{ "schema_version": "1.0", "source": "nih", "data_as_of": "2026-09-09T03:02:20.233Z", "selected_count": 30, "sampled": true, "records": [ { "source": "nih", "source_id": "11608585", "title": "Endoscopic versus Shunt Treatment of Hydrocephalus in Infants", "summary": "Hydrocephalus primarily affects infants under one year of age. The traditional treatment for hydrocephalus is\ncerebrospinal fluid (CSF) shunt. Life-time complications of CSF shunts are high and expensive, with annual\nhospital charges of nearly $2.0 billion, accounting for 3.1% of all pediatric hospital charges. As shunt\ncomplications also adversely impact quality of life, it is not surprising that surveys of families affected by\nhydrocephalus show that they desperately desire shunt-free treatment options. The most promising shunt-free\ntreatment for infant hydrocephalus is endoscopic third ventriculostomy with choroid plexus cauterization\n(ETV+CPC), which our Hydrocephalus Clinical Research Network (HCRN) and others have shown to be safe\nand viable. However, the cognitive outcome of ETV+CPC compared to shunt is not known. Our data suggest\nthat most families would accept the risks of ETV+CPC for the chance to be free of shunt, but only if initial\ntreatment with ETV+CPC will not lead to noticeable sacrifice in cognitive outcome compared to shunting. With\nthis U01 proposal, we aim: 1. To determine, in infants ≤12 months corrected age, with hydrocephalus requiring\ntreatment at tertiary care pediatric neurosurgery centers in North America, does ETV+CPC compared to shunt\nresult in non-inferior cognitive outcome at 12 months from surgery, as measured by Bayley Scales of Infant and\nToddler Development (Bayley-III) Cognitive Scale with a non-inferiority margin of 1.5. 2a. To determine, in\nthe same cohort, if ETV+CPC compared to shunt results in non-inferior Bayley-III Motor/Language Scales or\nVineland-3 Scales. 2b. To compare other measures of treatment performance (brain/ventricle volume,\ntreatment failure, hospital days, repeat surgery, use of imaging) and complications between treatment arms.\n3a. To determine the effect of ETV+CPC and shunt on cerebral structural connectivity, with diffusion MR\nfractional anisotropy (FA) in the corpus callosum 12 months after surgery. 3b. To define the relationships\nbetween pre-operative brain/ventricular volume and cerebrospinal fluid (CSF) NCAM-1 level to post-operative\ncorpus callosum FA and Bayley-III Cognitive Scale 12 months after surgery. 3c. To define the relationships\nbetween change in brain/ventricular volume (pre-operatively to 12 months post-operatively) to FA in the\ncorpus callosum and corticospinal tract and Bayley-III Cognitive and Motor Scales 12 months post-operatively.\nTo do this, we plan an RCT comparing ETV+CPC and shunt in infants with hydrocephalus, within the HCRN, a\ncommitted group of 14 leading North American pediatric neurosurgical centers with a long track-record of\nsuccessful collaborative clinical research and RCTs in hydrocephalus. Optimal cognitive outcome, the primary\nconcern of families, will therefore, be our primary outcome. Assessment of dMRI, a validated, non-invasive\nmethod of measuring white matter microstructural integrity and structural connectivity in the developing\nbrain, will provide further insight into the developmental consequences of these 2 treatments. This RCT will\nhelp families determine the optimal treatment of hydrocephalus for their child.", "published_date": "2026-09-05", "url": "https://reporter.nih.gov/project-details/11608585", "metadata": { "project_num": "3U01NS107486-07S3", "award_amount": 20739, "activity_code": "U01", "organization": "UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH", "principal_investigators": [ { "profile_id": 9141003, "first_name": "Richard", "middle_name": "", "last_name": "Holubkov", "is_contact_pi": false, "full_name": "Richard Holubkov", "title": "PROFESSOR" }, { "profile_id": 9512632, "first_name": "John", "middle_name": "", "last_name": "Kestle", "is_contact_pi": true, "full_name": "John Kestle", "title": "" }, { "profile_id": 9866364, "first_name": "Abhaya", "middle_name": "V", "last_name": "Kulkarni", "is_contact_pi": false, "full_name": "Abhaya V Kulkarni", "title": "" }, { "profile_id": 9628945, "first_name": "David", "middle_name": "Delmar", "last_name": "Limbrick", "is_contact_pi": false, "full_name": "David Delmar Limbrick", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11595537", "title": "Mexican Teachers Cohort Study: Genetics and Cognitive Function", "summary": "This is a resubmission of a U01 application for the “Alzheimer’s Disease Sequencing Project (ADSP) Follow- Up Study 2.0: The Diverse Population Initiative” (PAR-21-212). The overall goals are to: (i) contribute nearly 20,000 GWAS and 5000 whole genome sequences to ADSP from participants of the “Estudio de la Salud de las Maestras” (Mexican Teachers Cohort), and (ii) detect novel genetic drivers of cognitive function in this large Mexican cohort, in combination with existing ADSP cohorts. US Hispanics are projected to experience the largest increase in ADRDs of any ethnic group. Moreover, dementia onset occurs at younger ages, on average, in Hispanic (HL) populations in the US; expected years lived with cognitive impairment is up to 4-8 years longer for older HL individuals, than non-Hispanic whites. Mexican-Americans represent 65% of US Hispanics; cohorts in Mexico can thus complement those in the US to maximize dementia research in diverse populations. Mexican Teachers Cohort (MTC) was established in 2006, and is an ongoing cohort of female teachers, which has maintained high followup. MTC spans 12 culturally diverse states in Mexico and was designed to support research on genetic and social determinants of health. In particular, ancestry analyses demonstrate genetic separation of Mexican from Central and South American backgrounds (Mexicans have distinct AmerIndian substructure). Thus, addition of MTC to ADSP can substantially contribute to identification of novel and relevant genes/pathways underlying health. Central to this U01, we propose to extend MTC by (i) implementing up to 2 waves of cognitive evaluations in 13,500 existing women plus 3,500 newly-recruited men, age 55+ years, and (ii) collecting blood specimens in all participants. In Aim 1, we will genotype 17,000 participants using the Illumina Global Screening Array; perform whole genome sequencing in 5000 participants age 65+ years; process/harmonize array and sequencing data. In Aim 2, we will perform discovery admixture analyses to identify global ancestry, and then local ancestry-associated regions, related to the powerful quantitative trait of global cognitive function, and secondarily to cognitive impairment (MCI+dementia); this will include fine mapping to identify credible causal variants, and replication in ADSP cohorts. We will also examine known AD-related SNPs in this large HL population. In Aim 3, we will generate measures of telomere length using TelSeq on WGS, and measures of mitochondrial DNA (mtDNA) variation (mtDNA copy number and mtDNA heteroplasmy) from WGS; we will examine associations with cognitive function and cognitive impairment, addressing differences by ancestry. Finally, in Aim 4, we will share all specimens via the NCRAD repository, and data via NIAGADS. IMPACT: The proposed application will provide a strong and sustained impact on the field by substantially broadening the platform for discovery regarding cognitive aging in Hispanic individuals.", "published_date": "2026-09-05", "url": "https://reporter.nih.gov/project-details/11595537", "metadata": { "project_num": "3U01AG084547-03S2", "award_amount": 1678461, "activity_code": "U01", "organization": "RUSH UNIVERSITY MEDICAL CENTER", "principal_investigators": [ { "profile_id": 1866048, "first_name": "FRANCINE", "middle_name": "", "last_name": "GRODSTEIN", "is_contact_pi": true, "full_name": "FRANCINE GRODSTEIN", "title": "EPIDEMIOLOGIST" }, { "profile_id": 12335396, "first_name": "Martin", "middle_name": "", "last_name": "Lajous", "is_contact_pi": false, "full_name": "Martin Lajous", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11535252", "title": "Consortium for Advancing Management and Prevention of Cancer in People with HIV", "summary": "The mission of the AIDS Malignancy Consortium (AMC) is to investigate through clinical trials new\ntreatment and prevention interventions and study the pathobiology of malignancies and their precursors in people\nliving with human immunodeficiency virus (PLWH) in the United States (U.S.) and internationally. The vision of\nAMC is to reduce incidence, morbidity, and mortality of cancers occurring in PLWH.\n Since the AMC was established in 1995 (and as of 11/18/24), it has initiated over 97 interventional clinical\ntrials including 10,787 subjects, resulting in 319 publications and 197 abstracts/presentations, and generated\nevidence that has transformed practice guidelines in the U.S. and low-middle income countries (LMIC) that have\na high HIV burden. AMC has established a network of 39 clinical trial sites (including 29 in the U.S, 6 in sub-\nSaharan Africa, and 4 in Latin America) that are uniquely qualified to carry out its mission, created a network of\ntranslational scientists and their research laboratories that support AMC clinical trials, and developed a Career\nEnhancement Program (CEP) that has fostered a new generation of AMC leaders. AMC has also actively\nengaged PLWH and cancer survivors in its scientific planning and community outreach in order to better identify\nthe needs of the community, both within the U.S. and globally, as evidenced by the establishment of a Global\nCommunity Advisory Board (CGAB) and inclusion of advocates in strategic and protocol planning.\n AMC has functioned as a single cooperative group since 2005 under the supervision of the Office of HIV-\nAIDS Malignancies (OHAM) within the Office of the Director of the National Cancer Institute (NCI). This\ncentralized leadership and accountability has helped create a more cohesive structure and uniform approach to\ngroup operations and strategic planning. Although AMC focused initially on small pilot, phase I and II trials, the\nscope of its activities has broadened to include 3 practice-changing randomized phase III trials, including 2 in\nKS in collaboration with the AIDS Clinical Trials Group (ACTG), and the landmark ANCHOR trial in the U.S.\nwhich demonstrated that treatment of anal high-grade squamous intraepithelial neoplasia (HSIL) reduced the\nincidence of invasive anal cancer, having a profound impact on clinical practice and future research priorities\nregarding how to most effectively screen for and treat high-grade anal HSIL.\n Despite challenges posed by the Covid-19 pandemic during years 14-18 of the current funding period,\nAMC launched a new generation of trials that built upon its prior work, increased overall accrual, began new\ninitiatives in cancer control, prevention, and survivorship, expanded its collaborations with other NCI-funded\nnetworks, expanded its laboratory network and biorepository program, and expanded its career enhancement\nprogram. AMC will continue to developing hypothesis-driven pilot, phase I, I-II, and III trials designed to address\nits mission and vision.", "published_date": "2026-09-05", "url": "https://reporter.nih.gov/project-details/11535252", "metadata": { "project_num": "3UM1CA121947-20S4", "award_amount": 163250, "activity_code": "UM1", "organization": "ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI", "principal_investigators": [ { "profile_id": 8451712, "first_name": "Joseph", "middle_name": "A.", "last_name": "Sparano", "is_contact_pi": true, "full_name": "Joseph A. Sparano", "title": "CHIEF DIVISION OF HEMATOLOGY ONCOLOGY" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11443962", "title": "Aina-Based Engagement and Social Epigenomic Pathways to Metabolic Health in Native Hawaiian Youth", "summary": "PROJECT SUMMARY/ABSTRACT\nNative Hawaiians and other Pacific Islanders (NHPIs) experience among the highest rates of type 2 diabetes\nmellitus (DM) in the United States, with onset nearly a decade earlier than other groups. These disparities arise\nfrom historical, social, and environmental adversities that influence behavior, metabolism, and opportunity. Yet\nthe biological mechanisms through which these social-environmental conditions become physiologically\nembedded remain poorly understood, particularly among Indigenous youth for whom early intervention could\nmore effectively alter disease trajectories. This application responds to PAR-25-379: Intervention Research to\nImprove Native American Health by testing an innovative, community-anchored intervention that integrates\nIndigenous knowledge with multi-omic science. The MAʻO Organic Farms Youth Leadership Training (YLT)\nprogram, a Native Hawaiian-led ʻāina-based intervention, provides workforce training, higher education, and\nmentorship through organic farming grounded in the values of aloha ʻāina (care for the land)\nand kuleana (reciprocal responsibility). We hypothesize that participation in ʻāina-based practices improves\nglycemic control by reducing inflammation and decelerating immunoepigenetic (biological) aging, with the gut\nmicrobiome acting as a biological modifier of these effects. A 12-month longitudinal, mixed-methods cohort study\n(N=400) will compare YLT-engaged participants (n=200) with propensity-matched NHPI controls (n=200) drawn\nfrom the Waiʻanae community and/or our established Hawaiʻi Social Epigenomics of Early Diabetes (HI-SEED)\ncohort unaffiliated with MAʻO. Participants will complete behavioral, psychosocial, and clinical assessments, and\nprovide fasting blood and stool specimens at baseline and 12 months for quantification of HbA1c, insulin\nresistance, cytokine profiles (e.g., IL-6, TNF-α, hsCRP), monocyte-based DNA methylation (Illumina\nMethylationEPIC v2 arrays), and gut microbial diversity and function (16S rRNA sequencing). A delayed-start\nsubcohort of HI-SEED participants who later enroll in YLT will enable causal inference using difference-in-\ndifferences and marginal-structural modeling. Aim 1 evaluates the impact of the ʻāina-based intervention (the\nMAʻO-led YLT) on glycemic and behavioral outcomes; Aim 2 determines whether behavioral and psychosocial\nimprovements mediate reductions in immunoepigenetic (biological) aging and inflammation; and Aim 3 defines\nthe gut microbiome as a biological modifier linking social-behavioral change, immunoepigenetic regulation,\nbiological aging, and glycemic health. Results of these aims will meet our goal of learning how an Indigenous,\nʻāina-based intervention biologically embeds social experience to promote metabolic resilience and healthy\naging. Findings will establish a scalable, community-governed model of precision health promotion that advances\nNIH and Native health priorities through rigorous, culturally grounded interventions by integrating Indigenous\nknowledge with cutting-edge multidisciplinary systems biology with the potential to enable meaningful prevention.", "published_date": "2026-09-05", "url": "https://reporter.nih.gov/project-details/11443962", "metadata": { "project_num": "1R01MD021856-01", "award_amount": 712197, "activity_code": "R01", "organization": "UNIVERSITY OF HAWAII AT MANOA", "principal_investigators": [ { "profile_id": 15767683, "first_name": "Ruben", "middle_name": "", "last_name": "Juarez", "is_contact_pi": false, "full_name": "Ruben Juarez", "title": "" }, { "profile_id": 7674310, "first_name": "Alika", "middle_name": "Keolaokalani", "last_name": "Maunakea", "is_contact_pi": true, "full_name": "Alika Keolaokalani Maunakea", "title": "PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11426177", "title": "Modeling second hit somatic mutations in HHT to uncover mechanisms of vascular pathologies and assess therapeutic strategies.", "summary": "PROJECT SUMMARY\nHereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder characterized by inappropriate connections\nbetween arteries and veins called arteriovenous malformations (AVMs) and leaky small vessels\n(telangiectasias). AVMs form in major organs (brain, liver and lung) and can rupture causing severe hemorrhage\nand anemia, as well as aneurysms, stroke and death. HHT affects ~1 in 5000 people and the genetic causes\nare linked to the Transforming Growth Factor-ß signaling pathway, with >90% of patients carrying heterozygous\nloss-of-function mutations in the Activin receptor-like kinase 1 (ACVRL1/ALK1) or Endoglin (ENG) co-receptors,\nor the transcription factor, Smad-related protein 4 (SMAD4). Despite knowing the disease-causing mutations,\nour molecular understanding of HHT pathologies, including AVMs and especially vascular leakage, remains\ninsufficient. Due to this knowledge gap, it is crucial that we uncover the disease mechanisms and identify\ntherapeutic targets because a cure for HHT does not exist. Genetic analysis indicates HHT lesions can form via\nloss-of-heterozygosity (LOH) whereby a second somatic mutation of the functional allele leads to complete loss\nof gene function in some endothelial cells. However, current HHT models do not accurately depict an LOH setting\nand thus, there is an incomplete understanding of how AVMs and vessel instability arise. We created Smad4\nand Eng LOH-HHT mouse models to assess LOH contributions on HHT pathologies. Our preliminary data\nstrongly indicates compromised vascular integrity in LOH-HHT mice leading to increased blood vessel\npermeability, in addition to a potential regulator of this process (CDH13). Research on vascular leakiness is\ncritical because bleeding is a chronic and debilitating issue for HHT patients, yet basic research on vessel\nintegrity is sorely lacking. Anti-VEGFA drugs have shown beneficial effects for reducing bleeding, however some\npatients do not respond and the impacts of inhibiting VEGF signaling on AVMs is unclear. In this regard, ANG2\nis a strong clinical candidate: excess ANG2 is linked to vascular leakage in several ocular diseases, while our\nprior data demonstrated ANG2 inhibition could ameliorate AVM formation. We hypothesize that targeting ANG2\nand VEGFA may provide a robust avenue to combat AVM development and vessel instability. The central\nobjective of this application is to answer 3 fundamental questions: 1) how does LOH contribute to the\ndevelopment of AVMs; 2) what are the mechanistic drivers of vascular leakiness in HHT; 3) do dual approaches\ntargeting ANG2 and VEGFA provide superior effectiveness to prevent, stabilize or regress AVM formation and\nbleeding? We will address these topics by testing the following specific aims: 1) Evaluate the impact of LOH on\nAVM formation; 2) Characterize vascular permeability and bleeding and assess CDH13 contributions; 3) Assess\nANG2 and VEGFA based therapeutics on HHT pathologies. Together, this investigation will utilize new models\nto more accurately represent the pathobiology of HHT patients, thereby enhancing our knowledge on the\npathogenic mechanisms of AVM formation and bleeding, leading to therapeutic advancements for HHT.", "published_date": "2026-09-05", "url": "https://reporter.nih.gov/project-details/11426177", "metadata": { "project_num": "1R01HL187693-01", "award_amount": 565442, "activity_code": "R01", "organization": "TULANE UNIVERSITY OF LOUISIANA", "principal_investigators": [ { "profile_id": 10566827, "first_name": "Stryder", "middle_name": "Medoah", "last_name": "Meadows", "is_contact_pi": true, "full_name": "Stryder Medoah Meadows", "title": "PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11402627", "title": "Regulation of Proteasome Activity", "summary": "PROJECT SUMMARY / ABSTRACT\n The focus of my laboratory’s efforts is the proteasome, the protease that degrades ubiquitin-protein\nconjugates. That the proteasome is the central activity within the ubiquitin-proteasome system (UPS) was known\nfrom the time the UPS was charted, but its significance was not fully recognized at the time because the\nproteasome was presumed, incorrectly, to be unregulated and passive–essentially a dumb enzyme. But this\nperception has been overturned by the progressive identification of diverse mechanisms that finely regulate\nproteasome synthesis, turnover, localization, substrate specificity, and specific activity. These mechanisms are\nof special interest because they provide the means for global control of UPS output. In parallel, evidence of the\nimportance of proteasome activity in disease has accumulated. For example, even a modest elevation of\nproteasome levels substantially increases the lifespan of D. melanogaster and C. elegans, as well as their ability\nto withstand stresses such as the expression of toxic polyQ proteins. A fascinating mode of proteasome\nregulation is that involving the dynamic reconfiguration of ubiquitin chains on a substrate at the proteasome. Two\nsuch chain-editing factors are highly active as well as conserved across eukaryotes: Ubp6/USP14 and\nHul5/UBE3C. Ubp6 is a deubiquitinating enzyme and Hul5 is a ubiquitin ligase, and they work in opposition to\none another; Ubp6 will remove ubiquitin groups added to the substrate by Hul5. Both are recruited to\nproteasomes when the UPS is impaired or challenged. The specificity of Ubp6 is remarkable in that it acts only\non substrates that carry multiple ubiquitin chains. We will characterize this specificity further and investigate its\nmechanistic basis. We have reported that Hul5 functions as an E4 on the proteasome–it ubiquitinates proteins\nthat are already ubiquitinated. We will focus now on how this E4 activity promotes the processivity of the\nproteasome, as Hul5 appears to be the main regulator of processivity. We will reconstitute the processivity effect\nin a purified system and use highly specific mutants in Hul5 in single-molecule analysis. We will also investigate\nthe mechanisms by which Ubp6 and Hul5 are controlled by stress. The third major factor recruited to\nproteasomes under proteostasis stress is Ecm29, which has the unique feature of binding both the RP and CP.\nEcm29 regulates both the activity and assembly of the proteasome, most likely by bridging these complexes.\nOur studies will focus on how Ecm29 is recruited to faulty proteasomes and how it affects their structure and\nstability. Finally, substrate recognition by the proteasome is mediated by six distinct ubiquitin receptors. However,\nour detailed genetic analysis in yeast indicates the existence of at least one additional, unknown ubiquitin\nreceptor within the proteasome. We will attempt to identify this receptor, and once we generate suitably precise\nmutants we will explore this receptor’s role in substrate recognition and processing. In summary, we propose,\nby applying the methods of genetics, enzymology, structural biology, and quantitative global proteomics, to\nelucidate major pathways of proteasome function and regulation.", "published_date": "2026-09-05", "url": "https://reporter.nih.gov/project-details/11402627", "metadata": { "project_num": "5R35GM145246-05", "award_amount": 497226, "activity_code": "R35", "organization": "HARVARD MEDICAL SCHOOL", "principal_investigators": [ { "profile_id": 1898343, "first_name": "Daniel", "middle_name": "J", "last_name": "Finley", "is_contact_pi": true, "full_name": "Daniel J Finley", "title": "PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11397429", "title": "The Harvard Chan Education Program in Cancer Prevention and Control", "summary": "The Harvard Education Program in Cancer Prevention and Control, in its 30th year, is a dynamic transdisciplinary collaboration that brings together the extensive expertise of the Harvard T.H. Chan School of Public Health, the Dana-Farber Cancer Institute and Dana-Farber/Harvard Cancer Center, and Harvard Catalyst, our Clinical and Translational Science Center. We have trained 129 fellows in transdisciplinary approaches to cancer prevention and control, and over 80% of trainees hold a research- focused position. In the current cycle, we have met or exceeded all of our benchmark goals. In this renewal, we are requesting continued support for 4 predoctoral and 4 postdoctoral trainees each year who have an average length of training of 4-5 years and 2 years respectively. The overall goal of the Program is to train fellows to become the next generation of scientists who are: (1) knowledgeable about the current state of the science of cancer prevention and control; (2) skilled in transdisciplinary cancer research; (3) skilled in formulating and writing research proposals and scientific manuscripts for publication; and (4) anchored in peer and professional networks that support continual professional development and access to resources to translate their knowledge into new cancer research areas. Transdisciplinary training is further enhanced by leveraging our transdisciplinary PhD program in Population Health Sciences that integrates training in five public health disciplines, and by instituting continuing to enhance our evidence-based approach to mentorship training. We recently conducted a strategic evaluation of the program and have developed additional activities to address areas for growth. We will continue our training focus in 4 areas of emphasis: (1) cancer control outcomes; (2) cancer implementation science; (3) cancer-focused health communication; and (4) global cancer prevention. Robust and engaged internal and external advisory committees, and a very strong team of mentors with extensive research portfolios ensure that the program will continue to thrive and innovate in cancer prevention training. The maturity of this Program, extensive resources available through Harvard and synergy across the focal training areas provide an outstanding platform for training the next generation of cancer prevention scientists.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11397429", "metadata": { "project_num": "5T32CA057711-33", "award_amount": 55235, "activity_code": "T32", "organization": "HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH", "principal_investigators": [ { "profile_id": 1863832, "first_name": "Karen", "middle_name": "M.", "last_name": "Emmons", "is_contact_pi": true, "full_name": "Karen M. Emmons", "title": "PROFESSOR" }, { "profile_id": 1888633, "first_name": "ANNE", "middle_name": "LINDSAY", "last_name": "FRAZIER", "is_contact_pi": false, "full_name": "ANNE LINDSAY FRAZIER", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11396828", "title": "Targeting the immune synapse for programmable cellular function", "summary": "PROJECT ABSTRACT\nEarly successes in the field of immunotherapy have demonstrated the ability to treat disease by influencing\nimmune cell signaling. However, our ability to control immune signaling and the emergent immune response\nremains limited. The immune synapse can be thought of as the cellular command center where the signaling of\nmultiple receptors is integrated and functional decisions are made. While many existing drugs form synapses\n(e.g., monoclonal antibodies, T cell engagers), few can meaningfully influence their composition and function.\nWe recently developed a new kind of protein drug with the ability to engineer receptor composition and\nsignaling at immunological synapses. This proposal will build on our recent discovery to comprehensively\nexplore synapse-targeted drugs as a therapeutic modality. We will focus our efforts on engineering phagocytic\nsynapses in macrophages due to our limited understanding of their signaling logic and their potential to\naddress a wide range of human diseases. Specifically, we will engineer a suite of bispecific antibody chimeras\ndesigned to mediate recruitment or exclusion of various immunomodulatory receptors from the synapse\n(Projects 1 & 2). In parallel, we will establish a pipeline to express a large library of multispecific antibody\nchimeras and measure their activities in high-throughput, enabling more complete understanding of the effects\nof synapse composition on cellular function (Project 3). Finally, we will demonstrate the potential of synapse\nengineering to improve the safety and efficacy of targeted therapy by developing molecules that can activate\nmacrophages in response to cancer-specific antigens (Project 4). Our preliminary data indicate that this work\nwill reveal new insights into macrophage immunobiology and define a novel modality of targeted\nimmunotherapies with improved safety and efficacy.\nImportantly, the molecules and approaches we will develop have impacts beyond immunology and\nimmunotherapy. While this proposal focuses on engineering immune synapses, synapses play important roles\nin a variety of biological systems and processes (e.g., neuronal synapses, cellular adhesion, viral fusion and\nhost cell entry). The ability to engineer synapses thus has the potential to transform multiple biomedical fields\n(e.g., regenerative medicine, organoids and synthetic organ systems, antivirals and drug delivery). This work\npromises to advance our understanding of cellular synapses and result in a molecular platform with broad\napplications for engineering biology.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11396828", "metadata": { "project_num": "1DP2AI207711-01", "award_amount": 762122, "activity_code": "DP2", "organization": "MASSACHUSETTS INSTITUTE OF TECHNOLOGY", "principal_investigators": [ { "profile_id": 12410006, "first_name": "Jessica", "middle_name": "C", "last_name": "Stark", "is_contact_pi": true, "full_name": "Jessica C Stark", "title": "ASSISTANT PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11396338", "title": "Elucidating the network design principles of biological signal processing", "summary": "Project Summary\nCells live in diverse environments and cellular communities, from the cells in our bodies to single-celled\norganisms surviving in the soil. To navigate these complex environments, cells must be able to sense and\nrespond to a variety of signals. This is done through biological signaling pathways, consisting of sensors and\ninteracting proteins, which process external signals and transmit information. My research program focuses on\nunderstanding how these biological networks transmit information about external signals to the activity of\nintracellular effectors, such as transcription factors, to generate an appropriate cellular response or state and\nhow these cell states affect community-level phenotypes. Understanding this signal processing represents a key\ngap in our knowledge of how healthy and diseased cells make decisions and guide the behavior of cellular\ncommunities. Specifically, we ask (1) How do signaling networks transform extracellular signals into appropriate\nintracellular signals? (2) How are intracellular signals interpreted by the cell to generate appropriate responses?\nand (3) How do individual cell decisions affect population-level community phenotypes?\nOur research is focused on understanding signaling specificity and kinetics in the mitogen-activated kinase\n(MAPK) pathways as well as transcription factor dynamics and subsequent gene expression in response to\nenvironmental stress. MAP kinase pathways are conserved from yeast to humans and control vital cellular\nprocesses including proliferation, differentiation, and stress response. We use a variety of systems to address\nthe questions outlined in this research proposal including Saccharomyces cerevisiae, the human fugal pathogen\nCandida albicans, synthetic signaling pathways, and mammalian cell culture. We take a multi-pronged approach\nthat uses microfluidic and optogenetic tools to perturb signaling pathways and combine these perturbations with\nmathematical modeling to understand how different properties of signaling pathways, including bandwidth and\ncrosstalk, allow them to appropriately transform their input signals. Furthermore, we use these tools to drive\ndynamics of intracellular effectors, such as transcription factors, and ask how these different effector dynamics\ngenerate cellular responses. And finally, we use the exquisite spatiotemporal control available with light to\ngenerate desired states in individual or populations of cells, including fungal biofilms, and ask how this affects\ncommunity-level phenotypes.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11396338", "metadata": { "project_num": "5R35GM128873-09", "award_amount": 421552, "activity_code": "R35", "organization": "UNIVERSITY OF WISCONSIN-MADISON", "principal_investigators": [ { "profile_id": 14218970, "first_name": "Megan", "middle_name": "N", "last_name": "McClean", "is_contact_pi": true, "full_name": "Megan N McClean", "title": "PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11395590", "title": "Disc-Facet Crosstalk During Spinal Degeneration and Repair", "summary": "The anterior intervertebral disc and posterior diarthrodial facet joints form what is referred to the three-joint\ncomplex of the spine, working in concert to resist large magnitude axial loads and constrain range of motion to\nnon-injurious levels. Degenerative pathology in both spinal structures is a known contributor to back pain, which\nhas become the number one cause of years lived with disability globally. Intervertebral disc degeneration is\nassociated with structural and biochemical changes to the disc tissues, which compromise the ability of the disc\nto bear load, potentially leading to overloading of the facet joints. The study of disc degeneration has been\ndominant in the field for decades, and as such, little is known the pathophysiology of facet osteoarthritis (OA), or\nhow altered disc mechanical function may contribute to the progression of facet degeneration. This proposal will\nbring a new perspective to the study of spinal degeneration by investigating the mechanical crosstalk between\nthe disc and its adjacent facet joints during degenerative processes and in the scenario of disc repair, using\nanimal models and human tissues. In Aim 1A, we will first utilize a large animal model to characterize the\nprogression of facet OA in an initially healthy spine following experimentally induced degeneration of the adjacent\ndiscs. Facet cartilage and subchondral bone pathology will be probed across length scales as a function of disc\ndegeneration to determine the temporal relationship between disc degeneration and facet OA. In Aim 1B, we\nwill also utilize human cadaveric tissues to determine how facet pathobiology and disc-facet crosstalk differ in\nmales versus females, factors less easily studied in large animal models. In both goat experimental and human\ncadaveric tissues, we will assess inflammation, innervation and immune cell infiltration into the disc and facet\njoint synovium and capsule as surrogate measures of pain and biological dysfunction. Finally, quantitative\nstructure-function outcomes from both goat and human spinal tissues (Aims 1A and B) will then be utilized to\ngenerate patient/animal-specific finite element models, which will be used to quantify stress distributions in the\nfacet joints under simulated six degree of freedom physiologic loading to understand mechanistically how altered\ndisc mechanical function during degeneration may contribute to the progression of facet OA. In Aim 2, we will\nthen elucidate whether restoring intervertebral disc mechanical function can mitigate the progression of disc\ndegeneration and facet OA. Using the same large animal model as Aim 1, we will deliver an injectable, granular\nhyaluronic acid hydrogel to the degenerative nucleus pulposus to acutely augment disc mechanical properties.\nThe acute effects of NP augmentation via the granular hydrogel on facet loading will be assessed using the\nanimal-specific finite element models utilized in Aim 1. The extent of disc repair and concomitant progression of\nfacet OA in vivo will be assessed across length scales via a variety of structure-function outcomes. Overall, the\nknowledge gained from this study of disc-facet crosstalk can contribute to developing advanced diagnostics for\nspinal degeneration and elucidating new targets for tissue engineering and regenerative medicine strategies.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11395590", "metadata": { "project_num": "5R01AR083007-03", "award_amount": 542597, "activity_code": "R01", "organization": "UNIVERSITY OF PENNSYLVANIA", "principal_investigators": [ { "profile_id": 14571063, "first_name": "SARAH", "middle_name": "E", "last_name": "GULLBRAND", "is_contact_pi": true, "full_name": "SARAH E GULLBRAND", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11393769", "title": "An improved low-endotoxin Clean Genome E. coli strain for production of biological products", "summary": "Abstract\nE. coli has played a vital role in the production of recombinant proteins and plasmid DNA (pDNA) for therapeutic\nuse since the advent of the biopharmaceutical industry. E. coli remains the workhorse in the production of\nheterologous proteins and pDNA because of its short doubling time, its ability to grow to high cell densities and\nits relatively straightforward scale-up potential. About 30% of all approved therapeutic proteins and 70% of anti-\ncancer agents continue to be made in E. coli. As the need for high quality pDNA has increased due to success\nin gene therapy and mRNA vaccines, there is a growing need for high quality, low toxicity bacterial strains for\nproduction of plasmids. The goal of this direct to Phase II application is to develop a versatile next-generation E.\ncoli strain built using Scarab Genomics’ Clean Genome® platform that combines low endotoxin levels with\nenhanced genetic stability characteristics for nucleic acid and protein production. Specifically, we propose to use\ngenetic techniques to substantially lower the level of contaminating endotoxin in pDNA and recombinant protein\npreparations.\nScarab Genomics has developed and patented its reduced genome E. coli strains, which has removed 650\npotentially contaminating proteins and all transposable elements. We propose to further eliminate genes that are\nresponsible for the activation of the Toll-like receptor-4 (TLR-4). We propose that phosphorylation sites on lipid\nA and on carbohydrates on the LPS side chains activate the Limulus amebocyte lysate (LAL) assay. These will\nbe removed and pDNA and protein products from this strain tested in a TLR-4 and LAL assay. Success of the\nproposal will culminate in an E. coli strain that is low in endotoxin and increased genetic stability but continues\nto generate high levels of nucleic acid and protein under fermentation conditions.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11393769", "metadata": { "project_num": "5R44GM156147-03", "award_amount": 851745, "activity_code": "R44", "organization": "SCARAB GENOMICS, LLC", "principal_investigators": [ { "profile_id": 1877812, "first_name": "FREDERICK", "middle_name": "R", "last_name": "BLATTNER", "is_contact_pi": false, "full_name": "FREDERICK R BLATTNER", "title": "" }, { "profile_id": 8820232, "first_name": "David", "middle_name": "A", "last_name": "Frisch", "is_contact_pi": true, "full_name": "David A Frisch", "title": "SENIOR SCIENTIST" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11389591", "title": "Imaging Biomarkers of Freezing of Gait Response to Deep Brain Stimulation", "summary": "Freezing of gait (FOG) is a common and debilitating manifestation of advanced Parkinson’s disease (PD) for\nwhich there are limited treatment options. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is\neffective in approximately half of patients with FOG (PwF), and its effects wane over time. We propose a\nmultimodal neuroimaging study which uses diffusion MRI to understand the structural connections of the\nindividual stimulation area, as well as the microstructural integrity of key nodes in the network. This study will\nalso study the blood oxygen level dependent (BOLD) response to STN-DBS in PwF. The long-term goal of this\nresearch is to optimize FOG response to STN-DBS by identifying contributing modifiable factors. We propose to\ndo so by: 1) studying differences in BOLD response to STN-DBS between responders and non-responders, 2)\nstudying how the site of stimulation affects structural connectivity in responders compared to non-responders,\nand 3) studying differences in microstructural integrity of regions directly affected by STN-DBS (STN, GPi, PPN).\nSpecifically, we aim to: 1) identify differences in BOLD activation based on FOG response to STN-DBS, 2)\nidentify differences in structural connectivity to the stimulation site based on FOG response to STN-DBS and 3)\nidentify differences in microstructural integrity of key network nodes. We will recruit PwF selected to undergo\nDBS surgery and perform structural imaging and behavioral assessments at baseline followed by combined\nDBS/fMRI studies and further behavioral assessments postoperatively and longitudinally. By achieving these\naims we will have evaluated the contribution of lead placement, stimulation parameters, structural connectivity,\nand BOLD activation to FOG response which will be integrated to generate a mechanistic model of FOG\nresponse to STN-DBS. The proposed study is innovative in two major ways: 1) we propose a novel conceptual\nframework incorporating intrinsic and extrinsic factors that may affect FOG response to STN-DBS, and 2) we\npropose a novel approach which integrates structural connectivity with microstructural integrity along the circuit\nand to identify in-vivo functional network effects of STN-DBS activation in PwF. By developing a comprehensive\nintegrated mechanistic model of STN-DBS response we can begin to develop optimization strategies to enhance\nengagement of the network. This approach will also further our understanding of the long-term therapeutic effects\nof STN-DBS by capturing longitudinal changes in functional network activation.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11389591", "metadata": { "project_num": "5R01NS131396-03", "award_amount": 577744, "activity_code": "R01", "organization": "MEDICAL UNIVERSITY OF SOUTH CAROLINA", "principal_investigators": [ { "profile_id": 10801822, "first_name": "Gonzalo", "middle_name": "Javier", "last_name": "Revuelta", "is_contact_pi": true, "full_name": "Gonzalo Javier Revuelta", "title": "ASSOCIATE PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11387185", "title": "New TREM-1 therapy for inflammatory bowel disease", "summary": "Project Summary/Abstract\nInflammatory bowel disease (IBD) involves chronic inflammation of the gastrointestinal (GI) tract and\nincludes ulcerative colitis (UC) and Crohn's disease (CD). Annually, over 1.5 million people in the United\nStates suffer from IBD with the annual financial burden exceeding $31 billion. Intolerance or lack of\nresponse to conventional therapies as well as high treatment failure rates and serious side effects\nassociated with existing biologics shows an unmet need for novel approaches. The goal of this project is to\ndevelop a novel, effective and well-tolerable therapy for the treatment of IBD.\n Macrophages are central to intestinal inflammation and play an important role in the pathogenesis of\nIBD. Triggering receptor expressed on myeloid cells (TREM-1), an inflammation amplifier, is involved in\nIBD. TREM-1 is not generally expressed in the normal intestine. In experimental colitis and in patients with\nIBD, TREM-1 on the intestinal macrophages is upregulated and correlates with disease activity. In animals,\nblockade of TREM-1 attenuates inflammation and ameliorates colitis.\n Current TREM-1 blockers, including Inotrem's peptide LR12 (failed recently in Phase IIb sepsis trial), all\nattempt to block binding of unknown TREM-1 ligand(s). To reduce risk of failure in the clinic, we developed\na ligand-independent TREM-1 inhibitory peptide sequence GF9 that can be used in form of free peptide\n(\"pan-TREM-1\" blocker that targets TREM-1 on all TREM-1-expressing cells) or as a part of peptide GA31\nformulated into macrophage-specific lipopeptide complexes (LPC) to improve its half-life and targeting.\n Previously, we showed that GF9 and GA31-LPC: 1) reduce systemic and local inflammation in\nexperimental arthritis, cancer and sepsis, 2) inhibit macrophage infiltration/activation at local inflammatory\nsites in arthritis and cancer, 3) ameliorate these and other inflammatory diseases. This study aims to test if\nligand-independent TREM-1 blockade using GF9 and GA31-LPC reduces colitis in two well-established\nmodels of IBD: dextran sodium sulfate (DSS)- and adoptive T cell transfer (ATCT)-induced colitis.\n Phase I specific aims are to: 1) generate and test GF9 and GA31-LPC in vitro, and 2) test GF9 and\nGA31-LPC in two mouse models of IBD. We will generate GF9 and GA31-LPC, characterize their size,\ncomposition,stability and test them in lipopolysaccharide(LPS)-stimulated THP-1 cells.We will test GF9 and\nGA31-LPC in vivo in two mouse models of IBD. LR12 will be studied comparatively. Endpoints will include\ncolitis score, weight, blood in stool, diarrhea, histology, colon length/weight. Cyto/chemokines will be tested.\n It is anticipated that these studies will provide a powerful platform for development of a well-tolerable\nand effective therapy capable of treating patients with IBD. If successful, the Phase I will be followed in the\nPhase II (if granted) and follow up studies including lead and administration regimen optimization, IND-\nenabling studies, filing IND and subsequent evaluation in humans.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11387185", "metadata": { "project_num": "1R43DK148026-01", "award_amount": 353264, "activity_code": "R43", "organization": "SIGNABLOK, INC.", "principal_investigators": [ { "profile_id": 10750414, "first_name": "Alexander", "middle_name": "B", "last_name": "Sigalov", "is_contact_pi": true, "full_name": "Alexander B Sigalov", "title": "PH.D." } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11378724", "title": "Metabolic Basis of Disease - Phase 2", "summary": "Project Summary:\nThe overall goal of this Phase 2 COBRE is to facilitate the growth of young intellectual talent and strengthen and enhance the scientific infrastructure that will promote biomedical research discoveries that will enhance our understanding of the metabolic aspects of different diseases. Specifically, we have identified three research project leaders (RPLs) with scientific interests in different, but complementary aspects of disease research. Each Research Project focuses on the metabolic aspect of a disease (HFpEF/heart failure with preserved ejection fractions, HCC/hepatocellular carcinoma, and undernutrition and iron metabolism). Despite the breadth in tissues and metabolic diseases of interest, each project strongly fits into Pennington Biomedical’s general mission, to discover the triggers of chronic diseases through innovative research that improves human health across the lifespan. Within this Metabolic Basis of Disease (MBD) COBRE proposal, we established two scientific cores in Phase 1. The Preclinical Research Core brings together strengths from our Comparative Biology Core, Animal Models and Behavior Core, and Genetically Engineered Models Core. The Molecular Mechanisms core integrates aspects of our Genomic Cores and Cell Biology Bioimaging Core and provides mentoring and technical support for the RPLs and PBRC faculty. In Phase 2, this core will have a stronger emphasis on bioinformatics and new leadership. We will also establish a new Pilot and Feasibility Program to identify new RPLs and promote metabolic basis of disease research.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11378724", "metadata": { "project_num": "5P20GM135002-07", "award_amount": 2197409, "activity_code": "P20", "organization": "LSU PENNINGTON BIOMEDICAL RESEARCH CTR", "principal_investigators": [ { "profile_id": 2084705, "first_name": "Jacqueline", "middle_name": "M", "last_name": "Stephens", "is_contact_pi": true, "full_name": "Jacqueline M Stephens", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11378185", "title": "De novo designed Ras tools to uncover the mechanisms underlying drug resistance", "summary": "The Ras family of proteins contain four major isoforms, and altogether these proteins are constitutively activated\nin a third of cancers. In the past decade, inhibitors to mutant Ras (RasG12C) have been developed, but most\npatients administered RasG12C inhibitors (RasG12Ci) relapse. Interestingly, these Ras inhibitor resistant tumors\nhave Ras signaling reactivated and the signaling mechanisms underlying this drug resistance are unknown. To\nuncover these drug resistance mechanisms, I developed Ras activity sensors and Ras activity dependent\nproximity labelers, applied them to RasG12C-addicted cancer cells treated with RasG12Ci, and observed that\nRasG12Ci blocked mutant Ras signaling at the plasma membrane while wildtype (WT) Ras is activated at\nendomembranes to fuel oncogenic signaling and cell growth. While these results are preliminary as these studies\nwere done in 2D cell culture and do not delineate which particular Ras isoforms enable RasG12Ci resistance,\nthese exciting findings beg the question of whether cancer cells can evade other recently developed Ras\ninhibitors targeting RasG12C, G12D, G12R, or G12S by also reactivating Ras signaling. Therefore, the objective\nof this K99/R00 proposal is to expand the molecular toolkit for Ras and utilize these tools to profile and uncover\nthe molecular mechanisms driving Ras inhibitor resistance. The central hypothesis driving this work is that WT\nRas compensation for mutant Ras inhibition is a general feature cancer cells employ to evade Ras inhibitors.\nProfiling the subcellular Ras activities during Ras inhibitor treatment and uncovering the molecular components\ndriving this reorganization of Ras signaling will allow better understanding of Ras inhibitor resistance and\nillumination of new therapeutic targets. To investigate this hypothesis, the following specific aims will be\naddressed: (1) Developing and applying Ras sensors in complex cancer cell models (K99); (2) De novo design\nof Ras isoform selective tools (K99/R00); and (3) Profiling and dissecting the mechanisms underpinning Ras\ninhibitor resistance (R00). In the proposed research, I will protein engineer current and new Ras tools (sensors,\nproximity labelers, perturbators) along with microscopy and proteomic techniques to determine how Ras\ninhibitors impact compartmentalized Ras signaling. The expected outcomes are (1) an expansion of tools that\ncan be applied to in vivo models and probe specific Ras isoforms and (2) a better understanding of how Ras\ninhibitors operate and how drug resistance can occur. Of note, I believe these new Ras tools will be of great\ninterest to the cancer community (e.g. NCI’s Ras initiative) and can be useful for other applications beyond the\nscope of this proposal such as diagnostics and therapeutics. Towards completion of the proposed work, I will be\ntrained in protein design methods and complex cancer models and guided by an advisory committee composed\nof experts in cancer, Ras signaling, and cell culture. The long-term goal of this project is to develop an\nindependent research program that bridges protein design with cancer cell biology to understand how oncogenic\nsignaling pathways rewire themselves during oncogenesis and drug resistance.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11378185", "metadata": { "project_num": "5R00CA293001-03", "award_amount": 321209, "activity_code": "R00", "organization": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "principal_investigators": [ { "profile_id": 79350314, "first_name": "Jason", "middle_name": "", "last_name": "Zhang", "is_contact_pi": true, "full_name": "Jason Zhang", "title": "PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11367253", "title": "Chronic Alcohol Consumption Dysregulates Lung Hyaluronic Acid", "summary": "PROJECT SUMMARY/ABSTRACT:\n Alcohol use disorder (AUD), which affects over 26 million people aged 21 years+ in the US, increases\nthe risk for pneumonia by 2-4-fold, resulting in high healthcare costs due to comorbidities and hospitalizations.\nLung macrophages are critical for innate immune defense against inhaled pathogens by engulfing and killing\nthem. Chronic ethanol (EtOH) consumption impairs phagocytosis in lung macrophages, but our prior work and\npreliminary data indicate there is heterogeneity in lung macrophages’ immune response to bacterial infections.\nIn response to insults, subpopulations of macrophages are recruited into the lung as interstitial macrophages\n(IMs), monocyte-derived alveolar macrophages (MoAMs), and tissue-resident alveolar macrophages (RAMs).\nUnderstanding how phagocytosis is suppressed in macrophage populations specifically dysregulated by EtOH\nis critical to being able to develop targeted therapies to decrease susceptibility to pneumonia in people with\nAUD. The primary objective of this project seeks to address this critical knowledge gap by determining the\nimpact of EtOH-induced reactive oxygen species (ROS) production on the composition of IMs, MoAMs, and\nRAMs in the alveolus plus their immune phenotype at baseline and in response to a bacterial infection.\nHyaluronic acid (HA) is an extracellular matrix polysaccharide whose signaling directs inflammation in\nnumerous lung diseases. Low molecular weight HA signaling is pro-inflammatory, while high molecular weight\nHA signaling is anti-inflammatory. ROS perturbs HA molecular dynamics, which could alter mitochondrial\nbioenergetics where ATP generated from mitochondria is key for phagocytosis. Our work shows that chronic\nalcohol consumption increases ROS in the lungs and promotes anti-inflammatory and metabolically\ndysregulated phenotypes in lung macrophages. We hypothesize that chronic EtOH consumption increases\nROS in the bronchoalveolar lavage fluid (BALF) and differentially alters HA synthesis and fragmentation in IMs,\nMoAMs, and RAMs which leads to alternative/deactivated and dysregulated metabolic phenotypes that impair\nphagocytosis. Preliminary studies also show that treatment with pioglitazone (PIO), an agent with antioxidant\neffects, restores lung redox balance in EtOH-fed mice and decreases HA content in the lungs of AUD\nindividuals. We postulate that PIO treatment will restore redox balance; thereby, reversing EtOH-induced\nalterations in HA dynamics in dysfunctional lung macrophages and improving their phagocytic abillity. Using a\nscientifically rigorous approach, state-of-the-art techniques, translational models, and samples from people\nwith AUD, we will (1) define how chronic EtOH consumption affects alterations in HA, activation state,\nmetabolic phenotype, and immune phenotype of lung macrophage subpopulations and (2) determine how\nEtOH-induced lung redox imbalance dysregulates HA dynamics in lung macrophage subpopulations. These\nstudies can aid in specifically targeting treatments to dysfunctional macrophages and improve lung immunity in\npeople with AUD while also providing valuable insights into HA derangements in other pulmonary diseases.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11367253", "metadata": { "project_num": "1R01AA032629-01A1", "award_amount": 418923, "activity_code": "R01", "organization": "EMORY UNIVERSITY", "principal_investigators": [ { "profile_id": 8868638, "first_name": "Samantha", "middle_name": "M.", "last_name": "Yeligar", "is_contact_pi": true, "full_name": "Samantha M. Yeligar", "title": "ASSOCIATE PROFESSOR OF MEDICINE" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11362458", "title": "Research Training Program in Disease-Oriented Neuroscience (R25)", "summary": "SUMMARY\nThis Research Training Program in Disease Oriented Neuroscience is designed to facilitate the transition between graduate training and a research-based career in neurology and neurosurgery. R25 program trainees receive career mentoring from experienced clinician scientists in Neurology and Neurosurgery along with research mentoring from leading clinical neuroscience laboratory research faculty drawn from multiple departments and schools within the University of Pennsylvania. A focused educational program supplements laboratory research and includes training in translational research methods, applications, and the responsible conduct of research. The program is conducted in a large research-oriented institution with leading residency programs in adult and child neurology and in neurosurgery that trains some of the best candidates in the country and has an outstanding track record of fostering research oriented careers in a wide array of scientific topics. Over the past program period, 6 of the 7 graduating R25 trainees have received K awards. The R25 pathway has been further integrated into the residency training program at all phases including residency application review, applicant visit and interview procedures, advance mentorship and research opportunities for matriculated applicants, intensive support for the selection of mentors and the development of an R25 supplement request, and multiple levels of clinician scientist career development support. Between the neurology and neurosurgery residencies, there are over 200 faculty members in our departments, ranging from master clinicians, clinical educators, and clinical investigators to physician/scientists and basic scientists. 80% of graduating residents over the past 15 years have remained in academic medicine, and many have chosen careers as clinician scientists. The Hospital of the University of Pennsylvania and Children’s Hospital of Philadelphia at the Perelman School of Medicine, where most of the clinical residency and fellowship training occurs, are located within a highly compact university campus in West Philadelphia spanning a radius of less than one half mile. Penn is also home to the first neuroscience institute in the country, the Mahoney Institute for Neurosciences, which consolidates almost 200 faculty members from 32 departments and six schools engaged in neuroscience research at Penn. The range of research opportunities for our R25 trainees can thus be extended to the wider neuroscience community inside and outside of our clinical departments through co-mentorship of trainees by an array of eminent scientists carrying out research relevant to the NINDS mission to reduce the burden of neurological disease.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11362458", "metadata": { "project_num": "5UE5NS065745-18", "award_amount": 52822, "activity_code": "UE5", "organization": "UNIVERSITY OF PENNSYLVANIA", "principal_investigators": [ { "profile_id": 1869099, "first_name": "Geoffrey", "middle_name": "Karl", "last_name": "Aguirre", "is_contact_pi": true, "full_name": "Geoffrey Karl Aguirre", "title": "ASSISTANT PROFESSOR" }, { "profile_id": 8195567, "first_name": "HAN-CHIAO", "middle_name": "ISAAC", "last_name": "CHEN", "is_contact_pi": false, "full_name": "HAN-CHIAO ISAAC CHEN", "title": "ASSISTANT PROFESSOR" }, { "profile_id": 1866335, "first_name": "JOHN", "middle_name": "A", "last_name": "DETRE", "is_contact_pi": false, "full_name": "JOHN A DETRE", "title": "PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11351765", "title": "Advancing population-based research on cognitive aging and dementia with minimally-invasive methods for quantifying biomarkers of neurocognitive function", "summary": "PROJECT SUMMARY\nMore than 6 million Americans currently live with Alzheimer’s Disease. The annual cost of care for Alzheimer’s\nDisease and related dementias (ADRD) exceeds $300 billion and is projected to surpass $1 trillion by 2050.\nAddressing this emerging public health crisis requires a deeper understanding of the processes that contribute\nto brain aging in order to reduce the human and financial costs of ADRD. Biomarkers of neurodegenerative\nprocesses can be measured in peripheral blood samples to identify risk for ADRD before the onset of clinical\ndisease, but collection of these samples is limited to clinical settings where it is possible to draw venous blood.\nMethods for measuring ADRD biomarkers in non-clinical settings are needed to support new research on the\ngenetic, lifestyle, and environmental factors that increase risk for dementia. This project will validate methods\nfor quantifying ADRD biomarkers in a few drops of capillary blood as a low-cost, scalable approach to\nadvancing research on cognitive aging and brain health in non-clinical settings. Dried blood spots (DBS)—\ndrops of whole blood collected on filter paper following a simple finger stick—represent a minimally-invasive\nalternative to venous blood collection that is widely used in population-based and epidemiological studies. The\npaper dries and preserves the sample and reduces costs of collection, processing, and shipping. The project’s\nfirst aim involves optimizing laboratory assays that will accurately and reliably measure the following ADRD\nbiomarkers in DBS: neurofilament light chain, glial fibrillary acidic protein, amyloid 𝛽𝛽 42/40, and Tau proteins\n(total, pTau181, pTau217). Each assay will be evaluated for precision, reliability, accuracy, lower limit of\ndetection, as well as potential sources of pre-analytic variation, including sample volume, drying conditions,\nand stability during transport and storage. The second aim will test assay performance in capillary blood\nsamples collected with devices that are designed for self-collection in the home. The third aim will analyze\nagreement in results between serum samples and matched DBS samples to provide information on assay\naccuracy and validity, and to generate formulas for conversion of results across sample types. New methods\nfor measuring ADRD biomarkers in small volumes of capillary blood that reduce the costs, sample processing\nrequirements, and cold chain logistics of venipuncture will have a major impact by moving ADRD research\nbeyond the clinic and into large epidemiological and behavioral/demographic surveys.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11351765", "metadata": { "project_num": "1R21AG101733-01", "award_amount": 440000, "activity_code": "R21", "organization": "NORTHWESTERN UNIVERSITY", "principal_investigators": [ { "profile_id": 2089229, "first_name": "THOMAS", "middle_name": "W", "last_name": "MC DADE", "is_contact_pi": true, "full_name": "THOMAS W MC DADE", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11350268", "title": "Integrated Multiomics Diagnostics at the Point of Care for Healthy Living", "summary": "Abstract\nTimely cancer diagnosis remains a major public health challenge, particularly in communities with limited clinical access, including rural areas, military bases, and urban health deserts. These populations face disproportionate delays in diagnosis due to structural barriers such as clinician shortages and limited access to centralized diagnostic infrastructure. Head and neck squamous cell carcinoma (HNSCC), including both HPV-positive and HPV-negative subtypes, presents an urgent case for intervention due to its rising incidence and poor survival when diagnosed late.\nWe propose Recognize™-HNSCC, a saliva-based, point-of-care (PoC) diagnostic platform designed for rapid, non-invasive detection of both major subtypes of HNSCC. This platform is intended for decentralized settings such as dental clinics, community health centers, and mobile outreach units, with the goal of achieving CLIA-waivable status. The system, based on our patented and patent pending technologies integrates multiplexed detection of genotypic (HPV16, HPV18) and phenotypic (five-gene panel) biomarkers and delivers actionable results within 30 minutes using a disposable test cartridge and portable fluorescence reader. AI integration for clinical decision support is planned for Phase II; Phase I will focus on metadata capture and prototyping of algorithmic frameworks.\nPhase I of this project will achieve three major goals: (1) design, optimize, and validate multiplex RT-RPA-Exo assays using contrived saliva spiked with HNSCC-relevant cell lines; (2) demonstrate analytical performance and reproducibility using the Recognize™ device in a blinded, randomized format; and (3) assess feasibility and optimize assay conditions using clinically annotated and de-identified saliva samples representing HPV-positive, HPV-negative, and healthy individuals. Diagnostic performance will be benchmarked against clinical diagnoses to evaluate assay sensitivity, specificity, and robustness.\nCompletion of these milestones will de-risk assay integration, validate platform readiness, and support the design of a Phase II clinical validation study and subsequent regulatory submission under the FDA’s De Novo pathway.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11350268", "metadata": { "project_num": "1R43DE035900-01", "award_amount": 365004, "activity_code": "R43", "organization": "INNOTECH PRECISION MEDICINE, INC", "principal_investigators": [ { "profile_id": 2191319, "first_name": "ROYA", "middle_name": "", "last_name": "KHOSRAVI-FAR", "is_contact_pi": true, "full_name": "ROYA KHOSRAVI-FAR", "title": "CEO" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11339687", "title": "Interplay between common and rare variants associated with schizophrenia", "summary": "PROJECT SUMMARY\nGenetic architecture of schizophrenia shows that both rare loss-of-function variants with large effect sizes and\ncommon variation with small effect sizes contribute to schizophrenia risk. Traditionally, these two sets of\nvariation in the opposite allelic spectrum have been studied as distinct entities, but growing evidence supports\nthat common and rare variants need to be studied together as they may additively contribute to schizophrenia\nrisk. Here, we propose a human induced pluripotent stem cell (hiPSC)-based experimental paradigm to\ninvestigate the interplay between common and rare variants across the two neuronal cell types predominantly\nimplicated in schizophrenia: glutamatergic and GABAergic neurons. First, we will investigate the molecular and\ncellular impacts of high-penetrant schizophrenia risk gene perturbations. Second, we will empirically evaluate\nthe functional impact of non-coding common variants associated with schizophrenia to uncover their regulatory\nlogic and pinpoint causal variants. Finally, we will establish the extent to which the regulatory logic of common\nvariants is impacted by high-penetrant schizophrenia risk gene perturbations, investigating the impact of rare\nvariants on the regulatory activity of common variants. The successful completion of this proposal will: (1)\npinpoint functional regulatory variants associated with schizophrenia risk in a neuronal cell type-specific\nmanner, (2) identify molecular convergence between schizophrenia rare and common risk variants, (3) provide\nthe biological underpinning of how common and rare variants have additive effects on schizophrenia risk, and\n(4) inform the design of future functional genomic studies of schizophrenia.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11339687", "metadata": { "project_num": "1R01MH143807-01", "award_amount": 827625, "activity_code": "R01", "organization": "UNIV OF NORTH CAROLINA CHAPEL HILL", "principal_investigators": [ { "profile_id": 12151322, "first_name": "HYEJUNG", "middle_name": "", "last_name": "WON", "is_contact_pi": true, "full_name": "HYEJUNG WON", "title": "ASSOCIATE PROFESSOR" }, { "profile_id": 11155497, "first_name": "Nan", "middle_name": "", "last_name": "Yang", "is_contact_pi": false, "full_name": "Nan Yang", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11328404", "title": "Exploring the Molecular Link between Bioenergetics, Latency, and Neuro-cognitive Impairment during HIV-associated progressive Aging", "summary": "Abstract\nAging is an inevitable biological process characterized by continuous deterioration of physiological, molecular,\ncellular, biochemical, and functional changes. The effects of aging are critical to the population of people living\nwith HIV (PLWH), as the overall cohort of infected individuals is getting older, with over 4 million over the age of\n50, and the number is increasing. While PLWH are experiencing improved life expectancy due to significant\nadvancements in the combinatorial antiretroviral therapy (cART), they continue to face a higher burden of aging-\nassociated co-morbidities like diabetes, cancer, frailty, and neurological disorders, which led researchers to\nbelieve that HIV infection leads to a form of early aging. Aging and HIV infection have been shown to have\nnegative impacts on the form and function of the central nervous system (CNS). Combinatorial ART’s poor\npenetrance across the blood-brain-barrier leads to continuous low-level viral replication in the CNS and could\nresult in premature aging in PLWH. Though the brain makes up only 2% of the body’s weight, it consumes over\n20% of the oxygen the body takes in, a 10-fold greater energy requirement than any other organ. The brain\nundergoes a steady decline in energy metabolism during normal aging, and HIV infection adds another level of\ncomplexity to it. The changes in the brain energy level could be one key contributing factor in accelerated aging\nin PLWH. Whether HIV alone, cART alone, or both HIV and cART acting synergistically contribute more to the\naging-associated perturbations is not well studied because of limitations regarding longitudinal clinical sample\navailability and suitable human-aging mimicking animal models. Approaches to visualize and comprehend\nneuroimmune dysfunction, brain bioenergetics, and associated cognitive deficits in the setting of new-age cART\nare the knowledge gap. Thus, deciphering how chronic ART-treatment affects aging and the brain immune\nhomeostasis will provide a clue to understand the mechanism involved in accelerated aging in PLWH and\nultimately its therapeutic targeting. Recently, we used chronically HIV-1-infected CD34-NSG humanized mice to\nmodel older people living with HIV and uncover associations between HIV-1 infection and aging\n(PMID:38399364). We are the first to report human aging-associated gene changes in the brains of hu-mice\nusing transcriptomics by maintaining the HIV-infected mice for more than one year without ART. With an\nappropriate model in hand and new preliminary data sets, we propose to study progressive aging and associated\nchanges in the CNS during chronic, clinically relevant oral cART and injectable long-acting ART regimens. How\nmuch brain bioenergetics, latency, and cART regimens would contribute to premature aging (we termed as\nBLAAGING) and functional neuro-immune interaction at the molecular and behavioral level will be answered. By\nemploying the proposed animal model under highly suppressive cART treatment regimens, the proposed three\naims will measure axonal fiber integrity, neuronal metabolites, using diffusion tensor imaging and CEST-MRI,\nand brain functional deficits using behavior analysis, gene-level changes using transcriptomics, and\nbioenergetics changes from brain-derived mitochondria during progressive aging. The outcome will help identify\nnew biomarkers of aging in the CNS and will provide mechanistic evidence for future therapeutics to delay the\naccelerated aging process in PLWH.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11328404", "metadata": { "project_num": "1RF1NS153514-01", "award_amount": 2571326, "activity_code": "RF1", "organization": "UNIVERSITY OF NEBRASKA MEDICAL CENTER", "principal_investigators": [ { "profile_id": 10216130, "first_name": "Prasanta", "middle_name": "Kumar", "last_name": "Dash", "is_contact_pi": true, "full_name": "Prasanta Kumar Dash", "title": "ASSOCIATE PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11324333", "title": "An ecological momentary investigation of associations between PTSD, alcohol use, and medication adherence among young adults", "summary": "PROJECT SUMMARY\n People living with HIV (PWH) and those at risk of acquiring HIV, relative to the general population, have\nelevated rates of alcohol use and heavy episodic drinking (up to 41.1% compared to 11.2%) as well as post-\ntraumatic stress disorder (PTSD; up to 74% compared to 8.3%). Post-traumatic stress disorder and alcohol\nuse are highly interrelated with the former increasing risk of the latter and each of these serving as key\nproximal risk factors for medication non-adherence. For example, those with PTSD may have difficulty\nconcentrating which can result in forgetting to take one’s medication. Meanwhile, alcohol use and heavy\nepisodic drinking reduce adherence to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) as\nprescribed by up to 55%. Taken together, both PTSD and alcohol use may be key risk factors for medication\nnon-adherence among PWH and those at risk of acquiring HIV.\n People living in rural environments tend to engage in more heavy episodic drinking and have elevated\nrates of PTSD, potentially magnifying the risk for medication non-adherence, not to mention geospatial\nvariation in ART success and HIV care in rural areas. Although individuals living in urban settings report higher\nlevels of traumatic event exposure and subsequent PTSD symptomatology, those living in rural areas report\nhigher rates of HIV-related psychological distress, itself associated with elevated rates of alcohol use and\nheavy episodic drinking. Further, rural inhabitants report lower access to HIV-related care, lower awareness of\nPrEP, and reduced access to primary care providers to initiate ART/PrEP prescriptions. This is alongside other\nbarriers to rural healthcare such as a greater distances to services, higher cost of health care, and more limited\naccess to services. Taken together, these differences suggest a need to focus on how the relationship\nbetween PTSD, alcohol use, and medication adherence differs based on urbanicity of residence.\n The goal of this R01 is to address two sides of the HIV prevention coin: sustained viral suppression\namong PWH and adherence to PrEP among HIV-negative individuals, focusing on the mechanistic pathway\nfrom PTSD through alcohol use as well as differences based on urbanicity. We will recruit a sample of 600\ntrauma-exposed young adults with probable PTSD and elevated heavy episodic drinking, aged 16-29, to\naccomplish the following aims: 1) Identify within-person associations between PTSD and medication\nadherence; 2) Examine alcohol use as a within-person mechanism of the association between PTSD and\nmedication adherence; and 3) Test for moderation based on urbanicity of residence.\n The proposed study is in response to PAS-25-208 and NIAAA priorities to understand HIV Prevention\nand Alcohol. This R01 will inform the development of interventions to reduce heavy episodic drinking and\nPTSD and to increase medication adherence.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11324333", "metadata": { "project_num": "1R01AA032464-01A1", "award_amount": 713536, "activity_code": "R01", "organization": "OHIO STATE UNIVERSITY", "principal_investigators": [ { "profile_id": 14141657, "first_name": "Ethan", "middle_name": "", "last_name": "Morgan", "is_contact_pi": true, "full_name": "Ethan Morgan", "title": "ASSISTANT PROFESSOR" }, { "profile_id": 11998517, "first_name": "JaNelle", "middle_name": "", "last_name": "Ricks", "is_contact_pi": false, "full_name": "JaNelle Ricks", "title": "ASSISTANT PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11315161", "title": "Advancing Actionability in Oncology: Enhanced Detection of Head and Neck Cancer Recurrence", "summary": "Project Summary\nHead and neck cancer (HNC) remains a significant cause of mortality, with patient survival drastically\ndeclining once recurrence advances beyond local disease. This SBIR Fast Track proposal seeks to\ndevelop a fully automated, high-throughput assay that isolates extracellular vesicles (EVs) from\nplasma or saliva and employs vibrational spectroscopy to detect HNC recurrence at earlier, more\ntreatable stages. Phase I will focus on integrating validated EV-isolation and spectral analysis\nmodules into a robotic platform, establishing comprehensive design controls and a quality\nmanagement system to meet CLIA and future FDA requirements. Phase II will then validate the\nassay’s clinical performance in a longitudinal HNC cohort, refining a machine-learning classifier and\ncompleting the steps necessary for a Laboratory Developed Test (LDT) submission. By enabling\ntimely, cost-effective detection of recurrent disease across diverse HNC subtypes, this project aims to\nimprove patient outcomes, enhance clinical decision-making, and reduce the healthcare burden\nassociated with late-stage recurrence.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11315161", "metadata": { "project_num": "1R44DE035769-01", "award_amount": 396280, "activity_code": "R44", "organization": "ILLUMIFYDX, INC.", "principal_investigators": [ { "profile_id": 79327827, "first_name": "Maria", "middle_name": "", "last_name": "Navas-Moreno", "is_contact_pi": true, "full_name": "Maria Navas-Moreno", "title": "CEO" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11314950", "title": "Audiom: Developing an Indoor Non-Visual Mapping System", "summary": "Project Abstract\n The proposed project aims to address the significant challenges faced by the 12 million blind and low\nvision individuals (BLVIs) in the U.S. in orienting and analyzing complex indoor spaces. Current solutions have\n“blank” maps. To overcome these limitations, this application proposes further development and optimization of\nAudiom, a digital visual, auditory, and interactive text-based virtual reality web map viewer and editor. Audiom\nallows BLVIs to explore, learn, and orient to indoor environments through an avatar-based interface, enhancing\ntheir spatial knowledge and data analytics abilities.\n Phase I of this project demonstrated the feasibility of Audiom, showing that it effectively communicates\nspatial information such as distance, direction, shape, size, orientation, and general layout of all points,\npolygons, and lines. Audiom then received a third-party Report demonstrating that it is the first digital map tool\nlegally compliant with the Americans With Disabilities Act. The goal of Phase II is to optimize both the user\nexperience and the implementation pipeline, facilitating the widespread adoption of Audiom to make indoor\ncartography usable by BLVIs for the first time. The specific aims are:\n 1. Improve BLVI usability. Systematically optimize and evaluate new features to improve\n the user experience on complex maps. Features that will be evaluated by BLVIs against the\n baseline Audiom interface from Phase I include object notification radar, rotation, optional walls,\n route navigation, mobile interface, and large language model chat interface. This should result in an\n interface that is easier to use than the one evaluated in Phase I.\n 2. Streamline map implementation process. Create, evaluate, commercialize, and distribute\n a production-ready content management platform for venue owners to quickly and easily onboard\n and update their space in Audiom. This will include a platform-specific editor and tools to reduce\n manual drawing. This should reduce the time and expense to onboard and manage new maps in\nAudiom.\n 3. Integrate Audiom into a third-party application to demonstrate that Audiom can function\n as a stand-alone system (as in Phase I) and be embedded into third-party event management, real\n estate, architectural, seat selection, and turn-by-turn navigation applications. The integration will be\n evaluated by BLVIs.\n In addition to pre-trip planning, Audiom provides robust data analytics functionality that extends beyond\nnavigation. It can be used for a variety of tasks, such as reserving airplane seats, directing janitorial staff to\nspecific cleaning zones, managing assets within a building, and coordinating equipment positioning for event\nmanagers. This functionality ensures that BLVIs can independently perform tasks that require detailed spatial\ninformation, thereby enhancing their autonomy and efficiency in various settings.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11314950", "metadata": { "project_num": "2R42EY034411-02A1", "award_amount": 977598, "activity_code": "R42", "organization": "XR NAVIGATION INC.", "principal_investigators": [ { "profile_id": 15976755, "first_name": "Brandon", "middle_name": "", "last_name": "Biggs", "is_contact_pi": true, "full_name": "Brandon Biggs", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11285676", "title": "Modulating ER stress-induced lipotoxicity to ameliorate mitochondrial myopathy", "summary": "Myopathy is one of the most common manifestations of mitochondrial diseases. Although genetic\nand bioenergetic causes of oxidative phosphorylation (OxPhos) impairment are well established,\nthere is a limited understanding of the metabolic drivers of muscle degeneration. This knowledge\ngap contributes to the lack of effective treatments for these disorders. Our recently published\nstudies indicate that OxPhos defective muscle initiates a multiorgan metabolic response\ncoordinated by endocrine signals and suggest that this response contributes to the pathogenesis\nof mitochondrial myopathy. During the metabolic remodeling, which progresses over the course\nof the disease, increased mobilization of fatty acid (FA) from adipose tissue and enhanced muscle\nlipid uptake, combined with impaired FA -oxidation (FAO) in muscle, result in muscle intracellular\nlipid accumulation. Ectopic lipid deposition in the form of lipid droplets serves as storage of neutral\nesterified FA. Upon triglycerides hydrolysis, however, if resulting FA are not efficiently utilized by\nFAO, free FA and their byproduct ceramides can cause muscle lipotoxicity. Although FAO is\nclearly impaired in OxPhos defective muscle, the role of lipotoxicity in the pathogenesis of\nmitochondrial myopathy and whether it can be targeted therapeutically remain unexplored. One\npotential mechanism of pathogenesis entails ceramide-induced ER stress leading to muscle\nprotein translation inhibition, as part of the integrated stress response. In this exploratory R21\napplication, we hypothesize that excess ceramides cause unabated induction of ER stress leading\nto muscle protein dyshomeostasis and atrophy, which contribute to mitochondrial myopathy. To\ntest this hypothesis, we propose to target pharmacologically two steps of ER stress-induced\nlipotoxicity, ceramide biosynthesis and the PERK kinase signaling. The overall goals are to\nprovide proof of concept that ceramide accrual and the resulting ER stress are pathogenic and\nthat they can be targeted therapeutically in mitochondrial myopathies.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11285676", "metadata": { "project_num": "1R21AR087068-01", "award_amount": 396206, "activity_code": "R21", "organization": "WEILL MEDICAL COLL OF CORNELL UNIV", "principal_investigators": [ { "profile_id": 10315848, "first_name": "Marilena", "middle_name": "", "last_name": "D'Aurelio", "is_contact_pi": false, "full_name": "Marilena D'Aurelio", "title": "ASSOCIATE PROFESSOR OF RESEARCH IN NEURO" }, { "profile_id": 3150937, "first_name": "Giovanni", "middle_name": "", "last_name": "Manfredi", "is_contact_pi": true, "full_name": "Giovanni Manfredi", "title": "PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11262948", "title": "UniProt: AI-Driven Scaling of Protein Knowledge for Biomedical Research", "summary": "Project Summary\nThe mission of UniProt is to support biomedical research by providing a stable, comprehensive, richly and\naccurately annotated reference knowledgebase of protein sequences and functional information. Proteins\nare an essential bridge between human genotypes and phenotypes and the environment. As we enter an era\nof unprecedented growth in data volume, computational capacity, and advances in artificial intelligence (AI),\nUniProt will harness these advancements to enhance its scope, accuracy, and utility for biomedical research.\nWe will focus on human proteins, genomic variants, and proteins found in pathogens and the human\nmicrobiome and their functional interactions in basic biology as well as rare and common infectious and\ngenetic diseases, along with cancer, metabolic, cardiovascular, endocrine, immune, eye, and\nneurodegenerative diseases.\nHosting the world’s protein knowledge, UniProt integrates, interprets, and standardizes information from a\nvast corpus of publications and a multitude of resources to deliver the most comprehensive catalog of protein\nsequences and functions. We will leverage the power of AI, particularly Large Language Models (LLMs), to\nhelp expert curators to synthesize protein knowledge from an expanded pool of publications while maintaining\nhigh quality. We will engage the scientific community in collaborative curation, using LLMs to assist authors\nmaking contributions. We will automatically annotate uncharacterized proteins and evaluate new approaches\nusing protein Language Models that promise greater scalability. We will provide AI-ready training and\nbenchmarking datasets for the development and validation of trusted, reproducible, and explainable methods.\nUniProt is an exemplary FAIR (Findable, Accessible, Interoperable, and Reusable) resource. We will optimize\nour infrastructure and streamline production processes to scale efficiently and sustainably with both the\ngrowing data volume and complexity. We will continue to apply community standards for open data and\nmetadata and broadly disseminate our resources through the UniProt website, FTP and APIs. UniProt is an\ninternational hub of protein data that serves hundreds of thousands of users monthly. We will continue to use\nuser-centric approaches and engage with our stakeholders to develop UniProt for new use cases and data\ntypes as the needs of our user community evolve. Our outreach programs will be expanded to cover new\ninterfaces and tools and increase support for users in low/middle-income countries to broaden the\naccessibility and use of our data. With these collective efforts, we will transform UniProt into a next-generation\nprotein knowledge resource to serve the global scientific community more effectively with broader impacts\nthan ever before.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11262948", "metadata": { "project_num": "2U24HG007822-13", "award_amount": 875383, "activity_code": "U24", "organization": "GEORGETOWN UNIVERSITY", "principal_investigators": [ { "profile_id": 10239361, "first_name": "Alex", "middle_name": "", "last_name": "Bateman", "is_contact_pi": false, "full_name": "Alex Bateman", "title": "" }, { "profile_id": 12683314, "first_name": "Alan", "middle_name": "James", "last_name": "Bridge", "is_contact_pi": false, "full_name": "Alan James Bridge", "title": "" }, { "profile_id": 1879376, "first_name": "CATHY", "middle_name": "H.", "last_name": "WU", "is_contact_pi": true, "full_name": "CATHY H. WU", "title": "" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11260522", "title": "Bacterial Survival in Fluctuating Environments: Stochastic Switches, Recombination, and Memory", "summary": "Project Summary\nBacteria employ a large repertoire of responses and strategies to survive under different types of\nenvironmental stress and metabolic fluctuations. Changes in carbon sources cause cells to turn on specific\nmetabolic genes, which are later repressed when those sources are depleted. In a continually fluctuating\nenvironment, the process of turning genes on and off can be inefficient and cause growth lags. To avoid\ngrowth lags, bacteria combine gene regulation with phenotypic memory – the passage of stable proteins from\nmother to daughter cells – which allows cells to avoid growth lags in fluctuating environments. Stochastic\nswitches are a broad class of genetic mechanisms that enable single cells to switch certain genes on and off\nrandomly, without responding to their environment. Stochastic switches maintain subpopulations of cells in pre-\nadapted states that are prepared for future, possibly unpredictable, environmental stresses. An important\nexample is antibiotic persistence in which cells stochastically and reversibly switch into a physiological state\nwith enhanced tolerance for antibiotics. In addition to responsive and stochastic switching, bacteria use\nrecombination to adapt in changing environments. Recombination is a key process in the emergence of\nantibiotic resistance and in the adaptation of bacteria to ecological niches that are important in human health.\nUsing quantitative microbiology, microfluidics, microscopy, sequencing, and modeling, we study the costs and\nbenefits of stochastic and responsive gene regulation in fluctuating environments. We perform competition\nexperiments in fluctuating environments using libraries of strains with altered phenotypic memory levels. We\nuse barcode sequencing to track frequencies of different strains over time and measure their selective\ncoefficients. Using quantitative microscopy and synthetic biology, we investigate why bacterial aggregation, a\nbehavior that enhances survival under antimicrobial treatment, is regulated by stochastic switching, and how to\nreverse aggregated states using small molecule inhibitors of key genetic pathways. We use a novel custom\nmicrofluidics setup that enables single-cell lineage tracking on hundreds of thousands of cells to observe\nantibiotic persister states that could not previously be observed, and apply transcriptomics to reveal molecular\nmechanisms of persistence. We use a powerful computational method to infer recombination parameters from\nlarge-scale genomic and metagenomic sequencing datasets. We apply this method to study recombination and\nits impacts on bacterial evolutionary dynamics in microbial communities such as the human gut microbiome.\nThe proposed research will substantially advance understanding of the role of stochastic and responsive\nswitches, phenotypic memory, aggregation, and recombination in bacterial adaptation. Through its emphasis\non precise quantification using powerful single cell microfluidics and microscopy, the research will yield new\navenues to address antibiotic persistence of bacteria, to perturb bacterial aggregated states, and to understand\nhow the human gut environment selects for and maintains antibiotic resistance and surface antigen genes.", "published_date": "2026-09-05", "url": "https://reporter.nih.gov/project-details/11260522", "metadata": { "project_num": "1R35GM161539-01", "award_amount": 585658, "activity_code": "R35", "organization": "NEW YORK UNIVERSITY", "principal_investigators": [ { "profile_id": 2190358, "first_name": "EDO", "middle_name": "L", "last_name": "KUSSELL", "is_contact_pi": true, "full_name": "EDO L KUSSELL", "title": "ASSISTANT PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11251234", "title": "Engineered extracellular vesicles for the delivery of mitochondria and therapeutic proteins to the BBB", "summary": "The damage borne by brain endothelial cells (BECs) disrupts the structure and function of the blood-brain barrier\n(BBB) and contributes to poor patient outcomes post-stroke. In this R01 proposal, we will determine whether\nengineered microvesicles (MVs) can co-deliver innate MV mitochondria and an exogenous 27 kDa heat shock\nprotein (HSP27) to protect the BBB via increasing BEC survival and BEC tight junction integrity in a mouse model\nof transient cerebral ischemia/reperfusion injury (stroke). This one-two punch strategy using engineered MVs\ncan protect the post ischemic-BBB metabolic function and structural integrity via effects of the innate MV\nmitochondria and the exogenous HSP27 protein. Mitochondrial ATP regulates actin dynamics and maintains\nproper organization of the actin cytoskeleton. Further, ATP depletion-induced changes in the actin equilibrium\ncontributes to dysregulation of the tight junctions, eventually leading to BBB disruption and long-term\nneurological dysfunction. Endothelial but not neuronal expression of HSP27 in a transgenic mouse model\nsuppressed I/R-induced aberrant actin polymerization, stress fiber formation, and junctional protein\ntranslocation—that overall ameliorated neurological damage for as long as one month post-stroke. This scientific\npremise strongly supports the importance of decreasing damage to the BBB to improve post-stroke outcomes.\nMVs are a subtype of extracellular vesicles that naturally incorporate mitochondria in addition to its constituent\nlipids, nucleic acids and proteins. HSP27 is a cationic protein and requires a carrier for its delivery across anionic\ncell membranes. In our feasibility studies, we have detected mitochondria in MVs and engineered HSP27-MVs\nusing a simple formulation process that allows to retain its functional mitochondrial load. To this end, we have\ndemonstrated that (1) the innate mitochondria in naïve MVs can be transferred to recipient primary human BECs\nand mouse brain cortical and hippocampal slices, (2) MVs but not the smaller exosomes increase mitochondrial\nfunction in oxygen-glucose deprived BECs (3) a simple formulation process resulted in >60% loading efficiency\nof HSP27 into MVs and (4) mice injected with naïve MVs showed nearly a 50% reduction in infarct volume and\nlower neurological deficit scores compared to vehicle-injected mice after middle cerebral artery occlusion\n(MCAo). We hypothesize that the delivery of engineered HSP27-MVs, along with the innate MV mitochondria\nwill protect the metabolic function and structural integrity of the BECs lining the BBB—that in combination will\nameliorate the BBB disruption-induced changes in stroke. We will test the proposed hypothesis by first\ndetermining protective effects of the HSP27-MVs in hypoxic brain slices, OGD BECs and in isolated brain\nmicrovessels (Aims 1 and 2), conduct a pharmacokinetics study to determine the optimal MV dose that shows\nthe greatest brain uptake (Aim 2b) and we will determine the therapeutic efficacy and mechanistic effects of\nHSP27-MVs in aged MCAo mice in Aim 3. Overall, successful completion of these studies will demonstrate if\nBBB protection via increasing BEC energetics and decreasing BBB permeability improves post-stroke outcomes.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11251234", "metadata": { "project_num": "5R01NS136752-03", "award_amount": 405531, "activity_code": "R01", "organization": "UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON", "principal_investigators": [ { "profile_id": 15600496, "first_name": "Devika", "middle_name": "", "last_name": "Soundara Manickam", "is_contact_pi": true, "full_name": "Devika Soundara Manickam", "title": "ASSOCIATE PROFESSOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11212088", "title": "Neural basis of structure learning for value inference in the orbitofrontal cortex", "summary": "All animals live in structured environments. Learning the statistical structure of the environment can thus offer\nsurvival benefit to animals. Understanding how the brain learns and infers the structure of the environment is\ncritical for elucidating the mechanisms underlying decision-making and adaptive behavior. Reinforcement\nlearning (RL), a framework inspired by psychology and computational theories, has emerged as a powerful tool\nto investigate these processes. Structure learning within RL involves the identification and representation of\nlatent structures, such as task rules and environmental contingencies, to update values more efficiently. Many\nstudies have indicated that brain regions like the orbitofrontal cortex (OFC) are critical for structure learning.\nHowever, the exact neural basis underlying structure learning in those brain regions is still unclear.\nIn this proposal, I will investigate how OFC contributes to structure learning and value inference. The central\nhypothesis is that activity within OFC is critical for value inference, and that structural information of the task is\nstored via synaptic plasticity within OFC. First, I will test the necessity of OFC during a task that requires value\ninference based on structural knowledge of the task. Second, I will simulate a biologically realistic reinforcement\nlearning model that stores structural information within OFC. Third, I perform cell-type specific recording in the\nOFC to validate predictions of the modelling. Completing this proposal will give us a better mechanistic\nunderstanding of structure learning and value inference in the context of reinforcement learning.\nDuring this project, I will receive training in computational modelling and two-photon imaging from experts in the\nfield. Training in these techniques and ways of thinking about structure learning in the brain will allow me to\nsuccessfully complete this proposal and launch my career as an independent investigator.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11212088", "metadata": { "project_num": "1K99MH141710-01", "award_amount": 120582, "activity_code": "K99", "organization": "HARVARD UNIVERSITY", "principal_investigators": [ { "profile_id": 16370119, "first_name": "Jaeeon", "middle_name": "", "last_name": "Lee", "is_contact_pi": true, "full_name": "Jaeeon Lee", "title": "POSTDOC" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" }, { "source": "nih", "source_id": "11169415", "title": "A randomized trial to determine impact, cost and cost effectiveness of pharmacy-based PrEP on PrEP continuation for women at high risk of HIV", "summary": "Globally women continue to be at disproportionally higher risk of HIV than men. In the most affected women groups, HIV prevalence can be as high as 30% to 46.2%. Mathematical models suggest that 40-80% of new infections predicted to occur in African adults by 2035 will be directly or indirectly attributable to unsafe sex with key populations.\n\nIn Zimbabwe and elsewhere in the region, the majority of key populations who initiate PrEP stop taking it within the first few months due to barriers that include burden and cost of clinic visits. To address PrEP barriers, we conducted a pilot study of a pharmacy-based PrEP distribution strategy to increase participants’ motivation, access, and effective use of PrEP. The intervention, Together Optimizing Pharmacy PrEP Access in Zimbabwe (TOPAZ), was co-developed with key populations in their gender diversity, pharmacists, and Zimbabwe Ministry of Health and is embedded within the Zimbabwe National Key Populations (KP) Program. In TOPAZ, women at high risk of HIV (n=100) starting PrEP in one of four suburbs in Harare can opt to collect refills from community pharmacies or from KP program clinics. Pharmacy collection is bundled with short-term incentives aimed at habit formation and fostering relationships between participants and pharmacists. The pilot study showed that TOPAZ is highly acceptable among pharmacists and participants, with very promising indications of effectiveness when compared to standard services; thus, a trial to determine effectiveness is now warranted. However, in the pilot, we were unable to determine how much of the impact can be attributed to pharmacy collection alone versus the incentives, and we have opportunity to explore that unanswered question in the proposed study.\n\nWe propose to conduct a 3-arm, Hybrid Type 2 Effectiveness-Implementation individually randomized trial in 600 sex workers at four clinics, to determine the effectiveness of the TOPAZ intervention on PrEP persistence and compare TOPAZ to pharmacy-based refill collection without incentives (Aim 1). Intervention cost and cost effectiveness is important for scale-up, hence we will determine the cost of intervention implementation and access and use mathematical modelling to determine cost effectiveness under different scenarios (e.g., targeted injectable PrEP) over 20-50 year time horizons (Aim 2). Finally, given the growing importance of injectable PrEP, we will conduct policy-maker focused implementation research to co-create an action plan for roll out of pharmacy-based injectable PrEP (Aim 3). This is an important study that will provide evidence to inform scale-up and sustainability of pharmacy-based PrEP, including paving a way for policy and practice for pharmacy-based injectable PrEP. We are conducting the study in Zimbabwe because of efficiency gains in a setting with high HIV prevalence, where we will leverage the unique resources offered by the KP Program which we have run since 2009. Our findings will inform strategies to improve the lives of women in the US and across the globe.", "published_date": "2026-09-04", "url": "https://reporter.nih.gov/project-details/11169415", "metadata": { "project_num": "1R01MH140751-01", "award_amount": 504476, "activity_code": "R01", "organization": "CENTRE/SEXUAL HLTH/HIV AID RES/ZIMBABWE", "principal_investigators": [ { "profile_id": 79892757, "first_name": "Loveleen", "middle_name": "", "last_name": "Bansi-Matharu", "is_contact_pi": false, "full_name": "Loveleen Bansi-Matharu", "title": "" }, { "profile_id": 7017562, "first_name": "FRANCES", "middle_name": "MARY", "last_name": "COWAN", "is_contact_pi": false, "full_name": "FRANCES MARY COWAN", "title": "" }, { "profile_id": 79885670, "first_name": "Valentina", "middle_name": "", "last_name": "Cambiano", "is_contact_pi": false, "full_name": "Valentina Cambiano", "title": "" }, { "profile_id": 79901232, "first_name": "Andrew", "middle_name": "", "last_name": "Copas", "is_contact_pi": false, "full_name": "Andrew Copas", "title": "" }, { "profile_id": 11367710, "first_name": "Euphemia", "middle_name": "Lindelwe", "last_name": "Sibanda", "is_contact_pi": true, "full_name": "Euphemia Lindelwe Sibanda", "title": "DEPUTY EXECUTIVE DIRECTOR" } ] }, "fetched_at": "2026-09-09T03:02:20.233Z" } ], "next_cursor": null }