Utah State University

NSF Awards · FY 2024 · 2024-11

This project intends to support three postdoctoral fellows focused on access and accessibility in science, technology, engineering and mathematics (STEM) education research, practice, and policy. Because issues of STEM access and accessibility are inherently transdisciplinary, with relevant challenges spanning contexts, disciplines, and populations, this program plans to work with postdoctoral researchers to develop depth and breadth of knowledge in their areas of interest. Project leadership intends to collaborate with both supervising faculty and the postdoctoral fellows in their engagement in ongoing projects as well as in their independent research. This collaboration is designed to serve as a sustaining partnership extending from postdoctoral training through subsequent careers as tenure-track faculty within the institution. Postdoctoral research positions are invaluable opportunities for early career researchers to both establish themselves as independent scholars and to benefit from ongoing training. These roles also typically entail precarity, because they are designed to be temporary, may lack clear definitions of work responsibilities, and do not guarantee access to subsequent academic positions. However, the model of postdoctoral training proposed in this project is intended for early career scholars to transition directly into tenure line positions in the Emma Eccles Jones College of Education and Human Services (CEHS) at Utah State University, pending adequate performance. The training provided within this model fully immerses the postdoctoral fellows in a highly collaborative and supportive environment rich in opportunities for the development of independent scholarship and for engagement with existing projects of senior colleagues. The performance criteria that structure the goals of independent scholarship are the need to develop a grant proposal for a new project and to lead on at least two manuscripts in two years. The supports provided include mentorship networks and formal training in methodology, grant writing, and pedagogy. The supports also include funds in each year to cover the research costs of fellows, full access to both the statistics consulting studio and the grant development office which are staffed and fully funded by CEHS, and monthly collaborative cohort meetings. This project is funded by the STEM Education Postdoctoral Research Fellowship Program (STEM Ed PRF) in partnership with the NSF Improving Undergraduate STEM Education (IUSE: EDU) Program. The STEM Ed PRF Program aims to enhance the research knowledge, skills, and practices of recent doctorates in STEM, STEM education, education, and related disciplines to advance their preparation to engage in fundamental and applied research that advances knowledge within the field. The NSF IUSE: EDU Program supports research and development projects to improve the effectiveness of STEM education for all 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 2024 · 2024-10

As described in the elementary Next Generation Science Standards, computational thinking (CT) is an essential part of understanding the ways in which scientific phenomena can be represented by numerical data and analyzed to represent and interpret patterns. Integrating CT into other areas of the curriculum—specifically science, technology, engineering, and mathematics (STEM) disciplines—is a promising mechanism for increasing students’ access to computing. Specifically, developing computational strategies to model phenomena foster both science content and Computer Science (CS) learning. However, the curricular materials adopted by schools and districts do not often include computational thinking as part of STEM lessons. For example, FOSS (Full Option Science System) kits provide meaningful inquiry-based learning that sits at the basis of many schools’ science learning but lacks opportunities for integration of computing and computational thinking. Further, these kits were developed in line with typical educational conditions on the mainland United States, which introduces some stark limitations for Hawaiian teachers and students. This project engages teachers on the island of Molokai and researchers at Utah State University in developing a research practice partnership (RPP) to co-design curricular units that integrate FOSS science modules with computing and computational thinking projects for elementary students. RPPs involve building and sustaining a long-term relationship of mutual benefit between classroom practitioners and researchers. In partnership, the project team will address the common problem of practice – a lack of community centering and culturally relevant STEM+C learning materials for Hawaii generally and Molokai specifically. The project team will conduct design-based research (DBR) through the lens of cultural historical activity theory to understand how the collaborative co-design of integrated STEM and computing curricula can both shift the content and use of curricular materials. The team will also investigate teachers’ sense of empowerment for shaping their students experiences to match the needs and resources of the community. The proposed work conceptualizes school spaces as activity systems within which teachers and researchers jointly endeavor to expand the capacity of curricula to meet state standards within the local context. This project is funded through the Computer Science for All: Research and RPPs program. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

Learning materials that align with students’ lived experiences and that are relevant to the challenges and issues that confront their communities have been shown to improve student engagement and learning outcomes. Yet, students in rural spaces often find themselves taught through lessons and curricular materials not directly relevant to, or seemingly counter to, their lived experience. This project seeks to co-develop and implement a locally relevant and integrated computer science curriculum that centers the lived experiences of rural Hawaiian students and communities. It is hypothesized that understanding and engaging local educational needs creates opportunities for students to learn in ways that make schooling meaningful and relevant to their experiences, culture, community, identity. These impacts will increase interest, belonging and pursuit of STEM coursework and careers. Using a mixed methods approach, researchers and educators will work together to iteratively co-design and evaluate curricular materials that center Hawaiian students’ experiences and sense of community to support youth in developing strong connections to STEM learning that foster their future engagement and interest in STEM. Before, during, and after co-design activities, the research team will directly observe interactions amongst teachers and students during instructional time. As implementation, design, and refinement of the curriculum proceeds, the research team will leverage interview, focus group, and observational data collection from multiple stakeholders (i.e., school administrators, staff, teachers, students, and parents of students), to develop survey items. These items reflect distinct perspectives on what schooling and school success are and should be, the perceived value of and interest in future opportunities associated with Computer Science, s well as the level of empowerment and inclusion experienced. The surveys will be administered 3 times per year. The team will initially conduct exploratory factor analyses on the responses to establish a tentative factor structure that links the meanings for items held by stakeholders within the community to broader concepts. As those components stabilize within groups across the three deployments of the first full academic year (Fall, Y1-Spring Y2), analyses will move to a confirmatory factor analytic framework to validate the within-group measurement structure, moving next to assessing measurement invariance between groups and across time. The results of this study will allow the team to develop an evidence-based, transferable model of curriculum development that centers the experiences of local students to meet the educational needs of rural communities. Further, the team will develop locally responsive measures of educational success, student sense of belonging, and agency in schooling to gauge its development in context over three years of middle school and to ascertain impacts of materials developed using this model for rural curricular development. The Discovery Research preK-12 program (DRK-12) seeks to significantly enhance the learning and teaching of science, technology, engineering and mathematics (STEM) by preK-12 students and teachers, through research and development of innovative resources, models and tools. 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 proposed projects.  This project is also supported through the Computer Science for All: Research and RPPs program. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-09

To address the critical need for a more diverse and inclusive engineering workforce, this project will establish a pioneering university-industry-student partnership aimed at facilitating equitable access and transition into civil engineering careers for individuals with disabilities. Despite calls from the National Science Foundation and the National Institutes of Health, people with disabilities remain severely underrepresented in STEM fields. In industry, engineers with disabilities constitute less than 10 percent of the workforce and are less likely to be employed than non-disabled engineers; those who are employed generally experience lower pay. To-date, scholarship examining the accessibility of academic institutions has focused on the programmatic experiences of undergraduate engineering students with disabilities, with little to no work continuing past the point of graduation. As a result, this project, aligned with the National Science Foundation's commitment to fostering inclusivity and innovation in engineering education, represents a pivotal step towards broadening the participation of engineers with disabilities in the civil engineering industry. Focused within the civil engineering sector, pivotal to national infrastructure development, this endeavor will lay the groundwork for transformative programming supporting disabled students' transition from academia to professional practice. People with disabilities have been referred to as “the original lifehackers” due to the innovative ways they alter everyday products, systems, and spaces to access a world not built for them. While innovation and problem solving are core competencies in engineering, the role of people with disabilities as engineers has not been realized for many reasons. These reasons include social and professional stigma and a lack of support structures that facilitate the entry of engineering graduates with disabilities into the workforce. Beyond diversification, the project aspires to promote genuine inclusion, illuminating the underrepresented cohort of disabled engineering students and laying foundational steps for accessible engineering education and practice. This planning grant will contribute to a deeper understanding of existing scholarship and current industry perspectives, provide a framework for developing partnerships between academia and industry, and blaze a trail forward for creating a more diverse and inclusive engineering workforce through the following outcomes: (1) synthesizing relevant literature; (2) identifying and engaging industry stakeholders to explore collaborative tensions and synergies among industry stakeholders; and (3) developing a robust research agenda for the next phases of the project. In Phase 1, we will employ systematic review techniques to conduct a literature review to examine the research landscape of the engineering school-to-work transition, industry practices for hiring people with disabilities, and university/industry partnerships. In Phase 2, we will conduct interviews to help us foster interpersonal relationships with the industry partners recruited in Phase 1. In Phase 3, we will apply the outcomes identified in Phases 1 and 2 to establish a robust research agenda for project continuation. By bridging academia and industry, this research will enrich scholarship, provide a framework for sustainable partnerships, and foster a more inclusive engineering workforce. Moreover, this initiative holds broader impacts by pioneering inclusive career pathways that destigmatize disability in industry, promoting transparency, and emphasizing the unique contributions of individuals with disabilities in infrastructure design. Most importantly, it will provide the critical first steps to creating inclusive and accessible pathways to and through engineering for all engineering 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 2024 · 2024-09

Plants are the original source for many of the drug compounds we now use. These compounds are often only slightly soluble in water (hydrophobic). This works fine once inside the human body, because our cell membranes are also hydrophobic. It is a problem when developing large-scale processes for biomanufacturing of these processes. Cells are grown in water-based environments. Hydrophobic compounds will tend to stay in the cells, making separation and purification difficult. The project will investigate a new strategy for producing these compounds. They will be modified inside the cell to make them water-soluble. This will allow them to achieve high concentrations in the growth medium. The focus of this project will be on characterizing how these molecules are transported out of the cell. The long-term goal of this project is to develop a novel strategy for producing hydrophobic biomolecules by synthesizing them inside the cell as water-soluble conjugates and then hydrolyzing them to final form after they are excreted from the cell into the aqueous medium. This would take advantage of the large concentration gradient across the cell membrane as a driving force for transport of the molecule into the medium. The immediate goal of this project is to characterize the mechanisms controlling the transport of the model compound, curcumin, in E. coli with a specific focus on the surface binding mechanisms involved in the process. 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 · 2024-09

PROJECT SUMMARY/ABSTRACT People with dysarthria due to Parkinson's disease (PD) frequently present with reduced intelligibility, which can have significant consequences, including reduced participation in situations involving communicating with others and resulting in social isolation.1–5 Few effective treatments exist to ease the intelligibility burden of dysarthria in PD, and most require significant cognitive and physical effort on the part of the speaker to achieve and maintain gains.6,7 Once people with PD have progressed beyond the early stages of the disease, and their cognitive and physical impairments limit their ability to use traditional speech therapy techniques, they are not realistic treatment candidates for current interventions; and no other interventions are available to support their communication. This is a serious and consequential gap in clinical care for people with PD. The current proposal addresses this critical gap by shifting the weight of behavioral change from the speaker to the listener, specifically key communication partners such as family. Indeed, for older adults, most of their time spent with others is spent with family members.8 Further, key partners of patients with PD wish to have a more significant and active role in communication rehabilitation.9,10 A listener-targeted remediation approach for intelligibility impairments in people with dysarthria and PD is firmly grounded in theoretical models of perceptual learning11–13 and rigorously supported by our decade-long research program targeting perceptual learning of dysarthric speech.14–30 To date, this line of investigation has chiefly targeted the theory of listener adaptation to the degraded signal; however, robust intelligibility improvements of up to 20 percent across studies have been observed.15 With a rigorous account of how and what listeners adapt to, we are ideally positioned to move this work from bench to bedside, establishing listener (i.e., perceptual) training as a clinical intervention to improve intelligibility in people with PD. Here, we establish the efficacy of listener training for patients with PD and their primary communication partners using a repeated-measures, randomized controlled trial (SA1). Immediate acquisition and retention of intelligibility improvements will be examined as a function of speaker severity. We then evaluate three theoretically and empirically-motivated communication benefits of listener training that extend beyond intelligibility, including listening effort, comprehension, and communicative participation (SA2). Finally, we engage stakeholder input to inform clinical implementation of listener training using qualitative semi-structured interviews (SA3) with patients with PD and their partners. This will provide insights into the effectiveness and feasibility of the intervention approach, ensuring that their needs and preferences are considered and that they feel empowered and motivated for a listener training approach. Thus, in three independent aims, this proposal will address a current void in our clinical toolbox, establishing a new realm of clinical practice in which communication challenges in PD are managed by training partners to better understand the degraded speech.

NSF Awards · FY 2024 · 2024-09

Large earthquakes have the potential to have catastrophic impacts on humans and infrastructure when risks are not mitigated. Earthquakes nucleate at depth, but it is the upper ~1 km of a fault zone where seismic waves, rocks and sediments, fluids, humans, and their built environment intersect to drive earthquake hazard. This is the critical zone for earthquakes. This Frontier Research in Earth Sciences (FRES) project investigates how material properties that vary in space and time in the earthquake critical zone impact earthquake rupture propagation, radiation of seismic waves, ground shaking intensity, and surface deformation in between earthquakes. This research targets two similar faults, each with significant human impact, that are at different points in their earthquake cycle: the southern San Andreas fault, CA, in a quiet period between earthquakes, and the Çardak-Çığlık fault, Turkey, in the immediate aftermath of the 6 February 2023 Mw 7.6 Elbistan earthquake, part of the devastating Kahramanmaraş earthquake sequence. The research team will bridge geoscience and engineering concepts, approaches, data, and models, as well as leverage shared-use equipment and cyber-infrastructure, to deliver publicly available products on the NSF-funded Natural Hazards Engineering Research Infrastructure DesignSafe Data Depot that can improve earthquake hazard models and seismic site response analyses near seismogenic faults, which are needed for increased resilience of communities to earthquakes. Research and broader impacts are anchored in intellectual, educational, and cultural reciprocity to broaden STEM knowledge, perspectives, and participation. Research pathways will meaningfully intersect by training the next generation of Earth scientists at the nexus of geosciences and engineering, strengthening international partnerships with Turkish colleagues, and expanding a Utah State University (USU) mentoring program through geoscience-engineering research experiences to increase the transition rate of students from a 2-year campus at USU Blanding, UT, to the 4-year campus in Logan, UT. This FRES project investigates how the earthquake critical zone accumulates, redistributes, and releases earthquake energy on major strike-slip faults. Models of earthquake rupture, seismic wave propagation, and local surface ground shaking are commonly decoupled and limited because the detailed properties of the earthquake critical zone are generalized. This FRES research will overcome these limitations by characterizing the earthquake critical zone of two major continental strike-slip faults with five intersecting research pathways that will yield geologic, geophysical, geochemical, mechanical, and engineering data. The pathways are: (1) a field-based geologic framework, (2) time-series CO2 flux data, a proxy for fault permeability and healing, (3) in-situ earthquake engineering geophysics to characterize material moduli, attenuation, and fault architecture, (4) deformation experiments to quantify fault healing, permeability, and attenuation at conditions designed to inform different stages of a seismic cycle, and (5) geochemical, microstructural, and fault rock chronology analyses to bridge natural and experimental earthquake cycle processes. These datasets will be integrated in a sixth pathway to produce stacked quasi-static, dynamic, and seismic site response numerical models. Research and broader impact activities bring together six PIs with diverse but overlapping geoscience and engineering expertise to train the next generation of Earth scientists at the intersection of these fields (three postdoctoral fellows, four PhD students, one MSc student, and undergraduate researchers). Undergraduate researchers will be recruited through the USU Honors Program, a Brown REU, and California State University Fullerton (CSUF) Project RAISE. International partnerships will be strengthened by having two Turkish colleagues participate in field work along the SSAF and lead Turkey-based research and by having US-based researchers connect with Turkish counterparts at public seminars at Istanbul Technical University. PIs and mentees will create and offer a new multi-year program to expand a USU-based student mentoring program with a goal to improve recruitment and retention of students. These students will be hosted at PI labs at USU Logan, with help from Brown and CSUF researchers, where they will be taught earthquake and engineering concepts, and subsequently be taken to the south San Andreas fault for field work. Their progress will be tracked and assessed by evaluating learning outcomes and STEM engagement through these experiences. This project is funded by the Frontier Research in Earth Science (FRES) program as well as Education and Human Resources (EHR) in support of Research Experiences for Undergraduates and Postdoctoral Scholars. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

Physics-inspired mathematics has effectively laid the foundation and provided the terminology for the most advanced areas of modern physics. This project aims to create new algebraic and geometric tools to help formulate ideas and methods of quantum physics in a precise mathematical way. Low-dimensional topology is an area of mathematics that studies three and four dimensional spaces. Theory of quantum groups has been productively used in low-dimensional topology, particularly with the creation of quantum invariants. Within this context, the Principal Investigator (PI) and his collaborators have developed new systematic strategies. The focus of this project is to further investigate and develop these strategies, aiming to exploit the powerful properties of the “renormalized” quantum invariants in several areas of mathematics. The unique attributes of this work open the door to novel research avenues in algebra, topology, geometry, and mathematical physics. The broader impacts are through STEM education, mentoring, and outreach. The PI will advise graduate students and postdocs on projects related to the main objectives of the project. The PI has co-organized many conferences and will continue such outreach activities to develop communication and collaborative research with other mathematicians, as well as to foster broader applications of the work supported by this award. The past thirty years have witnessed a transformative influx of quantum field theory into low-dimensional topology, leading to a novel perspective on link and three-manifold invariants. The discovery of the Jones polynomial by V. Jones in 1984 and its interpretation through three-dimensional quantum field theory by E. Witten in 1989 have paved the way for the application of new algebraic methods to study topology. These advancements have given rise to a new field of mathematics known as "quantum topology”. Most of the theory of quantum invariants involves monoidal categories with certain additional properties, such as being semi-simple. The PI and his collaborators have created a theory of re-normalized quantum invariants (RQIs) of low-dimensional manifolds arising from categories that are not semi-simple. The RQIs have their own unique features and provide mathematical interpretations of Topological Quantum Field Theories (TQFTs) with categories of line operators that are non-semi-simple; furthermore, the RQIs are more powerful than their standard counterparts. This project will explore the nature and physical meaning of the re-normalized Reshetikhin-Turaev three-manifold invariants and their associated TQFTs via certain classes of examples appearing in the context of Chern-Simons theory and vertex operator algebras. It also proposes to enhance and generalize recently defined non-compact skein TQFTs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-08

The field of synthetic biology integrates fundamental engineering principles to design biological systems at the genetic level. These systems have beneficial applications in precision medicine, biosensors, and microbial production. Innovations from this field benefit society by improving treatments for cancer and infectious diseases, providing better access to life-saving drugs, and enhancing crop yields. A challenge to the design of reliable synthetic biological systems is the noisy environments in which they operate. These environments can cause unexpected behaviors that can be rare and detrimental. To ensure the reliability of these systems, provable quantitative guarantees must be provided. Probabilistic model checking (PMC) can provide these guarantees, but current tools struggle with the unique complexities of synthetic biology. This project aims to advance PMC tailored to the unique verification challenges of synthetic biology designs by improving the scalability, automation, and accuracy of PMC. The project’s novelties are a unified and robust PMC framework, an easy-to-use graphical user interface, and integration with existing genetic design automation tools. The project's impacts are a strengthened connection between PMC and synthetic biology and a user-friendly PMC tool for early-stage synthetic biological design, making PMC more accessible to practitioners for designing real-world synthetic biological systems. This project advances principled software tool development for synthetic biology designs. Specifically, it develops correct-by-construction implementation of major prototype PMC tools developed by the investigator's group using verification-aware programming languages, before integrating them as a unified PMC framework. To promote PMC accessibility to synthetic biologists, this project also develops a robust and easy-to-use graphical user interface for the unified PMC framework. This project then integrates this PMC framework into the genetic bio-design automation tool iBioSim. The resulting software tool will be benchmarked on a wide range of real-world case studies in synthetic biology. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY Hepatitis B virus (HBV) has infected more than one-third of the world’s population and that almost 296 million people are currently living with chronic infection including over 6 million children under the age of five. Each year, about 1.5 million people become newly infected and 820,000 people die from HBV infection and related complications. Therapeutics for HBV are available, but they hardly lead to a functional cure for chronic HBV infection. One of the biggest challenges in developing an HBV cure is the lack of immunocompetent animal models that are susceptible to HBV infection and support the entire life cycle of HBV. HBV has an extremely narrow host tropism, determined both by species-specific host cellular viral entry receptor, sodium taurocholate co-transporting peptide (NTCP), and the host factors needed to support the lifecycle of HBV post viral entry. HBV transgenic mice do not support the formation of viral covalently closed circular DNA (cccDNA), the bona fide viral transcription template, via the intracellular cccDNA amplification mechanism; genetically modified mice carrying human NTCP fail to establish HBV infection due to the failure of de novo cccDNA formation. In search of other laboratory animal species-derived hepatocytes that may support HBV cccDNA formation, our preliminary studies demonstrated that Ad-HBV-transduced primary hamster hepatocytes (PHaHs) are capable of supporting HBV DNA replication and cccDNA formation, and Ad-hNTCP-transduced PHaH cells are susceptible to HBV infection. Hence, the objective of this project is to establish a novel Syrian hamster (Mesocricetus auratus) model that is tractable, fully immunocompetent, and highly susceptible for HBV infection. To this end, we will pursue the following Specific Aims: Aim 1. Establish a humanized-NTCP (huNTCP) hamster model for HBV infection. We will use the validated CRISPR-mediated gene editing techniques developed by us in the hamster to humanize the two codons encoding the key amino acid residues in the hamster NTCP protein required for HBV infection. Aim 2. Establish acute and chronic infection in the huNTCP hamsters and characterize the pathogenesis and humoral immune responses to HBV. Under this Aim, we will infect huNTCP hamsters to establish acute and chronic HBV infections and carry out pathogenesis studies. We will also carry out studies to characterize the humoral responses during acute and chronic infections. Aim 3. Test direct-acting antivirals (DAAs), immunoregulators and epigenetic modifiers in suppressing HBV infection in the huNTCP hamster model. We will test the utility of this immunocompetent huNTCP hamster model in assessing the efficacies of a selected panel of anti-HBV drugs with different HBV-inhibiting mechanisms, including a direct acting antiviral (DAA), tenofovir (TDF), an immunoregulator, IFNalpahcon-1, and an epigenetic modifier, MS436, in suppressing chronic HBV infection. We envision that this novel hamster model will greatly facilitate the development of new therapeutics that are needed to achieve a functional cure for HBV.

NSF Awards · FY 2024 · 2024-07

Chronic diseases are a leading cause of preventable deaths in the United States. Exposure to air pollution has been linked to asthma, respiratory diseases, and lower cognitive ability. Once inhaled, air pollution metabolites can be found in urine, providing direct evidence of human exposure. The goal of this project is to demonstrate the link between air pollution, urine markers of pollution exposure, and wastewater monitoring in underserved communities. The benefit of utilizing wastewater monitoring is that it avoids the need for blood draws and urine sampling to understand community wide exposure or disease prevalence. While this specific project focuses on air pollution, community wastewater monitoring holds great potential as a more rapid means of assessing the prevalence of many diseases such as cancer or mental health disorders. Additional benefits to society result from the co-generation and dissemination of knowledge with underserved communities through high school outreach and community meetings. Investment in non-communicable disease prevention measures give a $5.6 return for every $1 spent. Improved community surveillance measures could facilitate earlier and targeted public health interventions. This project will develop community non-communicable disease surveillance tools utilizing wastewater-based epidemiology (WBE) methods. The overall aim of the project is to demonstrate that wastewater carries community exposome signals associated with air pollution that can be used in environmental justice communities as direct evidence of adverse health effects. The project will focus on socioeconomically disadvantaged communities with higher air pollution burdens of respirable particulate matter (PM2.5) and gas-phase polycyclic aromatic hydrocarbons. Multiple direct and indirect lines of evidence will be used including urine and feces associated extracellular microRNA monitoring in wastewater (i.e., transcriptomics). Pollution exposure will be validated through mass spectroscopy-based detection of polycyclic aromatic hydrocarbon metabolites in wastewater (i.e., metabolomics) and air sampling using passive biological collectors and dynamic indoor and outdoor sampling in disadvantaged communities with higher air pollution exposure (i.e., environmental justice). The project will co-generate knowledge in the environmental justice community by including Title 1, minority-majority high schools and community members in the sample collection and dissemination of the results through community public meetings. While this project is focused on air pollution exposure, the wastewater-based epidemiology approach can more broadly benefit society understand a wide variety of non-communicable diseases associated with environmental exposures, metal health disorders, and various other diseases (e.g., cancer, kidney failure, alcoholism). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

This project aims to serve the national interest by meeting industry demand for engineering bioprocessing workers to fill a significant gap in the biotechnology workforce across eight intermountain states. The Biotechnology companies in this region could benefit from a well-trained and abundant workforce that can contribute to process and production goals without the need for extensive in-house training. In this ExLENT project, Utah State University (USU) aims to leverage its decade of experience in synthetic biomanufacturing and its partnership with three leading biotechnology companies to develop an experiential learning program that will engage diverse participants in biotechnology skill development and expand career pathways in biomanufacturing and bioprocessing. Recruitment for program participants will begin with four partner institutions, including two Hispanic Serving Institutions (HSIs), one emerging HSI, and one Historically Black College and University, and then expand to 50+ regionally affiliated community colleges across the intermountain west region. The project benefits society by expanding participant recruitment across various professional and educational backgrounds, fostering a diverse pool of individuals equipped with biological engineering skills to bolster national health, prosperity, and welfare. This project creates an experiential learning program to achieve competency-based training in biomanufacturing and bioprocessing serving 50+ regionally affiliated community colleges in the Intermountain West. Utah State University (USU), in partnership with industries including Thermo Fisher Scientific, Cytiva, and Perfect Day, seeks to mentor participants to acquire skills through hands-on experiences and applications from industry experts. Program participants engage with one or more of the four technical tracks to learn emerging and novel biotechnologies, identified as critical by industry partners but not currently offered in traditional A.S. or B.S. degree programs. These experiences are integrated with science-based fundamentals and engineering principles provided through interactions with USU biological engineering faculty members. Furthermore, outreach to partnering school districts in the region provide a “shadowing” bioprocessing program for high school students. Measurable outcomes include the impact of training on employment and retention within the regional biomanufacturing industry sector. Overall, this project supports experiential leaning opportunities for individuals to increase interest in and access to career pathways in emerging biomanufacturing fields. The NSF ExLENT Program supports inclusive experiential learning opportunities that provide cohorts of diverse learners with the skills needed to succeed in emerging technology fields. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-07

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Professors Shina Kamerlin of Georgia Institute of Technology, Sean Johnson and Alvan Hengge of Utah State University are studying the evolution of archaeal protein tyrosine phosphatases (PTPs). PTPs are a family of enzymes that play crucial roles in regulating cellular signaling processes. A characteristic feature of these enzymes is a flexible region that plays an important role in controlling catalytic activity. However, it is not well understood how the flexibility of this region is regulated. The proposed experiments will explore how these motions are achieved in archaeal PTPs and evolutionary ancestors. The proposed work will shed light on the role of enzyme dynamics in evolution, and will ultimately impact multiple fields from drug discovery to protein engineering. This pursuit allows graduate students to acquire specialized training in computational biophysics, structural biology, enzyme biochemistry, and NMR spectroscopy. The project includes outreach and mentorship activities to increase the participation of women and other underrepresented students in STEM. Further, the project endeavors to bring science to the general public through participation in festivals, lecture series, and radio broadcasts. This research project seeks to quantitatively characterize the evolution of loop motion and allostery in archaeal protein tyrosine phosphatases, by using advanced biomolecular simulations, intimately coupled with X-ray crystallography, kinetic characterization, and NMR spectroscopy. This will be achieved through characterization of both several extant PTPs, as well as a range of ancestral archaeal PTPs predicted from ancestral sequence reconstruction. Comparison of these enzymes to human and bacterial PTPs will shed light into the factors governing loop motion in PTPs, and how it has changed over evolutionary time. This provides important fundamental insight into enzyme evolution more broadly, as well as identifying features that can be exploited for 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 2024 · 2024-06

Millions of tons of plastic waste are produced annually, creating a significant global challenge. Small pieces of plastic, called microplastics, have emerged as the most significant environmental threat resulting from this trend. Microplastics come from the breakdown of larger plastic items such as bottles and bags, as well as from the production of everyday products. The small size of microplastics makes it difficult for wastewater treatment plants to remove them from the water. This results in microplastics eventually finding their way to rivers, lakes, oceans, and even groundwater. While these problems have been recognized for several years, it is less well-known what role microplastics play in the mobilization of microbes in water. Small microbes form sticky coatings called biofilms on the plastic surfaces. These biofilms can harbor harmful bacteria that may lead to the spread of disease, thus creating a hazard to human health. Moreover, biofilms can alter the weight, shape, and size of microplastics. This influences their movement in water and makes it difficult to predict where microplastics will end up. This study aims to investigate how different types of biofilms impact the movement of microplastics. Results will be used to build computer models to more accurately predict the environmental movement of microplastics. Successful completion of this research will enhance our understanding of how biofilm-coated microplastics navigate through water. Society will benefit from information that can inform strategies to remove microplastics from water systems to protect human and ecological health. Microplastics (MPs), plastic particles smaller than 5 microns, have become a significant environmental concern. This is due to their widespread presence in aquatic environments and adverse effects on human and ecological health. Wastewater treatment plants are a critical process in removing MPs to prevent their release into the environment. However, the properties of MPs make them challenging to remove using conventional wastewater treatment processes, resulting in their release to receiving waters. MPs can also serve as substrates for microbial colonization, leading to the formation of biofilms on their surfaces. These biofilms may contain pathogens and bacteria resistant to conventional disinfection methods, posing risks to public health if released into the environment. Common MP particles found in water systems include fibers and films. For such thin particles, biofilm colonization can significantly increase MP thickness. The transport dynamics of biofilm-coated MPs are an under-researched topic. The goals of this multidisciplinary study are to (1) assess differences in the characteristics of biofilms of different microorganisms grown on MPs; (2) quantify the dispersion and settling dynamics for biofilm-coated MPs under turbulent conditions; and (3) develop a machine learning model to predict biofilm-coated MP transport in field-scale situations. Measurements will include biofilm thickness, topography, and adhesive strength, as well as other metrics generated from both pure strains and mixed cultures, across diverse MP materials and colonization periods. Results will be used to predict the transport of various biofilm-coated MPs in turbulent treatment systems and aquatic environments. Results will benefit society by enabling better design to remove MPs from water treatment systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-04

PROJECT SUMMARY/ABSTRACT When the future has little value, impulsive choices abound. Steeply discounting the future means a drug-high now is more valuable than future health, wealth and relationships. A large and robust literature reveals that steeply discounting the future is correlated with early substance use, substance-use disorders, and poor outcomes in drug-treatment trials. A small literature suggests that reducing delay discounting improves clinical outcomes in humans. Such findings have motivated nonhuman research seeking to discover interventions that can reduce impulsive decision-making. Those interventions might be adapted to prevention programs designed to reduce childhood impulsivity and adolescent substance use. A practical limitation of the effective nonhuman interventions (some of them conducted in our lab) is their duration (median = 123 operant-training sessions). In preliminary studies, we have obtained comparable reductions in rats' impulsive choice in a fraction of the time by using Pavlovian training methods. When Pavlovian training is complete (8 sessions), the newly established conditioned stimulus (CS) may be used as an antecedent to attract the rat toward the self-control choice; this significantly reduces impulsivity. The CS may also be used as a conditioned-reinforcing consequence that significantly increases future self-control choices. These practical interventions and clinically relevant improvements have obvious translational potential. Before undertaking that translational research, however, we propose two experiments designed to explore how parametrically manipulating training variables known to influence Pavlovian learning impacts the efficacy of these CS-as-antecedent and CS-as-consequence interventions. The knowledge gained from this project will provide a roadmap to guide the design of Pavlovian interventions seeking to prevent impulsive decision-making, and prevent the health deficits associated with those choices.

NIH Research Projects · FY 2024 · 2023-09

PROJECT SUMMARY The opioid epidemic has encouraged the biomedical research community to explore new pain targets and further study opioid’s most famous target, the mu opioid receptor. One underexplored arena is the study of the endogenous opioid peptide system, which we know very little especially in comparison to our knowledge of the receptors they activate. This is despite the commonsense understanding that the endogenous peptides must change as a result of the allostatic load imposed by chronic pain, opioids, and chronic opioid exposure. There are well established sex differences in the actions of opioids at the mu opioid receptor, but it is unknown whether there are also differences in the endogenous opioid peptides. The experiments outlined here lay the necessary and long overdue groundwork to understand the neural mechanisms of one class of the endogenous opioids, called enkephalins, and how they contribute to pain. In the first aim, we will quantify enkephalin mRNA expression in regions of the brain known to play a role in top-down pain modulation. Next, we will use a viral retrograde tracer to map the enkephalin containing neurons that synapse in the PAG, something that has never been done before. In Aim 2 we will probe the behavioral effects of activating enkephalin containing neurons that synapse in the PAG using excitatory and inhibitory chemogenetic approaches followed by assessment on pain assays. We expect that increasing activation of all enkephalin neurons that synapse in the PAG will result in increased antinociception. Further, we expect that inhibition will lower the endogenous opioid release and therefore produce pain. We will further isolate certain neural projections from one brain region at a time to elucidate which brain regions are driving the enkephalin mediated antinociceptive responses. This research will allow us to better understand how the endogenous opioid system facilitates pain control and whether there are underlying differences that lead to differences in pain modulation in males and females.

NIH Research Projects · FY 2025 · 2023-06

PROJECT SUMMARY/ABSTRACT People with Parkinson's disease (PD) experience restricted communicative participation [1,2], which means that they have difficulty “taking part in life situations where knowledge, information, ideas or feelings are exchanged” [3]. This restricted participation can have significant consequences for one's well-being, including social isolation, loss of employment, deterioration of relationships, and difficulty accessing services [3,4]. We currently do not have behavioral treatment targets that directly and effectively improve participation. The most basic form of communicative participation is an interaction between two people, a dyad, engaged in dialogue. The small body of research that has examined interaction behaviors (i.e., interdependent verbal behaviors) in people with PD (and/or dysarthria) has used descriptive or case study designs to qualitatively describe the dialogues [5-11]. In a prior R21, we extended this work, leveraging the existing rich literature on dialogue theory that was developed with neurotypical (NT) adults, coupled with speech signal processing techniques and advanced statistical modeling, to quantify interaction behaviors in task-controlled dialogue corpora [12-16]. Reasonable conclusions from this collection of studies are that the interaction behaviors of PD-NT dyads are fundamentally different from those of NT-NT dyads; and that these differences correlate to restricted participation in the dialogues of people with PD. The next step is to move from these simple correlations to deriving causal, mechanistic relationships between interaction behaviors and participation outcomes, allowing us to identify candidate treatment targets for improving participation in people with PD. We will use two aims to do this. The first aim, using a between-within design, will compare interaction behavior from the dialogues of PD-NT and NT-NT dyads and quantify their variation across typical communicative situations. We will audio-record people with PD and NT controls (dyad condition) engaged in a problem-solving and a rapport-building dialogue (goal condition) with a familiar and an unfamiliar partner (partner condition). The resulting 480 dialogues will be annotated, and automated metrics of interaction behaviors, including individual interaction behaviors of each person (articulatory precision, rhythmic predictability, language complexity) and coordinative interaction behaviors (entrainment, conversational repair, turn-taking), will be extracted. Linear mixed effects models will be used to assess these behaviors by dyad, goal, and partner condition. Our second aim looks to assess the impact of each interaction behavior on communicative participation outcomes in the dialogues of people with PD within a causal inference framework. Whereas SA1 compares the interaction behaviors across dyad types and communicative situations, SA2 uses the interaction behaviors as input to a causal inference model. This will allow us to quantify how much each interaction behavior contributed to the associated participation outcome for that dialogue and rigorously simulate the effects of intervening on each interaction behavior. Assessment of the impact of each behavior will be done using Bayesian multilevel modeling. Results will inform a subsequent hypothesis-driven clinical trial of interaction targets.

NIH Research Projects · FY 2026 · 2023-05

PROJECT SUMMARY Approximately 16 million Americans serve as family caregivers for a person with Alzheimer's disease and related dementias and this care can take a physical and emotional toll. Understudied is how this informal care can affect caregiver cognitive health and associated daily sleep and activities, all of which are modifiable health behaviors. Engaging in personally meaningful, and cognitively stimulating activities can benefit cognitive and sleep health among dementia care dyads. Despite the importance of activity engagement for cognitive functioning and sleep quality, existing assessment of activities and outcomes is often self-reported asynchronously at global levels. Contemporaneous assessment of activities, sleep, and cognitive health and well-being would significantly advance research in this area by 1) conducting objective assessments on daily sleep and activities within a dyadic context, 2) determining how the social context of caregivers' assistance for the individuals with dementia's activity engagement moderates the associations between cognitive health and well-being, and daily sleep and activities, and 3) determining how a chronic stress biomarker, hair cortisol concentration, mediates the activities- and sleep-cognition associations in naturalistic settings. The proposed mentored career development award combines a rigorous program of research, mentorship, and didactics to facilitate the candidate's growth toward an overall career goal of becoming an independent investigator focused on informing the design of interventions for aging caregiving dyads with complex care needs including dementia to improve both partners' well- being. The training aims will assist the candidate in acquiring: 1) grounded knowledge of clinical care and educational needs among care dyads relating to neurocognitive assessment, functioning, and understanding the clinical aspects of dementia, 2) specialized skills in the assessment, analysis, and interpretation of daily sleep and activity measures and the biological measure of chronic stress that link to the dementia care situation and specifically to caregiver cognitive health and well-being, and 3) expertise in the application of intensive repeated measures designs that will generate novel insights on proximal risk and protective factors for poor caregiver outcomes within the dyadic context. The training aims seek to further develop the candidate's expertise as an interdisciplinary researcher in the area of later-life dementia family caregiving and align closely with the research aims to: 1) quantify caregiver daily sleep characteristics with actigraphy and determine their associations with caregiver cognitive functioning and well-being; 2) quantify caregiver daily activity characteristics with accelerometry and determine their associations with caregiver cognitive functioning and well-being; and 3) To characterize how caregiver assistance for PLwD's activity engagement moderates, and how hair cortisol concentration mediates associations of sleep➔cognition and activities➔cognition. An integrated, biopsychosocial approach to identifying protective factors that promote resilience and reduce harmful risk factors will inform the development of future targeted caregiver interventions in the dyadic context for a highly vulnerable aging population.

NIH Research Projects · FY 2024 · 2022-04

PROJECT SUMMARY / ABSTRACT This is an application for an administrative supplement to the original R15 application "Arousal and Timekeeping in a Mouse Mode of Parkinsonism" to extend our studies to mouse models of Alzheimer's Disease. Neurodegenerative disorders like Parkinson’s Disease (PD), Huntington’s Disease, and Alzheimer's Disease (AD) are characterized by drastic impairments in planning, as well as cognitive deficits, some of which stem from deficits in estimating durations. Estimation and reproduction of durations in the seconds-to-minutes range are critical for fundamental processes such as associative learning, planned motor responses and decision-making. We propose to extend the original project to evaluate timed motor response deficits in a mouse model of AD. We will investigate the role of arousal in alterations of timed response selection using a newly developed model of timed response selection deficits. We will also evaluate pharmacological approaches to rescue motor timing deficits. The project will enhance our understanding of neuronal processes involved in cognitive and motor control deficits in neurodegenerative disorders, and will help develop new treatment strategies in animal models, with possible subsequent impact on clinical treatments.

NIH Research Projects · FY 2025 · 2021-09

PROJECT SUMMARY Cell behaviors and tissue developments often occur under spatial constraints (e.g., interstitial space, tissue lining, skull enclosure). The current in vitro systems are often open cultures, and thus miss the spatial constraints and other in vivo stimuli. The current in vivo models are often low throughput and hard-to-trace, therefore unable to unravel the complex interplay between intrinsic influences (e.g., genetics/epigenetics) and extrinsic ones (e.g., micro-environment). For example, cell membrane blebbing and brain folding are fundamental and impactful bio-behaviors under spatial constraints. Their biophysical and molecular mechanisms are not well understood. Lately, several experimental and theoretical tools have emerged to fascinate the modeling of complex bio-behaviors. This proposed study aims to parameterize morphological information, relate to the complex influences under spatial constraints, and unravel the mechanism of bio- behaviors in the two exemplified areas. It will be done through a morphome platform that integrates several experimental-theoretical tools (e.g., tissue-on-a-chip, data-driven modeling, machine-learning), which has been pre-defined by PI and Co-Is. We hope to 1) fill the compelling gaps in our understanding of membrane blebbing and brain folding process and 2) establish an effective strategy to uncover a broad range of basic biological processes.

NIH Research Projects · FY 2025 · 2021-04

Project Summary / Abstract Recent research has established that epigenetic information inherited from the father has an impact on the physiology of his children, and that this information varies depending on environmental exposure and metabolic status of the father. There is also now a substantial body of evidence that paternally inherited epigenetic information may contribute to childhood obesity and other significant public health problems, depending on paternal diet. Mechanistic insights are still scarce, however, and it remains unclear which dietary factors may be able to modify epigenetic programming of sperm in a way that affects metabolism in the offspring. Addressing this important problem, this project will test the central hypothesis that reduced paternal metabolic nicotinamide adenine dinucleotide (NAD+) levels result in heritable sperm-borne epimodifications that modulate offspring metabolism. NAD+ is a central molecule involved in energy metabolism and it also serves as a substrate of epigenetic regulators such as sirtuins, including histone deacetylases, and poly(ADP- ribose) polymerases involved in sperm epigenetic programming and the regulation of energy metabolism. Vitamin B3 (niacin, nicotinamide) is the main dietary precursor of NAD+ synthesis in humans. This project proposes to utilize an innovative transgenic mouse model of acquired niacin deficiency (ANDY) that permits for the first time to study effects of low NAD+ levels, as seen in parts of the human population, in a laboratory animal. Our preliminary data show that suboptimal levels of NAD+ in ANDY males resulted in progeny with smaller body size, altered insulin sensitivity, and altered carbohydrate and lipid metabolism, which indicates that the micronutrient niacin may be of previously unrecognized importance for epigenetic programming of sperm. The objectives of the proposed work are (1) to characterize the metabolism of NAD+-deficient males and their F1 progeny, where we expect to identify heritable adaptations of energy metabolism that depend on paternal nutritional status, (2) to test the hypothesis that low NAD+ levels in males result in elevated sperm histone acetylation and differential sperm histone positioning, which are expected to include metabolic genes whose regulation is affected in F1 progeny, and (3) to determine the nature and extent of altered gene expression profiles in F1 progeny. We further propose to determine the extent to which pharmacological intervention, e.g. supplementation therapy, can prevent such changes. We expect that DNA methylation levels will be altered in gene loci in offspring as a consequence of abnormal sperm histone acetylation in NAD+-deficient sires. In summary, the proposed studies are expected to establish NAD+ as a molecular link between paternal nutrition and metabolic state, sperm chromatin-mediated epigenetic inheritance, and the regulation of offspring metabolism, including metabolic disease. The expected results should be relevant for the future development of avoidance and periconceptional nutritional supplementation strategies for men with the goal to maximize chances that children are born healthy.

NIH Research Projects · FY 2026 · 2020-08

Project Summary Gaining a functional understanding of newly discovered immune systems (e.g. newly discovered CRISPR systems) will lead to novel molecular tools for use in science and medicine is the overarching hypothesis of my research program. Over the last 5 years we have generated a large amount of data supporting this hypothesis. Our efforts uncovered a distinct CRISPR associated (Cas) enzyme called Cas12a2 that can be programmed to selectively kill cells upon specific recognition of RNA sequence (project 2), creating new possibilities for targeted cell therapies and gene editing enrichment. With another CRISPR system (Type IV), we discovered another distinct programmable activity that may be able to be repurposed to silence gene expression while keeping targeted nucleic acid intact (project 1). The vision of my research program over the next five years is that we will determine, in deep enough detail, how the Type IV-A system and SuCas12a2 function to repurpose them as tools while expanding our studies into related but unstudied immune systems. Our specific goals for project 1 include (i) determining the role of CasDinG N-terminal domain that is essential for immune system activity, (ii) exploring how Type IV systems could be used to silence gene expression in mammalian cells, and (iii) determining the structure and function of other Type IV subsystems (e.g. Type IV-B and IV-C). Our goals for project 2 include (i) defining the determinants of SuCas12a2 activation by solving structures of Cas12a2 bound to mismatched targets and distinct PFS sequences and performing kinetic assay with diverse substrates, (ii) determining the distinct biochemical activities of Cas12a2 orthologs, and (iii) determining structures of Cas12a2 orthologs. To better understand the biological function of these immune systems, we are using cell-based and biochemical assays and are determining structures of immune system components at all stages of immunity using structural methods (x-ray crystallography and cryo-electron microscopy). We aim to determine how these systems identify their targets, how they distinguish self from non-self, and how distinctions from other immune systems (protein domains and genes) impact their function. Knowledge of these foundational mechanisms and their distinctions from existing CRISPR-based tools will be critical for repurposing these immune systems into novel molecular tools.

NIH Research Projects · FY 2026 · 2018-02

Project Summary Understanding complex, comorbid conditions of intellectual developmental disorder (IDD) is an NICHD priority. Severe problem behavior (e.g., self-injurious behavior, aggression) of children with IDD is prevalent, potentially dangerous, and negatively impacts social integration and quality of life. Function-based differential- reinforcement-of-alternative-behavior interventions reduce such behavior effectively, but treatment relapse is common when a caregiver cannot deliver reinforcement for the alternative behavior. Such relapse is known as resurgence. Previously, we developed a quantitative theory of resurgence based on two well-established principles: (1) individuals allocate proportionally more responding to options that produce proportionally more reinforcement, and (2) the value of past reinforcement decays hyperbolically as time passes. The theory provides a quantitative account of behavior in dynamically changing reinforcement conditions, including when all reinforcement ceases (i.e., extinction)—the conditions giving rise to resurgence. In Period 1 of this project, we showed the quantitative accuracy of many of the theory’s predictions with laboratory animals and we have shown similar relations in resurgence of severe problem behavior of children with IDD in the clinic. However, the most important and promising finding from Period 1 was one the theory failed to predict. We found that exposure to a treatment (i.e., contingency discrimination training, CDT) involving alternating sessions in which alternative reinforcement was and then was not available during continued extinction of a target response substantially mitigated resurgence. To account for these effects, we have developed a refined version of the quantitative theory suggesting that individuals exposed to CDT rapidly learn to discriminate the continued unavailability of reinforcement for the target behavior, even when reinforcement is not available for the alternative response, thus serving to inoculating them against later resurgence. These findings and the refined quantitative theory from Period 1 suggest promising, innovative, and unexplored procedures for treating severe problem behavior that are likely to produce better resurgence mitigation than existing approaches, while also avoiding some downsides of the current methods to mitigate resurgence of problem behavior (i.e., arbitrary stimuli that caregivers may lose or use incorrectly). Period 2 of this project will focus on this highly innovative approach identified in Period 1 in two aims by conducting: (1) the first randomized controlled trial evaluating the resurgence-mitigating effects of CDT on severe problem behavior of children with IDD and (2) a series of experiments with laboratory animals testing the refined theory under a range of conditions predicted to improve the efficacy, efficiency, and practicality of CDT in future clinical applications. This project represents a close collaboration between basic and clinical scientists with a demonstrated ability to use basic quantitative theoretical and empirical research to improve clinical practice to prevent relapse of severe problem behavior, and thus, to reduce its devastating impact on children and their families.