University Of Illinois At Chicago

NSF Awards · FY 2026 · 2026-08

This Faculty Early Career Development Program (CAREER) project is to support research and education on the design science for additively manufacturable Architected structured materials (ASMs). Architected structured materials (ASMs) are the building blocks for creating multifunctional, intelligent matter with unprecedented properties for a wide range of needs in health, energy, and aerospace applications. Existing ASMs' design paradigms produce optimal designs under the assumption of a perfect, defect-free, ideal topology, whose properties are theoretically optimized. However, due to the ASMs' intricate topologies and manufacturing process uncertainties, defects and imperfections are inevitable in the manufactured structures, which can severely degrade the ASMs' effective properties. The project will advance the realization of manufactured-as-designed ASMs by rethinking the design representation of ASMs to address the design-for-additive manufacturing (DfAM) abstraction and AM process-induced imperfections, while understanding ASMs' architecture-process-property relations to enable the generative design of manufactured-as-designed ASMs. The resulting knowledge will: 1) accelerate the ASMs' inverse design and facilitate the on-demand functional device design automation; 2) advance AM processes innovation by elucidating the material deposition for structure formation principles; 3) provide knowledge for generative design of next-generation responsive ASMs and intelligent devices. The education and outreach objective is to create an immersive learning environment and easily accessible design tools to increase participation in DfAM and AI in engineering design. This project will support participation of vertically integrated teams (VIT), the development of a virtual reality (VR)-assisted interactive design platform, the involvement of undergraduate researchers, and the integration of K-12 and NASA outreach activities. The aim of this research is to fundamentally understand the roles of DfAM and AM process-induced geometric imperfections, and to elucidate architecture-defect-property relations for achieving the generative design of manufactured-as-designed ASMs. This overarching goal will be achieved by: 1) deriving a unified design representation for both ASMs' topology and DfAM operations; 2) modeling the influence of process-induced imperfections on material property degradation; and 3) integrating this influence into the design loop to enable the generative design of manufactured-as-designed ASMs by developing a compositional geometric artificial intelligence (CGAI) framework. This research will transform the discovery and design of manufactured-as-designed ASMs. First, a neural-field design representation for simultaneously expressing topology and DfAM sequences. Second, statistical distributions of ASMs' geometric imperfections for modeling how AM process-induced imperfections influence the materials property degradation; Third, fundamentally understanding the intrinsic relations between manufacturing imperfections, mesoscale geometry, and macroscale mechanical properties of cellular structures to elucidate the structure-processing-property interplays for developing generative models of ASMs via generative AI methods. The education and outreach plan includes developing hands-on, interactive VR and haptic design course materials for students from K-12 through the graduate level; and increasing participation from high schools, community colleges, and the public to promote awareness of AI-enabled design, DfAM, and manufactured-as-designed thinking. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-06

Abstract Protein complexes carry out nearly all biological functions. When protein complexes are disrupted, they give rise to many diseases not limited to cancer, cardiovascular disease, and developmental disorders which collectively, affect 148 million Americans and kill nearly 1 million Americans each year. A grand challenge in molecular biology is the identification and characterization of protein complexes. While tremendous progress has been made in accurately identifying protein complexes, we still lack a basic understanding of many complexes. Specifically, we currently do not know the components of all human protein complexes including subtly altered variants which differ in function. We lack understanding of the degree to which complexes differ between cell types. Lastly, we lack high quality structural models for all protein complexes to aid interpretation of disease mutations. Here, we propose to 1) develop machine learning approaches to identify biologically relevant protein complex variants from >32,000 mass spectrometry experiments; 2) build computational workflows to construct cell-type specific protein complex maps focusing on early embryonic development; and 3) create a direct contact network of physically associated proteins which will prioritize structural modeling (e.g. AlphaFold) efforts to interpret disease mutations. This work aims to provide a more accurate and comprehensive understanding of protein complexes which will ultimately lead to novel therapeutic targets and strategies.

NIH Research Projects · FY 2026 · 2026-06

Project Summary/Abstract Obesity and metabolic disorders are leading causes of morbidity worldwide, driven in part by impaired thermogenic fat function and disrupted energy homeostasis. Beige adipocytes are inducible thermogenic fat cells within white adipose depots that play a critical role in regulating systemic metabolism by increasing energy expenditure and improving glucose and insulin homeostasis. Enhancing beige fat function represents a promising strategy for mitigating metabolic disease, yet the regulatory pathways governing beige adipogenesis, particularly in obesity, remain incompletely understood. Recent evidence from our group identifies 3- phenylpropionic acid (3-PPA), a gut microbiota-derived metabolite, as a key endogenous factor that promotes beige adipocyte formation and improves metabolic outcomes in vivo. Our preliminary data demonstrate that 3- PPA engages an immune–adipose axis involving GPR40 activation in macrophages, CXCL13 secretion, and T follicular helper (Tfh) cell recruitment. However, the broader physiological significance and therapeutic potential of this signaling axis in the context of obesity and insulin resistance remain unknown. We hypothesize that 3- PPA enhances beige adipogenesis and mitigates metabolic dysfunction through coordinated microbiota–immune–adipose interactions. To test this, we will: (1) characterize the role of GPR40-mediated signaling in macrophages during 3-PPA–induced metabolic remodeling; (2) define how CXCL13-Tfh cell interactions influence beige adipogenesis in obesity; and (3) assess the efficacy of 3-PPA-based interventions in mouse models of diet-induced obesity and metabolic disease. This research integrates metabolic physiology, immunometabolism, and microbiota-derived signaling to uncover disease-relevant mechanisms regulating thermogenic fat function. Findings may provide the foundation for novel microbiota-targeted therapies for obesity and metabolic disorders.

NIH Research Projects · FY 2026 · 2026-06

Ocular inflammation and infection remain major causes of vision loss worldwide, with conditions such as uveitis, keratitis, scleritis, retinitis, dry eye disease, graft-versus-host disease, and Stevens-Johnson syndrome continuing to pose formidable clinical challenges. These disorders often arise from complex interactions between infectious agents and dysregulated immune responses, and their management demands advances in diagnostics, clinical care, and the development of novel therapies. Despite the urgent need, few national forums exist where experts across basic science, clinical research, and patient care come together to address these issues in a truly integrated and less formal manner. The Symposium on Eye Inflammation and Infection (SEII) was launched in 2024 to meet this need and immediately demonstrated its value by convening over 160 participants, including 30 nationally recognized speakers and more than 15 trainee-led talks. Trainees also co- Chaired multiple sessions. SEII distinguishes itself from other vision science conferences through its unique thematic focus on the interplay of inflammation and infection across the entire eye and through its deliberate integration of basic scientists, clinician–scientists, and clinicians at all levels. The inaugural meeting sparked new collaborations, including a multi-investigator grant submission, and fostered rare dialogue that directly linked mechanistic discoveries with clinical management strategies and therapeutic development. Equally innovative is SEII’s structure, which positions trainees not at the margins but at the center of the meeting. Trainees are heavily involved in every aspect, from organizing through their own emerging scientists’ committee, to running sessions, to presenting podium talks and posters, co-chairing sessions, to receiving named awards for excellence. At present, SEII is the only national meeting in vision science that systematically integrates trainees into leadership, scholarship, and recognition at this level. This model not only strengthens the pipeline of future vision researchers but also creates unparalleled opportunities for mentorship and career development by ensuring that trainees share meals and formal and informal discussions with world-renowned experts. We now seek three years of NEI R13 support to sustain and expand SEII as a premier national platform dedicated to advancing the science and clinical practice of ocular inflammation and infection. By convening leading experts across disciplines, SEII will accelerate discovery, stimulate collaboration, and catalyze innovations in diagnostics and therapeutics that address some of the most pressing causes of vision loss. At the same time, it will foster the development of the next generation of clinician–scientists and vision researchers. With this continued support, SEII will establish itself as a nationally recognized meeting that transforms both the research and clinical management of inflammatory and infectious eye diseases.

NIH Research Projects · FY 2026 · 2026-06

Charcot-Marie-Tooth disease (CMT) is the eponymous designation for inherited disorders characterized exclusively or predominantly by neuropathy. CMT affects approximately one in 2500 individuals worldwide. For the most part, mutations in genes expressed exclusively in Schwann cells, the myelinating cell of the PNS, produce demyelinating CMT. However, disability in all forms of CMT likely arises from axonal loss. Nonetheless, mechanisms of axonal loss in diseases caused by mutations in Schwann cells is not well understood. This is particularly highlighted in CMT1X, caused by mutations of GJB, the gene encoding connexin 32 (Cx32), a gap junction protein expressed in Schwann cells but not elsewhere in the peripheral nervous system. In spite of this Schwann cell localization, CMT1X is characterized by significant axonopathy, especially in its earliest stages. This application is a discovery-based proposal which will integrate data from Schwann cells, other peripheral nerve cells, and spinal motor neurons (Anterior Horn Cells, AHCs) and will provide us with insights into both motor neuron signaling pathways as well as peripheral nerve signaling pathways which are disrupted in in the absence of Cx32. There is currently a paucity of identified targets for ameliorating axonal loss in demyelinating CMT, and our results will likely identify therapeutic targets to preserve axonal function in patients with CMT. Thus, this work will form the basis for future hypothesis driven investigations to treat axonal loss, the underlying cause of morbidity in CMT1X and all forms of CMT. In Aim 1 we ask, “what are the alterations in gene expression that characterize the spinal motor neurons (anterior horn cells, AHCs) of CMT1X mice after onset of axonopathy but prior to demyelination and after onset of demyelination?” We will use the RiboTag approach in conjunction with ChAT-Cre to examine RNA expression from Anterior Horn Cells (AHCs) in the spinal cord of a Cx32 knockout mouse model of CMT1X (Cx32 KO) as well as WT and appropriate controls (ChAT-Cre or RiboTag alone) at two and six months of age. In Aim 2 we ask, “what are the alterations in gene expression that characterize the myelinating Schwann cells of CMT1X mouse nerve after onset of axonopathy but prior to demyelination and after onset of demyelination? To identify cell specific signaling pathways that contribute to the axonopathy of CMT1X we will use single nuclear RNA-seq to examine the transcriptome of the resident cells in the sciatic nerves of WT and Cx32KO at the same timepoints as Aim 1. In Aim 3 we ask, ”how are patterns of gene expression in anterior horn cell and peripheral nerve cell complement affected by an effective treatment of neuropathy in a CMT1X model mouse?” We will utilize cemdomespib to investigate the effects on the patterns of gene expression in AHCs and resident nerve cells from WT and Cx32KO mice using the same approaches outlined in Aims 1 and 2. Thus, this work will form the basis for future hypothesis driven investigations to treat axonal loss, the underlying cause of morbidity in CMT1X and all forms of CMT.

NIH Research Projects · FY 2026 · 2026-06

Project Summary/Abstract: Our long-term goal is to elucidate the cellular and molecular mechanisms by which dysbiosis, organ injury, and the host systemic response lead to multiple organ dysfunction syndrome (MODS) in critical illness, ultimately identifying therapeutic targets. Trauma, burns, and surgery often cause microbiome imbalances (dysbiosis) and increased gut permeability, which are key drivers of systemic infallamtion and MODS in critically ill patients, significantly increasing ICU mortality. Clinical evidence indicates that the microbiota and host immunity function as an integrated system, where intestinal dysbiosis and injury compromise gut defenses and heighten susceptibility to nosocomial infections and systemic inflammation. Indeed, our recent findings suggest that dysbiosis substantially raises the risk of gut injury progressing to systemic inflammation and MODS. Despite this knowledge, the mechanisms linking the host immune response to gut dysbiosis and injury in sepsis and MODS remain poorly understood, and clinically relevant investigations are limited. Dysbiosis is characterized by the loss of commensal bacteria, reduced microbial diversity, and overgrowth of pathobionts. While earlier work mainly addressed adaptive immunity (T, B, and NK cells), critically ill ICU patients with MODS frequently exhibit innate immune dysregulation associated with dysbiosis. Thus, gut innate immunity, as the first line of defense, is essential in orchestrating systemic responses. Over the next five years, our research will (1) validate that dysbiosis, as a critical risk factor, exacerbates organ injury and systemic responses across various models, (2) identify organ-specific mechanisms in dysbiosis-initiated, organ-driven systemic inflammation and MODS, and (3) target dysbiosis-induced metabolic and epigenetic alterations, employing novel techniques to illuminate potential prevention and treatment strategies. Our broader vision unfolds in multiple layers. First, establishing direct evidence that dysbiosis contributes to organ injury severity and systemic responses will have significant implications for clinical care and public health. Second, we will integrate diverse approaches in our research program: clinical assessment systems to track disease progression, multiple injury models, germ-free and genetically modified mice, and advanced technologies such as single-cell RNA-seq, ATAC-seq, 16S rRNA-seq, shotgun metagenomics, metabolite profiling, Seahorse real-time metabolic assays, and ChIP-seq. These complementary methods will deepen our understanding of the complex interactions between microbiome and immunity. Finally, successful completion of these projects will expand our understanding of how intestinal conditions influence systemic host responses, provide deeper mechanistic insights, and guide the development of therapeutic strategies to mitigate the public health burden of critical illnesses.

NIH Research Projects · FY 2026 · 2026-06

Project Summary/Abstract: Sarcoidosis is a rare and understudied disease. It is characterized by a strong genetic predisposition, with risk often conferred by Major Histocompatibility (MHC) class II genes and a dysregulated immune response against an unidentified inhaled antigen. Antigenic exposure triggers interactions between antigen-presenting cells (APCs) and naïve CD4+ T-cells within lymph nodes (LNs), leading to a polarized Th1 response and granulomatous inflammation primarily observed in the lungs and LNs. Persistence of this heightened inflammatory immune response results in chronic sarcoidosis, with up to 40% of pulmonary cases progressing to irreversible and possibly end-stage fibrotic disease. Disease progression is associated with reduced quality of life, significant morbidity, higher mortality, and increased healthcare costs. Despite the negative impact, the exact immunological mechanisms driving persistent inflammation in sarcoidosis and progression to end stages have not been fully elucidated and pose a barrier to developing effective therapies. Our recent observations and those of other researchers indicate that up to 50% of sarcoidosis patients exhibit paradoxical peripheral lymphopenia, accompanied by CD4+ T-cell anergy and exhaustion, even in the early stages of the disease. This is associated with increased inflammatory activity, severe organ involvement, and disease progression. Loss of CD4+ effector T-cell function is thought to impair immune surveillance, leading to unmitigated inflammation and persistent granulomatous infiltration of affected tissues. Our prior research utilizing bulk RNA-seq analysis of peripheral immune cells suggests that compromised lymphocyte function and survival stem from aberrant, cell-specific, transcriptomic networks and interactions between lymphocytes and hyperactive innate APCs in lymphopenic sarcoidosis. Utilizing single-cell omic analyses, our novel preliminary data expands on this notion and reveals that peripheral naïve CD4+ T-cells from individuals with lymphopenic sarcoidosis possess a genetically imprinted, aberrant transcriptional program with multiple dysregulated immunoregulatory biological pathways that are involved in cell proliferation and death, predisposing them to impaired function and survival. Furthermore, we find an association between lymphopenia and MHC class II genes, and via single-cell RNA-seq of intrathoracic LNs fine needle aspirates, we find evidence that cDC1s in lymphopenic sarcoidosis have a limited ability to process and present antigens underscoring their crucial role in orchestrating adaptive immune responses. Thus, this research aims to elucidate the underlying mechanisms driving paradoxical peripheral lymphopenia in early sarcoidosis. We propose to utilize high-throughput analyses, such as single-cell RNA-seq and ATAC-seq, along with conventional immunology techniques to investigate how naïve CD4+ T-cells and cDC1s contribute to T-cell dysfunction and impaired survival. Focusing on these immune cell subsets will allow us to uncover intrinsic and extrinsic factors that influence immune dysregulation in lymphopenic sarcoidosis and provide critical insights for developing targeted therapies to mitigate disease progression.

NIH Research Projects · FY 2026 · 2026-06

The outcomes for acute myeloid leukemia (AML) have remained abysmally poor for the past 30 years. It has been shown that AML patients with wild-type FMS-like receptor tyrosine kinase (FLT3) and mutant nucleophosmin (NPM1mut) show improved overall survival and relapse-free survival. Transcription factor FOXM1 interacts with NPM in human cancer cells, including AML cells, and mutant NPM drives FOXM1 to the cytoplasm, where FOXM1 become inactivated. Our data indicate that favorable outcome for White AML patients with NPM1mut based on FOXM1 inactivation. However, this is not true for Black AML patients and recently it has been shown that black AML patients with mutant NPM1 do not have favorable outcome of treatment. For example, Black patients with NPM1 mutations who were FLT3-wt had worse DFS (3-year rates: 13% versus 55%, P = 0.002), EFS (3-year rates: 10% versus 46%, P = 0.01) and OS (10% versus 61%, P < 0.001) than White patients. First, we will determine if NPM1 mutant status determines FOXM1 cytoplasmic localization/inactivation in primary samples from Black AML patients. We will use de-identified AML bone marrow biopsy samples at the time of diagnosis that will be provided by Dr. Khan (NU). We will study correlations between NPM1 mutations, NPM/FOXM1 localization, BCL2A1 expression and prognosis in 80 primary AML patient bone marrow biopsies as follow: White patient samples: FLT3wt/NPM1wt (20 samples) and FLT3wt/NPM1mut (20 samples); Black patient samples: FLT3wt/NPM1wt (20 samples) and FLT3wt/NPM1mut (20 samples). Bone marrow biopsy specimens at the time of diagnosis of AML will be identified, sectioned and fixed on slides. Next, we will perform multiplex immunofluorescence imaging to examine simultaneous NPM and FOXM1 nuclear/cytoplasmic localization and BCL2A1 expression by quantifying its expression in the leukemia cells of interest. These experiments will show whether FOXM1 is localized in cytoplasm of Black AML patients with mutant NPM1. Next, we will test whether FOXM1- independent expression of BCL2A1 determines unfavorable outcome in Black AML patients with mutant NPM1. Additionally, we will identify differentially expressed gene(s) in primary AML samples from Black/White patients with mutant NPM1 that are potentially responsible for unfavorable outcome for Black patients. We will perform RNA-seq in 40 AML primary samples (20-White AML patients with mutant NPM1; 20- Black AML patients with mutant NPM1). We will isolate the RNA from AML primary samples and single-read sequencing for 40 bases will be done on an Illumina HiSeq Analyzer. We will identify the differentially expressed (DE) genes (log2 expression fold change >2 or <2, false discovery rate <0.05). The expression changes will be confirmed by qRT-qPCR. These experiments will reveal whether there are differences in gene expression in White versus Black AML patient samples with mutant NPM1 that could explain difference in Black/White NPM1 mutant AML patient outcomes.

NIH Research Projects · FY 2026 · 2026-06

PROJECT SUMMARY/ABSTRACT Suicidal thoughts and behaviors are increasingly prevalent among youth in the United States. Pediatric outpatient mental healthcare settings are critical sites for suicide prevention. Despite changes in clinical practice guidelines and accreditation standards recognizing pediatric mental health providers’ responsibility to implement evidence-based practices (EBPs) for suicide prevention, little is understood about how to optimize such practices for the outpatient context. Further, minimal research has captured the perspectives of youth patients who have received suicide prevention EBPs during treatment or those of their caregivers, who are often at the forefront of suicide prevention efforts. The specific aims of the proposed study are to: (1) Understand the lived experiences of key constituents and identify contextual determinants of implementation of a evidence-based suicide prevention pathway within outpatient pediatric mental healthcare, and (2) Develop a set of contextually tailored implementation strategies to optimize and sustain suicide prevention implementation in pediatric mental healthcare using a community-engaged approach. The current study proposes to recruit a sample of pediatric mental health clinicians, youth patients (ages 12-18), and patient caregivers from public, outpatient child psychiatry clinics to participate in qualitive interviews. Additionally, the current study proposes to form a group of implementation leaders (pediatric clinicians and clinic directors) to participate in the Implementation Mapping process. Researchers and leaders will partner to operationalize implementation strategies that are: responsive to the needs of youth patients and families and enhance EBP fit with the outpatient care context. Research aims support the applicant’s training goals to: (1) Enhance knowledge of dissemination and implementation science with a focus on qualitative research and Implementation Mapping, (2) Develop specialized expertise in suicide prevention research and practice in health systems, and (3) Gain foundational training in community-engaged research methods with a specific focus on partnering with community members to develop strategies to increase access to evidence-based mental health services. The applicant’s mentorship team is comprised of experts in youth mental health services and community-engaged research methods (Dr. Meinzer), implementation science and qualitative methods (Dr. Rudd), and suicide prevention research (Dr. Weinstock). The mentoring team will advance the applicant’s goals to pursue research training at the intersection of suicide prevention and implementation science and to utilize participatory methods. The proposed research and training plan ultimately supports the candidate’s long-term goal of pursuing a career as an NIH-funded, independent researcher dedicated to understanding strategies for enhancing suicide prevention within youth-serving systems. The proposed study centers the lived experiences of frontline clinicians, youth, and families in the development of implementation strategies that can be harnessed in future clinical research trials of suicide prevention interventions.

NIH Research Projects · FY 2026 · 2026-05

This NIH K08 Mentored Clinical Scientist Research Career Development Award has the overall goal of designing and developing an intervention to address delays in care that occur after an abnormal cervical cancer screening test in uninsured patients served by safety-net health systems. Timely follow-up care after an abnormal cervical cancer screening test result is critical to prevent disease progression and reduce cervical cancer. Uninsured populations served by safety-net health systems tend to have high rates of cervical cancer incidence and mortality despite comparable screening rates to insured populations. This could be due to the delays in care after an abnormal screening test and the fragmentation of care that separates primary and colposcopy follow-up care in safety-net settings. The goals of this study are to (Aim 1) quantitatively investigate follow-up care after transfer from primary to gynecology specialty care, (Aim 2) qualitatively evaluate patient-, provider-, and system- level facilitators and barriers when referring for follow-up and identify potential solutions, and (Aim 3A) synthesize an intervention package targeting the bottlenecks identified in Aims 1 and 2 and (Aim 3B) assess the acceptability and feasibility of the intervention with key stakeholders. Using the Obesity-Related Behavioral Intervention Trials (ORBIT) model, a structured, systematic, and progressive approach to developing robust, effective interventions, based on the phases of drug development, this K08 will encompass the first ORBIT intervention development phase: Design. A convergent mixed methods study will be conducted to evaluate delays and identify facilitators and barriers to follow-up care after an abnormal screening result in uninsured patients served by fragmented safety-net systems. We will leverage CAPriCORN, a patient-centered outcomes research network that includes two safety-net health systems and a network of over 40 federally qualified health centers (FQHCs) in Chicago, to develop a new database with comprehensive cervical cancer follow-up data and patient-, clinic-, and system- level variables. CAPriCORN’s linkage system will support a longitudinal analysis of the fragmentation of care that may influence referral of patients from FQHCs to gynecologic specialty care housed in tertiary safety-net systems. Simultaneously, we will explore the follow-up process through interviews with healthcare teams and patients at CAPriCORN safety-net sites to investigate other multilevel facilitators and barriers to referring patients from primary to gynecologic care and potential solutions. Finally, we will synthesize an intervention package from our findings and interview key stakeholders (clinic leaders, health system leaders, providers, and patients) to evaluate the feasibility and acceptability of intervention components for further optimization. The Training Objectives of this study are to gain expertise and skills in 1) using health informatics, NLP, and data science; 2) using mixed methods designs, 3) intervention development and design, and 4) conducting clinical trials. With the K08, I will be well-positioned for future grants that continue to develop and optimize this intervention through Phases II-IV of the ORBIT model to make impacts on uninsured populations served by safety-net health systems.

NIH Research Projects · FY 2026 · 2026-05

PROJECT SUMMARY Immunotherapies targeting adaptive immune checkpoints have improved cancer outcomes, but innate immune checkpoints also play crucial roles in cancer immune evasion and are promising targets for immunotherapy. The innate immune system uses "eat-me" and "don’t-eat-me" signals to regulate phagocytosis, essential for maintaining tissue homeostasis and preventing cancer. Phagocytic cells have also recently emerged as new key actors in the success of immunologically mismatched allograft transplants through human leucocyte antigens (HLA) allorecognition. Thus, identifying the molecular patterns and receptors governing phagocytosis is vital for understanding cancer clearance and transplantation. Recently published studies of the PI revealed novel functions for Vascular Cell Adhesion Molecule-1 (VCAM1) on healthy and malignant hematopoietic stem cells (HSCs). We have found that VCAM1 is highly expressed on healthy HSCs, serving as an innate immune checkpoint for entry into the bone marrow by providing a "don't-eat-me" signal in the context of major histocompatibility complex (MHC) class-I presentation. In addition, we found that leukemia cells exploit this tolerance mechanism to avoid innate immune recognition, suggesting that the VCAM1-receptor axis is a promising target for immunotherapy. However, the specific receptor mediating this interaction remains unknown. In preliminary studies, we employed proteomics and AlphaFold modeling to identify novel VCAM1 receptor candidates on phagocytic cells. Our Specific Aim 1 focuses on identifying the VCAM1 receptor promoting immune tolerance and leukemia evasion and validating its function in vitro and in vivo using mouse and human models of leukemia. Specific Aim 2 will assess the impact of inhibiting or deleting VCAM1 receptor signaling on myeloid and lymphoid leukemia cell clearance, as well as allogeneic transplantation outcomes. Successful completion of this research will advance knowledge of innate immune recognition mechanisms, identify new leukemia immunotherapy targets, and improve outcomes in stem cell transplantation. 1

NIH Research Projects · FY 2026 · 2026-05

Project Summary To reliably interpret information about the environment, animals must integrate sensory information from lateralized sensory organs. In the olfactory system of most animals, despite a single nose, each nostril operates as an independent sensor. Among the sensory modalities, the olfactory system is unique for its relatively conserved lateralization, with the first hemispheric crossing occurring within the cortex at the anterior olfactory nucleus. The anterior olfactory nucleus also sends dense feedback projections to both olfactory bulbs, which may help align neuronal ensembles that drive odor perception. Yet, the sensory information encoded by these projections, how they shape the activity profiles of neurons in the olfactory bulb, and their role in sensory processing are not well understood. Our approach will provide a detailed analysis of the connectivity and information broadcast between cortical axons and their postsynaptic targets in both olfactory bulb hemispheres. We will test the hypothesis that the stability of interhemispheric sensory coding is dependent on the ipsilateral and contralateral projections from the AON to both olfactory hemispheres. Aim 1 will characterize the synaptic and molecular architecture of interhemispheric projections from the anterior olfactory nucleus to the olfactory bulb. Aim 2 will determine how interhemispheric projections shape the activity profiles of olfactory bulb output neurons. Finally, Aim 3 will define the sensory representations and bilateral alignment of the information broadcast from the anterior olfactory nucleus to the olfactory bulb. The experiments and analyses we propose here will provide novel insight into the mechanism by which the two hemispheres of the brain coordinate robust and efficient sensory coding. The outcomes of our studies will be generally applicable to all sensory modalities by providing foundational information on how the brain integrates and processes lateralized sensory information.

NIH Research Projects · FY 2026 · 2026-05

Engineered mineralized hydrogels to study microcalcifications in breast cancer ABSTRACT Breast cancer (BrCa) remains a significant global challenge, with recurrence and metastasis posing critical obstacles to improving patient survival. Unfortunately, treatments that effectively eliminate metastasis are lacking, emphasizing the urgent need for early interventions to prevent BrCa progression. Such interventions can only be developed by understanding the primary tumor microenvironment (TME) and its role in influencing BrCa cells to initiate metastatic programs. This proposal aims to investigate potential risk factors and early mechanisms within the primary TME that predispose tumor cells (the "seed") to metastasize. One such factor is mammographic microcalcifications (MCs)- insoluble calcium deposits that aid in detecting over half of nonpalpable BrCa cases and 70-90% of pre-invasive BrCa cases. Type I MCs (calcium oxalate, OX) are observed in benign breast conditions, whereas Type II MCs (calcium phosphate, hydroxyapatite (HA)) are primarily associated with malignant disease. Despite their diagnostic value, the influence of the chemical composition of MCs in shaping the primary TME and BrCa progression remains unexamined mainly due to the lack of suitable experimental systems that accurately reflect the chemical composition of MCs within the primary breast TME. To address this gap, we have developed a novel, patented extracellular matrix hydrogels (ECM-mimics) that recapitulate the soft breast TME, and the distinct MC compositions observed in MC-positive BrCa —an otherwise difficult feature to study in vivo. Our study will evaluate how MCs, particularly their chemical composition, may contribute to aggressive tumor growth, bone mimicry, and metastatic BrCa progression. Aim 1 tests the hypothesis that malignant MCs promote tumor growth and bone mimicry in the primary TME through Na-Pi transporter signaling. In Aim 2, we test the hypothesis that the interactions of breast cancer cells with malignant MCs facilitate breast-to-bone metastasis through the acquisition of bone mimicry. In both aims, we test novel molecular mechanisms underlying the currently unknown role of malignant MC-mediated BrCa progression using in vitro, ex vivo, and in vivo CDX and PDX models and validate our findings in patient samples with and without MCs. Together, the successful completion of this project will provide valuable insights into the mechanisms underlying effects of the mineralized TME on BrCa progression, identify novel biomarkers to stratify high-risk patients, and inform local therapeutic interventions such as bisphosphonates, denosumab, and phosphate transporter inhibitors to block this metastatic cascade for those at risk.

NSF Awards · FY 2026 · 2026-05

The protein Piezo1 in human body allows cells to feel mechanical forces such as stress, strain, and trauma. Cells use Piezo1 to drive the sense of touch and direct joints, muscles, and tendons to gain strength when they are overloaded. E756del is a genetic variant in the gene for Piezo1 and those who have this variant are highly sensitive to mechanical load. For example, athletes with this variant develop stronger tendons so they can run faster and jump farther than others. However, individuals with the variant may also have an excessive response to mechanical load on the brain associated with concussion and traumatic brain injury (TBI). This CAREER project will study the impact of E756del variant in Piezo1 protein in cellular models of TBI using engineered stem cells. The project will compare cellular response to mechanical injury to determine how this variant leads to worse health outcomes. The project also includes a comprehensive education and outreach plan to engage high school students through hands-on demonstrations and activities to understand how genes and trauma together contribute to TBI. Piezo1 is a stretch-activated calcium channel expressed throughout the body. The E756del is a common gain-of-function allele in Piezo1 that enables prolonged excitation in response to mechanical stimuli. Such mechanosensitive response has far-reaching consequences such as enhanced athletic ability. Yet, boosting Piezo1 function is also known to exacerbate central nervous system injuries. The central hypothesis is that E756del variant enhances the calcium influx and ensuing pathology caused by TBI. This hypothesis will be tested by producing isogenic lines of induced pluripotent stem cells with and without the variant, and comparing their response to mechanical forces in cellular models of TBI. 2D monocultures of neurons or astrocytes will be injured with dynamic stretch while 3D organoid cultures will be dynamically compressed. Both injury models represent pathological processes relevant to neurotrauma and neurodegeneration as well as changes in mechanical properties that influence the deformation of the brain during future impacts. This study will help establish reliable human in vitro models as a novel, informative, pre-clinical approach to TBI, and establish a relationship between the E756del allele and trauma outcomes for broad translational impact. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-05

SUMMARY Axonal degeneration of cortical projection neurons underlies several debilitating neurodegenerative disorders including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. HSPs are a large heterogeneous group of inherited diseases characterized by length-dependent degeneration of corticospinal motor neuron axons, leading to spasticity and weakness of lower limb muscles. SPG11 and SPG15, two common autosomal recessive forms of HSP, are caused by mutations in the SPG11 and ZFYVE26 that encode spatacsin and spastizin protein, respectively. Spatacsin and spastizin are mediators for autophagy lysosomal reformation that is critical for maintaining lysosome homeostasis. However, how this impairment results in axonal degeneration and how this pathway can be targeted to rescue nerve degeneration in HSP remain unknown. Using patient induced pluripotent stem cell (iPSC)-based models of SPG11 and SPG15, our previous work has identified impaired mitochondrial dynamics in these patient stem cell-derived neurons. We further found aberrant autophagy influx and reduced lysosome transport in these neurons, implying their involvement in HSP. The goal of this proposed study is to dissect the interplays between these pathological processes and to determine their roles in axonal degeneration in HSP neurons. Based on strong preliminary data, we hypothesize that perturbed spatacsin and spastizin result in autophagy lysosomal defects and impaired mitochondrial dynamics, which interact with each other to impair cytoskeleton organization and axonal transport, leading to axonal degeneration in SPG11 and SPG15. This hypothesis will be tested by pursuing the following three aims: 1) to identify the role of spatacsin and spastizin in axonal and autophagy lysosomal defects of patient cortical projection neurons; 2) to determine the interplay between autophagy lysosomal and mitochondrial defects in axonal degeneration of SPG11 and SPG15 cortical neurons; and 3) to rescue axonal degeneration by targeting autophagy lysosomal and mitochondrial defects in vitro and in vivo. By regulating autophagy lysosomal and mitochondrial pathways both genetically and pharmacologically, this study will delineate their roles in axonal degeneration in HSP. The efficacy of targeting these pathways in rescuing axonal defects will be evaluated both in vitro using iPSC models and in vivo using HSP mouse models. Thus, the combination of iPSC model, gene targeting, and HSP animal model in this study provides unique opportunities to identify novel targets and develop potential therapeutics to effectively rescue axonal degeneration in HSP.

NIH Research Projects · FY 2026 · 2026-04

Nearly 2 million people in the United States are at increased risk for serious health outcomes due to hereditary conditions such as Hereditary Breast and Ovarian Cancer (HBOC) syndrome, Lynch syndrome, and Familial Hypercholesterolemia (FH), identified as CDC Tier 1 genomic conditions. Advances in genomic technologies offer significant potential for disease prevention and early detection. However, current healthcare delivery models often fail to identify individuals with these conditions during the presymptomatic phase due to complex testing criteria and limited access to specialized genomic care. These gaps contribute to under-ascertainment and exacerbate imbalances in adverse health outcomes. This project aims to advance genomically informed care by implementing population genomic screening (PGS) in primary care settings, with a focus on CDC Tier 1 conditions. To achieve this, we will leverage and expand upon a successful care delivery model (TestMiGenes) developed in Federally Qualified Health Centers (FQHCs), which has increased access to cancer genetic services. We will develop an innovative and scalable PGS model that integrates seamlessly into primary care workflows, in an environment serving a broad patient population. Three specific aims underlie our approach: 1. Develop a PGS program by expanding upon the TestMiGenes model and integrating community engagement, culturally appropriate patient education, provider training, and optimized clinical workflows to support sustainable PGS implementation; 2. Implement PGS in primary care settings: including six primary care sites (three in an academic medical center [AMC] and three in an FQHC network), enroll 5,000 patients, and provide follow-up care for patients with actionable findings; and 3. Evaluate implementation strategies that promote adoption of PGS at the patient, provider, and system levels using a hybrid effectiveness-implementation design, guided by the RE-AIM framework to assess the impact of PGS at the patient, provider, and system levels. Outcomes will include patient engagement, provider adoption, and feasibility of scaling PGS. In summary, this project seeks to improve health outcomes by developing and implementing a population genomic screening (PGS) program designed for primary care settings, including Federally Qualified Health Centers (FQHCs) that serve patients with elevated genetic or clinical risk profiles. Through community engagement, provider training, and integration of digital tools into clinical workflows, this project aims to expand access to genomic services. Study findings will establish a scalable and sustainable framework for incorporating PGS into multiple healthcare systems, addressing access to genomic healthcare and improving public health outcomes.

NIH Research Projects · FY 2026 · 2026-04

ABSTRACT Primary high-grade gliomas (pHGGs) constitute the leading cause of cancer-related mortality in children and adolescents aged. Initial treatment strategies typically consist of gross total resection, when feasible, followed by focal radiotherapy and chemotherapy. However, the choice/use of chemotherapy remains uncertain. Although numerous therapeutic approaches have been tested, outcomes remain dismal. Since there is no standard chemotherapy for pHGGs, new treatments are urgently needed. To overcome the clinical challenges related to developing new treatments for pHGGs, our primary objective for this project is to develop a new tumor-targeting therapeutic agent that is specifically designed for pHGGs on a molecular basis. Recent studies revealed significant differences in the miRNA expression profiles between pHGGs and normal brain tissues, indicating that several sets of miRNA are oncogenic and highly overexpressed in pHGGs. Specifically, our preliminary data showed that miR20a is aberrantly expressed and has an oncogenic function in pHGGs including glioblastomas (pGBM) and diffuse intrinsic pontine glioma (DIPG, diffuse midline glioma). Although pGBM and DIPG are pathologically different types of highly lethal pHGGs, they share oncogenic molecular profiles, suggesting that we can attack the same molecular targets for both pGBM and DIPG. Given that aiming to diminish oncogenic miRNA expression by using antisense-miRNA is a promising strategy, delivery of antisense-miRNA is currently the major challenge [e.g., lack of tumor targeting, poor transport, and cellular penetration]. To overcome these challenges, we developed a cell-penetrating peptide (p28)-conjugated with antisense-miR20a (namely AmiR20-p28). Our preliminary results showed that systemically injected AmiR20-p28 preferentially accumulates at the tumor lesion in the brain, and induces apoptotic cell death by significantly silencing endogenous miR20a in tumors and blood (circulating miR20a as a potential biomarker), thereby extensively prolonging the survival of mice bearing pGBM. Based on our data, we hypothesize that the development of a pHGG tumor-targeting AmiR20-p28 will provide a novel therapeutic tool. To test our hypothesis, we set realistic aims; Aim1) Determine the pharmacological activities of AmiR20- p28 in pHGGs. Aim2) Establish biomarkers, pharmacokinetics, and toxicity of AmiR20-p28. Our experimental plans were designed with multiple validations and blinded conditions, and our multi-disciplinary team integrates expertise in basic, translational, and clinical brain cancer biology, molecular biology, pathology, and biostatistics. We seek to overcome current limitations by using AmiR20-p28 for pHGGs for which there is no cure. Upon completing our aims, our unique approach can provide a broad impact on developing CPP/miRNA- based agents for pHGGs. It can also potentially provide better treatment strategies for pHGGs patients, which is a major milestone and relevant to the NIH focus area.

NIH Research Projects · FY 2026 · 2026-04

ABSTRACT Periodontal disease (PD) is a chronic inflammatory disease of periodontium that affects the supporting structures of the teeth. It is the sixth most common disease affecting ~750 million people worldwide and the prevalence and severity of PD is becoming a major health concern. This chronic disease is driven by an uncontrolled immune response to bacterial overgrowth. Multiple studies have shown the pro-inflammatory role of immune cells such as macrophages (Mφ), dendritic cells (DC), T cells, and B cells in the development of PD. Dendritic cells (DC) are key antigen-presenting cells (APC) and the predominant immune cells capable of activating T cell response. Three major DC subsets viz., myeloid DC (mDC), lymphoid DC (lDC), and plasmacytoid DC (pDC) are known in humans and mice. While their role in periodontal disease is well-described, how these subsets respond during the disease resolution and their functional interaction with periodontal bacteria remains unexplored. In this proposal, we will investigate the dynamic of DC subsets in ex vivo human gingival biopsies collected pre- and post-non-surgical periodontal therapy (NSPT). PD is mediated by dysbiosis of key bacterial species, including A. actinomycetemcomitans and P. gingivalis; therefore, we aim to assess how periopathic bacteria or their virulence factors impair the functions of DC subsets. We will evaluate antigen processing/presentation, phagocytosis, and IFN type I immune response functions of different DC subsets in the presence of periopathic bacteria. Our preliminary results show a differential expression of mDC and lDC in inflamed gingiva. In the presence of A. actinomycetemcomitans, mDCs promote proliferation of CD4+ T cells suggesting a role of periopathic bacteria in DC function. Understanding how these cells interact with periopathic bacteria and shape their immune activity could lead to new treatments for periodontal disease. Next, we will perform infiltration kinetics of various DC subsets and adaptive immune cells in the ligature-induced periodontitis (LIP) and resolution mice models. The immunoregulatory role of major DC subsets will be characterized using an adoptive transfer approach in LIP and resolution models. Finally, DC subsets exhibiting a pathogenic or immunoregulatory role identified in the adoptive transfer experiments, will be targeted by known DC subset inhibitors to mitigate PD or promote disease resolution, respectively. The knowledge gained will advance our understanding of DC subsets during periodontal disease and its resolution and provide valuable insights for developing targeted therapies to either prevent disease progression or promote healing.

NSF Awards · FY 2026 · 2026-04

This collaborative project will address a major challenge in food manufacturing – the annual generation of millions of tons of waste. This waste is called food industry byproduct. It cannot be recycled or used in agriculture due to possible contamination and its alkaline nature. This project will explore the possibility of using food industry byproduct to restore wildfire-impacted soils. Wildfires pose a growing threat to U.S. communities. They burn millions of acres annually and negatively influence soil, resulting in decreased soil nutrients, loss of vegetation, soil erosion, landslides, ash deposition, and soil and water contamination. The project will conduct experiments to determine conditions under which food industry byproducts can be used to stabilize and re-fertilize soils affected by wildfires. Undergraduate and graduate students will participate in the research. The team will engage K-12 students and high school teachers and students with hands-on experiences to stimulate interest in STEM fields. This project will develop a sustainable approach for wildfire-burned soil rehabilitation using waste from the food industry for soil stabilization and re-fertilization. The project will (i) characterize the physical-chemical-geotechnical, erosion, and leaching properties of food industry byproduct and wildfire-burned soil; (ii) evaluate the suitability and efficacy of food industry byproduct amendment for stabilization of burned soil under controlled lab conditions, simulating variable field conditions; (iii) evaluate the life cycle sustainability and develop a quantitative sustainability design framework for food industry byproduct amendment of wildfire-burned soil; and (iv) evaluate the feasibility and develop guidelines for field implementation. The outcomes from this project will be: (1) a comprehensive understanding of the fundamental mechanisms underlying the interaction between burned soils and the food industry byproduct and (2) a quantitative sustainable design framework and a decision-support matrix to recommend the required proportions of food industry byproduct under varying conditions such as fire intensity and burn severity, soil conditions, and climatic factors. Through comprehensive laboratory testing, statistical analyses, and life cycle resilience and sustainability assessment, the project will provide a comprehensive framework for sustainable wildfire recovery and an innovative waste management strategy for food industry byproducts. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-04

SUMMARY/ABSTRACT Neuro-epithelial interactions in corneal disease and repair, Elmira Jalilian (PI) Diabetes mellitus (DM) is a critical global health issue currently affecting 415 million adults and projected to exceed 640 million by 2040. Diabetic corneal neuropathy, defined by progressive nerve fiber loss in the cornea, occurs in approximately 50% of patients with DM. If these patients experience corneal damage, the regenerated corneal epithelium fails to recover full functionality, leading to further corneal complications. The reduced nerve density and impaired functionality of the remaining nerve fibers leads to disruption of corneal epithelial homeostasis (CEH) and the hindering of reparative processes essential for preserving corneal integrity. A key mechanism regulating CEH and repair is the interaction between corneal epithelial cells (CECs) and corneal nerves (the V1 ophthalmic branch of trigeminal nerves or TgV1s). Despite the recognized role of TgV1s in regulating ocular surface integrity through neurotrophic factors, these factors have not been able to fully explain the neuronal contribution to CEH and repair. In the field of ocular biology, there is growing interest in extracellular vesicles (EVs) as novel mediators of cell-cell communication. While the majority of EV-related research in corneal biology has centered on the therapeutic potential of mesenchymal stem cell (MSC)-derived EVs, there are few studies probing the role of cell-type-specific (CTS) EVs in regulating corneal health and disease. Our preliminary data demonstrated that healthy TgV1s secrete functional EVs. When these TgV1 EVs were internalized by CECs, the expression of proteins involved in proliferation, migration, and cell-cell adhesion were increased in vitro, and sequencing data from TgV1 EV-treated CECs showed a uniquely modulated transcriptional program compared with either untreated CECs or MSC EV-treated CECs. In vivo, TgV1 EV-treated corneas exhibited enhanced epithelial cell adhesion, barrier integrity, greater epithelial thickness, more uniform morphology, and stronger epithelial–stromal attachment. Therefore, we hypothesize that TgV1 EVs have selectively-enriched molecular cargo, targeted to CECs, that facilitates CEH and repair. We further hypothesize that TgV1 EVs are compromised in DM, and multi-omics analyses will specifically identify functional pathways altered by hyperglycemia-associated DM. In Aim 1 we will characterize TgV1 EVs from both healthy and DM mice and study their functional effect on both CECs (in vitro) and the epithelium (in vivo). Our in vitro studies will assess cellular proliferation, differentiation, adhesion, and barrier function. Our in vivo studies will examine the effect on corneal epithelial wound healing (nonpathologic) and non-wounded corneas (by blocking EV uptake), followed by histological and anatomical assessments. In Aim 2 we will conduct molecular studies (transcriptomic and proteomic) on TgV1 EVs (healthy and DM) and CECs (healthy and hyperglycemic, before and after introduction of TgV1 EVs) to identify regulatory mediators that promote or degrade epithelial homeostasis and repair. This research will advance our understanding of the crucial role of CTS EVs and pave the way for the development of novel therapeutics targeting EV-mediated mechanisms in corneal and other ocular diseases.

NIH Research Projects · FY 2026 · 2026-03

PROJECT SUMMARY/ABSTRACT This project responds to PAR-24-075, “Stephen I. Katz Early Stage Investigator Research Project Grant.” The PI is a methodologist with expertise in sensor-based assessments of physical activity (PA), and the project will transition him into a new area of research focused on glycemic control in night workers. As of 2015, nearly 11 million Americans engaged in frequent night work (defined as working between 1:00am and 5:00am), which is a known correlate of impaired glycemic control. PA can combat this issue, but the effects are timing-dependent, with current guidance suggesting the ideal time window falls <3 hours from the largest meal of the day and >1 hour before bed. Night workers are underrepresented in this evidence base, and because of their unique biological, behavioral, and environmental characteristics, it is unclear if their ideal time window matches the current recommendation. The current project’s central hypothesis is that the windows do not match, i.e., that optimal PA timing differs between night workers and day workers. To test that hypothesis, a sample of non-diabetic night workers (n=200) and day workers (n=200) will be recruited from the transportation, healthcare, manufacturing, retail, and leisure/hospitality industries in the Chicagoland region. Each participant will wear a continuous glucose monitor and a PA monitor in their everyday settings for two weeks. Throughout the measurement, they will also provide information about their work schedule, meal/sleep timing, and perceived barriers and facilitators to PA at different times of day. With this information, the first aim will be to compare the timing-related profiles of night workers and day workers, in terms of when participants are most active, how their PA bouts are timed with respect to other daily events (e.g., meal times, sleep onset, and work/leisure context), and day-to-day regularity of PA habits. This information—alongside the reported barriers and facilitators of PA at different times—will give an overall picture of the unique behavioral patterns and PA-related attitudes of night workers versus day workers. The second aim will be to determine associations between PA timing and glycemic control by cross-referencing each group’s timing-related profile of PA against data from the continuous glucose monitors. This will provide evidence to suggest whether night workers should adhere to current timing-related guidance, or whether customized guidance is needed. Either result would provide critical information, but the latter is more likely, in which case the study data would be positioned to support the development of preliminary guidance for night workers. Broader impacts of the project will be to 1) suggest potential mechanisms of action for examination in future laboratory studies, and 2) support the development of interventions that deliver strategically-timed PA for improving glycemic control in night workers.

NIH Research Projects · FY 2026 · 2026-03

Project Summary/Abstract Amid an unprecedented youth mental health crisis, adolescents and young adults (AYA) have the most barriers to receiving mental healthcare. While digital tools are a scalable and accessible way to provide timely mental health screening and referral options, these tools have failed to engage AYA in their daily lives. This failure is driven by multiple factors, including a lack of: 1) understanding of implementation determinants for digital tools in community spaces; and 2) partnership with AYA, their caregivers, and support staff who work in key community settings where AYA spend their time. Consistent with the NIMH Strategic Plan and National Advisory Mental Health Council report, the goal of this R34 proposal is to target AYA engagement in the design and implementation of a digital low-intensity treatment for AYA in Chicago Park District (CPkD) Teen Programming. The CPkD is the largest park district in the country, and more than 40,000 youth are served daily across all 77 Chicago neighborhoods. This project harnesses on a partnership with CPkD and is grounded in the Accelerated Creation-to-Sustainment (ACTS) Model to guide the development of a technology (the “CPkD D-LITe”), as well as its service and implementation plans for CPkD sites. Aim 1 follows the first phase of the ACTS Model, Create. Human-centered design and community-engaged research methodologies will be used to collaborate with the existing CPkD Youth Advisory Board and Teen Programming participants, caregivers of AYA served by CPkD, and CPkD staff. Design activities will focus on targeting mechanisms that are believed to influence engagement: 1) individual-level barriers to care; 2) leveraging spaces where youth spend their time, including assessing determinants in these spaces; and 3) elevating key player input throughout design. The products of Aim 1 will include: an initial version of the “CPkD D-LITe” that demonstrates usability and acceptability by key players, a service protocol for integration of the “CPkD D-LITe” and potential higher clinical needs reported by AYA as a result of using the tool, and an implementation blueprint for integration into CPkD programming. Additionally, extended usability testing will pilot all trial activities to be conducted in Aim 2. In Aim 2, the second phase of the ACTS Model, Trial, will be followed by conducting a pilot randomized controlled trial in CPkD sites using an Optimization, Effectiveness, and Implementation trial methodology. The “CPkD D-LITe” will be compared to a control condition (digital workbook) across a pragmatic, rollout implementation trial. Primary outcomes include acceptability and feasibility, along with reductions of individual levels to mental healthcare, DMH use, and, secondarily, clinical outcomes (anxiety, depression). Optimization activities will occur across the trial period. In sum, the naturalistic approach of this work addresses multiple barriers to real-world digital tool engagement failures for AYA. It will provide key insights into engagement strategies, adaptations, and both service and implementation practices that will support AYA in community settings, both broadly and in a future R01 proposal.

NSF Awards · FY 2026 · 2026-02

The 21st Graduate Student Combinatorics Conference (GSCC) will be held at the University of Illinois Chicago on March 27-29, 2026. The conference will support and benefit graduate student researchers in combinatorics working at institutions across the United States of America. There will be plenary talks given by known and highly-regarded researchers in distinct subfields of combinatorics. The rest of the conference will be made up of talks given by graduate students from a broad range of subfields. The conference addresses a critical need for early-career researchers in combinatorics to engage with the broader scientific community, share their findings, and develop presentation skills. Combinatorics is an active and dynamic field whose applications are becoming increasingly important to broader mathematics, computer science, and machine learning. The keynote speakers will include Greta Panova, who studies algebraic combinatorics, having landmark results on the Kronecker and Littlewood--Richardson coefficients, as well as applications in molecular biology and computational complexity theory. The other keynote speaker is Jinyoung Park, who specializes in probabilistic combinatorics and random graph theory, and is known for her proof of the Kahn--Kalai conjecture. The conference will stimulate collaboration and mentoring between graduate students and the senior faculty. The website for the conference is at https://sites.google.com/view/gscc2026/home This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2026-02

Project Summary Adult hippocampal neurogenesis represents one of the most transformative yet contested concepts in neuroscience. While robustly demonstrated in rodents and other mammals, including non-human primates, the existence, extent, and functional relevance of neurogenesis in the adult human brain remain unresolved. Confirming adult hippocampal neurogenesis in humans would profoundly reshape our understanding of brain plasticity, resilience, learning, and memory, and inform new therapeutic strategies for neurodegenerative and psychiatric disorders. However, conflicting evidence from isotope-labeling, immunohistochemistry, transcriptomics, and cell culture studies—paired with challenges in postmortem tissue analysis and methodological reproducibility—have fueled intense debate within the field. This Banbury meeting will convene leading experts from multiple disciplines to critically assess the current body of evidence, including leaders who have recently generated new unpublished data to support or defer the presence of human neurogenesis, evaluate the potential of emerging methodologies such as spatial transcriptomics and single-cell analysis, and chart a collaborative path forward. Specific aims include: (1) critically evaluating existing data and technical limitations, (2) identifying promising technologies for resolving key questions, (3) fostering interdisciplinary collaborations, and (4) defining strategic priorities and standards for future research. The meeting will culminate in a consensus report that outlines current knowledge, identifies gaps, and provides actionable recommendations to guide the field. By bridging experimental, technical, and conceptual divides, this effort aims to resolve one of neuroscience’s most pivotal questions and advance our understanding of human brain function and plasticity.

NIH Research Projects · FY 2026 · 2026-02

Methicillin-resistant Staphylococcus aureus (MRSA) strains are antibiotic resistant bacteria that are the leading cause of healthcare associated infections in the United States and around the world. While research has focused on the development of new and more powerful antibiotics, the strains keep evolving resulting in ‘super bugs’ that are difficult to eradicate. Therefore, a key knowledge gap is the lack of an efficient approach that can target these superbugs ubiquitously with minimal effects on host cells. CRISPR-based gene editing can be a promising approach to address this knowledge gap. However, translation of CRISPR therapeutics faces a tremendous challenge as current technology focuses mainly on vector-based approaches to constitutively express CRISPR components (Cas9 enzyme and the targeting single guide RNA (sgRNA)) in recipient cells. This approach is fraught with logistical challenges as well as severe side effects. These are major hurdles to clinical translation. The translatability of CRISPR therapeutics can improve tremendously if the rhCas9 enzyme and the sgRNA can be delivered directly as a ribonucleoprotein (RNP) complex. However, this has not been achieved in bacteria. This application is an ambitious effort to address both the knowledge gap as well as the translational hurdle to CRISPR-based antimicrobials. Utilizing our foundational knowledge gained by studying extracellular vesicles (EVs) for the past decade, we hypothesize that: Artificial vesicles (AVs), mimicking the bioactivity of natural EVs can be used to deliver antibacterial CRISPR RNP complex to MRSA strains without ectopic activity on mammalian cells. To test this hypothesis, we propose two specific aims. Aim 1 will engineer artificial vesicles capable of bacterial entry with specific focus on MRSA strains found predominantly in the USA and Aim 2 will develop CRISPR RNPs targeting the conserved regions of 16s rRNA gene to produce vesicles that are capable of bactericidal activity upon entry into MRSA. This aim will also study the effects (absence of) the vesicles in representative mammalian cells as well as evaluate the efficacy of the strategy in a systemic model of mouse MRSA infection. Overall, successful completion of these aims will establish a system for delivering CRISPR-based therapeutics for combating antibiotic resistance super bugs.