Washington University

NIH Research Projects · FY 2026 · 2025-04

High-quality communication between clinicians and parents is critical to providing optimal care for pediatric cancer. Yet, almost no communication interventions exist in pediatric cancer. To address parents’ unmet communication needs after diagnosis, it is imperative to develop an effective, parent-centered, and scalable communication tool specific to the needs of families affected by pediatric cancer. This study proposes to engage parents of children with cancer to develop and pilot an electronic health record (EHR)-based communication tool using participatory design methods. To ensure this tool is useful, feasible, cost-effective, and designed for dissemination, the investigators will co-develop an EHR tool that adapts the existing Epic MyChart Care Companion to meet the needs of children with cancer and their families. Care Companion is an interactive, highly adaptable Epic MyChart add-on that can incorporate video- and text-based educational materials, symptom surveys, and links to initiate portal messages. The study team found that 74% of children’s hospitals use Epic EHR, which will support broad dissemination of this Cancer Care Companion. This study will fulfill the following aims. Aim 1: To develop, refine, and prioritize content and functions to be incorporated into the Cancer Care Companion, in partnership with parents of children with cancer and pediatric oncology clinicians. The study team will facilitate 6 participatory design workshops with 6 to 8 participants per workshop. The team will host 2 workshops for clinicians and 4 for parents. Each workshop will include 2 stages: discovery and prototyping. The team will identify essential topics for informational materials, sources of high-quality information, pertinent symptoms to track, and appropriate clinical workflows. In collaboration with the St. Louis Children’s Hospital Epic Build Team, the team will build the Cancer Care Companion. Aim 2: To pilot and evaluate the Cancer Care Companion at St. Louis Children’s Hospital with up to 40 parents of children with cancer. The investigators will assess the feasibility, acceptability, and appropriateness of the Cancer Care Companion among parents of children with newly diagnosed cancer. After 3 months of use, the team will perform qualitative interviews with parents to assess their positive and negative experiences and possible modifications to improve the tool. The team will track utilization and administer validated measures to assess the tool’s acceptability, appropriateness, and feasibility. This proposal aligns with research priorities of the National Cancer Institute and addresses the critical need for high-quality communication in pediatric cancer, especially near the time of diagnosis. Findings from this study could serve as a model communication tool for long-term cancer survivors or other serious pediatric illnesses. These findings will also be essential to support a future multicenter clinical trial.

NIH Research Projects · FY 2026 · 2025-04

Project Summary: Inborn Errors of Immunity (IEI) collectively comprise more than 500 different monogenic disorders of the immune system. Primary Immune Regulation Disorders (PIRD) represent a subset of IEI, that are characterized clinically by a lack of regulation of the immune response resulting in overlapping features of infectious susceptibility, autoimmunity, lymphoproliferation, inflammation, and/or atopy. While tremendous advances in patient diagnosis and disease mechanisms understanding have been made, significant gaps in the field remain. First, the molecular diagnostic rate for all IEI remains only 30-40%, even in multiplex families with high likelihood of genetic inheritance. Second, most diseases of immune dysregulation have variable penetrance (i.e, have or don’t have disease) and have variable expressivity (i.e, have mild vs severe disease). This phenomenon is by and large unexplained. Our emerging data suggests three evolving genetic concepts of disease including epigenetic, somatic mutations, and genetic modifiers. We propose to use the term Genetic Errors of Immunity (GEIs) to encompass these broad and novel molecular mechanisms. In Project 1 we will tackle a novel epigenetic mechanism, where despite heterozygosity on DNA level, transcriptionally only one allele is expressed in select cell lineages, a phenomenon termed autosomal random monoallelic expression (aRMAE). We propose to map genes that are prone to aRMAE in the immune system, define epigenetic marks governing this process, and validate these findings in individuals with identified genetic lesions within families with known incomplete penetrance. This will allow us to document discrepant genotype to “transcriptotype” and measure functional implication of this epigenetic phenomenon. In Project 2 we will investigate somatic mutations as a cause of GEIs, a concept in its infancy. Herein we propose to perform high-depth targeted sequencing to identify genetic mosaicism in patients with suspected GEI who were negative by standard genetic testing, and to develop single cell technologies for evaluating their functional impact on the immune response. Our preliminary data suggests that a mutation causative of PIRD can be both somatic and in a gene undergoing aRMAE, suggesting clear synergy among Project 1 and Project 2. Finally in Project 3, we will address known genetic risk variants in tandem with polygenic risk score (both of which would otherwise be clinically silent). This concept is of great interest in the IEI field. Understanding these modifier genes, whether germline, somatic or epigenetically regulated (undergoing aRMAE) forms a clear cohesive connection between Projects 1-3. To support this set of integrated yet distinct projects we propose: 1) an administrative core charged with coordination of meetings, regulatory compliance, and grant management; 2) Sequencing and sample core: tasked with patient and control sample WEG, WGS, Targeted Deep Sequencing, RNA Seq, and scRNASeq and 3) Bioinformatics and computational biology Core tasked with development and integration of bioinformatic pipelines. Combined, these 3 projects and 3 cores will synergize in defining novel disease mechanisms in GEI.

NIH Research Projects · FY 2026 · 2025-04

Abstract Brain tumors are the most common cause of cancer death in patients aged 0-19 and treatment advances are elusive. Pediatric high-grade glioma (HGG), diffuse midline glioma (DMG), recurrent medulloblastoma (MB), and recurrent ependymoma (EPN) are devastating diseases. The median overall survival (OS) of these diagnoses are less than 15 months. Current treatments for these malignant tumors typically entail surgical resection or biopsy, radiation, and sometimes chemotherapy. Pediatric HGG, DMG, MB and EPN express human cytomegalovirus (CMV) proteins that are not found in normal brain, thereby providing unique immunotherapeutic targets. Our group has developed a peptide vaccine (PEP-CMV) directed to the CMV antigen, pp65. Results from a recently completed Phase I clinical trial (PRiME, NCT03299309) of 42 patients age 3-35 with recurrent HGG/DMG and MB demonstrated significant antigen-specific T cell immune responses to pp65 and prolonged clinical/imaging responses in many patients. Importantly, PEP-CMV was well tolerated with only 3 Grade 3/4 adverse events. In PRiME, increased immune response to PEP-CMV and favorable baseline immune status (low percentage of immunosuppressive Tregs and high percentage of terminally differentiated cytotoxic T cells [TEMRAs]) were associated with better survival. The addition of checkpoint blockade such as anti-PD-1 therapies has not been explored in immunotherapies targeting CMV, however, it has enhanced the immunogenicity of cancer vaccines in preclinical brain tumor models and other non-brain solid tumors. Anti-PD-1 agents also decrease Tregs and increase TEMRA percentages. Given this, our hypotheses are that 1) the combination of PEP-CMV plus checkpoint blockade will be safe and feasible for the treatment of DMG, HGG, MB, and EPN, 2) the addition of checkpoint blockade will enhance the immunogenicity and effectiveness of PEP-CMV thereby improving survival (compared to PRiME), 3) patients with newly diagnosed DMG/HGG will have significantly more robust immune responses that patients with recurrent DMG/HGG, and 4) PEP-CMV plus checkpoint blockade will produce an antigen-specific response in patients with EPN. Our primary objective is to perform a multi-institutional Phase I/II trial to evaluate the safety, clinical efficacy, and immunogenicity of PEP-CMV plus checkpoint blockade in patients aged 3-35 with recurrent DMG, HGG, MB, or EPN or newly diagnosed DMG and HGG. To attain this objective, the following specific aims will be pursued: Aim 1: Establish the safety and feasibility of PEP-CMV in combination with checkpoint blockade for the treatment of patients with DMG, HGG, MB, or EPN. Aim 2: Determine the clinical outcomes of patients who receive PEP-CMV plus checkpoint blockade. Aim 3: Assess the immunogenicity of PEP-CMV plus checkpoint blockade in patients.

NIH Research Projects · FY 2026 · 2025-04

PROJECT SUMMARY / ABSTRACT The tumor microenvironment (TME) is a complex assembly of cells, stromal tissue, and extracellular matrix that collectively create physical, biochemical, and immune barriers to cancer therapies. Phosphatidylserine (PS), a phospholipid typically confined to the inner leaflet of the plasma membrane, is believed to play a central role in the immunosuppressive characteristics of many TMEs. Aberrant exposure of PS on tumor cell membranes has been associated with negative prognoses and resistance to various treatments. This project seeks to understand this aberrant PS exposure with the ultimate goal of finding ways to overcome the challenges that currently limit its clinical exploitation. The central hypothesis of this proposal is that the exposure of PS on live (non-apoptotic) tumor cells contributes to immune suppression via its interaction with neighboring cells, including tumor associated macrophages. In Aim 1, the molecule(s) responsible for non-apoptotic PS exposure on tumor cells will be identified and their impact on tumor progression and immune responses in syngeneic mouse tumor models will be determined. Preliminary data implicate TMEM16F, a caspase-independent lipid scramblase, in non-apoptotic PS exposure on tumor cells. In Aim 2, the direct roles that PS plays in the immune-suppressive polarization of tumor-associated macrophages will be defined. Chimeric receptors for efferocytosis (CHEFs) will be used to either amplify or reprogram tumor-associated macrophage responses to PS recognition. Understanding the key molecular players and downstream immune responses to externalized PS could reveal new therapeutic strategies to target PS in tumors and thereby improve the immune system’s ability to attack solid tumors. During the course of this fellowship, the applicant will hone a comprehensive skill set encompassing technical expertise, sophisticated analytical skills, and effective communication, all of which will be essential for a career as an independent clinician investigator studying tumor immunology. Under the guidance of Dr. Kodi Ravichandran, a renowned expert in immunological responses across many disease states, and supported by a network of leading cancer biology and immunology experts, the applicant is well-positioned for achieving her career goals. The applicant’s institution, Washington University School of Medicine has a proven record of helping physician-scientists build successful careers. This proposed training plan is designed to facilitate the applicant’s transition into a pediatric oncologist and independent investigator dedicated to devising innovative therapeutic approaches for pediatric cancers.

NIH Research Projects · FY 2026 · 2025-04

Abstract Endometriosis is a prevalent chronic painful condition in which an endometrial-like tissue lesion grows outside the uterus. The individual variability in endometriosis pain is large, and the factors contributing to it are unclear, but central and peripheral mechanisms have been proposed. Thus, this study aims to identify the mechanisms underlying endometriosis pain and the changes in pain after lesion removal surgery. We focus on central mechanisms of inhibitory pain modulation capabilities and systemic estrogen levels, as well as peripheral mechanisms involving estrogen receptor expression and local estrogen levels in the endometriosis lesion. We hypothesize that higher local and systemic estrogen levels and estrogen receptor expression in the lesion, and lower conditioned pain modulation (CPM) response will be related to greater endometriosis pain. In addition, we hypothesize that after the surgery, patients with higher estrogen receptor expression and higher local estrogen levels in the lesion (peripheral alterations) will have a greater reduction in endometriosis pain, while patients with lower CPM response and higher systemic estrogen levels (central alterations) will have a lower pain reduction. During the study, women with pelvic pain with and without endometriosis scheduled for an operative laparoscopic surgery for endometriosis diagnosis and/or treatment will complete a baseline study visit that includes a comprehensive characterization of their pain and endometriosis symptoms and psychophysical assessments of the CPM response. During the surgery, a blood sample for systemic estrogen level, a biopsy of the endometriosis lesion (if found), and a biopsy of healthy peritoneum will be collected and analyzed for local estrogen levels and estrogen receptor expression using quantitative PCR (qPCR), enzyme- linked immunoassay (ELISA) and western blot. After the surgery, patients will complete weekly surveys about their pain and symptoms for 3 months. Regression models will be used to identify the factors related to endometriosis pain and the change in pain after the surgery. A better understanding of endometriosis pain could improve the treatment of endometriosis pain. Future studies will identify new or repurpose existing pain treatments for endometriosis pain and develop a model that predicts which patients will have a significant pain reduction after the endometriosis removal surgery for a personalized medicine approach.

NIH Research Projects · FY 2025 · 2025-04

Project Summary/Abstract Anorexia nervosa (AN) is one of the deadliest psychiatric illnesses, and prognosis is worsened when comorbid with obsessive-compulsive disorder (OCD). Further, childhood OCD typically onsets before AN, indicating a possible developmental trajectory with childhood OCD preceding and predicting AN onset. Therefore, identifying and characterizing the mechanisms that underly the AN/OCD developmental progression and AN/OCD comorbidity is imperative for developing effective, targeted interventions for these difficult-to-treat psychiatric presentations. The overarching aim of this proposal is to use both a large, longitudinal, community dataset and a real-world clinical sample to (a) examine the developmental trajectory of AN/OCD comorbidity, including specific mechanisms that could be targeted in treatment and (b) examine a mechanism-based psychosocial treatment for this comorbidity. Results will help identify at-risk individuals and inform the development of targeted and effective transdiagnostic interventions. This project will also achieve the following training goals: (1) develop expertise in childhood development of AN and OCD psychopathology, (2) gain expertise in clinical translational work, (3) learn advanced analytic techniques and data science skills, (4) gain skills to be an independent investigator, including training in scientific rigor and reproducibility, professional development, and scientific communication. The assembled training team has extensive expertise in AN, OCD, treatment research, and advanced statistics, and will support the applicant in developing the skills and knowledge needed to achieve her career goals of developing an independent program of research examining AN/OCD psychopathology and treatment.

NIH Research Projects · FY 2026 · 2025-04

Project Summary / Abstract Immunotherapy has been shown to be effective in several cancer types leading to enhancement in long-term survival in subsets of patients. However, there are no proven effective immunotherapeutic approaches for pancreatic ductal adenocarcinoma (PDAC)1. There are many reasons why PDAC tumors do not respond to checkpoint immunotherapy, including modest tumor immunogenicity and T cell infiltration. However, another major factor in immunotherapy failure is the immunosuppressive tumor microenvironment (TME) characteristic of PDAC. The PDAC microenvironment is characterized by a desmoplastic stroma that is composed of an extracellular matrix rich in collagen and cancer-associated fibroblasts (CAFs)2,3. Three major subsets have been identified, including myofibroblast-like CAFs (myCAFs), inflammatory CAFs (iCAFs), and antigen-presenting CAFs (apCAFs). However, there is still no clear consensus on the role each CAF subtype plays in the TME. While the field supports the hypothesis that anti-tumor immunity is often blunted in highly fibrotic tumors, what is not well understood is how tumor-associated fibrosis is remodeled when anti-tumor immunity is activated by therapy and how this impacts tumor control. This is a critical gap in our understanding that likely limits the development of immunotherapies for PDAC. A second rationale for the lack of response to immunotherapy is a paucity of conventional dendritic cells (cDCs) in the PDAC TME11. cDCs are professional antigen presenting cells that take up, process, and present antigen to both initiate and sustain anti-tumor T cell responses12. In mice, our lab has shown that the combination of systemic FLT3L and αCD40 agonist antibodies (CD40/FLT3L) restore cDCs numbers and function and thus drive T cell-mediated tumor control in PDAC models11. In recent studies we have advanced this approach into PDAC patients (NCT04536077). Importantly, ECM and CAFs may play both immune-promoting and/or immune-suppressive roles during therapy. Herein, I will study the impact of activation of tumor immunity by CD40/FLT3L treatment on PDAC ECM dynamics and CAF functional phenotypes. I will determine if these changes in ECM and CAF phenotypes during immunotherapy stimulate or blunt activities of cDCs in sustaining T cell immunity. Understanding how extracellular matrix heterogeneity either biases or impairs successful antigen presentation in the tumor microenvironment will help design rational therapeutics that will hopefully enhance immunotherapeutic responses in PDAC. As an MD/PhD student, being involved in translational studies directly impacting patients with PDAC will allow me to interface with the clinical implementation of the type of cancer immunology-based science I want to perform as an independent investigator and physician-scientist.

NIH Research Projects · FY 2026 · 2025-04

Project Summary/Abstract The outer layer of the mammalian brain, the cerebral cortex, contains a mosaic of functionally and anatomically distinct areas. Understanding the organization and individual variability of these cortical areas is fundamental for decoding the unique brain function (i.e., individual differences in cognition, behavior, personality, psychiatric symptoms, substance use, susceptibility to brain disorders, etc.) and the heritability of these variations. High- resolution structural and functional magnetic resonance imaging data from 1071 healthy young adults aged 22- 35 years (485 males and 586 females, including monozygotic and dyzgotic twins, non-twin siblings, and unrelated individuals) provided by the Human Connectome Project (HCP) have revealed a group-average map of 180 cortical areas per hemisphere. Recent methodological advances have led to the generation of individual subject cortical area parcellations that show significant differences from the group average map. The proposed work focuses on understanding individual variability in human cortical areal organization, estimating the heritability of this variability, and identifying its behavioral correlates. To achieve such understanding, Aim 1 of this proposal will investigate cortical areas in terms of their size, scaling, shape, topology, and number, also testing the bilateral symmetry across the left and right hemispheres. The reproducibility of novel findings will be evaluated by the HCP test-retest dataset consisting of 205 young adults scanned twice at 3T or 7T. Aim 2 will estimate the heritability of the variations identified in Aim 1 by disentangling the genetic and environmental contributions using the twin-pair HCP data. Finally, Aim 3 will examine the relationship between individual variability in cortical organization and and individual behavioral measures from the HCP Individual Behavioral Assessment dataset. The expected outcomes of the proposed work include i) exploration of individual cortical area variability by developing measurable, quantitative, imaging-based metrics that objectively and reproducibly determine individual variability, ii) investigation of the reproducible existence and prevalence of atypical areal topologies, iii) determination of the reproducible prevalence of missing or extra areas among individuals, iv) estimation of the heritability of individual cortical area variability, and v) relation of individual cortical area variability to differences in individual behavior. The broad, long-term objective of this proposal is to map the brain-behavior relationship among individuals, while elucidating the genetic and environmental influences on this mapping, to better understand mental function and dysfunction that lead to adaptive and maladaptive behaviors, and to inform personalized approaches to diagnosis, treatment, and prevention of mental illnesses. The proposed work and the training plan will be conducted in the Glasser and Van Essen lab at Washington University in St. Louis and will prepare the applicant to become a successful independent researcher studying the organization of the brain in health and disease.

NIH Research Projects · FY 2026 · 2025-04

Project Summary Non-Hodgkin Lymphoma (NHL) is one of the most common cancers in the United States, with approximately 80,000 new cases and 20,000 deaths occurring each year. The two most common types of NHL are Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL). Up to 30% of germinal center- derived (GC)-DLBCL and FL cases exhibit gain-of-function events in the histone methyltransferase EZH2, including a heterozygous hotspot mutation (EZH2Y641F/+) or overexpression of wild-type protein (EZH2OE). This proposal addresses the major gaps in knowledge of (1) whether EZH2Y641F/+ and EZH2OE are functionally equivalent or distinct gain-of-function events and (2) whether they drive lymphoma as early or late events in the B lineage. We hypothesize that EZH2Y641F and EZH2OE are non-equivalent gain-of-function events that drive lymphoma by distinct mechanisms, and that the timing of each event influences its oncogenic activity. The first aim of this proposal investigates the impacts of EZH2Y641F/+ and EZH2OE in B cells. To achieve this goal, we will use genetically engineered mouse models of EZH2Y641F/+ and EZH2OE driven by the B cell- specific CD19-Cre and employ a combination of flow cytometric analysis of key GC phenotypes (i.e. proliferation, apoptosis, and differentiation), gene expression analysis by RNA sequencing, and chromatin profiling of histone methylation and EZH2 binding with CUT&Tag sequencing. These mechanistic studies will identify downstream targets that may function as biomarkers or lead to new therapeutic approaches in patients with these alterations. The second aim of the proposal is to determine whether EZH2 alterations drive lymphoma as early or late events in the B lineage. To achieve this goal, we will model EZH2Y641F/+ and EZH2OE in the early B lineage using CD19-Cre and in the later GC stage using Cγ1-Cre, overexpress the lymphoma oncoprotein BCL2 in bone marrow from each cohort, and transplant the cells into lethally irradiated recipient mice. The rates of lymphoma onset will be determined by monitoring each recipient group for disease and analyzing the resulting tumors by flow cytometry and histologic analysis. This aim will address a gap in knowledge about whether EZH2Y641F/+ and EZH2OE represent early or late events in DLBCL or FL pathogenesis. The proposed research will take place at Washington University in St. Louis, an outstanding environment to support the trainee’s development for a research career in cancer epigenetics. By completing the research tasks, the trainee will acquire or master technical skills including multi-channel flow cytometry and panel design, analysis and interpretation of genomic sequencing data, and mouse bone marrow transplantation, among others. The trainee will publish the results in a first-author manuscript and will present this work at national and international conferences, which will develop the trainee’s skills of scientific writing and communication. Finally, the trainee will mentor undergraduate students during the proposed research to develop the skill of mentorship.

NIH Research Projects · FY 2026 · 2025-04

PROJECT SUMMARY ABSTRACT The overall goal of our research is to develop novel strategies to prevent or treat secondary organ complications in multiorgan failure. Acute kidney injury frequently negatively impacts oxygenation in multiorgan failure, causing very high mortality due to a lack of therapies. Molecular mechanisms and mediators of this detrimental kidney- lung crosstalk are incompletely understood. We recently identified circulating osteopontin (OPN, Spp1) released by the injured kidney after acute kidney injury as a novel key mediator of remote lung inflammation with respiratory failure. Consistent with this, elevated OPN serum levels correlate with increased mortality and need for ventilation in multiorgan failure patients. OPN can interact with integrins and CD44 receptors and possibly through its two thrombin cleavage fragments. It is unknown which OPN receptor interactions are required for remote lung inflammation, which cells OPN targets, and which signals downstream of OPN attract neutrophils to lung capillaries. Our central hypotheses is that OPN or its thrombin-cleaved fragments bind to its receptor(s) integrin and/or CD44 on innate lung immune cells that in turn produce signals that attract neutrophils to lung capillaries. Our preliminary work provides evidence for a role of OPN in CD44+ innate lung immune cells in remote lung inflammation and for signals they produce that attract neutrophils. The rationale for this project is that completion will for the first time (1) identify lung target cells and receptors of remote lung inflammation, (2) define OPN domains involved in remote lung inflammation, and (3) directly visualize initiation of remote lung inflammation and the effect of blockade of predicted innate immune cell-derived neutrophil chemoattractant signals in vivo. We plan to test our central hypotheses with three specific aims: Aim 1: Determine which OPN domains are required to induce remote lung inflammation and whether OPN thrombin cleavage is required. We will test (1) whether OPN or OPN mutants reverse protection of AKI-injured OPN-KO mice when injected or (2) induce signaling and production of cytokines in monocyte or macrophage cell lines. We will also test knock-in mice with a mutation that renders OPN uncleavable by thrombin. Aim 2: Determine whether CD44 in lung innate immune cells is required for remote lung inflammation. We will (1) test cell-type specific knockout of CD44 in innate immune cells or transplantation approaches in remote lung inflammation and (2) test for OPN:CD44 interaction and CD44’s requirement for OPN action in remote lung inflammation. Aim 3: Test innate immune cell- derived signals predicted to recruit neutrophils in remote lung inflammation. Using intravital two-photon imaging, we will directly visualize initiating steps of remote lung inflammation after AKI and test the effect of blocking predicted neutrophil attractant signals. This contribution is significant because it is expected to have translational impact in the development of treatments for detrimental kidney-lung crosstalk in multiorgan failure, complications with high mortality. Our research is innovative, in our opinion, because it would identify critical mediators, target cells types, and mechanisms in remote lung inflammation, and provide guidance for translation into patients.

NIH Research Projects · FY 2025 · 2025-04

Project Summary/Abstract The current interventions for negative symptoms in psychotic disorders and mood disorders with psychosis, particularly the experiential symptoms of reduced motivation and pleasure (MAP), are ineffective and wanting. This is a critical area for improvement, given that MAP symptoms are highly prevalent and strongly associated with disability and distress. However, we have a limited understanding of these symptoms' cognitive and neural bases. Moreover, MAP symptoms are heterogeneous in their presence, presentation, severity, and origins across individuals. Globally, traditional methods of assessing symptoms, cognition, and functional connectivity (FC) do not capture important variability within and between individuals. Quantifying this variability is necessary to understand the etiology and heterogeneity of MAP symptoms and develop effective interventions. Recently developed approaches, ecological momentary assessment (EMA), repeatable mobile cognitive testing (RMCT), naturalistic fMRI stimuli, and individual-specific functional connectivity (IS-FC) hold promise in addressing this issue. The proposed project aims to integrate these methods to advance our understanding of MAP symptoms' cognitive and neurobiological underpinnings in psychotic disorders and mood disorders with psychosis to ultimately inform effective clinical interventions. The overarching aims of this proposal are to a) investigate whether ecological momentary symptom assessment and repeatable mobile cognitive testing reveal more robust relationships between MAP symptoms to cognition and FC compared to standard in-lab clinical and cognitive assessments, b) examine whether IS-FC metrics lead to more robust relationships between FC and MAP symptoms compared to group-based FC metrics while using FC acquired during the processing of naturalistic stimuli, and c) assess to what extent these relationships are transdiagnostic across psychotic disorders and mood disorders with psychosis. The principal goal is to bolster our current understanding of the nature and etiology of experiential negative symptoms, which will, in turn, inform the development of effective transdiagnostic interventions. This project will be realized through training goals about gaining expertise on functional connectivity, negative symptoms across psychotic and mood disorders, advanced statistical analyses, and developing rigor, reproducibility, and professional development skills.

NIH Research Projects · FY 2025 · 2025-04

PROJECT SUMMARY Early caregiving is a critical determinant of healthy socio-emotional development and the capacity for adaptive emotion regulation (ER). Parental socio-emotional signals (e.g., warmth, support, responsiveness) during infancy are critical for the development of ER and protection against emotion dysregulation, a transdiagnostic indicator of risk for child psychopathology. Yet, the mechanisms by which parent behavior influences brain systems that support ER to increase psychiatric risk are unknown. Animal studies identify unpredictability (UN), the entropy in the patterns in parent behavior, as one mechanism by which parenting directly alters the maturation of emotional circuits. In parallel human studies, high UN in parent sensory signals (UN-sens; transitions between visual, auditory, and tactile behaviors) during infancy predicts childhood deficits in effortful control. This K01 will expand upon these findings and test the hypothesis that the UN of parent socio-emotional signals (UN-emo; the inconsistency of nurturing/supportive behaviors) observed during the first year of life alters the neurodevelopment of ER to increase risk for child psychopathology. Specifically, this K01 will investigate how UN-emo observed in early parent behavior relates to subsequent brain function (functional connectivity and evoked responses) supporting ER in early childhood. This K01 offers an unprecedented opportunity to address critical gaps in the mechanisms underlying the relationship between early caregiving, development of ER, and risk for psychopathology by testing an integrative model that incorporates biological, behavioral, and experiential factors. This time-sensitive innovative proposal leverages a rich, ongoing longitudinal study from birth to age 8 years with existing or ongoing observational (parent-child interactions), behavioral (ER), brain imaging (resting- state fMRI), and clinical (psychopathology) data. The applicant will add new coding (UN) and data collection (movie-fMRI) to investigate the impact of UN in parent behavior (both UN-sens and UN-emo) at age 1 year on the development of ER (age 1-6 years) and the functioning of brain systems supporting ER (age 6 years) including their role in predicting child psychopathology. Dissecting how early ER and brain function that support ER are altered by early caregiving will motivate and inform the design of novel parenting interventions that decrease UN-emo and resulting psychiatric risk. When combined with her extensive neuroimaging experience, background in functional brain organization, and expertise in complex computational techniques, the proposed targeted training in 1) observation of parenting during infancy, 2) measurement of early indicators of child psychopathology, and 3) examination of brain function in early childhood using movie-fMRI will uniquely enable the applicant to apply a developmental neuroscience approach to investigate how the emerging parent-child relationship shapes developing brain function to predispose children to psychopathology. This K01 will facilitate an R01 proposal that uncovers the mechanisms by which early parent behavior impacts the development, organization, and functioning of brain systems that underlie mental health problems, beginning in infancy.

NIH Research Projects · FY 2026 · 2025-03

PROJECT SUMMARY Oropharynx cancer (OPC) incidence has risen annually by 2.7% in the U.S. and is expected to be among the most common cancers over the next few decades. The vast majority of OPC is now reliably linked to human papillomavirus exposure (HPV+). Because HPV+ OPC typically has favourable outcomes, de-intensification trials have been aggressively advanced to minimize treatment-related toxicity and morbidity. However, while most patients respond well and might benefit from treatment de-escalation, there remain 10-38% of HPV+ OPC patients who experience adverse outcomes including recurrence and death. Unfortunately, current de- escalation trials remain indiscriminate in their ability to stratify these patients as there is no marker that is available to classify HPV+ patients further than the dichotomous measure of HPV positivity. The goal of this proposal is to validate a novel prognostic biomarker that captures tumor biology and heterogeneity in >1,000 diverse HPV+ OPC patients from the United States, Europe and South America to guide clinical decision-making and reduce treatment-related toxicity and morbidity. The specific aims are to 1) analytically validate HPVhet scores to establish reliability across diverse patient populations, establish risk groups to maximise prognostic accuracy, and externally validate informative HPVhet scores on outcomes; and 2) translate the HPVhet score as an imaging biomarker through detection from standard hematoxylin and eosin (H&E) stains through optimization of a validated, advanced machine-learning algorithm, OPSCCNet. The OPSCCNet algorithm will combine the molecular HPVhet score with related spatial features for effective interpretation of HPVhet on a spatial scale. Validation of a clinically useful prognostic biomarker that utilizes molecular and spatial data to capture tumor heterogeneity in >1,000 diverse HPV+ OPC patients could lead to a paradigm shift in how these patients are treated and in their quality of life after treatment. Importantly, the inclusion of a range of clinical settings and patient populations ensures scientific rigor and health equity in these findings.

NSF Awards · FY 2025 · 2025-03

The stiffness of the heart’s right ventricle (RV) is a critical determinant of cardiac health. For example, RV stiffness is a strong predictor of disease progression in pulmonary hypertension. It may even be a more reliable indicator of clinical outcomes than traditional measures of RV function, such as contractility. This research addresses the current lack of fundamental understanding of how intra- and extra-cellular mechanisms contribute to the stiffening of the RV. This topic has largely been overlooked in favor of studies focused on the structure and function of the heart’s left ventricle (LV). Given the significant differences in physiology between the RV and LV, this critical gap in knowledge presents a barrier to advancement in the diagnosis and treatment of RV-related conditions. Thus, by filling this gap, this project will provide insight into the mechanobiology of RV stiffening while supporting the development of new diagnostic tools, prognostic markers, and therapeutic strategies. This research is well-aligned with NSF’s mission to advance scientific progress and contribute to public welfare by addressing a significant health challenge. Furthermore, the project will provide educational and training opportunities for underrepresented student populations and enrich open science initiatives through publicly accessible content, such as live-streamed cardiac anatomy lessons. This project aims to delineate and model the intra- and extra-cellular mechanisms contributing to RV myocardial stiffening using a combination of experimental and computational approaches. Experimentally, micro-scale mechanical tests will be conducted on individual cardiomyocytes, followed by mechanical testing of combined cardiomyocyte-extracellular matrix strip assemblies. Primary myocardial samples isolated from the RV of both healthy and diseased sheep with established pulmonary hypertension will be included. Among the many potential biological mechanisms of RV stiffening, investigation will begin on variations in titin isoform expression and phosphorylation states and changes in endomysial collagen composition, density, and cross-linking. Computationally, machine-learning-based surrogate modeling approaches will be used to bring micro-scale models of cardiomyocytes and extracellular matrix up to the organ scale, where ultimately the role of each stiffening mechanism on tissue-scale measures, such as RV diastolic function, will be interrogated. The primary outcome of this work will be a multi-scale model that enhances understanding of RV physiology and diastolic dysfunction, thus contributing both valuable mechanobiological insights into RV remodeling and a set of open-source computational tools for future cardiovascular research. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-03

ABSTRACT Vocal fold paralysis (VFP) occurs when the recurrent laryngeal nerve (RLN) is injured, most frequently during thyroid surgery. This occurs in over 100,000 patients on one side and over 20,000 patients on both sides annually in the US. Unilateral paralysis of the laryngeal muscles causes hoarseness of voice and aspiration with swallowing; bilateral paralysis causes airway obstruction, with about 50% of patients needing a tracheotomy for adequate breathing. Current treatments are often unsatisfactory, usually with an implant for unilateral cases that can be malpositioned, or by cutting out a portion of one or both vocal folds for bilateral cases, which negatively impacts both voice and swallowing. Recent tissue engineering work in our lab and others has shown that adult muscle progenitor (stem) cells (MPCs) can be isolated from a healthy skeletal muscle, cultured, and implanted back into denervated laryngeal muscles. The MPCs become incorporated into the muscle (engrafted) and increase its nerve recovery as well as its strength. In this proposal, the use of MPCs for VFP is tested in an established canine model. In preliminary work, we found MPCs implanted into the vocal fold muscles resulted in a significant increase in the strength of the laryngeal muscles as well as increased nerve recovery. This project proposes further investigation of these exciting findings. In Aim 1, we will repeat our preliminary experiment, and also alter the conditions to be more typical of patients with VFP, with treatment delays of 3 months and 6 months from the time of RLN injury. We will also vary the amount of cells implanted to find the optimum number. These results will provide data needed for a possible clinical trial. To best simulate the size, volume and function of human laryngeal muscles, these experiments will utilize canine larynges. In Aim 2, we will explore the finding that the implanted MPCs cause an increase in innervation. How does implantation of muscle progenitor cells cause an increase in nerve growth? We will use bulk RNAseq and mass spec imaging (MSI) to identify peptides or other potentially neurotrophic molecules that are increased by implanting MPCs. Testing laryngeal muscles, with and without implanted MPCs, at different time points will help characterize the cellular mechanisms. These findings could lead to additional approaches to further maximize recovery of the injured RLN. These experiments will mainly use a rat RLN model, with a few canines for validation in a larger model.

NIH Research Projects · FY 2026 · 2025-03

Project Summary/Abstract This proposal presents a five-year research career development program to prepare the principal investigator (PI) Samantha Adamson, M.D., Ph.D., to become an independent physician-scientist in the field of diabetes research. The PI obtained PhD training in metabolic research at the University of Virginia with Dr. Norbert Leitinger and completed clinical training in Internal Medicine and Endocrinology at Washington University in St. Louis. The PI is currently an Instructor in Medicine and post-doctoral researcher in the lab of Dr. Jing Hughes at Washington University, studying the role of primary cilia in the function and crosstalk of pancreatic islet cells. Dr. Jing Hughes, Assistant Professor of Endocrinology at Washington University, will mentor the PI with Dr. David Piston, Chair of Cell Biology and Physiology, as co-mentor. Dr. Hughes is an emerging leader in islet and cilia research with R01 funding and is a Gateway Investigator of the Human Islet Research Network. Her expertise spans from immunology to adipocyte biology to islet cell biology, currently focusing on intra-islet cell communication via primary cilia. Dr. Hughes is a respected mentor of students, postdocs, and fellows both in the lab and in clinics. She serves as a perfect example of a successful physician-scientist who asks fundamental questions in cell biology that are grounded in clinical perspective. Dr. Piston has 30 years of research experience elucidating the molecular mechanisms that underlie hormone secretion from islets. He has mentored 37 undergraduate and graduate students, 20 post-docs, and 3 K-award fellows. The PI will take advantage of this mentorship, an expert advisory committee, and the rich and diverse scientific resources available at Washington University to define a new area of mechanism-based research in diabetes. Precise control of hormone secretion from islet cells is crucial for glucose homeostasis. Primary cilia mediate paracrine communication in islets by virtue of ciliary enrichment of somatostatin receptor 3 to control somatostatin signaling to beta cells. Preliminary data show the protein TULP3 is responsible for trafficking of somatostatin receptor to cilia and that the calcium channel polycystin 2 is required for proper calcium signaling in beta cells, an important second messenger. The research goal of this proposal is to define the mechanisms of ciliary somatostatin-mediated paracrine signaling through three focused aims. To accomplish these goals, the PI will define the role of TULP3 in trafficking of somatostatin receptor to beta cell cilia by deleting TULP3 in islets and assessing ciliary receptor localization, intracellular calcium signaling and insulin secretion in response to somatostatin compared to control islets. Further studies will focus on understanding the contributions of calcium signaling occurring in the cilia versus the cell cytosol in response to somatostatin and the role of the ciliary calcium channel polycystin. These studies will provide new insights in the pathogenesis of beta cell failure and potentially lead to the development of cilia-targeted therapy to potentiate insulin secretion for individuals living with diabetes.

NSF Awards · FY 2025 · 2025-03

This project examines how political uncertainty during democratic crises influences citizens' trust in political institutions and their preferences for leadership. By surveying the same group of respondents at four key moments, the research identifies who regains trust in institutions after an institutional crisis, how quickly this occurs, and how uncertainty shapes leadership preferences. It also investigates how demographic factors, such as gender and prior experience with autocratic regimes, affect these dynamics. The findings will provide insights for restoring public confidence in governance after crises and promoting inclusive leadership. To maximize societal impact, the project emphasizes broad dissemination through peer-reviewed publications, academic presentations, popular media, and publicly accessible anonymized survey data. This approach ensures the findings are accessible to researchers, policymakers, and stakeholders, guiding future research on democratic resilience and fostering practical solutions for inclusive governance. This project examines how democratic crises influence citizens’ trust in institutions and preferences for political leadership. The study proposes a longitudinal survey, recontacting 1,000 respondents at four critical junctures: the current peak of uncertainty, post-impeachment ruling, during the presidential campaign, and post-election. The survey measures institutional trust, leadership preferences, and respondents’ perceptions of political (un)certainty across these time points. It also embeds a conjoint experiment where respondents choose between leadership types. Together, the surveys and experiments offer insights into trust recovery and demonstrate how uncertainty in the political environment leads citizens to prefer different leadership traits. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-03

1 PROJECT SUMMARY/ABSTRACT 2 HIV/AIDS remains a significant public health issue, with an estimated 39 million individuals currently living with 3 HIV globally, of whom only 76% are on combination antiretroviral therapy (cART). cART suppresses, but does 4 not eliminate, HIV and is associated with its own burden of lifelong treatment. Thus, there is a pressing need 5 for research to advance the field towards a novel cure for HIV. In the proposed research study, we aim to 6 address this through a unique perspective, by focusing on how the human immune system naturally restricts a 7 specific subset of HIV. HIV tropism is defined by coreceptor use after initial CD4 binding by the virus envelope 8 protein. During the early clinical stages of HIV infection, a subset of HIV which uses the CCR5 coreceptor, 9 termed R5-tropic virus, is dominant, while another HIV subset which uses the CXCR4 coreceptor, termed and 10 X4-tropic virus, is restricted and does not emerge until progression to late clinical disease stages, when the 11 immune system has been impaired. We propose to identify the molecular mechanisms that control the natural, 12 immune-mediated restriction of X4-Tropic virus. Using primary CD4 T cells, in vivo analyses in humanized 13 mouse models, experimental knockout of candidate genes, and analyses of banked patient specimens that 14 predate the widespread use of cART, the candidate will (1) characterize the molecular mechanisms that drive 15 restriction of X4-Tropic viral replication in the presence of R5-Tropic virus, and (2) characterize the mechanism 16 underlying the emergence of X4-Tropic virus during the late clinical disease stages. The overall goal of the 17 proposed study is to gain an understanding of how our immune system naturally restricts X4-Tropic viral 18 replication and how this restriction is lost in late-stage disease. This knowledge will be foundational to future 19 studies that will aim to develop novel treatments for HIV that empower the immune system to restrict R5-tropic 20 virus during early clinical stages in the same manner in which it naturally restricts productive X4-tropic viral 21 replication. The enclosed proposal includes a five year career development plan which focuses on improving 22 knowledge and skills related to the study of immune mediated restriction of X4-tropic viruses and includes a 23 comprehensive mentoring and didactic plan that will ensure the candidate’s successful transition to an 24 independent career in basic and translational HIV research focused on the host-pathogen interface. The 25 candidate is supported by expert mentors and has committed institutional support, with a promotion to 26 Instructor planned prior to the commencement of the K08 award period and 75% research time protected 27 during the award period. The proposed mentorship team, including a primary mentor who is a renowned HIV 28 researcher with prior experience in identifying novel immune mechanisms of HV reservoir clearance, will 29 support the candidate in developing key knowledge and skills. Successful completion of the proposed K08 30 training goals and specific aims will maximize the candidate’s chances of success in an independent research 31 career.

NIH Research Projects · FY 2026 · 2025-03

Project Summary/Abstract Malignant tumors characterized by rhabdoid features often display highly aggressive biology, frequently resulting in fatal outcomes, even when these features are localized to small areas within the tumors. Despite their relatively low occurrence, rhabdoid features have been observed across various tumor types and are linked with early metastasis. Notably, clear cell renal cell carcinoma (ccRCC) with rhabdoid features represents a recently identified histopathologic variant of renal cell carcinoma (RCC). The current management and clinical trajectory of these tumors exhibit significant variability with limited success. Researchers face challenges in accurately diagnosing rhabdoid features from biopsy specimens and lacking definitive data to comprehend these features thoroughly. To uncover the molecular mechanisms and understand the role of SERPINE family genes underlying rhabdoid tumorigenesis, Dr. Li will leverage recent advances and availabilities of the multi-omics data set and his integrative computational and experimental approach consisting of multi-omics, spatial, histopathology, and in situ analysis. During the K99 mentored phase of the award, Dr. Li proposes identifying the molecular signatures and mechanisms underlying rhabdoid tumorigenesis in ccRCC (Aim 1). During the R00 independent phase of the award, expanding on his earlier SERPINE-related findings in ccRCC, Dr. Li will apply multi-omics technologies and functional studies to understand the role of SERPINE family genes in rhabdoid tumorigenesis of ccRCC (Aim 2). Furthermore, Dr. Li aims to ascertain the aggressiveness and heterogeneity signatures of advanced tumors with rhabdoid features at the broader pan-cancer level, given their presence in varied cancer types (Aim 3). The results of this proposal have the potential to give fundamental new insight into the associated aggressiveness signature and mechanisms underlying the rhabdoid phenotypes, which will assist the clinical procedures for diagnosis and treatment. Notably, a better understanding of the role of SERPINE family genes in rhabdoid tumorigenesis can potentially lead to the development of effective treatment strategies for advanced tumors with rhabdoid features. This proposal also describes a detailed training plan to advance Dr. Li’s career as an independent investigator, combining computational and analytical approaches on varied data types with histopathology and experimental biology to uncover the mechanisms underlying tumorigenesis and progression better, identify therapeutic vulnerability and predict the treatment response. Throughout the K99 phase, Dr. Li will receive strong support from an interdisciplinary team of experts to expand his knowledge and refine his skill set for the transition into an independent investigator.

NSF Awards · FY 2025 · 2025-03

Cilia are tiny, slender structures that extend out from cells lining fluid-filled passages. In our bodies, cilia are present in the lungs, brain, and reproductive systems. These cilia beat back and forth with a wave-like motion that moves fluid along the passages. Failure of cilia beating can lead to severe health problems such as lung infections, brain swelling, or infertility. Cilia are also found on many single-celled organisms, in which cilia beating propels the organism through surrounding fluid. In both the human body and swimming cells, cilia beating must be coordinated to be effective. This project will support research that studies how coordination of cilia is maintained in the single-celled organism, Tetrahymena. How changing fluid resistance and altering connections between cilia changes the coordination of cilia beating and affects swimming speed will be studied. This research intends to help understand and potentially treat diseases related to cilia defects. Understanding cilia coordination could also lead to new designs of man-made systems to move fluid or propel objects using multiple coordinated wave generators. This project will also support workforce development through research, education, and outreach. The PIs will train graduate students at the interface of mechanics, biophysics and cell biology, involve undergraduates in summer research and independent study projects during the academic year, and engage K-12 students with hands-on activities to introduce design and problem-solving concepts. Motile cilia are powered by the “9+2” axoneme, an array of nine microtubule doublets surrounding a central pair of singlet microtubules, connected by a network of passive spokes and links and driven by dynein motor proteins. At the base of the cilium, the basal body (BB) is an array of microtubule triplets anchored to the cell cortex by microtubule bundles (post-ciliary and transverse) and connected to each other via striated fibers. Force transmission between BBs and the cell cortex to reveal how these interactions modulate ciliary beating and coordination will be studied. The first aim is to measure dynamic deformations of BBs in Tetrahymena, using expansion microscopy and super-resolution imaging, and uncover how BB deformations are affected by ciliary beating and intracellular connections. The second aim is to quantify metachronal coordination of Tetrahymena cilia and test the role of connecting fibers in controlling the waveform and timing of cilia beating. Laser ablation will be used to disrupt connections between adjacent cilia and quantify the effects on cilia waveform and coordination. The third aim is to model and simulate the mechanics of cilia beating in Tetrahymena. Two types of computer models will be built: (1) the Axoneme-BB model will be a detailed structural model of the ciliary cytoskeleton and its connections to the cell; (2) the Cilia Array model will be a coarse-grained model of multiple cilia that each exhibit autonomous oscillations, that includes intracellular coupling to mediate metachronal coordination. Comparison of model predictions to experimental measurements will clarify the role of intracellular force transmission in cilia coordination. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-03

The incidence of tick-borne diseases has increased significantly over the past 25 years due to ecological changes and shifting population demographics of both humans and ticks, and inadequate vector control. Including economic and societal burden, it is estimated that tick-borne diseases costs between 50 and 100 billion dollars each year. The Center for Disease Control and Prevention currently recognizes 18 different tick-transmitted pathogens in the United States. This number is likely to rise as novel pathogens are being discovered each year. One of these pathogens is Bourbon virus (BRBV), an emerging tick-borne RNA virus that can infect and cause disease in humans. No antiviral therapies or vaccines are available, highlighting the need to develop countermeasures against this life-threatening diseases. The primary objective of this application is to develop an mRNA vaccine against BRBV, evaluate its efficacy in vivo in a mouse model of BRBV and determine the mechanism of action. A secondary objective is to test different viral antigens and combinations of antigens and evaluate heterologous protection against divergent thogotoviruses, therefore developing a road map for panpathogen mRNA vaccines. Successful completion of the proposed studies will provide the preliminary data for a R01 application aimed at developing a universal vaccine that confers protection against tick-borne pathogens in the United States and beyond.

NIH Research Projects · FY 2024 · 2025-02

Anorexia nervosa (AN) is a psychiatric illness characterized by both distorted self-image and a restriction of energy intake relative to requirements, leading to significantly low body weight, and frequently resulting in severe medical complications. As such, numerous physiological changes in people with AN have been observed, including differences in both immunological and gastrointestinal function during the disease. However, these changes have not yet been related to the cognitive and behavioral symptoms observed during AN. This K23 Mentored Career Development Award proposal is a first step to address this gap in the literature. Our proposed research project will evaluate both immune dysregulation and gut microbiome composition in women with AN and healthy comparison participants. In Aim 1, we characterize the molecular components of inflammation by assessing both basal and innate cytokine production capacity. In Aim 2, we evaluate the composition of the gut microbiome and its relationship to eating disorder symptoms. Lastly we will explore (Aim 3) whether alterations in gut microbiome composition correlate with inflammatory marker levels. The career development portion of this award provides the PI with detailed training in 1) gut microbiome-immune system research; 2) psychopathology research methods necessary to conduct independent research investigating biomarkers in eating disorders; 3) translational science design, implementation and management; and 4) responsible conduct of research. An expert team of mentors and advisors will oversee both research and training aims, including an on-site primary mentor with expertise in eating disorders and translational science, Dr. Carrie McAdams, and an on-site co-mentor with expertise in how gut microbiome modulates host immune responses, Dr. Andrew Koh. Dr. Cynthia Bulik, a scientific advisor, will provide mentorship on relating biomarkers with complex human behaviors seen in psychiatric illness. Two additional scientific advisors, Dr. Robert Haley (expertise in biostatistics in relation to neuroimmunology) and Dr. Larry Borish (expertise on immune function and inflammatory pathways) complete the mentorship team. The research and training outlined in this proposal will provide crucial formal and experiential training to allow the PI, a board certified internist with a strong research background in gastrointestinal physiology and immunology, to develop into an independent translational physician-scientist.

NIH Research Projects · FY 2026 · 2025-02

There exists a research-to-practice gap that hinders the penetration of human papillomavirus (HPV) vaccination among adolescent girls and young women in Nigeria. To close this gap requires reliable, validated, easy-to-use tools to identify and measure elements of penetration that drive high performance of HPV vaccination uptake in resource limited settings. Penetration, defined here as the integration of evidence (i.e. HPV vaccines) within the culture of recipient setting or community through policies and practices remains incompletely understood in low resource settings. Currently, existing measures for penetration suggest that there are three stages that determine the extent of integration within service settings: 1) passages (i.e. single event); 2) routines (repetitive reinforcement of interventions) and 3) niche saturation (or extent in which intervention is integrated). However, these measures often confound several dynamic processes inherent with integrating evidence-based interventions within resource limited settings. They also provide no insight on the multidimensional nature of penetration or whether it may be influenced by important determinants such as: 1) perceptions of passages; 2) enablers or resources for routines; and 3) nurturers or assets for niche saturation. In response to NCI’s Strategic Plan to advance cancer prevention research and increase HPV vaccination coverage. The overall goal of this F31 is to develop a reliable, valid, and pragmatic assessment tool to identify core features of penetration related to high uptake of HPV vaccines. We proposed to develop the Implementation Penetration Assessment Criteria Tool (ImPACT) with the guidance of the perceptions, enablers, and nurturers domain of the PEN-3 cultural model developed by Airhihenbuwa to address the determinants highlighted above. This study, which builds on the recently funded ACCESS study (R01 CA271033: PI: Iwelunmor: Actions for Collaborative Community Engages Strategies for HPV), will develop the ImPACT Tool through the projects three specific aims: to (1) identify core domains and items that will comprise an Implementation Penetration Assessment Criteria Tool (ImPACT) via in-depth interviews with 20 young women and group concept mapping with 20 key stakeholders; (2) evaluate face validity of the ImPACT tool via cognitive interviewing and pilot test the drafted tool; and (3) evaluate the psychometric properties of the ImPACT tool across 18 sites of the ACCESS study using the Psychometric Evidence Scale criteria as a guide. The project is significant because, if successful, it would be the first reliable, valid, and pragmatic instrument for assessing the penetration of evidence-based HPV vaccination in low resource settings and will also provide a roadmap for building capacity and infrastructure for advancing the reach, adoption, and sustainability of HPV vaccination programs. This project will also prepare the applicant to become a leading independent researcher in the field of implementation science and support training in rigorous, solution oriented implementation research focused on improving population health outcomes.

NIH Research Projects · FY 2025 · 2025-02

Examining system-wide implementation of new flexibilities to the National School Lunch and Breakfast Programs PROJECT SUMMARY BACKGROUND: Cardiovascular diseases (CVD) are the leading cause of death in the US and the underlying pathophysiological processes are evident in adolescence. Risk factors for CVD include obesity and prevention of obesity during adolescence can minimize adult CVD. Unfortunately, the prevalence of youth obesity in the US has nearly doubled in the past 20 years. Disparities in nutrition and healthy food access in schools and within certain communities contribute to higher prevalence of obesity among Hispanic, black, and low-income youth. The National School Lunch and Breakfast Programs (NSLP/SBP) are a complex system involving food suppliers, school food service directors, and student consumers. In 2018, a significant policy change to the NSLP/SBP allowed schools to decide if they wanted to implement relaxed school nutrition standards for milk, whole grains, and sodium. Such policy changes can lead to inefficient and inequitable implementation, ultimately affecting youth food consumption and health-related outcomes. GOAL: This proposal seeks to describe the impact of NSLP/SBP policy changes and flexibilities on the many levels involved in implementing these programs and to identify leverage points for which effectiveness and equity of implementation might be meaningfully and sustainably improved. AIMS AND METHODS: This is a three-phase study that takes a comprehensive approach, leading to the elucidation of more effective and equitable school food policy development and implementation. Phase 1 will assess current flexibility implementation practices and determinants of decision-making process. For this phase, we will engage School Nutrition Association (SNA) members: a nationally representative sample of over 4,000 school districts. Data collected will be merged with state level school data to understand how decisions relate to participation and health-related outcomes. Phase 2 involves interviewing food industry actors to understand how NSLP/SBP policy changes result in decisions to change food supply and distribution. Phase 3 seeks to develop an agent-based model (ABM). We will use this ABM as a “virtual policy laboratory,” analyzing ways to improve effective and equitable district-level implementation of the NSLP/SBP in silico and providing tools to inform real-world policymaking. All study phases will rely on close collaboration with key practice partners. INNOVATIONS AND IMPACT: This study is innovative and impactful because it will be the first to: (1) use the combination of an implementation science framework- the Consolidated Framework of Implementation and the Racial Equity and Policy Framework to assess and document implementation of flexibilities among school districts nationwide; (2) examine how decisions to implement flexibilities to NSLP/SBP result in inequitable food provision to youth; and (3) inform USDA rule- making and final rules in real time. These findings will contribute toward addressing school nutrition-related health inequities including those associated with enhanced risk of cardiovascular disease into adulthood.

NSF Awards · FY 2025 · 2025-02

Quantum computers leverage quantum phenomena such as superposition and entanglement in quantum bits (qubits), enabling them to solve certain computational problems exponentially faster than classical computers. The successful realization of quantum computers has the potential to transform diverse fields such as drug discovery, quantum chemistry, biology, cryptography, image processing, optimization, and machine learning by addressing computational challenges that are infeasible for classical systems. Estimates suggest that general-purpose quantum computers capable of solving real-world problems will require 10⁴–10⁵ physical qubits. A significant obstacle to scaling quantum computers to this level is the hardware infrastructure, which currently relies on room-temperature rack electronics for qubit control and readout, along with bulky, connectorized microwave components—such as circulators and amplifiers—inside dilution refrigerators. This project aims to address these limitations by developing energy-efficient, low-cost, and compact cryogenic chips that enable scaling quantum systems to support thousands of qubits. The research focuses on advancing cryogenic Complementary Metal-Oxide-Semiconductor (CMOS) integrated circuits (ICs) for qubit control pulse generation and superconducting chip technology for on-chip circulators. These innovations are expected to accelerate breakthroughs in quantum computing while also benefiting related fields such as satellite communication, space-based telescopes, and cryogenic electronics. Furthermore, the project seeks to foster seamless integration between circuit design and quantum physics, laying the foundation for a diverse and skilled workforce in this multidisciplinary research domain. To achieve this, the project will implement a range of educational and outreach initiatives, including online courses, undergraduate research opportunities, career development workshops for K-12 students, and the creation of open-source infrastructure. The research activities are organized into three thrusts: cryogenic (4K) CMOS IC development, superconducting chip development, and system integration with superconducting qubits operating at 10-100mK. First, a fully analog, low-power, and scalable qubit control scheme will be demonstrated using CMOS ICs operating at 4K, eliminating the need for room-temperature rack electronics. Unlike current digital-intensive control schemes, this project explores low-power microwave pulse generation using analog filter synthesis, enabling significant power savings compared to state-of-the-art digital qubit control circuits. Analog multiplexing schemes will be explored to reduce the cabling overheard between the 4K to 10mK stages. Second, time-modulated Josephson Junction-based non-reciprocal devices will be developed to replace the bulky and costly ferrite-based circulators and isolators currently used in dilution refrigerators. These on-chip, superconducting circulators are expected to offer drastically reduced size and cost when compared to their ferrite counterparts. To aid easier integration with the qubits, these superconducting circulators will be designed to achieve to low intermodulation power while achieving low-loss transmission and high isolation at the input frequency. Finally, the cryogenic-CMOS ICs and superconducting circulators will be integrated with superconducting qubits to demonstrate a fully integrated closed-loop system for qubit control and readout. 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.