University Of South Florida

NSF Awards · FY 2026 · 2026-10

This Research Experiences for Undergraduates (REU) Site award funds a renewal of a site focused on cryptography, coding theory, and quantum computing at the University of South Florida. Modern life depends on the secure movement, storage, and processing of digital information. Cryptography protects the confidentiality, integrity, and authenticity of data, while coding theory helps preserve data when noise, transmission errors, or equipment failures occur. These areas are increasingly shaped by the rise of quantum technologies, which create both new opportunities and new threats to digital security. The project’s novelties are the integration of cryptography, coding theory, and quantum computing within a single undergraduate research program, the use of research teams that pair undergraduates with faculty and near-peer mentors, and an expanded scope that connects foundational mathematics with applications to national security, secure communication, and privacy in emerging technologies. The project's broader significance and importance are that it helps prepare a future workforce with the technical depth needed to address pressing challenges in cybersecurity, quantum information, and trustworthy data-driven systems. For each of three summers, this REU Site offers 10 undergraduate students the opportunity to perform research for 10 weeks under the mentorship of an interdisciplinary team with expertise spanning mathematics, computer science, engineering, and physics. This REU Site focuses on active and interdisciplinary research problems in post-quantum cryptography, quantum error correction, and related areas of coding theory and quantum information. Students investigate cryptographic constructions based on code equivalence and lattice isomorphism, including algorithms, security analysis, and implementation issues relevant to future quantum-resistant systems. Additional projects study quantum low-density parity-check codes and decoding failure mechanisms, the design of highly nonlinear functions for block ciphers, locally recoverable codes for distributed storage, physical models for reliable qubit implementation, and privacy-preserving methods for collaborative training of artificial intelligence models. The site combines these research activities with technical training, mentoring in computational tools, workshops on intellectual property and graduate school applications, and a summer symposium in which participants present their results. 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 2026 · 2026-07

Different species often arrive at similar solutions to recurring challenges through convergent evolution. Such events provide some of the strongest examples of adaptation, yet understanding the molecular mechanisms and constraints that result in such convergence has only recently become possible due to advances in computing and genomics. Among animals, traits such as flight have arisen independently numerous times (e.g., in lineages giving rise to birds, bats, and insects), defining the ecologies and enabling the success of the resulting species. Similarly, venoms have arisen independently more than 100 times in animals and play diverse roles in, for example, predation and defense. These recurring traits represent optimal systems for investigating the rules and limitations of how evolution can yield complex adaptations, a major open challenge in evolutionary biology. This project will use integrative approaches including AI in multiple venomous animals to understand how complex traits repeatedly arise and evolve. Such an approach will enable not only the identification of how complexity originates but also catalyze future biotechnological innovations in the bioeconomy by uncovering functional solutions to common problems across the Tree of Life. Convergent evolution is a hallmark of adaptation and provides a means for delineating the roles of genetic and functional constraints in determining evolutionary trajectories. Venoms are one of the most common and convergent functions among animals, with more than 200,000 venomous species from more than 100 venom-origin events, and venom function requires recurrent evolution of specialized tissues and gene-regulatory networks to express, process, secrete, and store toxins. Substantial convergence in recruited protein families, tissues of origin, and contributing gene-regulatory networks has been observed, yet venoms are exceptionally variable at all taxonomic levels. Venoms therefore represent a unique opportunity for discerning rules and idiosyncrasies of complex trait origin and subsequent evolution under parallel constraints. Eighteen species representing three independent venom origins in centipedes, scorpions, and snakes will be used to investigate the impacts of deep evolutionary events during trait origins on ongoing complex trait evolution. A hierarchical phylogenetic framework will be used to link macro- and microevolutionary processes, focusing on how deep-origin events bias evolutionary trajectories. Overall, our sampling strategy will allow us to bridge macro- and microevolutionary processes and investigate convergence at multiple biological (genome, tissue, organismal) and phylogenetic (within species, across species, and across lineages) scales, specifically focusing on how trait origin and secondary innovation events influence ongoing evolution among close related 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.

NIH Research Projects · FY 2026 · 2026-06

Project Summary Natural products have a long history of use in biomedical studies of physiological pathways but have recently declined as a proportion of small molecules entering the clinic. Among the serious challenges of natural product discovery studies is ensuring a reliable supply of products for developmental studies, the re-isolation of known and well-studied chemotypes, and mitigating undesirable toxicities. Among solutions to these problems include biological and chemical synthetic strategies for abundant supply, seeking new unstudied or understudied biodiversity as sources of natural products to reduce the re-isolation of known chemotypes, and diversification of natural product analogs to produce new compounds with modulated toxicity and enhanced drug-like properties. This project executes a deep dive into the synthetic biology and genome engineering of an important natural product chemotype that displays a unique and promising bioactivity profile. Progress in this effort will not only address our knowledge gaps in polyketide biosynthetic pathways, but inform biomedical applications of small molecules with similar bioactivity profiles. Additional natural product chemotypes will be developed from biodiversity that has had little prior exploration. These organisms include marine invertebrates from Antarctica and the deep-sea, which are largely understudied due to the difficulty of accessing and working in those environments. Metabolites discovered in these studies will be diversified through analog synthesis to fully probe their potential for biomedical utility while minimizing off target bioactivity and toxicity. Natural products and their derivatives with promising bioactivity profiles will be further studied in compound development initiatives to assess their drug-like properties.

NSF Awards · FY 2026 · 2026-06

Engineers use life-cycle assessments to analyze the total impacts and costs of manufacturing facilities over their lifetimes. These assessments are challenging because manufacturing facilities experience changes in the resources they consume, operating conditions, and costs. Facilities also are susceptible to unexpected disruptions such as power outages, floods, or public health crises. This CAREER project will develop a reliable and adaptable way to evaluate the environmental sustainability of manufacturing systems. It will combine real-time operational data with advanced analytical tools that can respond to changing conditions. The outcome of this project will inform manufacturers, so that they can design environmentally sustainable systems. The project will help train engineering students in the assessment of environmental impacts. The project will offer a “Rising Innovators” engineering camp for elementary and middle school students in the Tampa Bay region. The project will promote environmental literacy and create pathways into engineering. It will also help equip the next generation of sustainability and manufacturing engineers with tools to establish resilient manufacturing systems. The goal of this project is to improve the reliability of environmental sustainability assessments and support adaptive decision-making in net-zero manufacturing systems. The project will integrate real-time process data and probabilistic modeling via Bayesian inference. The research objectives are to 1) establish an uncertainty-resilient framework for life cycle environmental and economic assessments, 2) understand the limitations of achieving net-zero energy in discrete manufacturing systems, and 3) train the next generation of sustainability engineers. The uncertainty-resilient framework will be tested on a pultrusion-based recycling system that produces filament for additive manufacturing from post-consumer plastics. The framework will include production monitoring, life cycle assessment, and probabilistic modeling. This research will generate new insights into the effect of system-level variability on environmental trade-offs and production resilience. It will also dynamically reduce uncertainty and support decision-making under evolving conditions. 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 · 2026-05

Summary The maternal-fetal interface in eutherian mammals is a uniquely complex immunological environment, tasked with the dual challenge of maintaining immune tolerance to the semi-allogenic fetus while mounting robust defenses against pathogens. Central to this protection are trophoblasts, the placental barrier cells, which constitutively secrete type III interferons (IFNLs) to restrict viral infections within the placenta and adjacent maternal tissues. Recent discoveries have highlighted that two lineage-specific placental miRNA clusters— primate-specific C19MC and rodent-specific C2MC—have independently evolved to be enriched with short interspersed nuclear elements (SINEs), such as Alu or B1 repeats. These SINE-rich regions produce double- stranded RNA (dsRNA) that triggers a viral mimicry response, activating IFNL signaling and conferring potent antiviral protection independent of classical miRNA pathways. Despite the conservation of this mechanism across species, critical gaps remain: specifically, how C19MC-derived Alu dsRNA is sensed by human trophoblasts and how this process shapes antiviral immunity at the maternal-fetal interface. To address these questions, the Totary-Jain and Coyne laboratories have joined forces to elucidate the mechanisms by which human trophoblasts constitutively produce IFNLs and defend against viral threats. Their central hypothesis posits that SINE dsRNAs derived from C19MC (in humans) and C2MC (in rodents) are recognized by distinct cellular sensors in trophoblasts, leading to the sustained release of type III IFNs. The project is organized around two specific aims. Aim 1 will define the mechanisms by which C19MC-derived Alu dsRNA is sensed and drives cell type-specific IFNL release from human trophoblasts, using advanced organoid models and genetic tools to pinpoint the relevant sensors and signaling pathways. Aim 2 will investigate the role of C19MC in placental antiviral defense and barrier integrity in vivo, leveraging innovative mouse models. Collectively, these studies aim to uncover how human C19MC orchestrates IFNL-mediated antiviral defenses, preserves placental barrier integrity, and prevents congenital viral infections, ultimately paving the way for novel strategies to bolster placental immunity.

NIH Research Projects · FY 2026 · 2026-04

Project Summary/Abstract: Traumatic brain injury (TBI) affects over 2.87 million people annually, with nearly 50% reporting chronic psychological health conditions (PHCs), including sensory, cognitive, and sleep deficits, which often differ between men and women. The most common pathology associated with TBI is diffuse axonal injury (DAI), leading to chronic neurodegeneration and maladaptive circuit reorganization. PHCs are strongly linked to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates corticosterone (CORT) in rats. Dysregulation of brain glucocorticoid receptors (GR) impairs HPA axis feedback, disrupting neuroplasticity and reducing the efficacy of rehabilitation (Rehab). While the connection between HPA axis dysregulation and neuroplasticity is known, the specific impact of TBI-induced HPA axis dysregulation on neuroplasticity, Rehab efficacy, and sex differences remains poorly understood. Published and preliminary data from our lab indicate that early circuit-directed Rehab reduces the severity of late-onset sensory deficits and addresses chronic HPA axis dysregulation. The goal of this proposal is to evaluate how TBI-induced HPA axis dysregulation affects neuroplasticity and the long-term efficacy of Rehab initiated after sensory deficits are established, focusing on sex differences. We hypothesize that TBI causes sex-dependent HPA axis fluctuations, resulting in temporal shifts in circulating CORT and brain GR levels, which influence neuroplasticity and Rehab efficacy. We will test this hypothesis in the following proposed aims using a midline fluid percussion injury (mFPI) model in male and female Sprague-Dawley rats. Aim 1: Establish a comprehensive profile of sex-dependent HPA axis dysregulation and neuroplasticity between 1- and 3-months post-injury. Aim 2: Quantify the short-term efficacy of circuit-directed Rehab administered during HPA axis fluctuations on the upregulation of BDNF in sensory circuits. Aim 3: Assess the long-term efficacy of Rehab, administered during HPA axis fluctuations, on the severity of sensory sensitivity and associated circuit structure and function. These experiments will elucidate how TBI-induced HPA axis fluctuations impact neuroplasticity and Rehab outcomes. By examining sex differences in these processes, this study aligns with NIH’s focus on women’s health research (NOT-OD-24-079) and will guide the development of more effective, sex-specific rehabilitation strategies for TBI patients. Impact: The findings have broad implications for improving patient outcomes and quality of life, providing a foundation for future studies aimed at optimizing Rehab for TBI-related conditions.

NIH Research Projects · FY 2026 · 2026-04

SUMMARY Recent setbacks in malaria control have led to a significant rise in global malaria incidence. While Plasmodium falciparum remains the predominant malaria parasite, non-falciparum species are increasingly recognized. Among them, Plasmodium malariae is the second most common malaria parasite in Africa; yet its epidemiology remains poorly understood and likely underestimated due to inadequate diagnostic tools. This parasite exhibits a highly patchy and seasonal distribution, and ecological factors appear to play a crucial role in its transmission. Studies in Cameroon have revealed a P. malariae prevalence ranging from 0 to 32%, mainly as mixed infections with P. falciparum. Our study in Bangolan, a lakeshore area in the Northwest Region, identified P. malariae in 100% of malaria cases, with 93.6% being mixed infections. Building on these findings, we aim to test the hypothesis that the patchy distribution and seasonal variations of P. malariae are driven by specific ecological factors. Specifically, we will (1) assess the spatial distribution and seasonal trends of P. malariae in Bangolan through molecular surveillance by conducting repeated, cross-sectional, community-based and hospital-based surveys; and (2) conduct comprehensive vector surveillance to investigate the ecology, species diversity, seasonal patterns, and competence of malaria vectors. By uncovering key transmission reservoirs and vectors, this research will provide essential insights into P. malariae epidemiology, paving the way for targeted control strategies against this neglected parasite.

NSF Awards · FY 2026 · 2026-03

An integrated sensing and communication (ISAC) system design is important for delivering the quality-of-service needs of emerging wireless services (e.g., digital twins) over 5G and beyond cellular systems. Although ISAC system design provides a variety of benefits (e.g., spectrum efficiency, and reduced hardware complexity), it introduces several unique privacy and security challenges due to their dual-purpose nature (i.e., using one signal for both sensing and data transmission) and shared resources (e.g., frequency and hardware). First, ISAC signals used for both sensing and communication can be intercepted to extract sensitive information, such as environmental data or user location. Second, attackers can tamper with sensing signals to deliver false data or manipulate the communication link, disrupting system operations. To address these challenges, this project develops privacy-preserving and secure ISAC system. The project's broader significance and importance are transforming wireless systems into multi-functional networks and improving the security and privacy ISAC systems. The project integrates research insights into new networking courses and hosts outreach activities. The US-Germany collaboration will foster an international transfer of expertise across the aforementioned areas, thus ensuring broad societal and technological impacts. The joint US-Germany project develops a holistic zero trust ISAC framework that utilizes radio frequency based communication and sensing functions for confidentiality preservation, transmitter and receiver secure authentication, and data communication privacy protection via 1) designing a novel secure authentication framework to ensure the integrity of wireless ISAC devices in zero trust environments; 2) creating a suite of effective tools to achieve the confidential wireless channel to conceal sensitive information, even when an eavesdropper knows the keying information for encoding; 3) developing novel information bottleneck and neural network based data transmission system for both sensing and communication data privacy protection; 4) building an open-source software platform and hardware testbed to validate the zero trust wireless ISAC solutions. This project provides a rich environment and platform that facilitates educating and training students at multiple levels. 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 2026 · 2026-02

Tiny insects are surprisingly good flyers, but their aerodynamics are poorly understood because they are so small. Understanding their flight aerodynamics and abilities could lead to improved micro-aerial vehicle designs and new control strategies for agricultural pests. Measurements of the flow around flying tiny insects could help, but measurements are challenging because of the insects’ small size and because they beat their wings hundreds of times per second. This project will develop and validate a new approach to measuring flow based on techniques that improve imaging at small scales. The approach will be applied to measure the flow around a variety of tiny insect species. Results will lead to new understandings about tiny insect flight aerodynamics. This project also includes development and dissemination of new flow measurement software and mentoring of undergraduate and graduate students in an interdisciplinary environment that blends fluid dynamics, biology, computational imaging, and artificial intelligence. This project will support the advancement of artificial intelligence and advanced manufacturing of aerodynamic vehicles. The aerodynamics of tiny insect flight is poorly understood but is thought to rely on drag and unsteady flow for lift generation. Flow measurements of freely flying insects are needed to elucidate their aerodynamics and validate prior computational models, but such measurements are challenging owing to the minute time and length scales of tiny insect flight. The objective of this project is to develop and validate a brightfield micro-particle image velocimetry system capable of performing these measurements. Crucially, this system incorporates insights from the field of imaging inverse problems to address one of the biggest shortcomings of brightfield micro-particle image velocimetry systems, namely a low signal-to-noise ratio arising from the out-of-focus particles along the line of sight. This novel system will be validated using experiments that compare measured velocity profiles in milli-fluidic channels to analytically known solutions at various magnifications. The validated system will then be automated and extended to enable it to perform three-dimensional flow measurements. Finally, this technique will be applied to measure the flow around five tiny insect species that fly at various Reynolds numbers with different wing morphologies. The knowledge gained from this project may lead to improved designs for tiny micro-aerial vehicles and to better control strategies for agricultural pests. 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 · 2025-12

Over the past two decades, the use of biometric recognition such as fingerprint or facial recognition, has grown significantly and found applications worldwide due to its ability to provide accurate authentication and convenient user experiences. However, ongoing issues related to privacy and security have emerged, raising concerns within both the scientific community and the general public. Balancing these concerns without compromising system security and performance is a significant challenge. The goal of this NSF CAREER research project is to investigate biometric system security vulnerabilities and develop template data protection mechanisms to enhance the safety and privacy of these systems. The proposed effort also includes educational and outreach activities: Youth Cybersecurity Research (YCR), a program to match interested high school students with faculty with shared research interests; Datathon, an annual full-day focused on the intersection of cybersecurity and biometrics; a student context at a major Biometrics conference; and development of new course materials related to biometric security, for use in both existing and new courses. The goal of this project is to develop a comprehensive and standardized framework for analyzing both hardware and software attacks on biometric systems while addressing issues of fairness and bias. The research focuses on two main thrusts: investigating vulnerabilities and developing robust countermeasures. This project aims to establish a research infrastructure that identifies unexplored vulnerabilities of biometric systems, such as side-channel and hardware fault injection attacks, as well as leakage through bias sources. It also seeks to develop a general evaluation methodology for side-channel attacks in biometrics, including metrics, protocols, and result-reporting procedures. Additional avenues of exploration include developing scalable and universal approaches to enhance existing anti-spoofing biometric techniques and to deepen the understanding of ethical considerations in biometric security. This exploration can lead to advancements in biometric security and contribute to the knowledge base surrounding the protection of sensitive biometric information. 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 · 2025-11

This incubation project provides scientists with a platform to develop best practices for the use of generative artificial intelligence (GenAI) in research. The project will identify Questionable Research Practices (QRPs) as they pertain to the use of GenAI with the aim of enabling researchers to avoid these problematic practices. The project will inform policies and training on the use of AI in academic publishing. The project also contributes to the development of training approaches for graduate students and early career researchers on responsible research practices pertaining to GenAI. The project examines how GenAI is being used in academic publishing with a focus on QRPs that researchers may confront. The project will generate a taxonomy of AI-related QRPs in academic publishing. The project team will develop the taxonomy by conducting a Delphi study, which is equivalent to an iterative asynchronous focus group that involves building systematic group consensus. Delphi study participants include editors, editorial board members, and contributing authors from behavioral and cognitive science journals. In addition to these perspectives, the taxonomy will be informed by a linguistic analysis of publisher policy documents and ethical guidelines, and a comprehensive review of AI-related literature across the social sciences. 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 · 2025-11

PROJECT SUMMARY A recent study involving whole-exome sequencing of 640, 000 human subjects showed that variant of anoctamin (ANO4) gene is linked with human obesity. Our lab revealed that Ano4, a calcium-activated chloride channel, is highly expressed in the ventromedial hypothalamic nucleus glucose-inhibited neurons but minimal in glucose- excited neurons. Furthermore, Ano4-mediated currents are functionally required for their activation in response to low glucose. In a brain-wide mapping of Ano4-expressing neurons, I found that many area postrema (AP) neurons express Ano4 (APAno4 neurons). In a pilot study, I found that genetic deletion of Ano4 specifically in the AP results in decreased body weight and low blood glucose levels. Additionally, chemogenetic activation of APAno4 neurons promotes feeding and increases blood glucose levels. Asprosin is a hunger-induced glucogenic and centrally acting orexigenic hormone, and protein tyrosine phosphatase receptor δ (Ptprd) serves as the asprosin receptor in the brain. My preliminary data showed that APAno4 neurons express Ptprd, and asprosin can activate APAno4 neurons, but the effect is largely abolished by the Ano blocker CaCC(inh)-A01. Here I put forward a general hypothesis that the Ano4 channel in the AP is required for orexigenic action of asprosin. In the Aim 1 of the proposal, I will continues to probe the physiological functions of APAno4 neurons in the contexts of type 1 diabetes and diet-induced obesity - whether loss-of-function of Ano4 would alleviate hyperglycemia and obesity. Ano blocker CaCC(inh)-A01 was show to attenuate diet-induced obesity, but whether the effect is specifically mediated by APAno4 neurons is still unknown. Thus, I will test the effect the CaCC(inh)-A01 when APAno4 neurons are activated. Since APAno4 neurons express Ptprd, in the Aim 2, I will characterize the metabolic phenotypes of mice with deletion of Ptprd in APAno4 neurons. Asprosin can activate APAno4 neurons during brain slice recording, but it is not known if Ano4 in the AP is required for asprosin’s action in vivo. Toward this, I will test the effect of asprosin in mice when Ano4 are deleted in the AP. Furthermore, I will also characterize the cellular functions of APAno4 neurons (e.g., Ano currents, sEPSC and sIPSC) in response to asprosin when Ptprd or Ano4 is deleted. Overall, these proposed studies will reveal Ano4 in the AP as a potential target for treating obesity and associated complications, and further unravel the role of Ano4 in mediating asprosin’s action. In addition, this project will provide an ideal training opportunity to prepare me for an independent research career focusing on the central regulation of energy and glucose homeostasis, in particular on the circulating hormones and chemicals regulating neuronal activity and their roles in metabolic control.

NSF Awards · FY 2025 · 2025-10

Barrier island breaches have occurred during many tropical storms, constituting a major mechanism for tidal inlet formation, dune and beach erosion and development. Thus, they represent a major challenge to coastal management. The current understanding of the fate, physical processes, and impacts surrounding new and evolving breaches is limited due to the lack of comprehensive longitudinal studies capturing the breaching event and post-breaching evolution on monthly and annual time scales in a holistic and transdisciplinary manner. To address the current gaps in knowledge and data, this EArly-concept Grant for Experimental Research (EAGER) study investigates the development of two barrier island breaches from their original formation over multiple seasons and years, and their potential impacts on coastal management and infrastructure systems. The "high-risk high-outcome" study is expected to reveal new insights into the roles of hydrodynamics, land coverage, and geomechanical sediment properties on barrier island breach evolution, as well as into the impacts of these newly formed inlets on coastal infrastructure systems. It looks to unravel the importance of barrier island breach data collection for informed coastal management, planning, engineering design, and decision-making in coastal regions affected by storms. The data are expected to become a benchmark data set that will serve the wider coastal research community for calibration and validation of numerical and physical models and the development of new concepts, relationships, and theories regarding the geomorphological evolution of storm-induced barrier island breaches, local hydrodynamics, surrounding sediment and land-use conditions, coastal infrastructure, and the built environment. Midnight Pass breach in Venice, Florida, and Milton Pass breach in Englewood, Florida, opened during the 2024 sequence of Hurricanes Helene and Milton and are located in the same geological and meteorological region. The two inlets will be investigated with focus on post-breach geomorphodynamics driven by small-scale variability in hydrodynamics, sediment properties, geomorphology, vegetation, and anthropogenic influences from engineering actions and land use. The study seeks to leverage and extend the interdisciplinary field data collections following the storms and in 2025, complementing the effort with analyses and initial application to existing numerical models. The project intends to also test and assess newly emerging instrumentation and cross-disciplinary data collection strategies for storm-related geomorphodynamics and infrastructure system performance research. The study seeks to build on and strengthens an interdisciplinary network of natural hazards sciences and engineering researchers. 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 · 2025-10

Carbon cycles between the earth, ocean, and atmosphere on geological timescales. The relative amount of carbon stored in each of these respective locations is one important control on Earth’s average temperature. During the last ice age 18,000 years ago, carbon moved out of the atmosphere causing decreased global temperatures. However, it remains unknown where that carbon was stored. This project uses radiocarbon dating to test whether the deep Indian Ocean stored substantial amounts of carbon across the last ice age. The researchers will study microscopic fossils in four sediment cores from across the Indian Ocean basin. These tiny fossil shells made by single-celled organisms record the radiocarbon content of the seawater they lived in at the time of their growth. By comparing the radiocarbon age recorded in these microfossils to the age of the sediment, researchers will determine if deep Indian Ocean carbon was abnormally old during the last ice age. The size of the sediment grains will reveal how quickly currents at the bottom of the ocean flowed and how quickly this old, stored carbon could be transported out of the deep Indian Ocean and released back to the atmosphere. Combined, these data will tell researchers whether changes in deep Indian Ocean carbon were—or were not—important for past changes in Earth’s temperature. The work will support early career scientists and provide research opportunities for graduate students. Seawater radiocarbon content is a powerful tracer of air-sea carbon dioxide exchange and ocean carbon storage. Existing observations suggest that Indian Ocean Bottom Water radiocarbon was significantly lower (i.e., having a much older radiocarbon ventilation age) than all other ocean basins during the Last Glacial Maximum, which could reflect a much slower overturning of these waters and enhanced carbon storage via the biological carbon pump. If these existing measurements accurately reflect the entire Indian Ocean, they suggest that the carbon sequestration capacity of the glacial Indian Ocean has been greatly underestimated. In this project, researchers will create four new glacial- interglacial records of Indian Ocean Bottom Water radiocarbon to answer the following question: Do the existing (very old) Indian Ocean Bottom Water records accurately represent the region? In addition to answering this primary question, collaborators will analyze sortable silt content to estimate ocean current speeds and build this data into an inverse model to improve understanding of the processes driving the observed changes. This project will fund a graduate student and will continue the “First Gen BEES” (Becoming an Earth & Environmental Scientist) program initially designed and produced by first generation college students. 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 · 2025-10

Vast midwater regions away from the surface and coasts remain largely unexplored and sparsely sampled, both temporally and spatially. This project develops biohybrid jellyfish instrumented with pressure and temperature sensors as a novel, low-cost platform for oceanographic measurement, addressing limitations of traditional methods such as ships, buoys, and autonomous underwater vehicles. Biohybrid jellyfish leverage natural propulsion and pressure tolerance to enable low-energy, scalable ocean monitoring. By electronically controlling their swimming, jellyfish can be directed for targeted environmental measurements. This research focuses on four species: Aurelia aurita (moon jelly), Cassiopeia sp. (upside-down jellyfish), Chrysaora sp. (sea nettle), and Mastigias sp. (lagoon jellyfish) that encompass a spectrum of distinct jellyfish morphologies and ecological adaptations. Field studies will occur in the Florida Keys, Cape Cod, and southern California in order to test the efficacy of biohybrids across different oceanic and environmental regimes. Activities are planned for engaging a broad audience including K-12 schools, undergraduate and graduate students, and the general public. The bioinspired robots would provide opportunities for K-12 students to learn about the principle of operation and hands-on experience on neural control. The project offers interdisciplinary training for early-career researchers in biology, engineering, and environmental sensing. This multidisciplinary project will pursue three key objectives. Studies of jellyfish neurophysiology will investigate microelectronic pacemaker control and develop bioelectronic interfaces for precise movement regulation in each species. Measurements of metabolism during robotic control will quantify energy costs of biohybrid locomotion and compare the measured efficiency with purely mechanical, robotic alternatives. Assessments of swimming performance will evaluate speed, maneuverability, and station-keeping ability in controlled laboratory testing facilities and in dynamic ocean environments. 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 · 2025-10

PROJECT SUMMARY Despite the tremendous efforts in obesity research, pharmacological interventions that solely suppress appetite alone have proven largely ineffective in addressing this global health issue. Therefore, increasing energy expenditure has emerged as an alternative means to combat the obesity epidemic. Emerging evidence suggests that cold exposure is a promising approach to alleviate obesity and related metabolic disorders, but the neurobiological mechanisms mediating cold response remain poorly understood. In my pilot studies, I demonstrated that cold exposure evokes a profound activation of neurons in the posterior periventricular hypothalamic nucleus (PVp), most of which are GABAergic. I further showed that activation of GABAergic neurons in the PVp (GABAPVp neurons) increases both food intake and energy expenditure. Strikingly, repeated activations of these GABAPVp neurons resulted in improved glucose tolerance and insulin sensitivity, despite the fact that mice constantly ate more. Together, I developed a hypothesis that GABAPVp-originated neural circuits mediate metabolic benefits during cold exposure. The K99 phase will focus on unravelling the physiological relevance of cold-sensitive PVp neurons in energy and thermal homeostasis. I will use intersectional genetics to dissect the functional relevance of different PVp subsets on energy and thermal regulations during cold exposure. In addition, I will employ the GRIN lens calcium imaging system to monitor the response to cold exposure and feeding in individual GABAPVp neurons. During the R00 phase, I will utilize the techniques and the problem-solving experience I acquire from the K99 phase to identify the downstream targets that mediate the effects of GABAPVp neurons and the cold-sensor. I will combine the Cre-loxP, Flpo-Frt strategies and retrograde viral vectors to determine the contributions of the lateral periaqueductal gray (LPAG) and lateral parabrachial nucleus (LPBN) to energy and thermal homeostasis during cold exposure. I will also assess the effects of Kcnk2 in GABAPVp neurons on cold-sensing as well as energy and thermal balance. The K99 phase will provide an ideal training opportunity to equip me with essential techniques, knowledge, and problem-solving skills, which will prepare me for the R00 phase of research and growing into an independent researcher focusing on neural mechanisms of obesity and energy balance.

NSF Awards · FY 2025 · 2025-10

This project investigates market-driven spectrum access and management approaches that leverage artificial intelligence (AI) to enhance radio spectrum allocation, sensing, and market optimization. The work facilitates evolution from current radio spectrum management strategies to more dynamic and efficient methods, thereby increasing the overall utility and efficiency of the radio spectrum which is a key resource for all sectors of modern society. The new approaches investigated in this project rely on private sector band managers, who dynamically allocate spectrum resources while ensuring compliance and mitigating interference. Band managers must contend with strategic behavior by market participants, who for example may share incomplete or incorrect information, and must handle attacks by adversarial users. This research addresses these challenges by developing AI-driven mechanisms that balance efficiency, security, and stability. Deployment of the new market-driven approaches could significantly enhance the spectrum available to and hence the capacity of next-generation wireless communication systems and other spectrum dependent systems. This research comprises three integrated thrusts considering different aspects of a future robust AI-powered market-driven spectrum system. Thrust 1 develops new learning-based spectrum allocation mechanisms that integrate multi-armed bandits with auction strategies to optimize spectrum sharing among strategic users. Thrust 2 focuses on securing spectrum sensing by detecting adversarial manipulations using novel decision-boundary-based techniques. Thrust 3 ensures market stability through adaptive monetary policies optimized via safe reinforcement learning. By integrating these components, the project creates fundamental understanding of how to establish an AI-driven spectrum market that is resilient to both environmental and strategic uncertainties. 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 · 2025-09

Alzheimer’s disease (AD) affects over 55 million people worldwide, and this number is expected to nearly triple by 2050. AD is characterized clinically by progressive cognitive decline, and pathologically by amyloid plaques, neurofibrillary tangles, and loss of neurons in the brain. A thorough understanding of its mechanism is a prerequisite for discovering effective therapeutic interventions. N6-methyladenosine (m6A) is the most prevalent post-transcriptional RNA modification that plays important roles in gene regulation and many other biological processes including neurodevelopment, learning and memory. m6A is particularly abundant in the brain and its dysregulation has been associated with neurological disorders. Yet, we still do not have a complete map of m6A in the brain of older individuals and the mechanism by which m6A dysregulation may causally contribute to AD also remains an enigma. We have recently developed several novel technologies for transcriptome-wide quantitative m6A profiling at base-resolution. We have also validated the methods in a pilot study consisting of 60 postmortem prefrontal cortex and identified multiple m6A alterations associated with cognitive phenotypes and AD neuropathology (e.g., amyloid-β, tau tangles). Using these novel technologies, the current study will test the hypothesis that brain m6A dysregulation is causally implicated in AD pathology. Our objectives here are to 1) create the first high-resolution reference map of brain m6A methylome (i.e., all m6A sites in brain) in the brain of older adults; 2) identify specific m6A alterations associated with AD and its clinical and pathological endophenotypes; and 3) elucidate the mechanism by which m6A dysregulation may causally contribute to AD pathogenesis. To achieve these goals, we leverage a large collection of human postmortem brain tissue samples (dorsolateral prefrontal cortex) in two community-based cohorts of aging and dementia: Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). Deep clinicopathological phenotypes and rich brain omics data sets (e.g., GWAS, epigenomics, transcriptomics, proteomics) are available in both cohorts. In Aim 1, we will perform quantitative profiling of brain m6A methylome and identify specific m6A alterations associated with AD neuropathology. Aim 2 will integrate m6A data with other brain omics data, including genomics (GWAS), epigenomics (DNA methylation, histone acetylation, and miRNA), transcriptomics (RNA-seq) and proteomics, in the same brain cortex of same individuals, to decipher the mechanism by which altered m6A methylation may trigger AD pathology. In Aim 3, we will use a dCas13b-FTO fusion for m6A editing in human induced pluripotent stem cells (iPSC)-derived neurons to functionally validate the top-ranked genes and determine the causal role of m6A dysregulation in AD pathogenesis. Such results will provide novel mechanistic insight into the role of m6A dysregulation in AD pathology and inform the development of therapeutic interventions targeting m6A and its regulatory pathways for AD treatment.

NIH Research Projects · FY 2025 · 2025-09

Summary Postoperative atrial fibrillation (POAF) is the most common complication of cardiac surgery in the world, affecting 30- 50% of patients and incurring significant morbidity and mortality with elevated risk for postoperative stroke, heart failure, and death. Despite extensive research and advancements in antiarrhythmic therapy, the incidence of POAF remains high and has not changed in decades. Growing evidence indicates that endothelial dysfunction is correlated with chronic atrial fibrillation (AF). However, the direct relationship between atrial microvascular/endothelial (dys)function following cardioplegic arrest and cardiopulmonary bypass (CP/CPB) and the development of new onset of POAF is largely undefined. Moreover, the changes that occur in the atrial microvasculature/endothelium following CP/CPB and cardiac surgical procedure in patients with POAF are poorly understood. Thus, the goal of this patient- oriented proposal is to investigate how dysfunction in the cardiovascular physiology of atrial microvasculature and endothelium affects POAF. Importantly, our preliminary studies indicate that enhanced atrial arteriolar vasomotor tone and impaired atrial endothelial function following CP/CPB are associated with the new onset of POAF. Furthermore, atrial microvascular fibrosis in aged patients is significantly corelated with POAF. Therefore, we hypothesize that atrial microvascular/endothelial dysfunction and altered vascular/endothelial signaling at baseline (pre-CP/CPB) and pos-CP/CPB contribute to the development of POAF. In Aim 1, we will evaluate microvascular signaling pathways responsible for myogenic/vasomotor/endothelial dysfunction of the atrial microvasculature in patients with POAF; In Aim 2, we will investigate cellular/molecular alterations of atrial endocardial endothelial dysfunction in patients with POAF; In Aim 3, we will analyze the differential genomic expression in vascular smooth muscle cells/pericytes, endothelial cells, and fibroblasts in the harvested atrial tissue samples pre- and post-CP/CPB from patients with and without POAF. We will further analyze the impact of age, sex, diabetes, and hypertension on atrial microvascular/endothelial dysfunction correlated to POAF. To achieve these goals, we will recruit a cohort of 500 cases with and without POAF, along with human atrial tissue samples of both pre- and post-CP/CPB, atrial arterioles, atrial cardiomyocytes, and endothelial cells from patients with or without POAF. We will employ multiple cutting-edge approaches, including a human CP/CPB model, microvascular physiology, cardiovascular electrophysiology, and novel cellular/molecular approaches. This proposal will develop a novel concept that microvascular/endothelial dysfunction/signaling of atrial microcirculation play important roles in POAF; bring new insights into endocardial endothelial dysfunction related to POAF by exploring novel cellular/molecular changes of the endocardial endothelium related to POAF; and identify novel genetic mechanisms of atrial microvascular/endothelial dysfunction related to POAF. By doing so, this proposed research will provide the basis for the development of new approaches to decrease the incidence of POAF in patients undergoing cardiac surgery.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT Age-related hearing loss (ARHL) is the leading communication deficit in older populations, the number one neurodegenerative disorder, and it is strongly associated with cognitive decline. One of the hallmarks of ARHL is difficulty understanding speech in noise, a chief complaint from most seeking audiologic treatment. Several investigations have recently shown that speech-in-noise thresholds are substantially poorer for listeners with extended high frequency hearing loss (EHF HL; >8 kHz) relative to controls. To date, however, EHF is not measured commonly in the clinic despite its potential usefulness as a key indicator of listening and speech understanding difficulties. ARHL also poses a risk of lower cognitive performance, making daily communication harder. Previous work has established a relationship between poorer speech-in-noise performance for ARHL and changes in brain biomarkers such as GABA. Additionally, neuroinflammation and accumulation of amyloid deposits along the auditory pathway have been seen in animal models and are associated with cognitive decline. The connections among ARHL, speech-in-noise listening, and cognitive decline are still poorly understood, however, and further research is needed to directly link these factors before clinical translation can be pursued. We propose parallel human and animal studies to assess associations between extended high frequency hearing, speech-in-noise performance, and cognition. In Aim 1, adult human participants will be assessed via conventional and extended high frequency audiometry, electrophysiological assessment, speech-in-noise testing, and cognitive subdomains (working memory and processing speed). Aim 2 will use a mouse model of ARHL and assess them longitudinally and cross-sectionally in a mixed design using analogous electrophysiology as in Aim 1. In addition, at 15 and 25 months, molecular and anatomical analyses of amyloid beta levels, inflammatory markers, and GABA markers will be performed on the mice to examine the age-related changes in cognitive biomarkers. The applicant is a highly productive early-career scientist seeking to follow her audiology doctoral degree with a PhD in auditory neuroscience. She has assembled a training and mentoring team that are experts in age-related hearing loss using techniques that span human psychoacoustics, electrophysiology, and molecular biology. The parallel aims will provide the applicant with a comprehensive skillset in both animal and human physiology, critical to her career goals. As a clinician scientist, the applicant seeks a truly bench-to- bedside research program of her own, and the proposed experiments in this study are the first step toward that goal.

NSF Awards · FY 2025 · 2025-09

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Dr. Merkler from the University of South Florida (USF), Dr. Dempsey from Boston University, and Dr. Richards from the Foundation for Molecular Evolution are investigating peptidylglycine α-monooxygenase (PAM), the enzyme responsible for making a diverse family of neuropeptides in humans and many other organisms. Their experimental procedures will provide the first understanding of how full-length PAM binds to biologically relevant neuropeptide precursors. In addition, their work will provide new insights into the interaction of PAM and the molecular precursor for atrial natriuretic peptide (pro-ANP), setting the scene for discovering why PAM is present in tissues that do not make neuropeptides. The project will provide training for a number of graduate, undergraduate, and high school students in the use of a broad array of modern biochemical methods. The results of these studies will form the basis for a series of interactive, in-person talks at the Museum of Science and Industry (MOSI), located close to the USF campus, that will be tailored for students in grades 3-5, 6-8, or 9-12, and members of the general public. These talks will aim to not only improve scientific literacy in Florida but also inspire young people to pursue scientific research in neuroscience and medicine. This research project will provide a detailed molecular understanding of how the full-length, bifunctional form of PAM is able to recognize and modify a wide range of neuropeptide precursors as substrates. They will also provide the first information about how the dynamical properties of PAM impact both catalytic mechanism and communication between the two active sites, which are located in different domains of the enzyme. In addition, we will explore the structural basis of how bifunctional PAM binds to pro-ANP, a peptide that is not a substrate for the enzyme. Our studies will yield the first molecular understanding of the PAM/pro-ANP complex, test current hypotheses about the importance of this complex for cells in tissues that do not make or secrete α-amidated peptides. These project objectives will be accomplished using a multidisciplinary approach that combines biochemical assays, peptide synthesis, hydrogen/deuterium exchange (HDX) measurements, computational modeling, and cryogenic electron microscopy (cryo-EM). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-09

This award supports the convening of a nine-month workforce development program for anthropology students in conjunction with roundtables and mentoring sessions at the Society for Applied Anthropology (SfAA) Annual meeting in Spring 2026. The proposed program operates across three strategic phases designed to maximize participant success and career placement for anthropologists in AI focused careers. The conference results in a number of broader impacts including the development of essential knowledge and the groundwork for a foundational understanding necessary for successful participation in advanced training and career development for scientists in AI careers. It provides training and professional networking opportunities through speaking events and hands-on workshops and focusses on workforce readiness and sustained mentorship to ensure successful career transitions into high-skilled AI roles. Responding to federal priorities for AI workforce development, this project provides a robust program within and after the annual meetings for the Society for Applied Anthropology (SfAA) to help build a pipeline to address critical workforce gaps in the United States’ AI innovation capacity through systematic skills development and mentorship networks. 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

Acid-base homeostasis is critical for normal physiological function. Chronic metabolic acidosis is an independent risk factor for the progression of chronic kidney diseases (CKD) and can contribute to increased morbidity and mortality in patients with CKD. Patients with KCNJ16 (the gene encodes the inwardly rectifying potassium channel Kir5.1) mutation display metabolic acidosis; however, the underlying mechanism is still not fully understood. The overarching goal of this study is to unmask the interaction between Kir5.1 and Kir4.2 channels and how such interaction regulates acid-base balance in the kidney. Mentored K99 Phase: Our preliminary data revealed that loss of Kir5.1 impairs renal ammonia metabolism in the proximal tubule. I hypothesize that loss of Kir5.1 depolarizes the proximal tubule cell membrane and inhibits the exit of HCO3- through NBCe1, resulting in increased intracellular pH (pHi) and thus, impairs the proximal ammonia metabolism. Specific Aim 1: Determine the role of Kir5.1 in regulating proximal tubule membrane potential and pHi .To test this hypothesis, I will use: 1) FluoVolt membrane potential kit and 2) pH-sensitive BCECF dye to measure the membrane potential and pHi of isolated proximal tubules from SSWT rats under the stimulation (VU206, agonist) and inhibition (VU720/VU992, antagonists) of Kir5.1 and compare the membrane potential and pHi of isolated proximal tubules from SSWT and SSKcnj16-/- rats. Independent R00 Phase: This phase of the project will develop an independent line of investigation into the physical and functional interactions between Kir5.1 and Kir4.2. Insights gained from these experiments will further explain the physiological mechanisms underlying inwardly rectifying potassium channels' regulation of acid-base balance. Previous studies suggest potential interactions between Kir5.1 and Kir4.2. However, the functional interactions between Kir5.1/4.2 in the kidneys still remain largely unknown. I hypothesize that Kir5.1 physically and functionally interacts with Kir4.2, and the Kir5.1/4.2 complexes determine the membrane potential of the proximal cell. Specific Aim 2: Investigate the physical and functional interactions of Kir5.1 and Kir4.2 in the proximal tubule. To test this hypothesis, I will: 1) use immunofluorescence and co-immunoprecipitation on isolated proximal tubules from SSWT rats to study the physical interaction between Kir5.1 and Kir4.2; 2) generate the Kir4.2 KO rat based on Dahl SS rat background (SSKcnj15-/-) to evaluate the effect of Kir4.2 on acid-base status, kidney function and blood pressure in SS hypertension; 3) use Western blot, immunofluorescence and patch clamp to study the expression and channel activity of Kir4.2 in SSKcnj16-/- rats and vice versa. The results of this proposal will unmask the molecular mechanisms of acid-base regulation by Kir5.1 and the physical and functional interactions of Kir5.1 and Kir4.2, which will not only help define the role of inwardly rectifying potassium channels in the proximal tubule but also contribute to developing new therapeutic strategies for metabolic acidosis.

NSF Awards · FY 2025 · 2025-09

Algorithms permeate our modern world, driving everything from navigation, information storage, and data retrieval. In contrast, biological information is inherently physical, carried by molecules whose shapes determine their interactions with the environment. This NSF-funded program aims to explore and harness the interface between the deoxyribonucleic acid (DNA) “software” and the geometric “wetware” of molecules. The research will begin by developing mathematical tools to distinguish molecules based on their 3D shapes and structures. These tools will then be used to create a new programming framework: “algorithmic shape encoding.” Using small DNA tiles as modular pieces in a molecular-scale 3D jigsaw puzzle, the team will construct increasingly complex structures—drawing inspiration from nature’s ability to link form and function. The expected outcomes include breakthroughs in self-assembling materials, biocomputing, and optical communication systems. In addition to scientific discovery, this program will foster interdisciplinary training across mathematics, engineering, and chemistry from high school to the postdoctoral levels. DNA, with its predictable structure and ability to self-organize at nanometer precision, offers a powerful platform for designing next-generation materials. This project builds on the well-established tensegrity triangle motif to create a diverse set of 3D DNA motifs that self-organize into authentic 3D DNA building blocks. In Aim 1—Unit Design: Encoding Information in 3D DNA Motifs—researchers will identify key structural features of DNA motifs that can encode information through molecular shape. This will involve developing computational tools to predict and constrain topologies and verifying motif structures using X-ray and related techniques. In Aim 2—Algorithmic Shape Encoding for Large 3D Nanomaterials—the focus will shift from individual motifs to overall structural organization. The team will (1) design and characterize quaternary structures with defined chirality, and (2) develop periodic, hierarchical, and fractal-based arrays that require supramolecular-level algorithms rather than sequence-level design. Finally, the project will prototype optical materials capable of light-based computation and readout, paving the way for new advances in nanomaterials and biomimetic 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 · 2025-09

Alzheimer’s disease (AD) is the most devastating dementia of global concern. Although the mechanism of AD pathogenesis is still under debate, it is agreed that Aβ aggregation are prominent hallmarks and the major risk of AD due to their toxicity to neurons. Therefore, Aβ aggregates, particularly oligomers, are the potential targets for the intervention of AD, as targeting and removal of Aβ fibrils or plaques is expected to eliminate the neuronal toxicity of Aβ aggregates. However, eradication of total Aβ peptides by therapeutic antibodies could lead to severe side effects, whereas anti-Aβ aggregation by β-sheet mimetics could only prevent or delay the process of aggregation process and could not disrupt the formed/existing Aβ aggregation. Therefore, development of more effective molecular probes that not only prevent but also disrupt Aβ fibril formation is still in an urgent need. In contrast to β-sheet mimetics to block Aβ fibrillar growth, recently we designed a class of peptide hybrid biomaterials that can specifically interact and stabilize Aβ helical conformation, thereby shifting the equilibrium of Aβ aggregation into off-pathway monomeric structure, leading to both prevention and disruption of Aβ aggregation. The lead compound could completely restore cell viability and boost the levels of neuronal PSD-95 and synaptophysin reduced by Aβ42 in primary neurons, and vastly prevent memory impairment in 5xFAD AD transgenic mice. Moreover, the lead compound could significantly mitigate mitochondrial and cell stress, and remarkably alleviate the systemic inflammation induced by amyloid pathology in the mice. As such, our long- term goal is to develop novel biomaterials that can prevent, halt and cure AD. The objective of this proposal, the first step to achieve the long-term goal, is to advance our preliminary work by rationally designing structurally related analogues of the current lead, so as to identify and develop more potent and effective peptidomimetics that can prevent and disrupt Aβ aggregation both in vitro and in vivo by helical Aβ42 binding and stabilization. We will first design helical peptidic foldamer bearing diverse functional groups and closely mimic the binding pattern of our lead compound. Then we will use our established in vitro assays such as 2D-NMR, EMS-IMS, CD, TEM, and other kinetic binding assays to identify and optimize our designed compounds that target and inhibit the aggregation of Aβ peptides. The compounds with activity equivalent or better than the lead compound will be used to study their ability to inhibit Aβ pathology both in vitro and in vivo. The proposed study is significant because there is no effective strategy for AD diagnosis and prevention. Our research will provide molecules with novel mechanism to unravel AD pathogenies and to develop potential molecular probes and therapeutic agents for cure of AD. The proposed research is innovative because we not only provide a new strategy for the development of novel class of peptidomimetics that prevent and disrupt Aβ aggregation, in addition, this approach of rational design for the recognition of Aβ surface can be easily extended to identify new materials targeting other amyloid diseases such as Huntington’s disease and diabetes diseases.