Grants

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Abstract Insulin resistance is a leading cause of type 2 diabetes (T2D), metabolic-associated steatotic hepatitis (MASH), and cardiovascular disease (CVD). Adipose tissue is a crucial regulator of insulin sensitivity and its dysfunction causes whole-body insulin resistance, in large part through adipokines–secreted proteins that influence the insulin responsiveness and metabolism of distal tissues. This project leverages advances in human proteogenomics to identify and credential novel adipokines impacting metabolic health. From human genetic and functional genomic work accomplished in the previous project period, we identified TNFAIP8 as a putative adipokine that promotes insulin resistance and T2D. Previously TNFAIP8 had only been implicated as a cell autonomous protein regulating autophagy. We hypothesize that TNFAIP8, and other yet-undiscovered adipokines, modulate insulin sensitivity and metabolic disease progression. We propose: 1) Identify and credential novel adipokines by integrating protein quantitative trait loci (pQTLs) for >3,000 serum proteins with Mendelian randomization to infer causality, direction of effect, and metabolic disease mediation. These analyses will be combined with human visceral and subcutaneous adipose tissue proteomic profiles. 2) Program visceral and subcutaneous adipocytes in vitro to evaluate adipokine dysregulation under metabolic stress. We will define transcriptional regulators of adipocyte depot fate and generate isogenic induced subcutaneous and visceral adipocyte cell models. These cells will be profiled for secreted proteins, using a novel intracellular protein biotinylation strategy to systematically identify canonically and non-canonically secreted proteins. 3) Perform in vivo adipose-specific biotinylation and genetic ablation studies to validate adipokines physiologically. We will generate a novel mouse model expressing an adipocyte-specific biotin ligase to enable proteomic identification of secreted adipokines under metabolic disease conditions. Adipocyte-specific Tnfaip8 knockout mice will be assessed for insulin sensitivity using hyperinsulinemic-euglycemic clamps. This research will elucidate the roles of novel adipokines in metabolic diseases, offering new therapeutic targets and advancing our understanding of adipose tissue biology.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Mycobacterium tuberculosis (Mtb) is a leading cause of death from infection. Curative drug regimens are long, plagued by resistance and often toxic. In addition to using antimycobacterial drugs, adjunctive host directed therapy (HDT) aims to modulate host immune and inflammatory responses to reduce tissue damage, treatment duration and relapse rate. Here we will explore a unique way to combine pathogen-directed and host-directed therapy by exploiting the contrasting ways that Mtb and macrophages, the predominant niche for Mtb, handle cholesterol, Mtb's preferred carbon source. Mtb-infected macrophages form droplets filled with cholesterol esters and triacylglycerides that sustain the bacterium and induce an antibiotic-tolerant state. However, Mtb's degradation of cholesterol generates a toxic intermediate, propionyl-CoA. Mtb avoids propionyl-CoA accumulation by assimilating propionyl-CoA into virulence lipids (PDIMs and sulfolipids). Inhibition of the essential Mtb enzyme phosphopantetheinyl transferase (PptT) blocks synthesis of PDIMS and sulfolipids by inhibiting charging of the acyl carrier proteins required for their synthesis. We found that anti-mycobacterial agents that inhibit PptT kill Mtb in association with propionyl-CoA accumulation and CoA depletion. Moreover, we found that propionyl-CoA directly inhibits Mtb CoaBC in vitro, an essential enzyme for CoA biosynthesis. This likely explains why propionyl-CoA accumulation is toxic. Here, we will harness the PptT–PDIM–propionyl-CoA– CoaBC axis to kill intracellular Mtb by the cumulative effects of inhibition of Mtb's PptT and the host macrophage's sterol-O-acyltransferase (SOAT), an enzyme crucial for conversion of free cholesterol to its esters. Inhibition of SOAT will lead to accumulation of free cholesterol rather than its storage as esters. Mtb's metabolism of free cholesterol will exacerbate killing of Mtb by PptT inhibitors and the consequent prevention of propionyl- CoA incorporation into lipids, leading to the blockade of CoA synthesis. Inhibition of both SOAT isoforms (1 and 2) can prevent lipid droplet formation, and chemical inhibition of SOAT and its knockdown by RNA interference have been shown to restrict intracellular bacterial growth. However, chemical inhibition of SOATs 1 + 2 has resulted in toxicity due to lack of isoform specificity. Herein, we will use a new series of SOAT1 inhibitors that are selective for the SOAT1 isoform, which predominates in macrophages. We will test the efficacy of SOAT1 inhibition on intracellular growth of Mtb in conditions of lipid droplet induction that lead to different ratios of cholesterol esters and triacylglycerides. We will treat macrophages with SOAT1 inhibitor and lipid droplet inducer, infect them with Mtb, treat with our highly potent and selective PptT inhibitors and monitor killing of Mtb.

NIAAA - National Institute on Alcohol Abuse and Alcoholism

PROJECT ABSTRACT Pain and problematic alcohol use have substantial public health consequences and co-occur at high rates. Pain-related alcohol use is common and concerning; although alcohol use may provide short-term relief from pain, it may also worsen pain and alcohol use consequences over time. Understanding the factors that underlie whether physical pain leads to alcohol can inform intervention efforts that address both pain and problematic alcohol use. This project will help understand (1) potential pathways from pain to alcohol use and (2) factors that impact the pain-alcohol relationship over time. Specifically, this project combines laboratory-based pain induction and ecological momentary assessment (EMA – i.e., daily text-message surveys) to investigate two hypotheses of pain-related alcohol use. First, we hypothesize that pain increases negative affect (e.g., anxiety, anger), which then leads to alcohol use (i.e., a mediation effect). Second, we hypothesize that pain-related alcohol use is most prevalent among people with low capacity to modulate their experience of pain (i.e., pain modulatory capacity) and high impulsivity (i.e., moderation effects). To test these hypotheses, we will recruit 225 community adults (aged 25-80). At a baseline laboratory appointment, we will assess individual differences (e.g., negative emotionality, impulsivity), systemic inflammation (via circulating cytokines), and pain modulatory capacity during laboratory pain induction. After baseline, participants will complete a 30-day EMA protocol consisting of five daily assessments via smartphone app. Each smartphone survey will assess substance use, pain, craving, and negative affect. Leveraging these data, we will first test whether the pain-alcohol relationship is mediated by negative affect in daily life (Aim 1). We will also test whether the pain-alcohol relationship is stronger among people with lower pain modulatory capacity and higher impulsivity (Aim 2). Finally, we propose that pain-related alcohol use cannot be fully understood without considering biological age. Age is related to increased pain and chronic pain conditions; decreased negative affect, impulsivity, and pain modulatory capacity; and increased sensitivity to alcohol. Age is also associated with greater inflammation, and the two have similar associations with key facets of pain and alcohol use. It is unclear whether inflammation and aging are independent risk factors for pain and pain-related alcohol use. Thus, we will examine whether effects tested in Aims 1 and 2 vary as a function of age, and whether age and inflammation independently affect pain- related alcohol use (Aim 3). Findings across all aims will determine whether modifiable risk factors are promising intervention targets and whether the relevance of these factors varies as a function of age or inflammation.

NIH

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neuromuscular disease that places extreme financial, physical, and emotional burdens on affected Veterans and their caregivers. Currently, ALS remains without a cure and is commonly diagnosed at advanced disease stages when treatments are ineffective. Though the loss of motor neurons is a disease hallmark, it is now clear that various tissues and cells play a role in the pathogenesis and progression of ALS. As such, multi-factorial therapeutic targeting is an increasingly necessary approach for developing and testing ALS treatments. This therapeutic gap represents an unmet need in ALS. My CDA-2 funding has supported pre-clinical animal studies to assess and optimize the therapeutic potential of the secretome, or conditioned culture medium, from adipose-derived stem cells (ASCs). We and others have determined that systemic mesenchymal stem cell (MSC) secretome therapy, including ASC secretome, imparts neurologic, survival, and other benefits in the mSOD1G93A mouse model of ALS. Preliminary studies have also revealed a significant ASC-CM-mediated reduction in key serum inflammatory biomarkers, which hints at a possible mechanism of its action. However, when given before, through and into late stages of disease, the benefits facilitated by this secretome therapy eventually declines. As such, a clinically relevant adjunctive treatment could enhance the therapeutic benefits of ASC secretome therapy. Trans-spinal direct current stimulation (tsDCS) represents an approach to potentially improve the efficacy of ASC secretome long-term. For the proposed study, we will treat mSOD1G93A ALS mice with ASC secretome derived from ASCs grown using our patented optimized culture approach for neurological disease treatment and test whether regular tsDCS extends the therapeutic benefits in ALS. Our hypothesis is that combining daily systemic ASC secretome therapy and weekly tsDCS beginning at symptom onset will synergistically slow disease progression and extend the therapeutic benefits of ASC secretome. Our long-term goal is to not only extend life, but also improve quality of life for ALS-afflicted Veterans and their families. SPECIFIC AIM 1. Demonstrate whether regular trans-spinal lumbar electrical stimulation supplemented with systemic ASC secretome therapy improves functional and survival outcomes in mSOD1G93A mice. The goal of this Aim is to determine whether weekly tsDCS combined with systemic ASC secretome or control medium therapy ameliorates motor dysfunction and prolongs lifespan in mSOD1G93A mice. As part of a modified Neuroscore we will assess limb extension, grip strength, and locomotor function to assess the onset and progression of symptoms. Overall survival and lifespan from symptom onset will also be analyzed. SPECIFIC AIM 2. Evaluate whether combined tsDCS and ASC serum therapy impart histological motor neuron survival and neuromuscular junction (NMJ) innervation benefits. To test the hypothesis that our proposed therapy could impact the underlying neurodegenerative characteristics differentially from outward behavioral and functional measures such as neurological function, quality of life, and survival, we will perform histologic analysis of lumbar spinal cord and hindlimb muscle to assess MN survival and NMJ innervation. As MN and NMJ are typically fully degenerated at humane end-stage (the endpoint in Aim 1), we will treat a separate cohort of mice with ASC secretome, control medium, and weekly tsDCS between 70-90 days of age, a period we have documented secretome effects on moderate stages of neuromuscular degeneration therapy. Following sacrifice at 90 days, lumbar spinal cord and gastrocnemius muscle will be sectioned and immunolabeled for MN quantification and NMJ innervation, respectively.

U.S. National Science Foundation

Combustion and Fire Systems

Chinese Information and Service Center

Host two civic engagement and digital media production training camps for 20 immigrant youth. Participants will use digital media to explore various civic issues and present possible solutions to the community.

St. Helens Public Library

Come to the Library extends programs, collections and services of the St. Helens Public Library to unserved families in the St. Helens School District. The Library will heavily subsidize family library card costs for the unserved, and send youth services staff to reach out to all children in the school district to encourage use of the library via afterschool programs, and off-site summer reading activities.

St. Helens Public Library

Come to the Library extends programs, collections and services of the St. Helens Public Library to unserved families in the St. Helens School District. The Library will heavily subsidize family library card costs for the unserved, and send youth services staff to reach out to all children in the school district to encourage use of the library via afterschool programs, and off-site summer reading activities.

St. Helens Public Library

Come to the Library extends programs, collections and services of the St. Helens Public Library to unserved families in the St. Helens School District. The Library will heavily subsidize family library card costs for the unserved, and send youth services staff to reach out to all children in the school district to encourage use of the library via afterschool programs, and off-site summer reading activities.

Performance Space 122, Inc.

Comm Fees: New Works by Maura Nguyen Donohue & David Neumann

National Endowment for the Humanities

COMMEMORATING AMERICA?S 250 [CIVIC SPIRIT?S COMMEMORATING AMERICA?S 250 PROGRAM WILL HONOR THE NATION?S SEMIQUINCENTENNIAL BY ENGAGING EDUCATORS AND THE PUBLIC IN CIVIC REFLECTION AND HISTORICAL LEARNING. THROUGH A YEAR-LONG WE THE EDUCATORS SERIES, MIDDLE AND HIGH SCHOOL TEACHERS IN FAITH-BASED SCHOOLS WILL EXPLORE FOUNDING TEXTS, PIVOTAL MOMENTS, AND CIVIC VIRTUES WHILE GAINING TOOLS TO FOSTER THOUGHTFUL CLASSROOM DIALOGUE. COMPLEMENTING THIS, THE WE THE PEOPLE SERIES WILL BRING SCHOLARS AND CITIZENS TOGETHER FOR LECTURES, TEXT-BASED DISCUSSIONS, AND CIVIL DISCOURSE ON AMERICAN PRINCIPLES AND DEMOCRATIC DEBATES. TOPICS WILL INCLUDE THE DECLARATION OF INDEPENDENCE, THE CONSTITUTION, CIVIC IDENTITY, FAITH AND DEMOCRACY, AND THE ROLE OF THE ARTS IN CIVIC CULTURE. THESE PROGRAMS WILL CREATE LASTING RESOURCES, STRENGTHEN CIVIC EDUCATION, AND MODEL PLURALISTIC DIALOGUE, ENSURING THE 250TH ANNIVERSARY SERVES AS A CATALYST FOR ENDURING CIVIC ENGAGEMENT.]

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ ABSTRACT: Currently, the therapeutic options available to individuals with inflammatory bowel disorder (IBD) are limited to small molecule drug and biologics with high toxicity and off-target effects. IBD (and gut dysbiosis) have been directly linked to a plethora of metabolic, neural, allergic and autoimmune diseases, further emphasizing the need for effective and safe therapy. Interestingly, gut dysbiosis is distinguished by deficiency in IL-10 in the inflamed areas. Moreover, there are defects in immune regulation affecting regulatory T cell (Treg) activity and IL-10 signaling. Tregs can inhibit inflammatory immune cells such as M1 macrophages and Th17 cells via secretion of anti-inflammatory cytokines (e.g. IL-10). Moreover, Tregs specific for a disease relevant antigen have been shown to be advantageous over polyclonal Tregs. Traditionally, IBD has not been considered an antigen-specific, inflammatory disease. However, groups have shown that there is generation of monoclonal antibodies to epitopes derived from host proteins (e.g. tropomyosin), as well as antibodies against gut pathogens. Ostensibly, localized generation of antigen-specific Tregs can curtail and counter gut dysbiosis. The immunomodulatory biomaterials lab at UF is currently engineering nanoparticles (NPs) from a polymer derived from commensal bacteroides - Polysaccharide A (PSA). PSA is found on the capsule of the commensal bacterium B. fragilis and directly interacts with antigen presenting cells (APCs), particularly dendritic cells (DCs) to direct and maintain the balance of immunity in the gut. Relevant to this application, we have shown that purified PSA can be used to generate nanoparticles with strong and specific activation of TLR2 on DCs, and robust downstream production of interleukin (IL)-10 from regulatory T cells. Here, we propose to develop an off-the-shelf-approach for ulcerative colitis (UC), which involves glycosylated antigen-loaded PSA nanoparticles (NPs) to drive tolerogenic DCs in the mucosal epithelium and induce effective numbers of UC specific-Tregs to ameliorate UC. Our long-term goal is to develop a modular, easily administrable, tolerance-inducing platform for treatment of gut dysbiosis. The overall objective of this R21 proposal is to engineer glycosylated antigen-loaded PSA NPs to attenuate UC in a murine model, and investigate the extent of immune modulation following oral administration. Our central hypothesis is that upon oral delivery, these engineered NPs will resist digestive tract degradation, target inflammation in the intestine and interact with innate immune cells in these areas to induce specific, anti-inflammatory responses and attenuation of gut dysbiosis. The overall objective of this R21 proposal is addressed by the following two specific aims: 1) Engineer glycosylated antigen-loaded PSA NPs and characterize their physico-chemical properties, in vitro modulatory capacity and biodistribution following oral delivery; 2) Evaluate the therapeutic capacity of PSA NPs in an OVA-DSS murine model of Colitis. The proposed research is novel and innovative due to the simplicity of its generation and administration to the patient, and huge potential as a therapeutic agent for IBD.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Abstract The intestinal epithelium acts as a physical barrier to separate the luminal contents from the underlying tissue compartment of the organ. Typically, any damage caused by medications or environmental toxins is promptly repaired to maintain homeostasis. However, in chronic inflammatory conditions such as inflammatory bowel diseases (IBD), ability to heal wounds is dysregulated perpetuating chronic inflammation. Healthy endogenous microbiota is being increasingly recognized to promote repair, yet the specific mechanisms by which microbes guide repair remains elusive. Moreover, majority of the studies have focussed on bacteria, how nonbacterial members such as fungi modulate wound repair remains unknown. Using murine models of injury and repair and human isolates of fungi, we discovered that endogenous fungi are critical for crypt regeneration post injury. Importantly, the repair promoting effects were specific to the fungal strains that are depleted in IBD. Our preliminary data suggests that endogenous fungi engage epithelial cells to induce Palmitoylethanolamide (PEA), a lipid metabolite, which in turn inhibits inflammatory activation of fibroblasts to promote wound repair. Here we will use conditional knockout mice, single cell RNA sequencing, primary epithelial and fibroblast cultures, and metabolomics to investigate how endogenous fungi alter epithelial transcriptome to induce PEA (Aim 1) and the specific mechanisms by which PEA inhibits inflammatory activation of fibroblasts to promote repair. Successful completion of these aims will give a mechanistic understanding of a previously unappreciated role of endogenous fungi in modulating epithelial cells and fibroblasts to enhance intestinal wound repair. Additionally, it will uncover novel targets for stimulating crypt regeneration in inflammatory conditions of the gastrointestinal tract.

DECD

Commercial façade improvement program

Centers for Disease Control and Prevention - ERA

Commercial Fishing Occupational Safety Research Cooperative Agreement (U01)

Centers for Disease Control and Prevention - ERA

Commercial Fishing Occupational Safety Training Project Grants (T03)

NINDS - National Institute of Neurological Disorders and Stroke

Helical Biosciences is a startup company formed to commercialize technology developed at Washington University School of Medicine. The goal of this project is to develop Lewy fold fibrils (LFFs), a new research tool that overcomes a significant barrier to developing effective treatments for Parkinson’s disease (PD) and Lewy body dementia (LBD). PD is a neurodegenerative disease that affects over 1 million people in the US and causes progressive impairment of movement and cognitive function. The majority of people with PD develop dementia, known as Lewy body dementia (LBD). The defining feature of PD is the accumulation of alpha-synuclein (Asyn) fibrils in neurons throughout the brain. These Asyn fibrils have highly ordered beta sheet protein structure and accumulate in neuronal cells to form cytoplasmic and neuritic inclusions known as Lewy bodies and Lewy neurites. Asyn fibrils are currently a major focus for research and development (R&D) efforts that aim to understand disease mechanisms, to develop diagnostics that quantify Asyn fibril accumulation in living individuals, and to develop therapeutics that prevent, slow or remove Asyn fibril accumulation. Current R&D efforts rely heavily on in vitro preparations of Asyn fibrils, prepared using methods that induce soluble Asyn protein to form fibrils in vitro. Recent studies indicate that the structure of in vitro fibril preparations is substantially different from the structure of ex vivo PD fibrils obtained from human postmortem brain tissue. However, the quantities of fibrils extracted from postmortem tissue samples are orders of magnitude lower than what are needed for R&D efforts. Lewy fold fibrils (LFFs) are an amplified preparation of ex vivo fibrils that replicate the structure of ex vivo PD fibrils and that can be produced on a scale sufficient to meet R&D needs. In this project we will determine the feasibility of commercial production of LFFs. We will produce batches of LFFs at increasing scale and then determine whether batches of commercially produced LFFs have the key structural features that distinguish LFFs from in vitro Asyn fibrils, based on analysis of cryo - EM data, fluorescent ligand binding assays, and fibril growth assays. The protocol for commercial production will be optimized to meet these structure-based criteria. The results of this project will provide key feasibility data for commercialization of LFFs and for the development of additional applications such as animal models based on LFFs.

DEPT OF DEFENSE.DEPT OF THE NAVY.SPAWAR.SPAWAR PACIFIC.NIWC PACIFIC

Commercial Solutions Opening for Data and Analytics for Maritime Domain Awareness

NEI - National Eye Institute

PROJECT SUMMARY This proposal aims to provide a first-in-class therapeutic to improve the quality of life for patients suffering from persistent corneal epithelial defects (PCED). PCED, whether caused by disease or trauma, can increase the risk of blindness by causing the corneal epithelium to heal slowly. If the cornea does not heal within 14 days, the condition is known as a PCED, a condition with an increased risk of recurrence and scarring that leads to vision impairment. CorneaClear eyedrops accelerate corneal healing and reduce the risk of scarring that leads to vision impairment. Our technology is unique; no products currently on the market address corneal wound healing time or the risk of scarring, regardless of the underlying cause. There is no FDA-approved therapy for the broad treatment of PCED. While Oxervate is approved for neurotrophic keratitis (NK), it only addresses one-third of PCED cases, is expensive, and is complicated to use. The long-term goal of this project is to develop an eyedrop formulation that can be prescribed to PCED patients that will speed up the healing time for corneal wounds and minimize the likelihood of scarring that can develop from extended wound-healing times. The eyedrops will be used at the onset of an abrasion for those diagnosed with PCED. Our Aim 1 states that we will demonstrate that the CorneaClear eyedrops accelerate corneal wound healing in a New Zealand White (NZW) Rabbit model. We hypothesize that, after wounding the eyes, corneal re-epithelialization will be ≥50% faster in CorneaClear- treated rabbits than in control using treatment concentrations as shown with fluorescein staining images and restoration of the epithelial layer to a thickness at least twice that of the control. Our Aim 2 states that we will confirm the systemic safety of the prolactin-induced protein eyedrops. We hypothesize no significant increase in PIP protein levels in the blood compared to the control (PIP ELISA assay) and no sign of systemic toxicity to the organs. In Phase II, we will conduct pre-clinical studies to support an Investigational New Drug Application to the Food and Drug Administration (FDA). These upcoming studies will include efficacy studies with male and female NZW rabbits and incorporate a repeated corneal wounding and healing process to simulate PCED. We also plan more rigorous safety studies under GLP/GMP conditions for Phase II. Although PCED affects almost 200,000 Americans yearly, the estimated U.S. market size for PCED therapies is estimated to be almost a billion dollars, with a predicted CAGR of 4.75% by 2030. Our regulatory strategy includes applying for an orphan drug and Fast Track designation with the FDA for PCED. We will partner with a reputable Contract Development and Manufacturing Organization and clinical research partners to advance the technology. Our target customers include corneal surgeons/ophthalmologists, patients/advocacy groups, investors, and future partners.

NEI - National Eye Institute

Abstract This project aims to develop and validate a novel Adaptive Optics Optical Coherence Tomography (AO-OCT) system tailored for high-resolution, wide-field retinal imaging in small animal models, specifically mice. The broad, long-term objective is to enhance our understanding of ocular diseases and neuronal dynamics by providing researchers with a powerful tool capable of capturing detailed in vivo images of retinal structures. By advancing imaging technology, this project seeks to contribute to the development of better diagnostic and therapeutic strategies for retinal disorders. Specific Aim 1 focuses on the development and optimization of a portable AO-OCT system with enhanced imaging capabilities using a customized contact lens. This aim involves designing and fabricating an optical system that integrates adaptive optics with a wide-field view of 150 degrees and a resolution of 2 microns. The completion of this aim will be marked by the successful testing of the integrated system, demonstrating its ability to reliably capture high-resolution images of photoreceptors and other retinal structures. Specific Aim 2 is centered on the validation and optimization of the AO-OCT system using wild-type mouse models. Initially, the system will be tested with a phantom eye model to evaluate its performance and refine the design. Following this, validation will be conducted using wild-type mouse models to ensure the system's reliability, reproducibility, and overall performance. Collaboration with Dr. Robert Zawadzki's lab at UC Davis will support animal preparation and data acquisition. The expected outcome is the successful acquisition of high- quality AO-OCT images with a 150-degree field of view and 2-micron resolution, validated through statistical analysis and comparison with histological data. The research design employs a combination of advanced optical engineering, adaptive optics integration, and rigorous validation using both phantom models and live animal imaging. This project has the potential to significantly advance the field of retinal imaging, providing valuable insights into retinal diseases and contributing to public health by improving early diagnosis and treatment options for vision-related conditions.

NIA - National Institute on Aging

Each day in the United States, over 100,000 patients receive general anesthesia, with about 40% being aged 60 and above. The current practice of general anesthesia is prone to over-sedating patients, either due to the lack of brain monitoring or using brain monitors with inaccurate indices. Over-sedation (at 28% incidence) contributes to post-operative delirium (POD) in the elderly population (≥60yrs). Notably, 11% of these elderly patients suffer from Alzheimer’s Disease and Related Dementias, placing them at an even higher risk of POD. PASCALL was founded to introduce a novel wireless neuroscience-based EEG-guided personalized anesthetic management. In our original grant, AG066325, we achieved a) (AG066325 Aim 1,2) the design, development, and FDA 510(k) pre-market clearance of a wireless anesthetic brain monitor, designated as M0 and b) (AG066325 Aim 3) the development of personalized algorithms to monitor anesthetic brain state in aging, dementia, and Alzheimer’s disease patients. In this grant, we propose concrete steps to commercialize M0 and the personalized algorithms developed in AG066325, collectively designated as PASCALL M1. We realize this innovation through the following specific aims: Aim 1 focuses on a pilot study to determine sample size, cost, and timeline for a Phase III multi-site trial while optimizing workflows, outcome measures and caregiver protocol adherence. Insights from the pilot will inform the development of a comprehensive Phase III protocol, site selection, and assembly of a cross-functional team to secure FDA clearance and support market adoption. Aim 2 and 3 focuses on enhancing the PASCALL M1 device's workflow and manufacturing capabilities. Key goals include developing FDA-compliant, in-house manufacturing under ISO 13485:2016 and achieving MDSAP certification for regulatory compliance. The device design will be streamlined to reduce application steps and improve workflow efficiency. If successful, this effort will demonstrate through clinical studies that our system can significantly reduce POD incidence, saving the healthcare system tens of billions of dollars annually by enabling early detection of POD risk and active anesthesia management, leading to shortened hospital stays by an average of 3 days for each patient developing POD after surgery.

NHGRI - National Human Genome Research Institute

PROJECT SUMMARY RNA sequencing (RNA-Seq) is routinely used to survey the expression of tens of thousands of genes. Analyzing such large datasets poses a significant challenge for many biologists, especially those with limited resources. Through an R01 from NHGRI and six years of dedicated work, we developed iDEP (integrated Differential Expression & Pathway analysis), an interactive web app for comprehensive, reproducible bioinformatic analysis of RNA-Seq data. iDEP integrates over 70 R packages for exploratory analysis, clustering, and differential gene expression. Pathway analysis is powered by an extensive database covering gene annotations in 14,000 species, including animals, plants, and microbes. With over 650,000 website visits and 1000 citations, it has garnered widespread usage across many fields, proving particularly invaluable for researchers lacking in-house bioinformatics support. A common issue plaguing many bioinformatics services is their tendency to cease updates or disappear once initial funding runs out. This project seeks to transform iDEP into a commercially viable product through a partnership between RTutor, LLC, and South Dakota State University (SDSU). We plan to reduce the cost of database updates, improve deployment, and enhance access to public RNA- Seq data. Aim 1. Streamline Database Updates: We will create workflows to automate annual updates from Ensembl and STRING. Aim 2. Develop a Desktop Application: We aim to package the iDEP web server as a desktop application to enhance user experience, data security, and reproducibility. Aim 3. Improve access to public RNA-Seq data using AI. We will adopt large language models (LLMs) to facilitate the reuse of public expression data, using multiple LLM agents to find and summarize published data. We will also create a tech support chatbot based on existing iDEP documentation to answer simple user questions, supplementing continued support via emails. The need for a secure, interactive, knowledge-based app for analyzing and interpreting RNA-Seq data clearly exists both in academia and industry. RTutor LLC secured an exclusive license from SDSU for sublicensing. Our business model is to generate revenue through licensing fees and customized databases. This revenue will fund R&D to improve and update iDEP, ensuring free access for non-profit institutions. This STTR project represents a crucial step toward long-term viability of iDEP to amplify its impact on a large, diverse scientific community.

Gamelan Galak Tika

Commission & Presentation of New Balinese Gamelan Work

TeCo Theatrical Productions

To support arts education activities in Texas through this public-private partnership. These funds are pass-through grants designated by the Texas Women for the Arts, a philanthropic arm of the Texas Cultural Trust.