University Of Illinois At Chicago

NSF Awards · FY 2025 · 2025-09

With the support of the Chemistry of Life Processes Program in the Chemistry Division, Dr. Ao Ma from the University of Illinois Chicago is studying how proteins bind small molecules, a process both common and critical in biology and medicine. In this process of ligand binding, the conformation of proteins changes. This project aims to understand how the conformational changes are coupled to ligand movement and how the changes are also affected by water molecules. The research will use novel computational methods to reveal the step-by-step pathways and driving forces behind ligand binding. The work will help advance the understanding of enzyme function and inform the design of more effective drugs. The project will also enhance education and training through graduate curriculum development, participation in an undergraduate research program, and mentorship of high school students. The proposed research will apply the energy flow theory and generalized work functional method to compute true reaction coordinates and directly simulate the unbiased, natural dynamics of ligand binding. This approach will enable a rigorous dissection of the molecular mechanism of binding. The project will focus on two model systems: HIV-1 protease and PDZ domains, which represent the two prevalent binding paradigms-conformational selection and induced fit. Key factors that determine binding free energies and rate constants will be identified. Information will be generated on how protein conformational transitions and water dynamics collectively control ligand binding. The methods and resulting insights will advance understanding of protein-ligand interactions and support research across molecular biophysics, drug discovery, and protein engineering. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-09

Mathematicians study many different mathematical objects, and some of these objects are more complicated than others. Combining ideas from different areas of mathematical logic, from computability theory, descriptive set theory, and infinitary model theory, the Scott analysis is a way of measuring and understanding the complexity of mathematical objects. The Scott analysis is robust in the sense that it captures several different kinds of complexity that all coincide: the complexity of describing an object, the complexity of identifying two copies of an object, and the complexity of an object's internal structure. Though there remain many questions, the Scott analysis has now been well-developed for the case of discrete structures such as many structures appearing in algebra. More recently there has been increasing interest in studying continuous structures such as those appearing in analysis, a setting in which we do not have a robust Scott analysis, as there are further complication which do not arise in the discrete setting. This project will develop a robust Scott analysis in this continuous setting, including applications, while also further applying developing the Scott analysis in the more classical discrete setting. The long-term goals are to give a more rigorous and formal understanding of why certain mathematical questions are difficult or even impossible to solve, and what the barriers are to solving them. This project includes the training of undergraduate and graduate students. Consider a discrete structure such as a graph, group, or Boolean algebra. The Scott analysis assigns to this structure an ordinal-valued Scott rank or more finely a Scott complexity. This is robust in the sense that it measures, simultaneously, the complexity of defining the automorphism orbits of the structure, the complexity of characterizing the structure up to isomorphism in infinitary logic, the Borel complexity of the set of copies of that structure in the topological space of all structures, and the computational complexity of building isomorphisms between copies of that structure. This project will develop such a theory in the continuous setting where the structures are metric or topological structures such as Banach spaces or manifolds. The main goal is to develop a bridge between syntactic characterizations in infinitary continuous logic and semantic characterizations in terms of computation or topology and descriptive set theory. Applications of this include studying how the Scott complexity of n-manifolds changes as n increases, or of studying the Scott complexity of Banach spaces and, for example, the impact of whether or not they have a Schauder basis. The project will also include further developments in the discrete setting, both in developing the theory at a finer level and in further 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 2025 · 2025-09

PROJECT SUMMARY / ABSTRACT Alterations in hormone levels during pregnancy significantly affect liver physiology, including organ size, lower insulin sensitivity, increased serum concentrations of several proteins/metabolites, and alterations in drug metabolism enzymes. While 80% of pregnant females take at least one medication (not including dietary supplements), most drugs used in obstetrics patients lack population-specific dosing information due to an incomplete mechanistic understanding of functional alterations in the pregnant liver and model systems for drug testing. Mice are useful for elucidating pregnancy-induced changes in the liver due to some morphological and molecular similarities with humans; however, species-specific differences necessitate complementing mouse studies with human-relevant models. We have utilized high-throughput droplet microfluidics to develop liver microtissues (~300µm) in which primary hepatocytes (mouse or human) are embedded within microscale extracellular matrix (ECM) protein hydrogels, and liver sinusoidal endothelial cells (LSECs) are coated on the surface of the hydrogels to create sinusoidal compartmentalization between hepatocytes and LSECs. Microtissues functionally outperform self-assembled hepatic spheroids and hepatocytes within bulk (macro) gels, and they can be further augmented with other liver cell types, such as hepatic stellate cells (HSCs) and Kupffer cells (KCs). Here, we will test the novel hypothesis that microtissues containing multiple primary mouse liver cells isolated from pregnant and non-pregnant livers can be used to elucidate the role of paracrine (blood-borne) factors and preconditioning in vivo on phenotypic changes in liver cells during pregnancy. In aim 1, we will fabricate non-pregnant mouse liver microtissues using the four liver cell types above and liver decellularized ECM (dECM). We will compare the responses of mouse liver microtissues and human liver microtissues to non- pregnant and pregnant mouse sera from different gestation days to determine how each species responds to the same pregnancy blood-borne factors. The functional and gene expression changes over prolonged mouse liver microtissue culture will be benchmarked to fresh cells before culture. In aim 2, we will fabricate mouse liver microtissues from liver cells and liver dECM isolated from pregnant mice at different gestation days. We will then elucidate the effects of non-pregnant and pregnant sera on phenotypic changes in the pregnant mouse liver microtissues. We will engineer the first long-term, in vitro 3D mouse liver model of pregnancy and elucidate how blood-borne factors and in vivo preconditioning affect the phenotypes of liver cell types during pregnancy.

NIH Research Projects · FY 2026 · 2025-09

This proposal focuses on dietary fiber supplementation, a promising way to help people lose weight and lower their risk of heart disease. These beneficial effects of fiber are largely attributed to the products of its fermentation by the gut microbiota, the Short-Chain Fatty Acids (SCFAs). The body can detect these SCFAs through mainly two receptors: Free Fatty Acid 2 and 3 (FFA2/FFA3). Interestingly, SCFAs can act directly on the central nervous system (CNS) to regulate energy balance and improve inflammation. On the last decade, high fat diet (HFD)-induced obesity has been associated with an inflammatory response orchestrated by the CNS resident microglia that appears on the hypothalamus on the first days of HFD feeding. Notably, blocking inflammation in microglia prevents diet induced obesity (DIO). These findings suggest that early onset inflammation in hypothalamic microglia plays a major role in the pathogenesis of DIO. Recently, we found that adding the fiber Fructooligosacharides (FOS) to a western diet (High Fat-High Sugar) for 8 weeks in mice, increased SCFAs in the blood, prevented weight gain and reduced hypothalamic inflammation markers. Curiously, we observed similar anti-inflammatory effects on the hypothalamus at the first day of diet. Interestingly, these effects were associated with decreased bodyweight gain and fat accumulation at the first week of treatment. These findings indicate that early blocking of hypothalamic inflammation may mediate the effects of fibers. However, the specific mechanisms remain unknown. Based on these results, we hypothesize that dietary fiber supplementation prevents western diet-induced obesity by reducing the inflammatory activation of hypothalamic microglia through modulating SCFAs-FFA2/3 signaling. We proposed to test if dietary fiber effects are mediated by SCFAs-FFA2/FFA3 signaling by using gut microbiota depleted (no SCFAs production) and FFA2/FFA3 double knock out mice models. Second, we propose to test if FOS supplementation inhibits microglia inflammatory activation to prevent acute hypothalamic inflammation and DIO in a mouse model with chemogenetic activation of microglial inflammatory signaling. Finally, we propose to study the effects of WD and FOS supplementation on the transcriptome of hypothalamic glia using two innovative technologies: PiP-seq scRNA17 for single cell resolution and translating ribosome affinity purification (TRAP) on microglial-specific cre-lines for microglia focused analysis. For the completion of the aims outlined above, the candidate counts with a unique background in transcriptomic and dietary strategies to treat metabolic syndrome. The mentoring team is composed of 5 experts: Pingwen Xu (Mentor), Terry Unterman (Co-mentor), Brian Layden (Co-mentor), Martin Valdearcos (consultant) and Mauricio Dorfman (consultant). Results from this proposal will increase our understanding in the mechanism by which FOS exerts beneficial metabolic effects. This is a crucial step for the design of new therapeutics to prevent/treat obesity based in FOS supplementation or related molecular pathways.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY / ABSTRACT Neutrophils are essential for host defense during bacterial infections, but their excessive activation can also promote tissue injury. Recent studies suggest that there are distinct subsets or states of neutrophils that allow them to engage in both exacerbation of inflammatory injury as well as repair and regeneration during the post-injury phase. Chemokine receptors such as CXCR2 and CXCR4 are expressed differentially on selected neutrophil subpopulations and are thought to regulate the trafficking of neutrophils between the bone marrow and the tissues during acute infections. However, the precise dynamics of how distinct neutrophil subpopulations are trafficked and how they contribute to discrete phases during lung injury and repair remain unclear. Identifying the distinct roles of CXCR2 and CXCR4 receptor signaling would allow for precision therapeutic targeting of neutrophil subpopulations in order to allow for their necessary host defense function during lung injury, minimize tissue injury caused by maladaptive neutrophil subpopulations and also enable resolution and repair of lung tissue in the post-acute phase. We have designed novel peptides that allosterically target CXCR2 and CXCR4, and our Supporting Data also suggest novel molecular mechanisms by which these chemokine receptors signal. We have furthermore studied phenotypes of activated neutrophils and assessed the dynamics of distinct neutrophil populations in the lung following inflammatory lung injury. Based on our provocative Supporting Data, we have formulated the overarching hypothesis that neutrophil subpopulations can be therapeutically targeted during key phases of inflammatory lung injury to minimize lung injury without compromising host defense or lung repair. We propose the following specific aims: In Aim 1, we will define the dynamics of neutrophil subpopulations in the bone marrow, blood and lung during the progression of injury using lung injury models and targeted genetic interventions to study the roles of neutrophils during distinct phases of lung injury and repair. In Aim 2, we will define the receptor clustering and signaling mechanisms for the chemokine receptors CXCR2 and CXCR4 in neutrophils. In Aim 3, we will assess the therapeutic efficacy of targeting neutrophil subpopulations during discrete phases of inflammatory lung injury.

NSF Awards · FY 2025 · 2025-09

With support from the Chemical Mechanism, Function, and Properties Program of the Division of Chemistry, Professor Neal Mankad at the University of Illinois Chicago is investigating small, well-defined clusters of copper atoms. These clusters can help scientists better understand nano-catalysts — materials that play vital roles in speeding up chemical reactions in both industry and research but are often difficult to study because their structures are not well understood. This project uses advanced X-ray techniques to map where electrons are located within these copper clusters, revealing how the arrangement of atoms affects their chemical behavior. By learning how electrons are distributed, scientists gain valuable insights that can help design better catalysts. This work sits at the intersection of physical, inorganic, and materials chemistry and offers top-tier training opportunities for students and researchers at all stages. Copper (Cu) catalysts are widely used to promote reactions including, but not limited to, hydrogenation and electroreduction of carbon dioxide. However, the active sites in these heterogeneous systems are often structurally ill-defined and difficult to probe with atomic-level precision. This project is guided by the central hypothesis that resolving the electronic structures of individual Cu atoms within atomically precise nanoclusters (APNCs) will enhance understanding by enabling correlations between molecular electronic structure and the local environments present in bulk materials. The objective is to apply advanced crystallographic methods spatially to map the electronic structures of Cu-rich APNCs, providing an atom-level understanding of chemical bonding as a function of molecular structure. This research is designed to address three key questions: 1) How do the atom-specific electronic structures of Cu sites vary across a series of APNCs, as revealed by resonant X-ray diffraction anomalous fine structure (DAFS)? 2) What are the quantitative bonding characteristics of “cuprophilic” Cu···Cu interactions, based on high-resolution charge density (HRCD) analyses and atoms-in-molecules (AIM) theory? 3) How do heterometal dopants influence the electronic structures of Cu nanoclusters, as assessed through Cu K-edge DAFS? This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-09

There are populations at risk for late stage breast cancer (BC) diagnoses and worse post-diagnosis quality of life, including Latinas, in part due to non-adherence to guideline-concordant screening. Education+navigation (educate) approaches offer community education to address psychosocial barriers (e.g., fear) and navigate individuals to free/low-cost breast cancer care. Our transdisciplinary team has developed a promising empowerment+navigation (empower) approach that may lead to greater BC screening. In the empower approach, individuals who are non-adherent to US Preventive Services Task Force (USPSTF) guidelines learn about BC; are navigated to free/low cost breast cancer care; and gain communication skills to promote BC screening throughout their networks. Our premise is that empowering non-adherent individuals as breast health agents may lead to greater BC screening among non-adherent individuals and their networks than treating non-adherent individuals as passive recipients of education. The current proposal tests our premise and identifies “active ingredients” of the empower approach. In Aim 1, we will conduct an individual randomized controlled trial (RCT). Among non-adherent individuals, we will compare the effects of empower and educate approaches on initial and repeat BC screening, in line with USPSTF guidelines. In Aim 2, we conduct an observational social network study. We will recruit network members through nonadherent individuals enrolled in our RCT. Among network members, we will compare the effects of empower and educate approaches on initial and repeat BC screening across four years. In Aim 3, we will explore theoretical mechanisms of change that could contribute to intervention differences in BC screening. For non-adherent individuals’ BC screening, we will examine the mediating roles of greater BC knowledge and motivation to be healthy role model. For network members’ BC screening, we will examine the mediating role of non-adherent individuals’ enhanced capacity to promote BC screening. Specifically, we will test the independent effects of volunteerism in community BC initiatives, potential to “bridge” network members with formal change agents (e.g., community health workers, navigators), acceptability to promote BC, feasibility to promote BC, and BC promotion to network members. Our innovative, robust approach has direct implications for expediting the translation of promising community interventions into practice.

NIH Research Projects · FY 2025 · 2025-08

The University of Illinois Chicago’s Center for Clinical and Translational Science (CCTS) envisions a healthier Illinois for all people. We will achieve our vision through designing and fostering collaborative and innovative research that advances translational science and health for all. We aim to speed the development, translation, and uptake of evidence-based strategies into practice and into communities. As part of our vision, the CCTS aspires to ensure that research is translated in an accessible, relatable, actionable, and relevant manner to all people. We embrace the concept of a “rapid learning research system” in which we bring together researchers, implementers, patients, community representatives, and health system stakeholders to develop strategies and ensure we address relevant questions. Since its inception in 2008, the CCTS has sought to integrate transdisciplinary systems across disciplines to address health problems within biological, individual, and environmental factors. In this next phase, the CCTS aims to serve as the translational bridge between research and the end-user (i.e., the clinician, patient, or community) by a) incorporating principles that promote the opportunity for everyone to achieve good health, implementation science, and human-centered design; b) ethically integrating informatics and data science; and c) applying a health advancement lens across the translational spectrum to enhance the relevance, informativeness, and impact of research. By advancing clinical and translational science (CTS) with synergistic principles of action, we will seek to address roadblocks to translational advances and deliver innovations that further improve opportunities for everyone to achieve their highest level of health. Our strategic goals address key barriers to progress in CTS: 1) Accelerate and support innovative research that advances the translation of science and data into action and practice; 2) Advance careers and train a broad, multifunctional clinical translational workforce that can respond to dynamic and pressing health problems; 3) Work collaboratively with key stakeholders to allow us to effectively translate science into practice; and 4) Align data science to support health for all.  These strategic goals will direct our course over the next seven years. As we develop, demonstrate, and disseminate innovative solutions and integrated efforts across our hub, across Chicago, and to the CTSA network, we hope to have an expanded positive impact on the science of clinical translational research and health outcomes.

NIH Research Projects · FY 2025 · 2025-08

Abstract Multiple sclerosis (MS) is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS) that is associated with impairments in cognitive processing speed (CPS). The impairments in CPS are poorly managed through medication or rehabilitation in MS, yet present considerable burden for persons with MS. There is recent evidence of vascular dysfunction in MS, and this have been associated with worse CPS in MS. Physical activity is associated with better vascular function and CPS in MS, but the possible mechanism has been incompletely described and characterized. Cerebral pulsatility index measured in the middle cerebral artery may reflect consequences of vascular dysfunction in large arterial and cerebral microvascular segments, however in closer proximity to the brain than previously measured metrics of vascular dysfunction in MS such as aortic stiffness. There are further data of elevated serum neurofilament light (sNfL) levels in MS, and sNfL has been associated with cognitive and cerebrovascular endpoints in MS. Collectively, this study compares and examines hypothesized associations among physical activity, measured by body-worn accelerometry, brain vascular function, as measured by cerebral pulsatility index, cognitive function, measured by CPS, and CNS neuronal integrity, measured with sNfL, in persons with MS compared with controls matched for age, sex, and body mass index. The study will further examine cerebral pulsatility index as a mediator of the associations among physical activity, sNfL, and cognition in MS. We hypothesize that people with MS will have lower levels of physical activity, higher levels of sNfL, and lower CPS compared with controls. Additionally, we hypothesize that higher physical activity will be associated with lower cerebral pulsatility index, lower levels of sNfL, and higher CPS. We further hypothesize that the relationships between physical activity and both sNfL and CPS will be indirect and accounted for by cerebral pulsatility index, and this indirect, mediation association may be stronger in MS. This study will provide the groundwork for developing a randomized controlled trial that changes PA behavior for preserving brain vascular function, neuronal integrity, and cognition in people with MS.

NIH Research Projects · FY 2025 · 2025-08

ABSTRACT Approximately 1 in 10 adults in the U.S. experience neuropathic pain, which is pain caused by a malfunctioning or diseased nervous system. Current treatments for neuropathic pain are only moderately effective and possess serious side effects. Therefore, there is a need for new and safer treatments for neuropathic pain. The α9α10 nicotinic acetylcholine receptor (nAChR) has been proposed as a potential target for neuropathic pain. Previous work has shown that α9-knockout mice exhibit decreased hyperalgesia in models of neuropathic pain. Additionally, antagonism of the α9α10 nAChR with α-conotoxin inhibitors reduces allodynia and hyperalgesia in rodent models. Despite this promising evidence supporting α9α10 as an analgesic target, current antagonists have poor oral bioavailability, low metabolic stability, and are non-selective. Due to poor expression in mammalian cells, previous studies of the α9α10 nAChRs have required the use of electrophysiology in oocytes, which has limited the discovery of novel α9α10 ligands. However, our group has recently developed a cell line that stably expresses α9α10, allowing us to identify and investigate new ligands for this receptor. My central hypothesis is that the development of a novel, drug-like α9α10 nAChR selective probe can be used to further the understanding of the α9α10 nAChR as a drug target. In Aim 1, I will use a structure-based approach to convert AT-1001, a partial α3β4 nAChR agonist with moderate antagonist activity at the α9α10 nAChR, into an α9α10-selective ligand. In parallel, Aim 2 applies a ligand-based approach with a lead compound identified from a high-throughput screen recently conducted by our lab. The proposed structure-activity relationship studies will focus on identifying a potent α9α10 antagonist. Upon identifying an improved α9α10 antagonist, the selectivity of this compound will be evaluated at other nAChR subtypes and central nervous system receptors. This research showcases two innovative approaches towards the development of a drug-like α9α10 nAChR selective probe as it employs tools and strategies that have not been previously used to develop ligands for this receptor and will advance the significance of the α9α10 nAChR in drug discovery.

NSF Awards · FY 2025 · 2025-08

This project will provide support for students to attend and participate in the 51st International Conference on Very Large Databases (VLDB 2025) to be held in London, UK. The grant will be used exclusively for students in US-based institutions, enabling the supported students to travel to London to participate in the conference and its associated workshops. The funding will defray the registration, travel, and lodging costs for the students. This grant will enable a life-enriching first-time experience for many students, giving them a taste of the research environment in both academic and industrial circles worldwide. VLDB is a premier conference in the area of databases that brings together technical research papers, tutorials, and workshops centered on various aspects of database research and practice. Participation in this conference will enable the students to enhance their scientific foundation and build their professional networks, and thus contribute directly to training the next generation of scientists who are both consumers and developers of technology in database management system design and implementation. The grant will have a direct impact on creating a highly qualified workforce who can take on the emerging data science challenges of the future. 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

This project investigates evidential markers, the grammatical coding of information source and speaker’s perspectives. Evidential markers indicate whether a statement is based on direct observation, inference, hearsay, or other types of evidence. Examining how different languages express source of information can provide insights into how speakers evaluate information, revealing deeper cognitive processes. The project's goal is to create treebanks/universal dependencies corpora to develop an automated deep-learning natural language processing (NLP) model. Considering the distributional characteristics around evidential markers, the model will be able to extract information from texts semi-automatically. The project explores a key linguistic question: why evidential markers in some languages behave differently from those in other languages, as they seem to have more than one function and allow more flexibility in how they appear in sentences. This flexibility may affect how language users show evidence or emphasis in longer conversations. The work will not only expand understanding of how these languages work but also support language technology development. Because the project will use a deep learning architecture to develop this NLP model, there are several other potential applications beyond the proposed linguistics goals: the development of machine translation tools; text summarization; and other types of human-machine interactions (e.g. chatbots) and AI 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

This doctoral dissertation project investigates how ancient empires expanded into and governed geographically distant and environmentally varied regions. The research focuses on how states adapt their strategies across different ecological zones to mobilize resources and integrate local populations into their systems. The project addresses larger questions about governance, economy, and frontier dynamics. Through archaeological survey and excavation, ceramic analysis, radiocarbon dating, and archival research, it generates insights into the timing, organization, and labor systems involved in expansion. These findings contribute to comparative studies of frontier administration, offering a more detailed understanding of how states manage peripheral regions. Broader impacts include training undergraduate and graduate students. The project also includes public outreach through school partnerships and community program and shares findings with a range of stakeholders to improve the public's understanding of science and the scientific method. The study's methodological approach advances NSF priorities for investments in biotechnological innovation. The research is guided by two central questions: How do state strategies change in response to different environmental and cultural contexts? And what are the material and social effects of these strategies on local communities? These questions are explored through a combination of archaeological, laboratory, and archival methods that trace long-term changes in production, exchange, and settlement. The research integrates regional survey and excavation with laboratory techniques, including ceramic analysis using laser ablation–inductively coupled plasma mass spectrometry (LA-ICP-MS) to determine provenance, and accelerator mass spectrometry (AMS) radiocarbon dating to establish precise timelines. Together, these approaches offer a detailed view of how the ancient communities reshaped local economies and landscapes over time. The findings will contribute to broader discussions about the material foundations of the interactions between states and frontier societies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-08

Project Abstract: Chemotherapy and radiotherapy treatments are the leading cause of acquired bone marrow (BM) failure and contribute to non-relapse mortality in many cancers. Several studies have pointed out that bone marrow failure is due to a deficiency in quality or engraftment of the hematopoietic stem and progenitor (HSPC). However, we propose that the overall survival and recovery of the BM niche microenvironment is equally important to the success of hematopoietic regeneration after preconditioning and HSPC transplant. We have established that robust Notch signaling is critical for survival and a timely recovery of the BM endothelial cells and by connection the hematopoietic system that relies on the functionality of this niche. Our findings suggest that a subset of progenitor myeloid derived suppressor cells (pro-MDSCs) express cKit, can upregulate the Notch ligand Jagged1 (Jag1), and play important roles in recovery of the niche by specifically promoting survival and regeneration of the endothelial cells in the BM. In addition, we propose a positive feedback mechanism where Notch activation in the endothelial cells actively promotes recruitment of damage resistant Jag1+ CCR2+ pro-MDSCs by production of CCL2. In this proposal we will determine the mechanistic aspects of how the interplay between BM niche cells and pro-MDSCs promotes hematopoietic recovery after chemo and radiation treatment. We will use cell-based therapy for recovery of the BM niche and cutting-edge bioengineering approaches to develop Jag1+ coated biomimetic nanoparticles (NPs) in cell-free treatments for acquired BM failure in relevant WT and transgenic model systems. In Aim 1, we will determine the mechanism by which Jagged1-expressing pro- MDSCs promote timely hematopoietic recovery after preconditioning. We will directly test the range of application of pro-MDSCs toward the recovery of the BM endothelial niche and endothelial cells in other tissues. To this end, we will design polymer-based NPs coated with lipid membrane overexpressing Jag1, determine their biodistribution and repair potential of the BM niche. In Aim 2, we will determine how endothelial cells promote their own survival and regeneration and ultimately support hematopoietic recovery by active recruitment of CCR2+ pro-MDSCs to the EC niche. We predict that following irradiation damage, BM endothelial cells recruit myeloid cells to sites of endothelial BM damage by secretion of chemokines. We will visualize interaction of pro- MDSCs with ECs in various tissues and measure pro-MDSC migration in several assays. We will test the effect of deletion of CCL2 in BM EC and CCR2 in donor pro-MDSCs during recovery. This project is multidisciplinary in that it will employ a combination of expertise in hematopoiesis, stem cell biology, and biomaterials to address the specific aims. The results will directly support the development of new therapeutic strategies to treat bone marrow failure.

NIH Research Projects · FY 2025 · 2025-08

The K12 program at the University of Illinois Chicago (UIC) program will focus on the development of scholars in clinical and translational sciences, with the overarching goal of bridging the divide between clinical scholar development and the needs of our research and external community. Our current faculty development effort is strongly linked to the core UIC mission of expanding health for all communities and uses the successful Clinical and Translational Sciences (CATS) Scholar development program and education core curriculum. This program benefits from a curriculum enhanced by our excellence in clinical and translational research across a full complement of clinical health sciences disciplines at UIC and strong interconnectedness to the CCTS (UM1) activities. At UIC, the CCTS CATS Scholars Program weaves together the collected resources and expertise of the UIC clinical and translational research enterprise into this training. Our goal is to build a community of K12 CATS Scholars prepared to engage in careers that advance science and health access to all communities and contribute to the generation of foundational knowledge in seven core translational scientist competencies. More importantly, we will deliver a program with full immersion in training principles of belonging, communication, and self-efficacy so that our scholars will become leaders in translating findings into practice. The specific aims are to: 1) Provide a mentored career development program that facilitates the long-term success of early career K12 faculty community engaged in clinical and translational science research across the clinical health sciences disciplines; 2) Support K12 scholars, regardless of discipline, to integrate individualized health experiences and translational science into their research via a multidisciplinary training program integrated with our career development workshops; 3) Facilitate K12 Scholars’ career development with unique training opportunities that will drive collaboration using innovative cross-discipline team science; and 4) Systematically evaluate the Program and provide for continuous improvement and alignment with the competency domains of clinical and translational scientists to better address the research needs of the communities we serve. The program is supported by more than 25 core mentors and more than 75 total mentors who maintain vibrant and relevant research programs along with a commitment to mentoring. Innovative components of the program include an institutional commitment to a 3rd year of support and strong institutional support of research, a focus on community health access and artificial intelligence and data sciences, institutional support for external experiences to enrich Scholar training, an “Affiliate” CATS Scholars that enhances the depth and breadth of the CCTS research community, engagement of former Scholars as mentors and advisors to the program through formal (peer review mentoring) and informal (networking) events, and a strong interactive career development program that interacts regularly with the three Chicago CTSA career development hubs. Further, UIC is a research-intensive institution with students and faculty from all backgrounds and a strong connection to our community through engagement, research, and healthcare delivery, and the scholars all benefit and collaborate within this community.

NIH Research Projects · FY 2026 · 2025-08

The overarching goal of this proposed Translational Resource Center, “Building Bridges Between Etiology/Epidemiology and Prevention of Substance Use Escalation: An Innovative Translational Resource Center,” is to catalyze innovative science to accelerate the translation of epidemiological research to prevention research and interventions designed to prevent escalation of substance use during the young adult years. Young adults aged 18-30 have often been overlooked in prevention efforts, despite being in the developmental age period when substance use peaks and substance use disorders usually emerge. The three most commonly used substances – nicotine, alcohol, and cannabis— escalate most during young adulthood, and nicotine vaping and cannabis use reached historically high levels in 2023. In addition, advances in reducing the escalation of problematic substance use during this age period have often been hindered by inefficient translation between substance use epidemiology/etiology and prevention research. We aim to serve as the translational bridge between epidemiology and prevention researchers by incorporating synergistic principles of community-engaged research, human-centered design, and implementation science to create and foster a collaborative and innovative research milieu that will advance substance use prevention, translational science, and health. We will consider a broad array of influences on substance use to enhance the relevance, informativeness, and impact of research. We will achieve these goals through our specific aims: 1) recruiting, engaging, and sustaining affiliate researchers from a broad range of disciplines to engage in collaborative team science focused on preventing escalation of substance use among young adults; 2) leading a set of interactive “Sandpit” meetings designed to encourage boundary-crossing ideation to delve into identifying predictors, mediators, and moderators of young adult substance use escalation and prevention implications; 3) hosting “datathons” that will focus on analyzing relevant datasets to deliver new insights about the escalation of substance use and its drivers; 4) creating and mentoring teams of affiliate researchers to provide ongoing guidance and resources for collaborative external research proposals; 5) Implementing a mentored Pilot Grant Program to enhance preliminary data leading to NIH grant applications; 6) developing educational resources hosted on a Center website that will serve as a national resource for researchers in the field; 7) disseminating broadly the resources and products of the Center; and 8) evaluating the impact of the Center to yield insights that will contribute to advancing the science of translation. Our ultimate goal will be to deliver innovations that further improve health and well-being and reduce the toll of problematic substance use among young adults.

NIH Research Projects · FY 2025 · 2025-08

Abstract COVID-19 increases the risk of vascular contributions to cognitive impairment and dementia (VCID). VCID is one of the most prevalent forms of dementia, so the potential public health impact of the COVID-19 pandemic on future VCID is substantial. However, the mechanisms by which COVID-19 modifies VCID are unknown. Identifying mechanisms that regulate how prior COVID-19 influences the brain endothelial cell response to vascular stress is important. Here, we provide preliminary evidence that COVID-19 decreases resistance to VCID by weakening the blood-brain barrier (BBB). This is accompanied by cerebrovascular inflammation. This grant will test the novel mechanism that SARS-CoV-2 infection accelerates VCID by suppressing cerebrovascular Wnt/β-catenin signaling. In Aim 1, we determine how prior SARS-CoV-2 infection influences BBB permeability and cognition upon subsequent vascular insult, by genetic and epigenetic modification. In Aim 2 we use endothelial-targeted genetic interventions to assess the contribution of Wnt/β- cat targets to resistance to post-infectious VCID. In Aim 3, we ask whether established post-infectious VCID can be reversed by increasing cerebrovascular Wnt/β-catenin. These studies could lead to novel approaches to identify individuals at high risk for VCID and novel potential therapeutic strategies to mitigate the impact of prior infection on the development of dementia.

NIH Research Projects · FY 2025 · 2025-08

Maternal iron deficiency anemia (IDA) is associated with maternal and infant mortality and profound perinatal and neonatal comorbidities, including adverse effects on offspring neurocognitive development and health. The use of oral prenatal supplements containing iron as a prophylatic approach to prevent IDA is suboptimal as evidenced by upwards of 18% of pregnant females still experiencing IDA despite being prescribed a prenatal supplement containing iron. Clearly, there is room for improvement and a need for novel and efficacious strategies to prevent the development of maternal IDA with a focus on those who are most vulnerable. Probiotics are “live micro-organisms which, when administered in adequate amounts, can confer a health benefit on the host”. There is increasing evidence that consuming the probiotic Lactiplantibacillus plantarum 299v (LP299V®) can enhance dietary iron absorption and improve iron status including in the context of pregnancy. The proposed study will be the first to test the efficacy of this accessible, low-cost, safe, innovative approach to optimizing iron status in individuals at risk for IDA in pregnancy [1st trimester hemoglobin (Hb) 11.0-11.9 g/dL and 2nd trimester Hb 10.5-11.5 g/dL]. We will conduct a prospective, double-blind, placebo-controlled randomized study of a commercially available oral LP299V® supplement taken twice daily with a standard prenatal supplement containing iron from 10-16 weeks gestational age (GA) until the time of labor in 200 individuals. Adherence will be monitored remotely by smart cap/bottle with associated researcher interface. We hypothesize that pregnant females consuming LP299V® will have stable or improved Hb and iron status parameters and lower rates of IDA at 24-28 weeks GA, 34-36 weeks GA and at the time of labor compared to participants taking a placebo and prenatal supplement with iron. We will extend findings to the neonate to determine if infants born to participants receiving LP299V®, compared to placebo, have superior markers of cord iron status and cord and heel stick Hb. We will explore intervention effects on infant neurodevelopment at birth using auditory brainstem response (ABR) testing. Lastly, we will examine gut microbial, placental and iron regulatory mechanisms through which LP299V® imposes its effect on iron metabolism. Our approach is rigorous given the double-blind placebo-controlled design and is comprehensive as we are: 1) targeting a sample of pregnant females at risk of IDA; 2) extending effects to the neonate; 3) determining mechanisms of effect and 4) exploring impact on child neurodevelopment. Our team is well positioned to successfully conduct the study given our history of collaboration and active perinatal research infrastructure. This trial has the potential to transform prenatal care and health outcomes for hundreds of thousands of pregnant females and their children in the U.S. annually and millions worldwide.

NIH Research Projects · FY 2025 · 2025-08

PROJECT SUMMARY/ABSTRACT The acute respiratory distress syndrome (ARDS) is a life-threatening condition that occurs frequently in critically ill patients. Sepsis and pneumonia are leading causes of ARDS, with methicillin-resistant Staphylococcus aureus (MRSA), a gram-positive, antibiotic-resistant bacteria, being a significant contributor. MRSA infection causes acute inflammatory injury to the lung (acute lung injury-ALI) that disrupts the vascular endothelial barrier leading to alveolar edema, a hallmark pathophysiologic feature of ARDS. Thus, the development of vascular-targeted therapeutic strategies aimed at restoring and preserving the lung endothelial barrier integrity is of critical importance for the effective management of ARDS. Sphingosine-1-phosphate (S1P) is an endogenous bioactive lipid that plays critical roles in regulating endothelial cell (EC) processes, including vascular barrier function. Lung EC predominantly express the S1P receptors 1-3 (S1PR1-3), where S1PR1 has a well-established role in in promoting barrier function, and S1PR3 is associated with barrier dysfunction. However, the role of S1PR2 remains much less well-defined. Our preliminary findings demonstrate that inhibition of S1PR2 exacerbates MRSA-induced lung injury in vitro and in vivo. Notably, S1PR2-deficient mice exhibit significantly worse injury compared to wild-type animals when infected with MRSA, while pharmacological inhibition of S1PR2 in human lung ECs exacerbates MRSA-induced lung barrier permeability. This proposal seeks to elucidate the novel mechanisms by which S1PR2 regulates vascular barrier function in response to MRSA-induced lung injury. Specific Aim 1 will investigate the effects of MRSA on the expression and subcellular localization of S1PR2 in lung ECs, as well as elucidate the role of S1PR2 in regulating endothelial injury caused by MRSA. Using advanced assays to assess barrier function and vascular permeability, key processes in ARDS pathophysiology, we will evaluate the effects of S1PR2 expression and activity on lung vascular function. Additionally, we will examine the potential key role of the transcription factor KLF4 in mediating S1PR2 effects through regulation of junctional proteins essential for endothelial barrier stability. Specific Aim 2 will determine the role of S1PR2 in MRSA-induced ALI in vivo. We will compare the injury responses in S1PR2-deficient and wild-type mice infected with live MRSA, evaluating multiple indices of lung injury. This aim will also utilize RNA sequencing to identify genetic differences between these two strains, providing insights into S1PR2-dependent pathways. Additionally, pharmacological inhibition of S1PR2 in C57BL/6 mice and endothelial specific S1PR2 knockdown will further clarify its role in vascular barrier regulation. This research will be conducted at the University of Illinois Chicago in the Division of Pulmonary, Critical Care, Sleep and Allergy. By advancing our understanding of endothelial barrier function in the context of MRSA-induced lung injury, this work will provide a foundation for my K99/R00 award application and facilitate my transition to independent investigator status.

NIH Research Projects · FY 2025 · 2025-08

Project Summary: Even in a developed country such as the United States, Salmonella enterica serovar Typhimurium (STm) infects 1.35 million people every year. Infection with STm causes acute intestinal inflammation and the disease can progress to life-threatening bacteremia in vulnerable populations. Numerous factors, including host immune status, gut microbiome composition, and co-infections with other pathogens, influence the pathogenesis of STm. Gut microbiota-derived metabolites such as short-chain fatty acids and secondary bile acids also significantly impact STm infection. We recently discovered that arginine, a semi- essential amino acid, increases STm virulence and its dissemination to peripheral organs. Arginine availability in the gut lumen depends on the diet and contributions from the gut microbiota and the host. We uncovered an additional source in the gut: commensal fungi. We showed that Candida albicans, a fungus present in 60% of people, increases de novo biosynthesis of arginine in the presence of STm and release millimolar amounts of arginine in the extracellular environment. In addition, the frequent use of arginine as a dietary supplement to ameliorate cardiac health issues also influences arginine availability in the gut. STm is therefore likely to encounter varying amounts of arginine when infecting a human. However, there is a huge knowledge gap in understanding how gut arginine metabolism influences pathogenesis of enteric pathogens such as STm. The main goal of this proposal is to understand how arginine availability modulates the gut environment in a way that results in increased STm virulence. We hypothesize that an increase in arginine will increase Salmonella pathogenesis by two mechanisms: (Aim 1) direct utilization of arginine by STm, gut microbiota, and host and (Aim 2) modulation of the host immune response by arginine. In particular, in Aim 1, we will dissect the contributions of arginine utilization by determining whether STm arginine catabolism is required for its pathogenesis in vivo in the gut; by identifying if arginine opens the niche for arginine-utilizing gut microbiota that influence Salmonella pathogenesis; by determining if the host utilization of arginine contributes to the increased pathogenesis of Salmonella. In Aim 2, we will investigate how arginine influences the immune response to STm infection. Our preliminary data showed a dampening of the immune response during STm infection. We will characterize immune cell recruitment to the gut and establish an in vitro model recapitulating the blunted immune response to STm infection in the presence of arginine. We will further determine the molecular mechanism behind this modulation of the immune response. This proposal will be a foundational study to understand if similar mechanism exist for other enteric infections such as EHEC. Executing this research program at the University of Illinois at Chicago (UIC) will allow the candidate to establish as an independent researcher and securing a tenured faculty position at a major research institution.

NSF Awards · FY 2025 · 2025-08

Tools that create visualizations of data are increasingly important for discovery and decision-making in a range of domains, from science and engineering to commerce. Data analysts use these tools to rapidly slice and dice their data, often inspecting a large number of visualizations in the process. Though useful for exploration, these visualizations can also expose random data fluctuations, which could be mistaken for real patterns. If analysts are not careful in interpreting these apparent patterns, they could inadvertently make false discoveries or take incorrect decisions. The goal of this research is to reduce the risk from spurious patterns arising in interactive data analyses. The project comprises three stages: (1) developing techniques for capturing analyst beliefs, expectations, and intentions as they conduct visual analysis; (2) using this data to develop algorithms that forecast the reliability of emerging visualizations; and (3) evaluating strategies for communicating the risk of false patterns. The resulting techniques will be validated and incorporated in tools for detecting RNA modifications from noisy sequencing data, in collaboration with bioinformatics researchers. The expected impact of this project is to aid analysts in assessing the reliability of insights, while guarding against visualizations that seem convincing but that are likely to be misleading. This in turn could broaden the adoption of visual analytics tools, increase the confidence in conclusions, and potentially reduce the incidence of false discovery. As part of this research, the team will develop interactive educational materials for training students in reliable data-driven inference. These learning modules will be disseminated in a format that allows customization by data science instructors for inclusion into existing curricula. Lastly, the project will provide opportunities for graduate research training and incorporate K-12 outreach activities that introduce young learners to data science. The project comprises three main activities: (1) Prototyping techniques to incrementally elicit analysts' belief and prior knowledge as they make sense of data. The elicited knowledge will then be used to distinguish between a gamut of intentions: from planned analyses with substantive hypotheses, to purely exploratory actions with minimal expectations. (2) The project will next develop a model to predict the reliability of apparent patterns and insights unearthed at different points in the analysis cycle. To build this model, the research team will use a variety of features, including the specificity of analyst intents, the degree to which their expectations are borne out in the data, as well as their behavior and interactions with visualizations. The elicitation techniques and the insight reliability model will then be refined in a series of visual analysis studies and through crowdsourced experiments, in which participants' declared priors and discoveries are used to improve the accuracy of the model in forecasting spurious patterns. Lastly, (3) the project will identify and characterize strategies for communicating the risk of spurious insights to analysts in real time. In particular, the team will evaluate techniques for directly visualizing risk indicators, as well as indirect methods whereby the visual encodings of the data will be adjusted depending on how risky it is predicted to be. The developed interventions will be evaluated both in experiments and in a bioinformatics application, to assess whether they reduce the rate of false discovery. The expected results include new methods for eliciting analyst beliefs, techniques to forecast and communicate the trustworthiness of insights, and instructional materials for teaching robust data analytic practices. The products will be disseminated in publications, and in the form of open-source software and learning modules. 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

Commutative algebra studies mathematical structures such as the integers and polynomials, and has broad applications in computer science, engineering, and other areas of mathematics. Execution of the planned research will deepen the theoretical foundations of the field and address problems in related disciplines such as algebraic geometry, which studies the geometric objects associated to polynomials. A central focus of this research is on singularities, or points where the geometric objects behave irregularly (for example, a curve crossing over itself), using techniques from modular arithmetic (also known as clock arithmetic or prime characteristic algebra) and mixed characteristic settings (where a prime is treated as a variable). These approaches, including the use of perfectoid algebras, help bridge distinct mathematical worlds and enhance our understanding of both. In addition, the principal investigators are dedicated to promoting mathematics education, developing future generations of researchers, and assisting in building a strong STEM workforce in the US. Towards these goals, the principal investigators will supervise, train, and mentor graduate students and postdoctoral fellows. The principal investigators will also facilitate seminars and workshops for undergraduate and graduate students. Recent advances, including past efforts of the principal investigators, have inspired a rapidly-emerging theory of singularities in mixed characteristic, bridging the existing notions from classical complex geometry defined using resolutions of singularities with those in positive characteristic commutative algebra that utilize Frobenius splittings and tight closure theory. Establishing finiteness properties is a crucial component in the study of singularities across characteristics. In prime characteristic, the principal investigators will study finite generation of the anticanonical algebra for certain singularities defined by Frobenius, and the existence and properties of boundary divisors in both prime and mixed characteristics, which in turn can be used to prove strong finiteness conditions. The investigators will also research log canonical singularities and ideal closure operations in the complex setting, better definitions of F-pure pairs in prime characteristic, and the theory of singularities outside the F-finite setting in prime characteristic. 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

Artificial intelligence (AI) and generative AI tools such as large language models (LLMs) are developing faster than many K-12 schools can keep pace. This issue creates challenges for schools, especially in small districts, to quickly design or adopt resources to help their students and teachers understand AI concepts, use AI responsibly and recognize ethical issues associated with AI. This project partners a small suburban school district and university AI education experts with the goal of creating AI resources and a curriculum to help students and teachers effectively integrate AI into their work. This partnership approach will help ensure a meaningful broader impact of the work on the school and surrounding community, where infusing these 21st century skills into learning will have long-term impacts on the future workforce. All materials developed in the project will be made freely available to the public to adopt or adapt to meet their needs. The partnership model for developing an AI curriculum will also build a greater scientific understanding of how to work together to meet the needs of a community that may be applied to other emerging technologies such as quantum computing and fusion energy. The curriculum developed will also provide a road map to build theory on organizing learning goals around AI, and other future technologies, that use a long-term partnership approach. The long-term outcomes of this project will impact knowledge and practice of building the technological literacy of the American public. In this Partnership Development proposal, the long-term goal is to build a lasting research practice partnership (RPP) for modern computer science education initiatives. The rapid onset of AI, and generative AI tools such as LLMs, amplify the need for AI literacies, including concepts, practices and ethics, for K-12 schools. Some AI literacy resources, such as AI4K12 and AI4ALL, have emerged, but it may be challenging for schools, particularly those in small districts, to navigate these resources. Furthermore, researchers need further guidance on how to support schools for AI literacy. These challenges for schools and researchers include how to coordinate planning across teachers, school leaders and researchers, how to implement across grade levels, classrooms, and content areas; how to provide training and preparation time to support lesson design and implementation; and how to support teachers in their own AI literacy. To address these needs, district leaders and teachers from Forest Park School District (FPSD) and researchers from the University of Illinois Chicago will engage in a one-year research practice partnership development to build a long-term RPP, co-design an AI literacy curriculum, and support professional development to implement the curriculum. This work will contribute to scientific understanding of how an RPP can be applied quickly to meet the challenges of rapidly evolving technology and provide structured road maps for developing technology literacy curricula for emerging and new learning objectives that can be applied to AI and other emerging technologies. This approach will demonstrate how integrating long-term planning with curriculum maps and scope and sequence guides with day-to-day lesson planning can foster cross-district buy-in for multiple stakeholders. The work will also have broader impacts on the surrounding community by creating curricular materials that benefit students and teachers at FPSD in developing the AI literacy skills essential to building 21st century skills. The Discovery Research preK-12 program (DRK-12) is an applied research program that seeks to significantly enhance the learning and teaching of science, technology, engineering, and mathematics (STEM) by preK-12 students and teachers. Projects in the DRK-12 program build on fundamental research in STEM education and prior research and development efforts that provide theoretical and empirical justification for funded projects. 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

Hodge theory is a branch of mathematics developed in the first half of the 20th century, which aims to study the non-linear geometry of shapes using linear invariants. More precisely, the shapes are complex projective manifolds and the linear invariants are Hodge structures. The famous “Hodge conjecture”, first presented in 1950 at the International Congress of Mathematicians, states that the essential geometry of a complex projective manifold is recovered by its Hodge structure. As one of the Millennium Prize Problems, this conjecture has attached to it a one million dollar prize for a solution. While complex projective manifolds involve a bit of abstraction to define, they are fundamental objects in mathematics and physics; for example, the “Calabi-Yau varieties” are a certain class of complex projective manifolds which can appear as the small dimensions of the universe in string theory. The main research goal of this project is to study the Hodge structures of Calabi-Yau varieties—to both gain insight into Hodge theory more generally for all complex projective manifolds, and to increase the depth of our understanding of Calabi-Yau varieties. Beyond pure research goals, the educational impact will be to develop an active community of young researchers and PhD students focusing on this circle of ideas. The project will continue lines of research of the PI on toroidal compactifications of Calabi-Yau moduli. Recent joint work of the PI with V. Alexeev constructs a modular toroidal compactification of the moduli space of degree 2d polarized K3 surfaces. One research goal is to extend this work to hyperkahler and Calabi-Yau varieties, with an eye towards understanding the combinatorial structure of degenerations. Additionally, the project aims to study and prove general results concerning variations of Hodge structure (VHS). Joint work of the PI with S. Tayou is advancing our understanding of finiteness properties of Z-polarized VHS, and it now seems within reach that conjectures of Deligne and Simpson on the algebraicity of the non-abelian Hodge locus can be resolved. The approach is novel, incorporating ideas from hyperbolic geometry. The PI will also pursue results about period mappings for Calabi-Yau variations of Hodge structure, such as questions of boundedness of moduli of Calabi-Yau varieties of various classes, and under what circumstances Torelli theorems hold. 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

When an elongated material sample is pricked at two opposite ends, induced mechanical stress will lessen in the sample interior. As a result, information about specific location and arrangement of those concentrated forces applied to the sample cannot be recovered by measuring deformation far away from the loaded ends. This award supports fundamental research that seeks to demonstrate novel materials, with engineered internal structure, able to transfer in full information about loading conditions from their boundaries and throughout the material interior. These materials look to feature a unique combination of useful mechanical properties not realized previously. Most interestingly, while keeping the overall amount of information constant, they could also modify it from point to point inside the material similar to as information is processed by a quantum computer. As a result, knowledge obtained could potentially help to build inexpensive quantum computers, advancing the national prosperity, welfare and technological superiority. The project will also provide opportunities to educate and train both graduate and undergraduate students in the inter-disciplinary area of metamaterials, micromechanics, lattice mechanics and computational mechanics by performing research in the PI’s lab. Realization of the Saint-Venant’s principle in conventional materials can be viewed as disappearance of higher harmonics in Fourier series decompositions of displacement fields when the distance to the load increases. This phenomenon could be understood as a loss of information in the material interior about any loading conditions or deformation profiles imposed at a material boundary. On the contrary, the proposed research intends conceptualize a class of mechanical metamaterials, where all the Fourier harmonics are preserved in the displacement fields, and the information about any boundary loads is fully preserved in the material interior. Most interestingly, mechanical deformation in some of these materials is anticipated to be governed by a unitary transfer matrix, a mathematical formalism that connects the states of polarization in the Fourier harmonics of stationary deformation profiles at different spatial positions in the material interior. This transfer matrix will also feature all the formal mathematical properties of a quantum operator. Actual material designs plan to be demonstrated, where the transfer matrix takes the form of an important quantum gate operator. Effective mechanical properties of these material systems will be investigated systematically in conjunction with the corresponding quantum phenomena they can represent. Open-source simulation tools to illustrate and interpret mechanistically, using a human-scale material structure, the action of several most common quantum gates will be developed and made available to the public. 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.