University Of Chicago

NIH Research Projects · FY 2025 · 2024-09

Summary In vertebrates, genes directing cell-type specific programs and embryonic development are frequently controlled by cis-acting enhancers located several hundreds of kilobases away from their target promoters. Disruptions or misregulation of long-distance enhancer-promoter (EP) interactions have been implicated in a growing number of human pathologies, including developmental abnormalities and cancers. Accordingly, the mechanisms that regulate EP interaction specificity and quantitative efficiency have a central role in establishing gene expression patterns: they constitute a new yet largely unexplored level of regulation of genome activities. The folding of the genome in different 3D structures has been proposed to help organize these distant regulatory relationships. Notably, the structural partition of vertebrate genomes in distinct 3D domains (TADs) has been shown to play an important role in defining the effective range of enhancer action. However, within TADs, enhancers distribute their activity in complex patterns that are not explained by the current models. Furthermore, because of the lack of proper tools to accurately assess the function of genomic architectural elements, we barely know anything about the genetic sequences that determine their activity. Thus, despite significant progress, the specific elements and features that organize and regulate within TADs the functional interactions that link distant regulatory elements to target genes remain mostly unknown. Consequently, we are too often unable to predict the consequences of non-coding and structural variants present in human genomes. To address these critical gaps, we will develop a set of complementary research initiatives combining state- of-art large-scale genome engineering in human cells and mouse models, innovative genomic screens and quantitative genomics and transcriptomics analyses to 1) identify the genetic instructions (e.g. insulators, tethering systems, relay elements) and processes (e.g. looping, non-coding transcription) that fold a linear genomic locus into a dynamic 3D regulatory ensemble and determine the specificity and efficiency of long- distance EP interactions 2) determine the regulatory grammar governing the activity of these different architectural elements 3) measure quantitatively how genetic variants found in these elements may influence their activity and contribute to phenotypic traits 4) integrate these different data to predict the impact of structural variants better and in the future design synthetic approaches to regulate EP interactions. Altogether, these complementary approaches will shed much-needed light on this additional yet poorly characterized layer of regulation of gene expression and provide unique insights to understand better how non-coding genomic variants may influence gene expression and lead to human pathologies.

NIH Research Projects · FY 2025 · 2024-09

ABSTRACT This research project aims to develop methods and tools and conduct collaborative research for the integrative analysis of data generated by the Developmental Genotype-Tissue Expression (dGTEx) initiative, non-human primate (NHP) dGTEx project, existing GTEx project, and other studies. In Aim 1, we will develop methods for mapping expression quantitative trait loci (eQTLs) across developmental stages in multiple tissue- and cell-types. Based on our prior work, we will employ novel multi-view learning (machine learning) methods into the proposed general QTL framework for detecting various types of QTLs. Our framework estimates the latent probabilities of QTL binary status (presence or absence), extracts common and specific low-rank patterns from multiple groups and tissues/cell-types, and incorporates the patterns in estimating the posterior probability of non-zero effect and posterior mean/standard deviation for each input statistic. These outputs can be used for further flexible inference in detecting various types of eQTLs. The proposed QTL framework is adaptive to a variety of integrative analyses of dGTEx, NHP, GTEx and other datasets. In Aim 2, we will develop a series of multi-age-group Mendelian randomization (MR) models to identify risk genes and assess their causal effects in multiple tissues/cell types and age groups. We will extend the models to multi-trait analysis jointly assessing the causal effects in child and adult populations, to multivariable MR analysis accounting for other molecular traits, and to multi-cell MR analysis for detecting sparse cell-level causal effects. In Aim 3, we will engage in the dGTEx data analysis. We will work with the Steering Committee to guarantee the scientific rigor and efficiency of dGTEx analysis, and to ensure the timely dissemination of initial findings to the broader research community. The project will develop scalable and efficient software. The insights gained through the analysis of dGTEx data will enhance the translational potential of genomic findings in medicine and healthcare, reshaping our approach to understanding and treating diseases rooted in developmental gene regulation.

NIH Research Projects · FY 2024 · 2024-09

ABSTRACT This research project aims to develop methods and tools and conduct collaborative research for the integrative analysis of data generated by the Developmental Genotype-Tissue Expression (dGTEx) initiative, non-human primate (NHP) dGTEx project, existing GTEx project, and other studies. In Aim 1, we will develop methods for mapping expression quantitative trait loci (eQTLs) across developmental stages in multiple tissue- and cell-types. Based on our prior work, we will employ novel multi-view learning (machine learning) methods into the proposed general QTL framework for detecting various types of QTLs. Our framework estimates the latent probabilities of QTL binary status (presence or absence), extracts common and specific low-rank patterns from multiple groups and tissues/cell-types, and incorporates the patterns in estimating the posterior probability of non-zero effect and posterior mean/standard deviation for each input statistic. These outputs can be used for further flexible inference in detecting various types of eQTLs. The proposed QTL framework is adaptive to a variety of integrative analyses of dGTEx, NHP, GTEx and other datasets. In Aim 2, we will develop a series of multi-age-group Mendelian randomization (MR) models to identify risk genes and assess their causal effects in multiple tissues/cell types and age groups. We will extend the models to multi-trait analysis jointly assessing the causal effects in child and adult populations, to multivariable MR analysis accounting for other molecular traits, and to multi-cell MR analysis for detecting sparse cell-level causal effects. In Aim 3, we will engage in the dGTEx data analysis. We will work with the Steering Committee to guarantee the scientific rigor and efficiency of dGTEx analysis, and to ensure the timely dissemination of initial findings to the broader research community. The project will develop scalable and efficient software. The insights gained through the analysis of dGTEx data will enhance the translational potential of genomic findings in medicine and healthcare, reshaping our approach to understanding and treating diseases rooted in developmental gene regulation.

NSF Awards · FY 2024 · 2024-09

The broader impact of this Partnerships for Innovation - Technology Translation (PFI-TT) project is in the development of a new conducting material, namely a conducting coordination polymer, and its application to conductive coatings and/or films for various technological applications. The material is stable in harsh conditions and is solution processable as an ink which can be applied to surfaces. This unique combination makes it different from known conductors and makes it an appealing candidate for inclusion into electromagnetic shielding coatings/textiles and flexible electronics. The goal of the effort is to further develop the material for these applications, both in terms of its scalability and cost, while exploring its applications and processing capabilities. In tandem with these efforts, this project will result in entrepreneurial training and career preparation for students at various levels of education. The project aims to investigate the technological applications of a newly discovered coordination polymer NiTTFtt. This material is highly conductive and is also stable to harsh conditions including acid, base, and even detergent washes. It is also stable to heating in air above 200 degrees Celsius. The material can be solution-processed either as a colloidal suspension or an ink. These solutions enable the deposition of thin films on many substrates, as well as dip coating of materials such as textiles. The goal of this research will be to optimize the above properties, and to then develop its applications in various technologies. Specific areas of interest include electromagnetic shielding and flexible electronics. Here, the unique stability profile of NiTTFtt promises the realization of new robust coatings or devices which should be amenable to operation in harsh conditions such as marine environments. Novel synthetic approaches will also be investigated in order to improve the scalability and cost of these materials and/or coatings. Finally, performance in specific applications will be tested on both pure NiTTFtt films, as well as coated composites which can be tailored for specific applications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2024 · 2024-09

Project Summary In this R13 application, we are requesting support for the European Behavioral Pharmacology Society (EBPS) 2024 workshop, “Novel Pharmacotherapies for Substance Use Disorders: From Basic Science to Societal Implications”, taking place September 25-27, 2024 in Banff, Alberta, Canada. The goal of this 3-day event is to bring together international experts in basic and clinical science who focus on novel pharmacology-based interventions within the domain of substance use disorders (SUDs). We will pursue the following four specific aims at the meeting: 1) create an international forum for leading basic and clinical SUD researchers to discuss cutting edge pharmacology-based SUD interventions; 2) facilitate discussion of factors “outside the lab” that can impact the implementation and/or efficacy of these interventions in the real world; 3) promote interaction among diverse groups of investigators to stimulate exchange of ideas that will define the future directions of SUD research; 4) to foster the development of the next generation of SUD researchers by encouraging the participation of students, postdoctoral fellows, and new investigators committed to SUD research. The scope of the keynote and symposia will be confined to basic and clinical studies involving pharmacology- based interventions that show promise in the treatment of SUDs, including cannabinoids, psychedelics, and neuropeptides. The content of these will range from cellular and molecular mechanisms to preliminary clinical efficacy, in an effort to highlight the value of translational science. The meeting will also include panels on “outside the lab” factors that may impact the effective implementation of these interventions, consisting of experts in public policy, regulatory frameworks, medical journalism, and clinical ethics. Further interactions will take form of Data Blitz and Hot Topics sessions, poster sessions, and ample discussion time. This conference setup differs from that of many others in the field and will provide a unique opportunity for close interactions among investigators at all stages of their careers. We chose an inclusive venue that hosts conference space, accommodations, and dining options to provide abundant opportunity for networking. We have aimed for a diverse lineup of invited speakers and will strive to promote meeting access (i.e., via travel awards and waived registration) to individuals from historically marginalized populations. We believe that this meeting will drive advances in novel pharmacotherapeutics for SUD treatments at a critical time in regards to the need of novel SUD treatment options on the backdrop of changes in regulatory access to many of these compounds.

NIH Research Projects · FY 2025 · 2024-09

Youth and young adults have elevated rates of HIV incidence, particularly young men (ages 16-29). HIV incidence in young men is in part driven by low uptake of pre-exposure prophylaxis (PrEP) due to multilevel barriers. In my prior work, I led a community-driven media campaign entitled “PrEPárate” (“Be PrEPared”) which promoted PrEP information and a website with affordable options to access PrEP. The campaign was associated with increased PrEP awareness and use among insured adults but had limited reach to young men with barriers to PrEP access. In this K23 career development award, I propose to develop, pilot, and evaluate a multilevel intervention that combines a refined media campaign and peer-based strategy, informed by social network analysis. For youth and young adults, social networks of peers and family are especially influential in decision making and present an opportunity to promote PrEP. Through this award, I will receive new training and mentored experience in (1) social network analysis, (2) multilevel intervention development, and (3) implementation science. This K23 will lay the groundwork for an R01 application to conduct a randomized controlled trial studying the effectiveness of a multilevel intervention to increase PrEP use among young men. This proposal will advance understanding of factors that shape young men’s social networks and also will help identify optimal strategies to promote PrEP among young men. Through this training, I will gain the skills required to transition to independence as an investigator with expertise in interventions to improve preventive health among youth and young adults.

NSF Awards · FY 2024 · 2024-09

During the past three decades, astronomers have developed a paradigm of galaxy formation explaining the origin of galaxies and larger structures of the cosmic web in which they are arranged. The main remaining puzzle that challenges this paradigm is the observations showing that dwarf satellites around the Milky Way and other nearby galaxies are spatially distributed in flattened, rotating “planes”. The main goal of the project is to figure out which of the two stark alternatives is true: observed satellite configurations and their orbits are a genuine challenge to the galaxy formation paradigm indicating new physics or their origin can be understood within its existing framework. As part of the project, a teaching model based on the simplified version of the galaxy formation model with a series of exercises and projects will be developed and made publicly available for educators to use. Additionally, simulations developed during the project will be used to produce high-fidelity, scientifically accurate visualizations of the evolution of our cosmic neighborhood for the Adler Planetarium and other planetariums. This project focuses on developing models and statistical frameworks for understanding the puzzling spatial and orbital configurations of dwarf satellite galaxies around the Milky Way and several nearby galaxies, which do not yet have a compelling physical explanation within the Cold Dark Matter (CDM) paradigm of galaxy formation. The team will develop a series of simulations of volumes resembling the local cosmic neighborhood of the Milky Way. These will be used to forward-model observed satellite systems of nearby galaxies and statistical comparisons of model results with observations. This project will elucidate how galaxies in our local cosmic neighborhood form and how the local mass distribution affects galaxy formation. The results of this project should clarify whether observed satellite configurations present a major challenge to the CDM paradigm that would motivate looking for different cosmological models of structure formation involving non-standard physics. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

This research project will advance the methodology for and practical implementation of adaptive experiments. Adaptive experiments dynamically update treatment assignment procedures based on observed responses. They offer significant advantages over conventional randomized control trials for addressing decision-oriented questions such as identifying the best treatment among alternatives or personalizing interventions for different populations. However, their uptake in research and decision making settings has been limited. Methods for adaptive experimental designs to date have not served researchers who wish to understand how to best design an adaptive experiment that adequately addresses concerns around estimation and hypothesis testing. This project will develop methods and a framework for the use of adaptive experiments by applied researchers. Undergraduate and graduate students will be involved in the conduct of the project and user-friendly software will be developed. By providing tools and a framework that improves experimental efficiency and ethical standards, the project will facilitate more effective and informed decision making in social science research. This research project will address methodological gaps for adaptive experiments through three primary contributions: advancing statistical methodology for experiment design, establishing a framework for adaptive experiment design, and developing software for complex experimentation. In terms of statistical methodology, the project will develop new methods for sample size calculations in adaptive setting and develop a heuristic algorithm for optimal treatment assignment using inverse probability weighted estimators. The project also will document a comprehensive framework for adaptive experiment design. Design decisions such as frequency of algorithm updates and probability floors will have a large impact on the eventual assignment of the adaptive algorithm and on the performance of estimators on the data ex-post. The goal of this framework will be to help applied researchers navigate these decisions. Finally, the project will support the development of user-friendly software to implement complex randomization procedures online, with a focus on accessibility for non-technical users and integration with online field experiments. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

This workshop will convene experts in rare and extreme event detection and characterization representing a broad range of application domains and disciplines, including statistics, machine learning, applied mathematics, operations research, space weather, materials science, and climate modeling. Unanticipated rare and extreme events can be catastrophic in the domains of damaging high energy solar flares, sudden fuselage failure, and extreme terrestrial storms, causing significant loss of life and livelihood. Progress in modeling and predicting of such high risk events will require novel multidisciplinary approaches and this is what this conference seeks to uncover. It also seeks to catalyze new collaborations across these methodological and applicational domains. The goal is of convening experts with complementary backgrounds is to identify key challenges and opportunities, with an emphasis on methodologies that may be leveraged across domains. The focus on data-driven methods encompasses recent efforts in machine learning, including physics-informed machine learning and generative models, and how such tools may advance rare and extreme event forecasting. The agenda will also include physics-driven approaches, including simulations, both as a source of fundamental insights into the modeling of rare events and as a mechanism for generating data to complement real-world data used to train data-driven models. This two-day workshop will be held at the University of Chicago on November 20-21, 2024. It will feature lectures from experts across the spectrum of disciplines listed above, panel discussions, poster sessions, and lightning talks. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

This project seeks to develop a new technology to improve the way neurons are stimulated during neuroscience experiments. Current methods have limitations such as invasiveness. The devices to be used here will allow localized chemical reactions to be initiated with light. Thorough testing will be done both in cultured cells and on living animals. This project aims to provide new approaches that may revolutionize the treatment of neurological conditions such as Parkinson's disease and epilepsy. Additionally, the project promotes STEM (Science, Technology, Engineering, and Mathematics) education and diversity by providing valuable learning opportunities for students from underrepresented groups. The technology to be developed here, the Monolithic Adjustable Photostimulation (MAP) platform introduces random-access and pixel-less photostimulation capabilities, significantly improving neuromodulation resolution. The device is designed for minimally-invasive delivery and precise, non-genetic modulation of neural circuits. The research involves meticulous engineering of advanced silicon heterojunctions, which are junctions between nanoporous and non-porous silicon, to optimize their photoelectrochemical properties. Rigorous evaluations will be conducted both in vitro and in vivo. Initial tests will be performed on cultured neurons and mice brains to validate the technology, followed by trials on minipig models that closely simulate human brain anatomy to ensure the efficacy and safety of the MAP devices. This work, at the intersection of semiconductor technology and biophotonics, promises significant advancements in understanding and treating neurological conditions. The broader impacts include transforming treatments for disorders such as Parkinson's disease and epilepsy through the development of these non-genetic, optically controlled neuromodulation devices. Through programs such as the University's Collegiate Scholars and partnerships with Chicago Public Schools, students can participate in summer research. The project also collaborates with the Logan Art Center at UChicago to inspire high school students by integrating science with art. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

The environmental impact of computing has raised concerns worldwide as the growth of both Artificial Intelligence (AI) and Cloud Computing continues to accelerate. These trends are exacerbated by the slowing energy-efficiency improvement of computing technology. Organizations that procure and operate computing equipment are increasingly viewed as accountable for the carbon-emissions impact, water use, and other environmental costs of computing. Yet today, there are few clear reporting standards for what can be practically done with a reasonable effort. In short, while the need is clear, there is a lack of clear pathways and practices. The project will develop recommendations for effective climate impact reporting at scientific research computing centers, with an accompanying community engagement plan to ensure broad adoption. The project proposes to analyze existing proposals and practices for reporting on the environmental damage caused by large-scale research computing. The study will explore and develop a range of methodologies for assessing carbon footprint (embodied, operational, and after-use) and other environmental impacts such as water use. The initial focus will be on facilities operated by academic institutions and government-funded centers. An important part of the study includes the engagement of the community that operates such systems to understand the effort required to produce rigorous reporting and the tradeoff between effort and accuracy. The plan is to engage the academic computing community collaboratively to create realistic, implementable reporting options. The project's hypothesis is that broad adoption of the proposed reporting methods, and accessibility to the accompanying data used in reporting, will lead to procurement, operation, and disposal practices that reduce environmental damage from scientific research computing. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Non-Technical Abstract: This project explores the areas or crash-zones where floating ice shelves in Antarctica compressively flow against obstructions such as islands and plugs of stagnant ice frozen to the sea bed. The significance of these crash-zones is that they are responsible for generating the resistive forces that allow ice shelves to slow down the flow of ice farther inland into the ocean. Ice conditions within these boundaries thus determine how Antarctica’s ice sheets contribute to sea-level rise. The research will feature on-the-ice glaciological and geophysical field measurements near pressure ridges near Scott Base and the transition to the ice road where large wave-like pressure ridges form on the ice-shelf surface. This field area is along the coast of Ross Island adjacent to major logistical stations of the US and New Zealand Antarctic programs. Thus the research will help station managers better preserve one of the key roadways that connects the stations to the major runway used to fly to virtually all other parts of Antarctica. The research will also interact with educational programs such as featured in the long-standing Juneau Icefield Research Project as well as potential involvement of an artist from the US Antarctic Program’s Polar STEAM in the second field season. Technical Abstract: This project explores the dynamics of boundaries where ice shelves compressively flow against obstructions such as islands and areas of grounded ice. The significance of these boundaries is that they are responsible for generating the resistive forces that allow ice shelves to impede or slow down the flow of grounded inland ice into the ocean. Ice conditions within these boundaries thus determine how Antarctica’s ice sheets contribute to sea-level rise. The research will feature glaciological and geophysical field surveys in a compressive boundary area near pressure ridges adjacent to Scott Base and the transition to the ice road along the coast of Ross Island, an area affecting access to major logistical hubs of the US and New Zealand Antarctic programs. Field data will be combined with remote sensing, numerical modeling and theory development to answer key questions about the dynamics of compressive boundaries such as: is there a limit to compressive stress due to ice fracture and the bending of the ice shelf into sinusoidal pressure ridges? Over what time scales does this compressive stress build, fluctuate and decay, and how is it related to the processes that form rumples? Are there ways in which the ridges actually protect the compressive boundary from damage such as by setting up a means to scatter ocean swell impinging from the open ocean? How should compressive ice-shelf boundaries be represented in large scale ice-sheet/shelf models for the prediction of future sea-level rise? A variety of broader impact work will be done both specifically targeting the research field area and more broadly addressing scientific and societal concerns. The field area contains a critical logistics roadway that connects McMurdo Station, Scott Base and a runway essential for continent-wide air logistics. The project will inform how to stabilize the roadway against excessive damage from summer ablation and other factors. Other broader impacts include: (a) Open-Science evaluation of climate systems engineering strategies for glacial geoengineering mitigation of sea-level rise, (b) cooperation with the Juneau Icefield Research Program (JIRP) education component, (c) support and facilitation of an online FieldSafe workshop and associated panel discussion to support early-career Antarctic field teams to mitigate environmental and interpersonal risks in remote field sites, and (d) potential involvement of an artist from the US Antarctic Program’s Polar STEAM in the second field season. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

The goal of the project is to advance the understanding of the neural and behavioral underpinnings of working memory, an “online” memory system that holds information in a readily accessible state to guide ongoing behavior. Individuals with better working memory abilities excel in tests of fluid intelligence, scholastic achievement, and broad measures of attentional efficiency. Many models of complex cognition acknowledge the central importance of working memory for the ability to exert voluntary control over which aspects of a busy environment will occupy the mind. Thus, better neural and behavioral models of working memory function are important for understanding a wide range of intelligent behaviors. This collaborative effort is made possible through the National Science Foundation and Swiss National Science Foundation Lead Agency Opportunity. One important advance has been the identification of neural signals in humans that track storage in working memory. For example, by applying machine learning and other analytic approaches to electroencephalogram (EEG) recordings of brain activity, both the number and type of visual objects stored in working memory can be tracked with relatively high temporal resolution. Approaches like this have been powerful tools for building neural models of working memory, but basic questions remain regarding the specific computational role of these neurally active representations. For example, recent work has shown that even when neural signals associated with storage in working memory are temporarily silenced, there is evidence for preserved storage in working memory, suggesting that persistent neurally active representations may not be needed for working memory storage. The project aims to test an alternative hypothesis that neurally active storage may serve as a gateway to passive forms of memory that can endure without requiring persistent neurally active representations. In addition, the project aims to examine whether there are specific operations that require neurally active representations, such as the active manipulation of the stored information. Thus, the goal is to improve the understanding of how neural activity related to working memory supports the ability to hold relevant information in the focus of attention. This collaborative U.S.-Swiss project is supported by the U.S. National Science Foundation (NSF) and the Swiss National Science Foundation (SNSF), where NSF funds the U.S. investigator and SNSF funds the partners in Switzerland. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Among the most compelling current questions in cosmology are: What is the origin of the Universe? What is the Universe made of? What is the mass scale of neutrinos? The South Pole Telescope (SPT), currently equipped with the SPT-3G camera, plays a unique role in the pursuit of these questions. The SPT is located at the NSF's Amundsen-Scott South Pole Station, which is the best operational site on Earth for millimeter- and submillimeter-wavelength observations. Furthermore, the unique geographical location of the site allows SPT to observe targeted low-Galactic-foreground regions of the sky at constant elevation 24 hours a day, year-round, resulting in the deepest high-resolution maps of the sky at these wavelengths. The SPT also plays a critical role in the Event Horizon Telescope (EHT), a global array of telescopes to image the event horizon around the black hole at the center of the Milky Way Galaxy and other, more distant galaxies. Sharing the spirit of scientific inquiry will be extended beyond the research community through a well-established education network at all levels of the education continuum, from early childhood through graduate school. The award will inaugurate an internship program in partnership with Joliet Junior College, which will fund students from underrepresented groups in paid internship positions at SPT institutions. These programs are part of the larger SPT initiative toward building a more diverse workforce, in our field and beyond. This award is to support measurements of the cosmic microwave background (CMB) with SPT-3G, the most powerful CMB camera in operation. The SPT-3G maps of the total intensity and polarization of the CMB signal already have an unprecedented combination of depth, resolution, and sky coverage, and this award would support expanding the sky coverage by over a factor of two. The measurements of the CMB temperature and polarization power spectra and the CMB lensing potential with SPT-3G play a central role in probing current cosmological tensions and determining if their explanation requires physics beyond the ΛCDM cosmological model. Recently, a key thrust of the SPT research program has been the use of high-resolution SPT-3G data to remove the gravitational lensing signal from the degree-angular-scale data taken with the BICEP Array, to enable the deepest search yet for primordial gravitational waves (PGW). Delensing with the SPT-3G dataset will extend the power of BA to detect PGW by more than a factor of 2.5, achieving constraints on the presence of PGW that will be unsurpassed for many years. This award also addresses and advances the science objectives and goals of NSF’s "Windows on the Universe: The Era of Multi-Messenger Astrophysics" program. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Countless hints, from natural phenomena like dark matter, to theoretical concerns such as the hierarchy puzzle, strongly suggest the existence of Beyond the Standard Model (BSM) particles at energy scales probed by the Large Hadron Collider (LHC). This award aims to address the question of why we’ve yet to see any evidence of these new particles thus far and enable discoveries by breaking traditional search paradigms and building next generation pixel detectors. The research funded by this award will also push the boundaries of the ATLAS experiment’s capabilities. This will ensure high quality science at the upcoming High Luminosity LHC by upgrading the ATLAS Pixel Detector, improving the overall tracking capabilities in the face of unprecedented pile-up. The broader impacts of this award extend beyond enabling discoveries at high energy colliders. The research funded by this award represents a complete program for training students and postdocs. Data analysis techniques and instrumentation are shared with the wider scientific community and industry. In particular, developing cross-cutting technologies such as silicon sensors and microelectronics is integral to enriching the broader scientific landscape. Finally, this award will inspire the next generation of scientists through outreach programs that emphasize diversity, equity, and inclusion. The vast majority of LHC searches have focused on scenarios where high energy jets, photons, or leptons originate from the primary collision. However, many compelling BSM scenarios with long-lived particles may have evaded these constraints, resulting in displaced or anomalous tracks. One of the most exciting targets for the next LHC run is to follow up on an excess of events in a search for highly ionizing charged particles. This award will investigate this excess in a statistically independent dataset and extend our sensitivity by adding complementary measurements from the muon spectrometer. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Therapeutic ultrasound technology kills cancer with high intensity, high frequency sound waves. The sound waves generate small bubbles that rupture nearby cancer cells. Therapeutic ultrasound procedures can achieve the same goals as surgery without an incision, leading to shorter recovery times and lower costs. One thing not well understand about therapeutic ultrasound is the amount of bubble activity needed for the procedure to be successful. In this NSF/FDA Scholars-in-Residence project, a molecule that shifts its chemical signature in response to mechanical forces generated by microbubbles will be developed. Changes in the chemical signature will be measured during application of ultrasound in a tissue phantom to help the U.S. Food and Drug Administration determine guidelines for bubble-based medical devices. Curriculum for high school physics classes will be developed in collaboration with Chicago Public Schools based on the findings generated in this study. Microbubbles are an active area of research, in part because of their ability to force soft materials like tissue into extreme loading conditions. Noninvasive focused ultrasound systems exploit this property of microbubbles to break down malignancies, achieving the same goals as surgery without requiring an incision. There is clear potential for this technology, though the conditions that result in the failure of tissue structures remain unclear. This gap-in-knowledge limits guidance the U.S. FDA can provide to medical device developers, which inhibits growth of the field. The development of ultrasound therapies is therefore outpacing regulatory sciences, indicating the need for fundamental research into the mechanisms of microbubble-induced fatigue for soft materials. To address this need, the scientific premise of this project is advances in mechanochemistry can be used to quantify microbubble-induced deformation. An imprintable mechanophore formulation will be used to capture transient microbubble stresses in the following aims: Studies in Aim 1 will develop and characterize a mechanophore-based tissue phantom. Data collected in Aim 2 will determine the extent over which soft materials are stressed by microbubbles. Finally, the link between stresses, cell death, and other markers of microbubble activity will be established in Aim 3. This project will produce new knowledge on the interaction of microbubbles with soft materials, and a regulatory tool (e.g., tissue phantom) to assess new focused ultrasound devices. Educational and outreach activities are planned to disseminate findings into public forums and didactic school curriculum. Further, the postdoctoral fellow trained in this project will contribute to a globally competitive STEM workforce. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

The Division of Chemistry and the Division of Materials Research in the Mathematical and Physical Sciences Directorate, along with the Division of Chemical, Bioengineering, Environmental, and Transport Systems in the Engineering Directorate provide continuing support to NSF's ChemMatCARS. This is a national user facility for frontier research in chemistry, materials science, biology, and engineering, employing synchrotron X-rays at the Advanced Photon Source, Argonne National Laboratory. Experimental facilities at NSF's ChemMatCARS serve a broad national and international community of scientists providing state-of-the-art capabilities including some not found anywhere else in the world. Research activities address vital societal issues, including the development of new energy sources, biomolecular materials inspired by biological processes, studies of biomembrane interactions to understand the rules of life, environmental remediation and chemical separations processes, and new materials and catalysts important for a wide range of industries. The facility serves as a training ground for researchers at all levels and carries out numerous activities to develop the future STEM workforce including specialized education, training, and career development of students, postdoctoral scholars, and faculty in forefront synchrotron X-ray studies in molecular science. This user facility provides a unique high brilliance X-ray resource for the study of advanced small-molecule crystallography, liquid surface and interface scattering, and anomalous small and wide-angle X-ray scattering. Advanced instrumentation at NSF's ChemMatCARS enables forefront research of ordered and disordered solids, complex fluids, and soft interfaces on the atomic, molecular, and mesoscopic length scales over a range of time scales from nanoseconds to minutes. Users of NSF's ChemMatCARS take advantage of its unique capabilities to address a wide variety of scientific problems. The many capabilities in advanced crystallography include the structural resolution of excited state and highly reactive species with photo-crystallography. Site-specific measurements can distinguish the same-site occupancy of similar atomic number elements, as well as relative oxidation levels of the same element at crystallographically distinct sites. Initiatives in structural dynamics, including a frontier effort in small molecule serial crystallography, will investigate systems undergoing reversible and irreversible chemical transformations. Molecular-scale structural studies of liquid interfaces using X-rays advance the synthesis of nano- and 2D materials for catalysis and energy applications, reveal the interfacial separation of critical minerals, and explore the underlying structure of sea surface microlayers and organic thin film coatings. Lipid bilayers are utilized as model systems of biomembrane structure and dynamics, protein-lipid interactions, and nonequilibrium processes. A recently commissioned capability in X-ray absorption spectroscopy can transform our understanding of elemental speciation and oxidation at liquid interfaces. A frontier initiative will probe elemental and structural heterogeneities at liquid interfaces on small length scales. Anomalous small and wide-angle X-ray scattering (ASWAXS) probes element-specific metal ion distributions in disordered materials to investigate metal interactions in supramolecular chemistry, metal ion interactions in solution, and elemental distributions in nanomaterials with sub-nanometer resolution. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY/ABSTRACT While immunotherapies have revolutionized cancer treatment, a subset of patients, particularly those with squamous cell carcinomas (SCCs) found in the skin, oral cavity, larynx, esophagus, lung, and cervix, exhibit varying responses to immune checkpoint blockade (ICB), resulting in a 60% relapse rate. These disparities in patient outcomes strongly suggest the existence of genetic variations that underlie their distinct responses to ICB. Although the specific oncogenic mutations responsible for driving relapse in SCC patients remain unclear, it is imperative to grasp the mechanisms of cancer immune evasion in individuals with specific genetic profiles to enhance the precision of immunotherapy. Recent research has identified a population of tumor-initiating cells (TICs) within skin and oral cavity SCCs that resist anti-tumor immunity and drive relapse. These rare TICs are often overlooked in tumor immunology studies despite their critical role in promoting cancer recurrence. We have identified that activating mutations in the PIK3CA gene, found in 20% of cutaneous and head and neck SCCs, can enhance stemness and intrinsic immune resistance in SCCs, resulting in rapid relapse after ICB. The proposed research will consist of two main aims. The F99 phase aims to determine how PIK3CA mutations expand the immune-resistant TICs in SCC tumors. I will investigate whether PIK3CA activating mutations induce TIC self-renewal and dedifferentiation following ICB treatment. I will explore the role PIK3CA mutants have on the Sox2 protein, a critical transcription factor for maintaining stemness, and its stability in TICs. This aim will provide insights into the ability to disrupt PIK3CA mutant-induced Sox2 stability to reduce SCC relapse after immunotherapy. The K00 phase is broader with the goal of identifying how genetic alterations enhance the intrinsic immune resistance of TICs. In the first part of the K00 phase, I will design a genome-wide CRISPR screen to identify candidate genes responsible for endowing PIK3CA mutant TICs with resistance to T cell- mediated ferroptosis. I will explore how PIK3CA mutations reprogram the metabolism of TICs to enhance their intrinsic resistance to T cell-induced ferroptosis. I will then expand the scope to identify other genetic determinants beyond PIK3CA mutations that drive immune evasion in TICs. By CRISPR gene editing, I will introduce other oncogene activation, tumor suppressor inactivation, chromosomal rearrangements, gene fusions, and copy number variations into keratinocytes and evaluate their potential to promote immune evasion in vivo. This work will discover potential drug targets and biomarkers for predicting patient responses to immunotherapy. My ultimate goal is to become an independent investigator at a leading research institution and to conduct interdisciplinary, NIH-funded research contributing to the fields of cancer biology, stem cell biology, and immunology, and by characterizing novel mechanisms of cancer stem cell-specific immune resistance.

NSF Awards · FY 2024 · 2024-09

This award funds the research activities of Professor Luca Delacrétaz at the University of Chicago. Quantum Field Theory (QFT) is a cornerstone of fundamental physics, unifying high energy, condensed matter, and statistical physics. It is also the most precise description we have of nature. This project aims to deepen our understanding of QFT beyond the relativistic vacuum traditionally studied in particle physics. The research will explore the behaviors and properties of matter under extreme conditions, such as high density and temperature, which are difficult to describe by existing methods. By investigating these states, the project seeks to uncover new principles of physics that could lead to advancements in various fields, including condensed matter physics and cosmology. Additionally, the research will involve the training of graduate students, and participation in outreach activities in Chicago's south side, thereby supporting education in the sciences. This work aligns with NSF's mission to promote the progress of science and to advance national prosperity and welfare. More technically, the project is structured around two main objectives: constraining finite density phases that can emerge from interacting QFTs, and understanding the high-energy spectrum of QFTs through the lens of thermalization, hydrodynamics, and chaos. For the first objective, the research will employ UV/IR constraints and effective field theory (EFT) techniques to map out the possible phases that conformal field theories (CFTs) can flow to at finite density, aiming to either rule out or confirm the existence of exotic phases such as non-Fermi liquids, pair density waves, etc. For the second objective, the project will develop precision tests of thermalization by extending EFTs to capture hydrodynamic behavior and chaotic dynamics in high-energy states. This comprehensive approach aims to bridge the gap between high-energy theoretical predictions and observable phenomena in many-body quantum 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.

NIH Research Projects · FY 2025 · 2024-09

ABSTRACT Background: Black men who have sex with men (MSM) are disproportionately impacted by HIV and face many barriers to care engagement, such as housing instability, unemployment, and criminal justice involvement. Interventions to address these factors are resource intensive and logistically challenging, and the best implementation strategies remain unclear. Agent-based models (ABMs) can be used to virtually evaluate candidate interventions and implementation strategies to facilitate more efficient and timely intervention development, and combined with iterative community and public health stakeholder feedback can provide important insights about which intervention strategies and implementation levers would be most effective and efficient in real-world settings. Objective: Building on an existing ABM platform, this proposal will utilize multiple existing local data sources and new data collected through qualitative interviews and focus groups to better understand barriers to linkage, engagement, and retention in HIV care among Black MSM. We will combine methods from epidemiology, agent-based modeling, and implementation science to understand the potential impact of strategies to increase engagement and retention in HIV care on population-level HIV transmission. Methods: We will characterize individual, clinical, and system level barriers to engagement and retention in care, identify relevant implementation levers, and use this information to simulate (Phase 1) and pilot (Phase 2) implementation strategies to improve re-linkage, engagement, and retention in care among previously diagnosed individuals who are not consistently engaged in care. Significance: A better understanding of where and how to focus efforts to relink out of care individuals and to improve HIV care engagement and retention has the potential to have an important impact on the HIV epidemic. Once developed, our methods and models can be adapted to other geographic areas to reflect local prevention priorities and can serve as an example application of implementation science and ABM methods to advance HIV prevention science.

NSF Awards · FY 2024 · 2024-09

Precise measurements of the motions of stars on the celestial sphere are critical for understanding the formation and content of the Milky Way galaxy. Astronomers create computer models of the motions of stars to help understand assembly history of the Milky Way, the nature of dark matter, and look for planets around nearby stars. However, the motions of stars are extremely and difficult to measure. Moderately bright stars have been measured with exquisite precision by the European Space Agency’s Gaia spacecraft, but larger telescopes are required to measure fainter stars. The investigators will develop and apply new techniques to measure the motions of faint stars using some of the world’s most powerful ground-based survey telescopes. As part of this project, the investigators will provide scientific and technical training for graduate and undergraduate students. Furthermore, the investigators will engage and educate the general public with visualizations of the dynamic motion of stars in the Milky Way. The investigators will measure the astrometric positions of stars in hundreds of thousands of images collected by the Dark Energy Camera (DECam) on NSF’s 4-m Blanco Telescope. The investigators will use the DECam data to perform best-ever measurements of the proper motions of hundreds of millions of stars that are too faint to have been measured previously. The DECam data cover nearly the entire sky area of the Vera C. Rubin Observatory’s unprecedented Legacy Survey of Space and Time (LSST). The investigators will combine the DECam and LSST data to measure the positions and motions of stars much more precisely than would be possible with the first year of LSST alone. This research award is partially funded by a generous gift from Charles Simonyi to the NSF Astronomy division. The project includes significant contributions to Vera C. Rubin Observatory’s Legacy Survey of Space and Time. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Prof. Esser-Kahn of the University of Chicago will explore a method of polymer synthesis mediated by electric fields. The research will focus on the mechanism of how electric fields can be used to control and mediate the vibration of particles that produce chemical reactions. By examining the mechanism of both vibration and chemical reaction, the team will explore a new method to generate polymers and materials that can, shortly, be compatible with programmable interfaces via computer. The potential impacts of this work include enabling new forms of adhesives. Understanding these processes could improve other materials developments. Prof. Esser-Kahn, plans to continue his new educational program for high school students at the University of Chicago. This program educates 30 students each year, selected from 120 applicants, provides them with coursework and hands-on training to develop an understanding of engineering and design and the fundamentals of energy storage and transfer. The team hopes to retain and improve the outcomes of the program, which has served more than 100 students with a launching platform for their enrollment in STEM programs across the United States, with 50% enrollment in STEM PhDs. The project will examine how the particle's surface, as it charges, induces new forms of reactivity. This reactivity is focused on ionic interactions that mediate particles' interactions with solutions and their ability to transfer electrons to reagents for polymerization. We will determine how the electric field influences the particles' rate of reactivity and their interplay with the solution based on the ionic interaction between the particle and the double layer formed by the solvent and secondary ions. The interplay between the solvent, ions, and dipole will be examined to determine how these ratios influence the reactivity of different species. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

The NSF Center for Multimodal Observations for Single Atom Imaging of Chemistry (MOSAIC) is supported by the Centers for Chemical Innovation (CCI) Program of the Division of Chemistry. The ability to visualize chemical reactions at the single-atom level and in real time would be truly transformative to the field of chemistry. Scientific achievements in this area would allow scientists to understand reaction mechanisms and the relationships between molecular structures and their properties at previously inaccessible resolutions. MOSAIC will achieve these goals via 1) the nanofabrication of novel liquid cells with enhanced functionality and 2) the coupling of these liquid cells with electron microscopy to reveal new insights into chemical reactions at a range of scales, from atoms to clusters to 2D materials. Activities within this center will include collaboration with a wide range of companies to commercialize the MOSAIC platforms and rotations for mentees between different institutions to broaden scientific expertise. The center will utilize various programs to recruit and support underrepresented students. Public science communication and outreach will be enhanced through programs such as the “South Side Science Festival” and collaboration with some of the largest science museums in the country, as well as the creation of educational multimedia materials in collaboration with school districts and public libraries. MOSAIC’s real-time, single-atom level visualization will elucidate (i) reaction mechanisms at the finest level, such as the atomic or molecular configuration of intermediates, the pathways by which intermediates are converted into products, and rate-limiting steps in those pathways, and (ii) how properties change with the instantaneous atomistic structures during reactions or in response to external stimuli. Achieving breakthroughs in the visualization of chemical reactions at the single-atom level and in real time will depend upon the development of specialized liquid cell platforms with enhanced capabilities in scanning/transmission electron microscopy (S/TEM). MOSAIC will employ nanofabrication to permit the spatial control of liquid cell compartments, the thickness of the liquid, and the geometry of viewing windows, thereby allowing quantitative and high-resolution analysis of chemical reactions. MOSAIC will utilize these novel liquid cell platforms in a highly integrated research program that focuses on single-atom catalysis, cluster chemistry, nanocrystal synthetic chemistry, and surface coatings on 2D membranes using organic molecules with surface-specific reactivities. Liquid cell platforms will also be integrated with cutting-edge capabilities in S/TEM, such as atomic-resolution vibrational electron energy-loss spectroscopy (EELS) with chemical sensitivity to visualize bonds and valence states of elements, 4D-STEM to map structures and chemical bonding, and electron tomography for 3D structures. The data analysis approach and chemical interpretations will benefit from theory-guided information extraction using artificial intelligence/machine learning (AI/ML) and density functional theory modeling. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Dark matter is a ubiquitous yet invisible presence in our universe. It dictated how galaxies formed in the first place, and now moves their stars at puzzling speeds. From these and other colossal gravitational effects the dark matter mass in the universe is known to be five times that of ordinary matter and composed of unknown particles, which interact weakly with ordinary matter. This award will support the Dark MAtter In CCDs (DAMIC) experiment, which searches for dark matter particles with a novel detector technology. The nature of dark matter constitutes one of the most fundamental questions in science. Its discovery as a yet unknown particle would have profound implications in our understanding of the universe, and open new directions in particle physics and cosmology. This award will enable immersive research experiences for students, engagement of the local community and the general public, and innovative partnerships bringing science to formal and informal audiences. The DAMIC experiment is designed to detect nuclear and electronic recoils induced by dark matter in silicon charge coupled devices (CCDs). Scientific CCDs are commonly used in the focal plane of astronomical telescopes for the digital imaging of faint astrophysical objects. DAMIC has pioneered their unconventional use as dark matter detectors at the SNOLAB laboratory (located in a mine 2 km beneath Sudbury, Canada); with this award a several-hundred-gram detector - DAMIC-M - will be installed at the Laboratoire Souterrain de Modane in France. Single ionization charges produced by a dark matter interaction will be detected in DAMIC-M with high resolution thanks to non-destructive, repetitive measurements of the CCD pixel charge. With this novel technology DAMIC-M will have unprecedented sensitivity to light dark matter (≈ eV energies are enough to free an electron in silicon). This award will support the participation and leadership roles of the research groups at University of Chicago and University of Washington in the DAMIC experiment construction, installation and commissioning. The award scope includes collecting a data sample corresponding to a target exposure of few hundred g-year and performing a first search for dark matter. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-09

Project Summary/Abstract Ion channels are proteins that allow the permeation of ions across the plasma membrane. These membrane proteins orchestrate the cellular excitability in neurons and muscle fibers by firing action potentials that are essential for neuronal communication and muscle contraction. In non-excitable cells, such as immune cells, the role of ion channels is much less understood. However, solid evidence demonstrated by null mutations of human or mouse genes have shown that ion channels play critical roles in immune cell function. Here, we aim to study the physiological role of swelling-activated ion channels that are present in T lymphocytes. To achieve this goal, i) we will use a systematic approach to discover the swelling activated Ca2+ (SWAC) channel that is active during the maturation of T lymphocytes and study whether this channel is necessary to provide Ca2+ signals for the positive selection of T cells in the thymus, and ii) study the mechanisms of transport by volume-regulated anion channels (VRACs) for large substrate such as cyclic dinucleotides signaling molecules. We will use cross- disciplinary approaches including functional genomics, systems immunology, electrophysiology, biochemistry and structural biology, and genetic mouse models to understand the complex molecular networks regulated by ion channels in immune cells. The long-term goal of my lab is to identify and characterize novel, specific and functional ion channels in immune cells to gain better understanding of how these proteins regulate the immune response, and make fundamental and translational advances in immunotherapy.