a valuable resource for the PD research community in the form of an AIMP2-linked PD mouse model for future studies on pathogenic mechanisms and the development of treatments. Additionally, it will shed new light on the study of sporadic PD.

NIH Research Projects · FY 2026 · 2025-07

Project Summary Multiple sclerosis (MS) is the most common neurodegenerative disease in young adults. Changes in the serum metabolome have been reported in MS and our preliminary data demonstrate that they are also associated with MS disease severity. We specifically show that aromatic amino acid-derived lactate metabolites, produced by the gut microbiota, are reduced in MS and higher levels are associated with lower disease severity. One of the metabolites indole lactate (ILA) besides being associated with lower disease severity also ameliorates neuroinflammation and promotes remyelination in animal models of MS. Our long-term goals are to demonstrate that ILA may be a novel therapeutic agent to promote myelin repair in people with MS. The objectives of this R01 application are to demonstrate that ILA promotes remyelination in vivo in the presence of barriers to remyelination that are present in MS and to understand the mechanism by which it promotes remyelination. The rationale for this project, supported by preliminary data, is that lower ILA levels in circulation are related to more severe MS and in vitro ILA promotes oligodendrocyte precursor cell (OPC) differentiation while also promoting remyelination in the cuprizone model of demyelination in vivo. The proposed research study will pursue two specific aims: 1) to demonstrate the ability of ILA to overcome barriers to remyelination in MS; 2) to identify the mechanism by which ILA promotes remyelination. For the first aim, we will first test the effects of ILA on remyelination in two models – the adoptive transfer cuprizone model of demyelination, the lysolecithin-induced focal spinal cord demyelination model and an adoptive transfer lysolecithin model to compare the effects of oral ILA to vehicle treatment using various histopathological measures. We will then test the ability of ILA to promote remyelination in the setting of aging by testing ILA in the cuprizone and lysolecithin models in aged (18-month-old) mice. For the second aim, we will utilize OPC-specific and myeloid-specific knockouts of arylhydrocarbon receptor (AhR) to understand the mechanism by which ILA mediates its reparative effects. We will also plan to utilize single cell RNA and ATAC sequencing of tissues obtained from cuprizone and lysolecithin mice treated with ILA or vehicle to determine whether additional mechanisms besides AhR may be involved and whether other cell types may be mediating the effects 0f ILA. This project is innovative in that it proposes to test a novel hypothesis that a gut microbiota-derived metabolite ILA promotes differentiation of OPCs and mediates myelin repair in animal models of MS and also utilizes several novel tools to accomplish the proposed aims. The proposed research is significant because it could identify a novel therapeutic agent that could promote myelin repair and be used to treat this common disabling neurological disorder.

NIH Research Projects · FY 2025 · 2025-07

Project Summary/Abstract Type II topoisomerases (TOP2s) are essenƟal enzymes that maintain DNA topology using an ATP-dependent “strand- passage” mechanism that physically moves one DNA segment through a transient, enzyme-mediated double-stranded break in another. Under normal condiƟons, TOP2s perform strand passage to facilitate fundamental processes such as DNA replicaƟon and transcripƟon; however, if improperly regulated, TOP2s also have the potenƟal to generate permanent DNA breaks, a property that has been exploited by successful chemotherapeuƟc drugs that “poison” TOP2 to induce cytotoxic DNA damage in cancer cells. MulƟple research approaches have helped characterize how TOP2 poisons bind the enzyme and stabilize key reacƟon intermediates that accompany DNA break formaƟon. Despite these advances, structural studies to date have only examined drug-bound TOP2s in complex with single, short DNA duplexes, precluding an understanding of how therapeuƟc agents interfere with the strand passage reacƟon on physiologically relevant DNA substrates such as chromaƟn and supercoils. Moreover, only one poison – etoposide – has been studied structurally in a naƟve context; all other drugs were imaged with TOP2 aŌer soaking into crystals pre-formed with etoposide, raising concerns that the binding mechanisms observed for these agents are arƟfactual and might differ substanƟally from what has been reported thus far. The objecƟve of the present applicaƟon is to capture currently elusive structural features of the TOP2 strand passage reacƟon on more naƟve-like substrates in the presence of different families of clinically used anƟ-TOP2 chemotherapeuƟcs. Human topoisomerase IIα (TOP2A), which is used by cells to support chromosome segregaƟon and cell proliferaƟon, will be used as a representaƟve model system. Strategies outlined in Aim 1 will employ chromaƟnized DNA substrates to beƩer understand how a large, disordered C-terminal domain (CTD) present in TOP2A helps to recruit the enzyme to mitoƟc chromaƟn, as well as how TOP2A may engage with the DNA entering and exiƟng a nucleosome. Binding assays using truncated TOP2A mutants and CTD pepƟdes will idenƟfy elements that are responsible for TOP2A’s interacƟon with nucleosomes, which will be imaged by cryo-EM. Aim 2 will use supercoiled minicircle DNAs and clinically deployed anƟ- TOP2 drugs for Ɵme-resolved cryo-EM studies to capture TOP2A as it is undergoing strand passage. This approach will not only enable a detailed structural analysis of elusive strand-passage intermediates, but also help resolve how diverse classes of TOP2 chemotherapeuƟcs poison the strand passage reacƟon to form toxic, double-stranded DNA breaks. Together, the proposed aims have the potenƟal to offer new mechanisƟc insights into the TOP2 strand passage reacƟon that will not only advance our understanding of how TOP2s safeguard genomic stability but will also unveil new possibiliƟes for exploiƟng the reacƟon for therapeuƟc benefit.

NSF Awards · FY 2025 · 2025-07

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Most animals maintain certain types of bacteria in their gut that aid the animal by improving the nutrition of the diet and modulating the immune system. Microbial associations are particularly important in insects, which are critically important to agriculture, ecology, and human health, including pollinators such as bees, pests such as squash bugs and fruit flies, and disease vectors such as mosquitos and ticks. How insects recruit and maintain their preferred bacteria is largely unknown in terms of the specific genes and molecules the host uses to regulate colonization. The proposed research aims to close this knowledge gap by identifying these genes and molecules and how specific host cells regulate them. Due to critical roles of insects in ecology, agriculture, and public health, outcomes of the proposed research could have major impacts by developing uses of symbiotic bacteria to aid and control insects. Furthermore, the high conservation of gene function across mammals means discoveries in insects could apply to other animals, including vertebrates. Broader impacts of this grant also include development and implementation of hands-on and online microbiology curricula in public schools. Across animals, there is a knowledge gap around the precise developmental genetic mechanisms that construct and maintain the host tissues that house symbiotic organisms as well as whether a host can use certain bacteria to control others. Drosophila has long been a workhorse of animal developmental genetics, with unparalleled resources of publicly available genetic stocks with defined gene perturbations, and the wide genetic conservation across the animal kingdom. The PI’s discovery of symbiotic bacteria that form an adherent, multispecies community in a precise and understudied section of the Drosophila foregut presents a transformative opportunity to apply Drosophila genetics to the study of symbiosis between diverse gut bacteria and the host. This research will define the Drosophila symbiotic organ in terms of the fly genes that support the bacteria. Host genetic pathways, in secretion and immunity will be evaluated by quantitative cell biology, microbiology, and genomics approaches as well as by isotope ratio mass spectrometry, which will be used to measure nutrient exchange between host and bacteria. This will advance the field by providing candidate genes and developmental programs to discover symbiotic niches in other insects and animals, possibly even humans. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-07

This award supports research on the fire behavior of timber structures to develop novel engineering methods to design mass timber buildings for fire resilience. Recent innovations in engineered wood products unlock benefits for the built environment, however, knowledge gaps in fire performance can limit adoption or lead to inadequate fire safety in buildings. To date, design has relied on empirical methods based on charring rates that do not capture the complex fire-structure interaction and the potential for collapse during the fire decay phase, highlighted by recent experiments. This project aims to derive novel modeling capabilities to enable the fire-resilient design of mass timber buildings. The research efforts will be integrated with dissemination activities involving professional committees, aimed at informing building codes. Through enabling resource-efficient designs with novel timber structures that address fire safety challenges, this award will contribute to NSF’s mission to advance the national prosperity, safety, and welfare. The goal of the research is to develop a computational framework for understanding and modeling the response of timber structures in fire and use this framework to derive design methods for fire-resilient timber buildings. The research methodology will combine computational modeling, machine learning, and topology optimization. By analyzing recent timber fire test data with Bayesian inference techniques and surrogate modeling, the project looks to derive accurate material models and properties for timber in realistic fire scenarios. The project will also seek to enhance current fire models to incorporate the contribution from bio-sourced structural materials in the fire intensities used for design. A finite element computational framework that captures the fire-thermal-structural response, validated against full-scale experiments, will then be used to construct fragility functions for timber frame structures. Additionally, the project will explore innovative design approaches to enhance fire resilience through topology optimization applied at different scales, including optimization of the cross-section and optimization of the column layout through a stiffness projection method. This effort looks to advance understanding of the effect of key design parameters on the vulnerability to fire-induced collapse and result in methodologies to uncover resilient designs optimized at both the member and system levels. The research has the potential to advance modeling capabilities and transform fire design for timber structures from an empirical to a performance-based design approach, addressing the complexity of the structural fire response and enhancing safety and resilience. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-07

This I-Corps project focuses on the development of a non-invasive neuromodulation oral appliance designed to relieve the symptoms of chronic rhinosinusitis. Chronic rhinosinusitis affects 40 million U.S. adults and causes persistent nasal congestion, facial pain, mucus overproduction, headaches, and poor sleep. Existing pharmaceutical treatments rely on nasal sprays and other anti-inflammatory drugs but fail to provide relief in around 50% of patients. When medications fail, some patients may qualify for invasive and costly surgery. However, symptom recurrence after surgery is common, leaving millions of patients without an effective solution to get symptom relief. This project addresses this gap in care by exploring an alternative method that targets the nasal nerve pathways shown to contribute to excessive mucus production and inflammation. The goal is to offer a drug-free, effective, and accessible approach to improve daily functioning, sleep, and quality of life. By reducing dependence on costly medications and surgical procedures, this technology has the potential to save up to $1 billion annually on healthcare costs, improve productivity, and reduce the burden of chronic sinus disease on patients, families, and the healthcare system. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of an oral device that delivers gentle electrical stimulation to nerve pathways in the nasal cavity. The technology introduces an innovative neuromodulation approach for treating the symptoms of chronic rhinosinusitis, addressing a critical gap in current therapies that overlook the role of neural overstimulation in sinonasal inflammatory disease. Unlike existing therapies that rely on immune suppression or invasive procedures, this approach is the first to address the neurological component of chronic sinus disease using a non-invasive, drug-free method. The device is a custom-fitted mouthguard that delivers gentle electrical pulses to the nasal cavity. This neuromodulation technology was validated in a successful animal model, showing significant decongestion and improved nasal airflow. Following successful preclinical validation, the device is undergoing human testing. This early success points to the device's potential to improve chronic rhinosinusitis management, giving patients greater autonomy over symptom control and relief. 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.