University Of Tennessee Knoxville

NSF Awards · FY 2024 · 2024-07

Age at death estimates are critical for the study of demography and health in past populations and for correct identifications in forensic cases. However, the accuracy and reliability of age estimation methods based on the human skeleton have limitations resulting from biases in the age, ancestry and sex composition of the collections originally used to develop them. This project advances research on an alternative skeletal age-estimation method based on the analysis of chemical changes that occur in human DNA as we age and can be preserved in the skeleton. To date, applications of such epigenetic methods have been primarily limited to blood and cheek DNA sources. This study advances epigenetic methods that use DNA extractions obtained from bone. Workshops to learn the theory and application of this new method are open to students, faculty and other researchers. Engagement and outreach opportunities are offered through Ohio State University’s Anthropology Outreach Program. These opportunities introduce participants to epigenetic methods as applied to studies of human variation, and aging and health in the past. A high-quality short film about the anthropology of aging and the epigenetic clock is made freely accessible to other researchers and the public. This study develops a new method for biological age estimation from the human skeleton, using a genome-wide age-associated DNA methylation approach tailored to damaged/degraded DNA. The project aims to: (1) develop and validate a cost-efficient, robust-to-degradation, genome-scale method for methylation typing, (2) develop a high-quality predictive model of age from methylation signals in bone, and (3) characterize the potential impact of lifestyle factors on any discrepancies between chronological and biological (DNA methylation) ages. Parts 1 and 2 of this study are based on an integrative genomic-osteological analysis of 100 individuals with documented age, sex, and postmortem exposure to various taphonomic conditions from the University of Tennessee, Knoxville, Donated Skeletal Collection. The project integrates epigenomic, osteological, and lifestyle data, broadening the applications of this method. The study analyzes the relationship between biological and chronological age in the context of osteological signs of aging and stress, differentiating the biological and developmental roots of osteological traits used to estimate age in past populations and individuals. This project is jointly supported by the NSF Biological Anthropology program and the National Institute of Justice, Office of Investigative and Forensic 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.

NSF Awards · FY 2024 · 2024-06

Non-technical Abstract: This award partially supports the International Symposium on Crystalline Organic Metals, superconductors, and magnets (ISCOM), which will be held from September 22 - 27, 2024 in Anchorage, Alaska (USA). This is the 15th workshop in the ISCOM series which was started in 1995. Typically, these meetings alternate between Europe, Asia, and North America but has not been held in the United States since 2005. The symposium will balance theory and experiment with coverage of many contemporary issues. This symposium is designed to inspire new collaborations and provide opportunities for the education and growth of a diverse group of young people including via a student tutorial session before the main conference. Technical Abstract: This conference aims at advancing the fundamental understanding of molecular and molecule-based materials, which includes cutting edge topics in condensed matter physics such as non-equilibrium phenomena, particularly in high magnetic fields; molecular ferroelectrics multiferroics and chiral system; and competing interactions, electron correlations, and superconductivity in low-dimensional systems. A diverse set of US and international researchers present in the student tutorial and the technical sessions, with a priority on highlighting the work of young 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.

NIH Research Projects · FY 2025 · 2024-06

Project Summary Controlling medical device associated infections is an unmet challenge due to high-level tolerance to antibiotics. An important mechanism of such tolerance is the formation of persister cells, which are non- growing phenotypic variants of bacterial cells. Because conventional antibiotics attack bacteria by inhibiting cell growth related behaviors such as cell wall and protein syntheses, they are not effective against persister cells. The capability to escape antibiotic treatment by persister formation and reestablish the bacterial population after treatment is an important intrinsic mechanism of bacterial multidrug tolerance, which leads to chronic infections and facilitates the development of multidrug resistance through acquired mechanisms based on mutations and drug resistance genes. Despite the significance of persister cells, the mechanism of persister formation is still not well understood and control of persister cells remains challenging. One major hurdle to persister research is the lack of an animal model of bacterial persistence that is essential for understanding host response to persister cells and for testing new antimicrobials and biomaterials for persister control. To address this grand challenge, this team will construct the first in vivo model to control and monitor persister formation using blue light. An Escherichia coli strain will be engineered using synthetic biology. Exposure to blue light will induce the toxin gene hipA and repress the antitoxin gene hipB in this strain, leading to high-level persister formation. This process will be reversed by moving cells to the dark, resulting in persister wakeup and reversion to normal cells. Additional components will be included to label all cells with constitutively expressed green fluorescence protein (GFP) and normal cells with bioluminescence expressed under a growth-rate-dependent promoter. After in vitro test, the constructed strain will be validated in an in vivo mouse model of subcutaneous biomaterial infection with an engineered device that generates blue light wirelessly. Persister formation and antibiotic treatment will be tested in this model. The effects will be monitored using whole-animal imaging and the results will be corroborated with microbiological and histopathological analyses after the mice are euthanized. This research team aims to better control persistent infections such as those associated with implanted medical devices. This project will lead to an important millstone toward this ultimate goal by constructing the first animal model of bacterial persistence. With the capability to control and monitor persister formation noninvasively and in real-time, this system will be useful for both fundamental study of bacterial physiology and for drug discovery and biomaterial design against this antibiotic tolerant population. Thus, this project falls well within NIH’s definition of being contributive to "improve people's health and save lives”.

NIH Research Projects · FY 2026 · 2024-01

PROJECT SUMMARY/ABSTRACT Obesity is a complex disease, and innovative treatments that enhance initial and long-term weight loss are needed. One novel treatment approach uses a biobehavioral framework, focusing on time-based energy intake goals (how energy intake is distributed across the day). Time-based dietary goals are believed to promote synchronization of biological and behavioral circadian rhythms, and determining the health benefits of these goals is an objective of NIH’s nutrition strategic plan. Empirical testing of this time-based strategy is limited, and what has been conducted has been short-term (< 3 months) interventions. That said, current findings support that eating more energy earlier in the day and less energy later in the day increases weight loss during obesity treatment. The effect usually starts early in treatment and increases over time, but sustained impact is unexplored. One mechanism for this relationship is enhanced appetite regulation. Within a reduced energy diet, goals that provide a morning-loaded energy distribution result in lower hunger, reduced desire to eat, and/or greater fullness ratings than goals that provide an afternoon/evening-loaded energy distribution. However, the relationship between appetite regulation changes and weight loss has not been examined. Finally, chronotype, an individual’s preferred timing of daily activities thought to reflect circadian rhythms, may moderate the effect of time-based dietary goals. No investigation has examined the influence of chronotype on the relationship between distribution of energy intake and weight loss. To address these gaps, we will test the more longer-term (12 months) effect of time-based energy intake goals on weight loss. We will explore if enhanced appetite regulation is a mediator of the relationship and whether chronotype moderates the effect. For this, 174 adults with overweight or obesity will be randomly assigned to one of three, 12-month lifestyle interventions: 1) Morning (a morning-loaded energy distribution); 2) Evening (an afternoon/evening-loaded energy distribution); or 3) Standard (no guidance on energy distribution). All conditions will receive the same reduced-energy, low-fat dietary prescription, in which the guidance on the eating window length and the number of eating occasions is identical; a physical activity goal; and a cognitive behavioral intervention. Assessments will occur at 0, 3, 6, and 12 months on anthropometrics, diet (24-hr recalls with time-stamped digital images verifying timing of intake, combined with continuous blood glucose monitoring to objectively assess for length of the eating window and number of eating occasions), sleep regularity (actigraphy), appetite regulation as assessed via ecological momentary assessment, and chronotype. We anticipate that Morning will have the greatest percent weight loss, earliest midpoint of energy intake, greatest sleep regularity, and better appetite regulation at 12 months. We will explore if appetite regulation mediates the relationship between time- based energy intake goals and weight loss, and if chronotype moderates examined relationships.

NIH Research Projects · FY 2026 · 2024-01

PROJECT SUMMARY/ABSTRACT Nutrient intake is a key factor in both maintaining and restoring good health but compliance with nutrition guidelines remains low. A better understanding of the factors controlling food choice and intake could inform more precisely designed dietary recommendations, thus improving compliance, and ultimately curtailing the personal and public health burdens of chronic disease. Chief among the factors that influence food intake is taste. Taste buds are distributed in relatively segregated fields in the oral cavity, with ~70% of taste buds located on the tongue. Taste buds of the anterior tongue are innervated by the chorda tympani (CT) branch of CN VII and the posterior field is innervated by the glossopharyngeal nerve (GL; CN IX). Decades of taste nerve transection studies in rodent models suggest that the signals in these nerves do not contribute equally to taste functions. Input from the CT, along with that from the greater superficial petrosal branch of CN VII which innervates palatal taste buds, is essential for taste identification and discrimination. Input from the GL, in contrast, is critical to both oromotor rejection reflexes and, combined with the CT, avoidance responses to bitter tastes. Central to this proposal, in rats, the GL is critical for maintenance of normal corn oil preference. Although the lingual gustatory nerves are among the first to provide sensory information about food as it enters the alimentary tract, there is little research investigating how the information these nerves provide affects critical nutritionally relevant behaviors like food selection and meal patterning. Recently, we found that, in male rats, combined CT and GL transection (2Nx) alters food choices, leading to increased fat intake and reduced carbohydrate intake, concurrent with an increase in meal size and decrease in meal number. Thus, in rats, 2Nx affects the choice of foods and how those foods are consumed. Here, we propose to use our custom 5-Item Food Choice Monitor (FCM) to assess intake and meal patterns in rats of both sexes offered a cafeteria diet after transection of the CT (CTx), GL (GLx), 2Nx, or sham surgery to determine the relative role each nerve plays and how they interact to produce the changes in macronutrient intake and meal patterns that were revealed in our preliminary study after 2Nx. In an intriguing contrast to our preliminary study, earlier research found that after GLx, rats had lower corn oil (i.e., fat) intake with no change in chow intake. The disparity between this earlier study and our preliminary findings suggest food form or energy density could be a factor. Therefore, we will additionally compare meal patterns and intake of foods varying in form/consistency, fat content, and energy density in rats after CTx, GLx, 2Nx, or sham surgery to determine the role food characteristics may play. The combination of selective lingual gustatory nerve transections with meal-by-meal intake data from our state-of-the-art FCM analysis will provide a direct readout of how selective changes in sensory input affect motor output in the service of nutritional regulation while generating both publications and strong preliminary data to support a future R01 application.

NIH Research Projects · FY 2026 · 2023-12

Project Summary Deaf children who reach the age of eight without a foundation in language have longitudinal struggles in the areas of receptive and expressive language, working memory, executive functions, literacy and academic skills, and behavioral, mental, social, and physical health. The lack of intervention programs targeting sign language competencies during the critical period of development is a critical barrier to making progress in preventing or addressing language delays in deaf children. Strategic and interactive approaches driven by sociocultural, cognitive, and language theories have accumulated a large body of evidence documenting improvements in more complex oral and written language skills. Cross-linguistic transfers between oral and writing skills within and across first and second languages are well-established in the literature. Taking these factors into account in addition to growing evidence that sign language skills positively predict literacy skills and may lead to improved health outcomes, it is critical to systematically support deaf children’s sign language competences as early as possible. To address the identified critical barrier to progress, these are the aims of this project: (1) develop Strategic and Interactive Signing Instruction (SISI), an intervention program to target the development of sign language skills in deaf children aged 5-8; (2) refine SISI training and implementation protocols; and (3) test the efficacy of SISI in improving deaf children’s sign language skills. First, a SISI manual will be developed for standardization and consistency in training, implementation, and fidelity. The SISI manual will include: (a) descriptions of strategic and interactive approaches and their new applications to develop sign language skills, (b) SISI intervention protocols, (c) SISI fidelity checklist, and (d) list of sign language skills that are targeted in SISI. Second, an experimental study will be conducted to assess the extent of training and support required from teachers to become proficient in SISI implementation. Meanwhile, child progress in meeting their target sign language skills will be monitored formatively, and modifications may be made in an iterative design fashion to strengthen the intervention design. Third, another experimental study will be applied to assess the efficacy of SISI in improving deaf children’s sign language skills. Findings will provide robust data on the mechanisms of successful training dose, intervention design and fidelity, and data collection protocols in preparation for subsequent R01 application involving a large randomized controlled trial with sufficient statistical power to further strengthen evidence of SISI in improving deaf children’s sign language skills along with examinations of cross-linguistic interactions in the written form. This project is innovative in its new applications of theory-driven strategic and interactive approaches to target sign language development in deaf children.

NIH Research Projects · FY 2025 · 2023-09

Many patients take surgical interventions to fight the battle against heart disease. Surgical successes are critical to the patients’ health and their family well-being. For e.g., atrial fibrillation (AF) is the most common arrhythmia in elder population. Catheter ablation is an established treatment for AF, which sequentially creates incision lines to block faulty electrical pathways. However, there are large variations in surgical outcomes. Modern healthcare systems are investing heavily in sensing and computing technology to increase information visibility and cope with disease complexity. Massive data are readily available in the surgical environment. Realizing the full data potential for optimal decision support depends on the advancement of information processing and computational modeling methodologies. Our long-term goal is to advance the frontier of precision cardiology by developing new sensor-based modeling and simulation optimization methodologies. The objective of this project is to optimize AF ablation by integrating simulation-enabled planning with physics-augmented machine learning of sensor signals from patients who underwent AF ablation. This objective will be accomplished by pursuing 3 specific aims: 1) Physics-augmented artificial intelligence (AI) for cardiac modeling – This approach will assimilate heterogeneous sensing data and incorporate electrophysiology prior knowledge into deep learning to increase the robustness of decision making under uncertainty, thereby driving computer simulation into clinical applications; 2) Optimal sensing and sequential learning of space-time AF dynamics – This approach will provide quantitative knowledge of disease mechanisms instead of subjective knowledge that is difficult to translate (or transfer), thereby reducing healthcare disparity due to the availability of human experts in rural areas; 3) Integrating sensor-based learning and simulation optimization for surgical planning - This approach will integrate physics-augmented modeling (Aim 1) and sensor-based learning (Aim 2) with simulation optimization to improve the clinical practice towards data-driven & simulation-guided surgical planning. This project will make a major breakthrough towards precision cardiology by (i) going beyond the current practice of largely expert-based or ad hoc decisions, (ii) capturing underlying complexities in space-time cardiac dynamics, and (iii) integrating physics-based modeling, sensor-based learning, and simulation-based planning for surgical decision support.

NIH Research Projects · FY 2026 · 2023-08

Project Summary/Abstract Genome integrity is essential to life. Considerable efforts are made to maintain the stability of genomes. Yet genomes also undergo constant changes, often random and small in scale, providing mechanisms for evolution and adaptation. In contrast, programmed DNA elimination is a dramatic form of genome change with large amounts of DNA, ranging from 0.5 to 95% of the genome, eliminated during development. DNA elimination is highly selective and reproducible and is an integral part of biology for diverse organisms, including single-cell ciliates, a variety of multicellular organisms across animal phyla and some plants. The broad phylogenetic distribution suggests DNA elimination has evolved independently and has important biological functions. A common theme for metazoan DNA elimination is the removal of both germline-expressed genes and repetitive sequences. This suggests that a possible function of DNA elimination in metazoa is to permanently silence certain germline sequences potentially harmful to somatic cells. Despite progress in genomics and cytology, functional and mechanistic studies of metazoan DNA elimination are limited, largely due to the lack of genetic and functional tools. Recently, we built upon and extended a genomic observation and established a genetic and functional model for DNA elimination in the free-living nematode Oscheius tipulae, a member of the Rhabditidae family, which includes Caenorhabditis elegans. We show that DNA elimination in O. tipulae occurs during 8-16 cell embryos. We identified and characterized a conserved sequence (Sequence For Elimination, SFE) motif associated with the DNA break sites and demonstrated its direct role in DNA elimination. DNA breaks occur within the motif, followed by end resection and telomere healing. Additional breaks occur simultaneously in the eliminated DNA, perhaps serving as a fail-safe mechanism for DNA elimination. We revealed the abundance and variations of this motif in many wild isolates of O. tipulae from around the world. In this proposal, we will (1) study the functions of DNA elimination in O. tipulae by characterizing the fail-to-eliminate phenotypes from CRISPR edited SFE mutants. We will use RNA-seq, ChIP-seq and small RNA sequencing to determine the changes of RNA expression and silencing mechanisms in these mutants. We will also (2) study the molecular mechanisms of O. tipulae DNA elimination by investigating the sequence and genomic position required for SFEs using CRISPR, as well as proteins that interact with SFEs using in vitro biochemistry, bioinformatic predictions, and genetics. We will further (3) study the variations of DNA elimination by building telomere-to-telomere genomes for divergent strains of O. tipulae, identifying SFEs, and carrying out comparative genomics. Overall, this proposal will use our established genetic model in the free-living nematode O. tipulae to examine the functions, mechanisms, and variations of DNA elimination. This work will reveal insights into the molecular details of DNA elimination in a metazoan.

NIH Research Projects · FY 2025 · 2023-07

PROJECT SUMMARY The vaginal tract is a harsh, polymicrobial ecosystem that has an active immune response, is rich in cervicovaginal mucins, and has a robust microbiota. Bacterial persistence within this environment requires the ability of organisms to adapt to changes in nutrient availability and to interact with the other members of the microbiota. The vaginal microbiota is classified by five community state types, in which state types I, II, III, and V are dominated by Lactobacillus species, while community state type IV is marked by increased community diversity and is loosely termed “dysbiotic”. Our definition of what constitutes vaginal health is evolving; however, our understanding of the fundamental principles that impact community structure and function, and the role individual microbes have in community stability is unknown. Determining the interactions that contribute to persistence within this dynamic environment is challenging, as these are multifactorial in nature. Here, we propose interdisciplinary approaches to understand the microbial ecology of the vaginal tract and advance our basic knowledge of vaginal health. Our objective is to determine how the nutritional landscape within the vagina impacts microbial community assembly, structure, and interactions, that together, contribute to persistent colonization. We will define metal availability within the vaginal tract and use these data to understand how changes in the environment shape composition and function of bacterial communities. From this, we will identify differential importance of bioavailable metals for persistence and expansion of community members. We will investigate the mechanisms of metal ion homeostasis and determine their impact on cellular metabolism, cooperation, and competition within microbial communities. We will develop in silica models and validate mechanisms of metabolic interaction between members of the vaginal microbiota and determine the role of these interactions in community synergy. Our goal is to define how vaginal ecology drives community interactions and crosstalk to promote colonization in this complex environment. These findings have the potential to link metal availability, cellular metabolism, and microbial community structure in vivo. Together, this proposal will use synthetic vaginal communities to profile the genetic, physiological, and ecological mechanisms that drive microbial interactions in the vaginal mucosa. These findings will provide a better understanding of the ecological factors that contribute to vaginal community composition, stability, and interactions. This work will advance our fundamental knowledge and identify relevant therapeutic targets that could serve to promote efforts in maintaining vaginal health.

NIH Research Projects · FY 2025 · 2022-09

Microtubule-based kinesin and dynein motors drive a plethora of cellular processes, including intracellular transport of cellular cargo, assembly and function of the mitotic spindle, and ciliary function. While the chemical and physical properties of kinesins are well studied in vitro, much less is known about the specific function and regulation of kinesin motors in cells. The KIF3A/KIF3B/KAP motor, subsequently referred to as kinesin-2, drives intracellular transport of various cargos and is also essential for intraflagellar transport (IFT), a specialized transport inside eukaryotic cilia. Cilia are protrusions of the plasma membrane that are supported by a specialized microtubule structure called the axoneme. Primary cilia are solitary and immotile cilia that sense various stimuli in a tissue-specific manner. They can, for instance, sense the presence of morphogens during development, odorants in the nasal cavity, or the strength of urine flow in kidney tubules. Given these essential sensory functions, it is not surprising that ciliary malfunction underlies many diseases that are collectively classified as ciliopathies. During IFT, large protein assemblies called IFT trains are continuously transported within cilia. The IFT trains are loaded with specific cargo at the ciliary base and subsequently recruit kinesin-2 motors for transport along the axonemal microtubules to the tip of the cilium. There, the kinesin-2 motors are released, specific cargo is unloaded, and the trains are remodeled for subsequent transport back to the ciliary base by dynein-2. It is well established that the loss of any subunit of the kinesin-2 motor leads to the complete absence of cilia, and interference with IFT leads to the disappearance of already established cilia. From experiments with the single-celled flagellate Chlamydomonas we know that tubulin influx into cilia via IFT is modulated as a function of cilium length. Based on this finding several recent models aimed at explaining the impact of IFT on cilium length and cilium maintenance attribute high importance to the ciliary tubulin concentration. However, the change in tubulin concentration in these models cannot explain all experimental findings and it is likely that other aspects of IFT in addition to tubulin import are important for ciliary length and structure. Thus, the importance of IFT for the ciliary structure and the regulation of kinesin-2 motor for IFT is only incompletely understood, especially in mammalian systems. In this proposal, we will use a combination of biochemical & cellular assays, protein & genome engineering, and high-resolution microscopy to study how kinesin-2 is regulated for IFT and to delineate the impact of kinesin-2 driven IFT on the structure of mammalian cilia. At the center of our approach are engineered kinesin proteins whose activity can be precisely regulated in time and space externally by the investigator. The work laid out in this proposal will shed light on the function and regulation of kinesin motors in mammalian cilia and thereby promote the development of therapies aimed at alleviating or curing motor protein-associated human diseases.

NIH Research Projects · FY 2025 · 2022-08

Project Summary Medication adherence is thought by many providers and researchers to be the most important self-care behavior, yet it is also the most problematic. Poor medication adherence can cause poor quality of life (QoL), hospitalization, and death. In the United States, approximately 125,000 deaths per year are due to poor medication adherence and up to 50% of heart failure (HF) patients are re-hospitalized within 6 months of a previous HF exacerbation and one of the most common causes is poor medication adherence. Lifelong and usually complex medication regimens are needed for patients with HF, yet 40-60% of HF patients have suboptimal medication adherence. Health literacy plays a significant role in suboptimal medication adherence. Support by a care partner (CP; usually a family member) can improve adherence and reduce hospitalizations. Although some interventions have improved HF patients’ adherence, improvements were small, and effects were not sustained. To enhance and sustain intervention effects, we will use an approach that is literacy- sensitive and incorporates social support. Using easy-to-understand language for patients and CPs, we will test an interactive, behavioral, family-focused and literacy-sensitive (FamLit) intervention delivered by nurses, incorporating evidence-based, multi-components (e.g., teach-back, coaching, role-playing, goal setting) to engage both patients and CPs in improving and sustaining medication adherence and health outcomes. We will conduct a randomized controlled trial to evaluate the efficacy of FamLit intervention on medication adherence, hospitalization, death, and QoL. We will randomly assign 164 dyads of patients and their primary CPs (patients-CPs) to either the FamLit intervention or an attention-control group. Both groups will have an in- person session (delivered on the day of a clinic appointment for regular follow-up) one month after baseline and phone boosters every other week for up to 3 months. FamLit group sessions will focus on improving medication adherence, and control group sessions will focus on general health issues. Our aims are to: 1) test the efficacy of the FamLit intervention compared to an attention control group on outcomes (i.e., primary: medication adherence, and secondary: a) HF hospitalization or all-cause death, b) QoL, c) social support, and d) communication) over 12 months; 2) determine if TPB-related intermediate outcomes (attitudes, subjective norms, perceived behavioral control) mediate the effects of the intervention on medication adherence; 3) examine whether each dyad member’s a) health literacy, b) social support, and c) communication moderate the effect of the FamLit intervention on medication adherence; and 4) determine how each dyad member’s attitudes, subjective norms, perceived behavioral control, social support, and communication affect their own and their partner’s QoL over 12 months using the innovative Actor-Partner Interdependence Model. The FamLit intervention, if efficacious, holds potential to improve/sustain medication adherence and reduce hospitalizations and death. We will follow up with an effectiveness-implementation hybrid trial as our next step.

NIH Research Projects · FY 2025 · 2022-08

PROJECT SUMMARY Intracellular membrane-bound organelles are a hallmark of all eukaryotic cells. Understanding how cells generate different organelles remains one of the central problems in cell biology. Some organelles, like the endoplasmic reticulum (ER) and mitochondria, are self-generating whereas other organelles can be generated de novo. The ER plays a central role in organelle biogenesis. Even though the ER is a single continuous membrane that extends from the outer nuclear envelope into the periphery of the cell, there are discrete regions in the ER membrane called ER subdomains. Nascent peroxisomes and lipid droplets (LDs) form at specialized ER subdomains. Remarkably, little is known about these ER subdomains and their role in regulating organelle biogenesis. The goal of our research is to determine the mechanisms of peroxisome and LD biogenesis by detailed characterization of the discrete ER subdomains using S. cerevisiae and mammalian cell culture. Previously, we identified a family of reticulon-like ER membrane tubulating proteins, Pex30 in yeasts and multiple C2 domains containing transmembrane proteins, MCTP1 and MCTP2, in higher eukaryotes. We demonstrated that both Pex30 and MCTPs are localized at discrete ER subdomains where nascent pre-peroxisomal vesicles and LDs are formed. Based on these findings, we proposed to identify the proteins and lipids enriched at the specialized ER subdomains using unbiased as well as candidate-based approaches. We will then test the effects of modulating the functions of candidate proteins and lipids on the formation, abundance, morphology, and distribution of peroxisomes and LDs. Investigating the mechanistic details of peroxisomes and LDs biogenesis from these ER subdomains is not only important for understanding basic principles of cell biology but also has critical medical implications. Several life-threatening neurological disorders including Zellweger syndrome associated with peroxisomal defects and metabolic disorders such as type 2 diabetes and fatty liver disease caused due to LD defects have no cure. Determining the mechanisms of organelle biogenesis will have implications in understanding the pathophysiology of these disorders and provide us hints for potential therapeutic targets.

NIH Research Projects · FY 2025 · 2022-07

Project Summary Deuterium labeled medicines are being used to develop safer alternatives to existing therapeutics and improve the safety of current drug candidates. Despite the tremendous promise that novel deuterated small molecules have in the development of new medicines, methods to incorporate deuterium into molecular scaffolds are primitive. While the synthetic organic chemistry community has grown accustom to highly selective transition metal-catalyzed reactions for the creation of new C–C, C–O and C–N bonds, deuterium installation should also be possible with full stereocontrol and minimal over- and under-deuteration impurities. Not only is highly selective deuteration rare, but spectroscopic techniques to support advances in this field are inadequate. We are launching a holistic research program to not only develop highly selective reactions for deuterium incorporation but pioneer the expansion of analytical techniques required to support the development and use of these reactions among the broader scientific community. Through our established collaboration with leaders in the spectroscopy field, we have started to develop analytical techniques that provide the foundation for accurate characterization and identification of deuterated small molecules. Our preliminary studies indicate that deuterium can be installed precisely into small molecules. In many cases, isotopomer and isotopologue impurities are so minimal that they are nearly undetectable. Our research is now positioned for expansion into broader classes of organic molecules. We will develop new Cu-catalyzed transformations for the selective deuteration and hydrodeuteration of alkenes and alkynes. These transformations will precisely insert deuterium in a small molecule and be compatible with compounds that contain functionality commonly found in small molecule drugs. We anticipate that in the next 5 years, our synthetic strategies and analytical methods will address significant portions of the outlined considerations. This will drastically expand the development of novel deuterated therapeutics to address many of the safety and tolerability problems plaguing modern medicine. Beyond deuterium incorporation, we are proposing to develop new reactions for the regioselective hydrofunctionalization of internal aryl alkynes. Powerful methods for regioselective Cu-catalyzed alkyne hydrofunctionalization exist but are mostly limited to terminal alkynes and symmetrical internal alkynes. Consequently, there exists a major void in the synthesis of a-substituted styrenes. To access these molecules from alkynes, we are proposing to develop a-selective Cu-catalyzed internal aryl alkyne hydrofunctionalization reactions. The research will benefit from deuteration studies performed in our group to develop new Cu-catalyzed alkyne hydrodeuteration reactions. The unprecedented regioselectivities obtained in our ongoing investigations will serve as the starting point for developing the proposed Cu-catalyzed a-selective internal aryl alkyne hydrofunctionalization reactions.

NIH Research Projects · FY 2025 · 2022-07

Project Summary/Abstract The objective of this proposal is to create dexterous steerable instrument sheaths that enable patients who currently are subject to invasive surgeries to receive minimally invasive endoscopic interventions. Clinical significance comes from (1) the high incidence of colon lesions – there are 6.3 million colonoscopies per year with 50% finding lesions, and (2) the difficulty of removing a subset of these (those with challenging sizes, shapes, or locations) due to the limited dexterity of conventional endoscopes. This results in over 60,000 patients per year in the USA with colon lesions that the very best endoscopists have demonstrated can be safely removed with an outpatient endoscopic procedure, who are instead subjected to invasive surgery to remove a section of their colon (i.e. colectomy surgery). This occurs because of the dexterity gap between the best endoscopists and typical endoscopists. We aim to close this gap with the new device described in this proposal. The innovation in our work is a new steerable sheath concept that harnesses elastic asymmetry to provide dexterity at the tip of a colonoscope. This dexterity reduces the difficulty of removing challenging lesions endo- scopically. Our controllably deflectable, thin-walled, tube-like device will be small enough to pass through the port of a conventional endoscope, while providing a large open lumen for surgical instruments to pass through. Its innovative mechanical design accomplishes this by dispensing with conventional pull-wires, hinges, and other bulky force transmission elements in favor of the push-pull interaction of two thin-walled tubes, which bend con- trollably via interacting regions of stiffness asymmetry at their tips. Our approach consists of three Specific Aims. Aim 1 addresses the construction of the steerable sheaths and their actuation systems. Aim 2 focuses on enabling dexterous physician control via a physician interface console, and optimization of device dexterity. Aim 3 consists of ex vivo and in vivo porcine experiments to demonstrate that the device enables physicians new to endoscopic dissection to perform with accuracy and efficiency similar to what elite endoscopists have shown can effectively and safely treat the 60,000 patients mentioned above. The endpoint of this project will be a device that has been validated in an animal model, setting the stage for rapid clinical translation after successful completion of this R01.

NIH Research Projects · FY 2025 · 2022-05

Project Summary/Abstract Wearable devices are the primary method for objectively assessing physical activity (PA) type and energy ex- penditure (EE) in free-living individuals. Current practice involves using only accelerometer-based devices, which are generally better for predicting outcomes at the group level rather than the individual level. A ceiling effect has been reached for accuracy and precision of accelerometer-derived predictions, and thus there is a critical need for other approaches that can yield more accurate and precise methods to classify PA type and estimate EE. A potential solution is to combine data from accelerometers with data from other sensors. Accelerometers record linear acceleration, which captures a large amount of human movement. However, many daily activities contain turning motions that are not captured by only using accelerometers. Gyroscopes record angular velocity, and thus may be useful in combination with accelerometers for capturing a richer picture of human movement. This can result in improved accuracy and precision when assessing PA type and EE. Using an ActiGraph GT9X (worn on hip, wrists, or ankles), we have previously shown that combining accelerometer and gyroscope data led to individual-level accuracy improvements of ~6%, compared to accelerometer only. Importantly, this in- cluded up to 30% improvement for classifying sedentary activities. In addition, classification accuracy between sedentary and non-sedentary behaviors when using only the accelerometer, ranged from 76.7-96.7% across wear locations, whereas the gyroscope correctly classified 100% of the time at all wear locations. The overall objective of this R01 application is to use gold standard measures of EE (doubly-labeled water, room calorimetry and portable indirect calorimetry) and activity classification (video direct observation) to develop and refine ma- chine learning algorithms using both accelerometer and gyroscope sensor data. The specific aims of the study are: 1) Develop and validate gyroscope-inclusive machine learning models that classify PA type and estimate EE in adults, using a 24-hr stay in a room indirect calorimetry (n=50) and 2-hr of semi-structured activities with portable calorimetry (n=50); 2a) Assess free-living performance of the models, and 2b) Re-train and refine the models using free-living data with ground truth from direct observation and portable indirect calorimetry (n = 100 participants during 12 hrs of free-living activity); and 3) Assess validity of EE models during a prolonged free- living period using the doubly-labeled water technique (n=100). The central hypothesis is that the gyroscope will provide meaningful and discriminative information on rotational movements that occur during human movement, thereby complementing the accelerometer data. Combining accelerometer and gyroscope sensor data will im- prove accuracy and precision for classifying PA type and estimating EE compared to using either sensor alone, and will have a significant impact on the ability to assess free-living PA in adults.

NIH Research Projects · FY 2025 · 2022-04

PROJECT SUMMARY/ABSTRACT Difficulty adhering to prescribed health behaviors significantly hinders the long-term benefits of lifestyle weight management programs, leading to an increased risk of cardiovascular disease (CVD) and early mortality. Although physical activity (PA) is one of the best predictors of sustained weight loss, long-term adherence to PA remains poor in adults with overweight or obesity enrolled in lifestyle weight management programs. Absence of accessible, effective, theory-based programs that account for each person’s values and preferences remains a major barrier. Thus, novel, person-centered, and scalable interventions are urgently needed to effectively promote PA adherence in adults with overweight or obesity to enhance weight loss maintenance and CVD prevention. The overall objective of this K01 Career Development Award is to expand and pilot test a theory- based PA program (called MOVE+) designed to enhance motivation in adults with overweight or obesity enrolled in a lifestyle weight management program. First, I will engage stakeholders to assess the initial acceptability of the MOVE+ intervention components. User-centered design testing will occur over 2 cycles: 1) initial stakeholder review of MOVE+ component design and content, and 2) a 12-week, single-arm field trial to pilot test delivery of the MOVE+ program. Second, I will evaluate the feasibility of delivering MOVE+ within an existing lifestyle weight management program (Prevent T2). I will recruit 80 adults with BMI 25-45 kg/m2 to receive 6 months (with 12 month follow-up) of remote delivery of the Prevent T2 program, integrated with the MOVE+ program. To isolate which MOVE+ components are “active ingredients”, I will employ the Multiphase Optimization Strategy and conduct a cluster randomized 2^3 full factorial pilot trial. Eight clusters of n=10 participants will be randomly assigned to a combination of 3, MOVE+ components. My long-term goal is to develop an independent research program that focuses on the prevention and treatment of chronic diseases, including obesity and CVD, by designing and disseminating theory-based, optimized PA interventions that promote sustained behavior change. Along with my mentorship team (Drs. Catenacci, Masters, Kwan, Conroy, Pfammatter, Pyle, and Ms. Barnard), I have developed a comprehensive training plan to support this career goal. My primary training goals include to develop expertise in: 1) the application of behavior change theory to PA intervention design, 2) dissemination and implementation science, 3) the use of novel frameworks and efficient trial designs, and 4) human clinical trial design and conduct. My past experience, complemented by my expert mentoring team, a robust training plan, and an exceptional environment (the University of Colorado Anschutz Medical Campus) will ensure my success. Completion of this K01 will generate critical preliminary data needed to support a competitive R01 application and will serve as both a superb training opportunity and as an original and meaningful scientific contribution to propel my career goal of becoming an emerging leader in PA and obesity research.

NIH Research Projects · FY 2025 · 2022-02

As the number and proportion of people aged 65 or older continue to increase in the United States, the number of Americans living with dementia is also growing. Among all dementia, Alzheimer’s disease (AD) and related dementia (ADRD) is the most common cause, accounting for approximately 60%-80% of the cases. Improving the care of people living with ADRD impacts the lives of not only the patients and their family but also the caregivers and their family, posing significant challenges to the well-being of the society. The purpose of this project is to exploit the autonomy and intelligence capability of a humanoid robot to comprehend, assist, relieve, and evaluate (CARE) patients with AD. The proposed Robotic CARE system has the capacity to detect the emotion and cognitive state of an AD patient, communicate and collaborate with the patient to accomplish basic instrumental activities of daily living (IADL) such as meal preparation, laundry, self-feeding, as well as help caregivers by reducing their levels of burden and stress. The proposed system could effectively bridge the CARE gap in our society, offering unprecedented potential for improving the quality of lives of both the patients and their caregivers. It is worth mentioning that the proposed Robotic CARE system is not to replace the caregivers, but rather to supplement the caregivers while providing companionship for AD patients since the system will learn to automatically assess patients’ cognitive state so as to better understand and respond to patients’ need. The CARE system is expected to advance the state-of-the-art in several related fields with its innovative and unique integration of cognitive assessment and rehabilitation with robot-assisted care. The proposed system makes contributions from three perspectives. First, cognitive assessment using instrumental activities of daily living (IADL) for patient-caregiver interaction will be conducted. Second, neurophysiological assessment using multimodal integration and unsupervised learning for patient-robot interaction will be conducted. Third, co-robot assessment using reinforcement learning for patient-robot-caregiver interaction will be conducted. The proposed team includes expertise from nursing with specialty in dementia care and gerontology, biomedical engineering with specialty in brain-computer interface, and computer science with specialty in machine/deep learning.

NIH Research Projects · FY 2025 · 2021-09

Project Summary/Abstract Our research program aims to directly probe how the complexity of living bacterial membranes impacts the adsorption, transport, and domain association of small molecules, including antibiotics. To address these points, we will leverage nonlinear spectroscopy and microscopy techniques, specifically second harmonic generation, to map the dynamic behavior. A key to our methodology is the ability to conduct the proposed experiments on living cells instead of model systems. For the next 5 years, our program goals are to (1) extract the key factors that influence the adsorption and membrane organization of small molecule membrane probes, (2) quantitatively assess the adsorption of tetracycline antibiotics and manipulate their movement within and through the membranes of different species of bacteria, and (3) examine the spatial dependence of small molecule-membrane interactions on individual bacteria as well as within biofilms. Together these studies will elucidate the role of how parameters including curvature, membrane domains, and the cell wall mediate small molecule uptake. We envision that this insight will provide new directions in the continued pursuit of improved antibiotics.

NIH Research Projects · FY 2025 · 2021-07

PROJECT SUMMARY/ABSTRACT The overall goal of my research project is to understand how the dynamic behavior of human G protein-coupled receptors (GPCRs) drives the assembly of GPCR complexes with drugs and partner signaling proteins at a single-molecule level. GPCRs are sensory membrane proteins that recognize a wide array of hormones, drugs, and neurotransmitters, representing the largest class of proteins targeted by FDA-approved therapeutics. The energy landscape of GPCRs is complex and populated by multiple conformers with distinct functions and structures. While the structures of some GPCR conformers have been characterized by x-ray crystallography and cryo-EM, the lifetimes of these different conformations and their rates of exchange are mostly unknown. We aim to map the energy landscape of GPCR complexes using single-molecule fluorescence (SMF), which enables the investigation of GPCR dynamics in real-time and in environments that recapitulate the cellular milieu. In the long term, we aim to apply this information to improve our understanding of how disease-associated mutations alter these energy landscapes, which may ultimately guide the design of new therapeutics. This proposal aims to apply SMF to map the energy landscapes of two human GPCRs. First, we will investigate the conformational dynamics of a representative class A human GPCR, the A2A adenosine receptor (A2AAR). A2AAR provides an important benchmark for single-molecule fluorescence studies and will enable us to compare our experimental measurements of dynamics to computational predictions. Our studies will reveal both similarities and differences in mechanisms of signaling between different class A GPCRs and will also show for the first time how lipids in the bilayer membrane can act as allosteric modulators of GPCR function. In the second direction, we will use SMF to study the conformational dynamics of the human glucagon receptor (GCGR). GCGR is a hormone- binding class B GPCR that is activated by one of the central metabolites, glucagon. GCGR is critical to glucose homeostasis and is a validated drug target for type 2 diabetes therapy. Crystal and cryo-EM structures of GCGR have shown that the large extracellular domains appear to act in concert with the transmembrane domain to bind hormones and small molecules, but the dynamics of ligand binding are as yet not understood. Our studies of GCGR will reveal in real-time the mechanisms of ligand recognition by the extracellular domain and quantify function-related dynamic fluctuations of the transmembrane domains. These studies will allow us to compare the dynamics of complex formation with hormones and with small molecules to understand the role of the extracellular domain in ligand recognition. This will help us understand how ligands with different chemical structures and pharmacological efficacies affect the receptor activation pathways and will ultimately aid in the design and screening of GPCR-targeted drugs with tailored pharmacological responses.

NIH Research Projects · FY 2025 · 2021-07

The Integrated Membrane Program (IMP) T32 Training Grant will address an important gap that exists in the biomedical workforce of the future. The IMP will address research training needs in the area of biological membranes (biomembranes), which are crucially important structures that define and separate physical spaces within and outside cells, making them fundamental to life on Earth. However, biomembranes do much more, as they control intracellular signaling and development, are required for energy production, mediate drug delivery and drug resistance, are essential for making essential cellular macromolecules, and affect growth and movement, which impacts cancer and other diseases. Thus, understanding biomembranes impacts many critical areas of biomedical research. Biomembranes research as a field covers the mechanisms by which membranes are synthesized from their constituent proteins, lipids, and carbohydrates, are trafficked and changed in response to the environment, and then in turn affect the many processes described above. Additionally, human manipulation of natural and synthetic membranes can be harnessed for myriad applications from computation to energy production to the development of new materials. Multiple fields and disciplines including biology, physics, chemistry, engineering, and computational science have applicability to biomembranes, but increasingly, there is a need for scientists who can bridge these fields and integrate different approaches to meet the next generation of research challenges. The University of Tennessee, Knoxville (UT) has unique breadth and depth in biomembrane research, with federally funded, collaborative researchers spanning 7 departments in 4 colleges. The 32 faculty in the IMP mentor pool have a shared commitment to establish a training program that will span fields and disciplines. These scientists are already working together through the establishment of the UT-facilitated Community of Scholars (COS) for Biomembranes, which has met 2-3 times every semester since 2018, and where many students have presented seminars on their research. The shared research, training, and overall momentum that exists within the Biomembranes COS forms the foundation for the IMP T32. Multiple investigators within the Biomembranes COS have ongoing collaborations that span fields and disciplines, and have co-mentored graduate students. The establishment of a T32-based IMP will formalize this integrated approach to training so these students can advance fundamental knowledge of biomembranes and apply this knowledge to improve human health. In addition to integrated training in science, the IMP will further enhance training in responsible conduct of research and reproducibility, which are already being addressed at UT, but will be formalized under this NIH T32 mechanism.

NIH Research Projects · FY 2025 · 2021-05

PROJECT SUMMARY We propose to develop peptide ligands that bind to membrane receptors known to malfunction in maladies such as cancer and autoimmune diseases. Our preliminary data indicate that we have designed several peptide ligands that can activate or inhibit different receptors. The basis of the efficacy of the peptides is that interactions between transmembrane (TM) domains is critical for receptor function. These peptides are intended to bind to the TM domain of their target to revert defective receptor activity. Membrane insertion of the peptides is controllable, as they are triggered by environmental acidity. We will also develop a new generation of peptides where membrane insertion is triggered by an array of different stimuli. This would provide means of targeting the peptides to the desired tissues. To improve our ability to study the interactions between TM domains, we will develop a new single-molecule method that allows us to obtain stoichiometric and thermodynamic information. These studies will be complemented with investigation of how TM domains influence lipid dynamics. In addition to the development of these peptide ligands, we will perform systematic analyses to understand the molecular mechanism by which similar peptides can activate or inhibit membrane receptors. Through this work we seek to provide promising new therapeutic approaches and invaluable functional knowledge of how peptide ligands can modulate disease- causing membrane receptors.

NIH Research Projects · FY 2024 · 2020-09

Project Summary/Abstract Ascaris remains a significant health problem in many parts of the world, infecting close to a billion people, many of them children, leading to significant morbidity. The related parasitic nematode Toxocara, causing human toxocariasis, also is increasingly being recognized as a significant public health problem in the United States. These parasitic nematodes undergo a novel form of genome re-organization, known as programmed DNA elimination. Very little is known regarding the function and molecular mechanisms of this DNA elimination process. Our recent work provides fundamental insights into this process demonstrating that DNA elimination is a conserved process in a group of parasitic nematodes serving to silence germline-expressed genes, particularly testis-specific genes, through their elimination in the somatic cells. Furthermore, we defined how holocentric chromosomes are dynamically re-organized to determine chromosomes regions that will be kept or eliminated. During Ascaris DNA elimination, DNA double-strand breaks are required to generate chromosomal fragments that will be eliminated. We identified 72 telomere addition sites where the presumed chromosomal breaks occur. These sites exhibit high fidelity in different somatic cell lineages and worms constrained within 3- 6 kb genomic regions and are called chromosomal breakage regions. Our analysis did not identify any specific sequence, structural features or common epigenetic factors that might specify or recruit molecular machinery to these regions. However, a prominent feature for these break regions is they become more chromatin accessible just before DNA elimination. Open chromatin is often a result of molecular processes that access the genome, including DNA replication and RNA transcription. In this proposal, we hypothesize that RNA transcription, R-loops, and/or DNA replication stress, as well as the three-dimensional genome organization may contribute to the key DNA breaks that initiate DNA elimination. We will examine these hypotheses in three specific aims: (1). Define when DNA break and telomere addition occurs during the cell cycle that leads to a DNA elimination mitosis; (2). Define DNA replication timing and stress, RNA transcription, and R-loops during DNA elimination; and (3). Map the 3D genome organization of the break regions. In addition to an understanding of the molecular mechanisms of the DNA breaks for Ascaris DNA elimination, the proposed studies will provide new information and insights into parasitic nematode chromosomes and chromatin organization, RNA transcription, DNA replication, DNA breaks and end resection, and telomere healing. Insights into these biological processes may identify novel molecular processes that could be potential drug targets in parasitic nematodes.

NIH Research Projects · FY 2024 · 2020-08

Project Summary Rural Appalachia is a medically underserved area whose residents experience significant healthcare disparities. Because of the insular nature of rural Appalachian communities, change from within is particularly important. Thus, attracting residents from these areas to the biomedical, behavioral, and clinical research workforce may be essential for reducing the critical health disparities in the region. However, we cannot assume that increasing science and math-related interest and skills will be sufficient to attract students from this region to these careers. Nationwide, high school graduates from low-income, low-minority, rural schools (which describes much of Appalachia) have the lowest college enrollment rate (44%; National Student Clearinghouse [NCS], 2015), suggesting barriers and supports related to higher education in general must be addressed in addition to barriers and supports related to science, technology, engineering, math, and medical science (STEMM) related careers. Our long-range goal in this effort is to develop efficacious interventions that reduce these contextual barriers and increase supports for and interest in both post-secondary education in general and STEMM in particular among Appalachian youth. Our objective is to determine the extent to which such a multifaceted intervention strategy leads to increased intentions to pursue an undergraduate STEMM degree. Our hypothesis is that students who experience such interventions will show increases in these important intrapersonal social-cognitive factors and in their intentions to pursue a postsecondary degree compared to students not exposed to such interventions. Our specific aims are to 1) Increase science identity, as well as self- efficacy, outcome expectation beliefs, and interests related to college-going and STEMM; 2) Teach skills to help students navigate barriers and increase supports for pursuing post-secondary education and STEMM careers; and 3) Determine the additive effects of multiple program experiences on college-going and STEMM beliefs. We will use a closely-matched comparison group to compare students who receive the interventions with those who do not. Achieving these aims will provide concrete tools for schools across rural Appalachia, and perhaps other rural regions, to use to increase the number of their students equipped with the skillsets required to join the high-growth biomedical and clinical research industry workforce.

NIH Research Projects · FY 2025 · 2020-07

PROJECT SUMMARY High prevalence of obesity contributes to stagnant mortality rates, increased health care spending, decreased employment, and lower wages. Current gold standard treatments are costly and burdensome, limiting accessibility to the majority of the public and having little effect on this public health crisis. Many attempts have been made to improve the delivery of the successful Diabetes Prevention Program (DPP), shown to produce an average of 6.5kg weight loss over 6 months. However, research to date has lacked a systematic optimization of the DPP treatment package, resulting in packages that have essential parts missing, continue to be burdensome for the patient, or do not produce enough weight loss. The proposed work represents the next step in an efficient, systematic process to identify active treatment components with the goal of assembling a treatment package that can produce sufficient weight loss at a reduced cost and burden. Our prior trial, Opt-IN, was a highly efficient, fully powered full factorial randomized trial designed to test main effects and interactions of additional treatment components (e.g., text messages, meal replacements), when added to a minimal intervention of self-monitoring, psychoeducation, diet and physical activity goals, and biweekly coaching calls. The results supported that significant weight loss could be attained from a minimal level of intervention with no additional components. One notable finding demonstrated that 24 coaching sessions was no better than receiving 12 sessions, significantly reducing potential cost of an intervention. While the Opt-IN trial was designed to test contribution of components, a full head-to-head randomized controlled trial will need to be conducted between the newly optimized intervention (EVO: Elements Vital to treat Obesity) and the current gold standard DPP. Furthermore, full economic analyses that use concurrent clinical trial data from weight loss treatments is lacking, and as such, we intend to do so to inform future dissemination, implementation, and/or further optimization of treatments. Aim 1 is to test whether weight loss from baseline to 6 months achieved by EVO is non-inferior to DPP. Aim 2 will focus on conducting a full economic evaluation consistent with current guidelines. Finally, exploratory aims will investigate weight loss maintenance at 12 months as well as change in self-regulation, moderators (i.e., Age, Sex, Socioeconomic status) and mediators (i.e., self-monitoring adherence, self-efficacy) of treatment effects.

NIH Research Projects · FY 2024 · 2020-07

Project Summary Dr. Thompson, PD/ PI, Professor and Dir. of the Center for Agriculture and Food Security and Preparedness and Co- Director of the TN Center of Excellence of Integrated Food Safety, at the University of Tennessee Institute of Agriculture will support FDA's efforts to improve the training of state, local, territorial and tribal (SLTT) food safety officials, set standards, and administer training and education programs to ensure a competent work force in program areas under its purview. Dr. Thompson, has assembled a strong team with experience in food safety, instructional design, information technology, and 508 compliance and will support OTED priorities to address the following four key components: 1) National Curriculum Standard (NCS) development; 2) Course Delivery and Planning for Course Offerings and Program Area; 3) Course Design, Development and Evaluation; and 4) Facilitation for Updating and Developing New OTED Business Processes. CAFSP has existing collaborative relationships with human and animal food regulators and laboratory SMEs at the federal, state, and local level. Our goal is to serve as a resource for OTED and provide flexibility in our approaches and plan to address the four key component areas. CAFSP can address any of the defined four professional levels: entry/basic mid/advanced, technical/expert and supervisory/leadership in this project. The project aims will be achieved thorough the following specific deliverables per Project Year, which can be adjusted to meet OTED priorities: 1) Participate in Annual Meeting with OTED; 2) Support 2 instructor led course development/redesign projects with 2 development meetings, 2 walkthroughs, and 2 pilots; 3) Develop or redesign up to 5 web courses; 4) Support up to 14 instructor led course deliveries in Years 1-3, 13 deliveries in Year 4, and 12 deliveries in Year 5 for federal and SLTT regulators; 5) Provide unlimited access to hosted web courses by federal and SLTT regulators; 6) Support NCS development work such as conducting gap analyses of existing course content and resource materials, and development or refinement of curriculum frameworks; 7) Support facilitation of online focus groups or development, administration and analysis of surveys to either evaluate the need for new OTED courses, revise existing courses, change course delivery modalities, or solicit input on OTED business processes; 8) Provide technical support to OTED on 508 compliance and instructional design practices, following the ADDIE framework; 9) Report all course performance and evaluation data to OTED; and 10) Submit required financial and progress reports.