Contact

  • Academic
    gnageeb@stanford.edu
    University - Student Department: School of Medicine Position: Graduate, Medicine

All Publications

  • SPP1-driven immunometabolic reprogramming of tumor-associated neutrophils in glioblastoma Abikenari, M., Choi, J., Medikonda, R., Kim, L., Verma, R., Liu, J., Sjoholm, A., Nageeb, G., Bergsneider, B., Wu, C., Cho, K., Tran, A., Bakalov, D., Banu, M., Lim, M. AMER ASSOC CANCER RESEARCH. 2026

    View details for DOI 10.1158/1538-7445.AM2026-3879

    View details for Web of Science ID 001734050100001

  • Biphasic, time-dependent neutrophil biology in glioblastoma revealed by <i>in vivo</i> survival and flow cytometry with single-cell transcriptomic corroboration Abikenari, M., Choi, J., Liu, J., Sjoholm, A., Nageeb, G., Poe, J., Hwa-Lin Bergsneider, B., Tran, A., Bakalov, D., Medikonda, R., Kim, L., Verma, R., Wu, C., Cho, K., Banu, M., Lim, M. AMER ASSOC CANCER RESEARCH. 2026

    View details for DOI 10.1158/1538-7445.AM2026-170

    View details for Web of Science ID 001734193700022

  • Next-generation immunotherapy biologics for glioblastoma. Frontiers in immunology Schonfeld, E., Sjoholm, A., Ha, J., Liu, J., Nageeb, G., Annagiri, S., Kim, L., Choi, J., Lim, M. 2026; 17: 1775093

    Abstract

    Glioblastoma (GBM) remains largely resistant to immunotherapy despite the success of immune checkpoint inhibitors in other solid tumors. Phase III trials have not demonstrated survival benefit for anti-PD-1 monotherapy, likely reflecting the GBM tumor microenvironment's profound myeloid-driven immunosuppression, low neoantigen burden, intratumoral heterogeneity, and adaptive resistance. These challenges have driven the development of next-generation immunotherapy biologics designed to reprogram the tumor microenvironment and overcome the innate and adaptive resistance of GBM. This review synthesizes advances in immunotherapy biologics including immune checkpoint combinations, cytokine and immunomodulatory proteins, adoptive cell therapies, vaccines, and oncolytic viruses, highlighting key preclinical insights and emerging clinical trial results. We conclude that improved tumor subtyping and immune profiling will be crucial to guide combination strategies that may achieve durable clinical benefit in GBM.

    View details for DOI 10.3389/fimmu.2026.1775093

    View details for PubMedID 41929511

    View details for PubMedCentralID PMC13039018

  • Endogenous immune recruitment in glioblastoma CAR T therapy: cytokine, myeloid, and chemokine circuitry. Journal of neuro-oncology Liu, J., Abikenari, M., Annagiri, S., Ha, J. H., Nageeb, G., Sjoholm, M. A., Velazhahan, V., Medikonda, R., Choi, J., Li, G., Lim, M. 2026; 177 (1)

    Abstract

    Glioblastoma (GBM) has remained relatively unresponsive to immunotherapy, with scattered durable responses reported in early CAR T-cell studies, but without clear benefit at the population level. The major challenge for GBM has been its heterogeneous nature with a significantly immunosuppressive microenvironment that is predominantly composed of myeloid cells, inhibiting T-cell infiltration, function, and providing a rapid pathway for adaptive resistance. The focus of this review is to reposition GBM CAR T-cell therapy as a systems-level issue, turning localized CAR T-cell cytotoxicity into sustained control of the disease by engaging endogenous antitumor immunity via cytokine myeloid chemokine networks.We integrated both mechanism- and translation-oriented evidence for how inflammatory mediators derived from CAR T cells (Type I IFNs, IFN-γ, TNF) may license microglia/tumor-associated macrophages for antigen presentation and chemokine secretion, thus recruiting host effector cells and promoting antigen epitope spreading. To place this work within the context of current engineering trends, the current paper undertook a structured meta-synthesis on registry trials for interventional CAR T therapy for GBM using ClinicalTrials.gov. Using a structured advanced search strategy, we searched 91 registry records, found 44 trials for interventional CAR T therapy, and evaluated 23 active trials commenced after January 2020. Trials were classified based on target antigen choice, multi-antigen OR-gated approaches, conditional AND-gated synNotch logic, as well as safety and controllability measures (inducible off-switches).The effectiveness of CAR T cells for GBM is not likely to be actualized by targeting alone and needs to incorporate both killing and productive self-reinforcing endogenous immunity via myeloid licensing and chemokine amplification. Current trials are increasingly integrating this paradigm with a focus on more comprehensive antigens, gated CARs, immune-conjugate payloads, and safety designs amenable to the CNS without major toxicity such as ICANS. Future translation will require a focus on implementing endogenous immune activation as a quantified endpoint (including cytokine and chemokine analysis within CSF) and a simultaneous focus on immune set points that maintain cross-priming and memory without unmasking neuroinflammatory toxicity.

    View details for DOI 10.1007/s11060-026-05497-4

    View details for PubMedID 41820710

    View details for PubMedCentralID 11456825

  • Nexus of IDO1/Kynurenine Pathway to T-Cell Exhaustion: Hypoxia-Induced Tryptophan Metabolism in Glioblastoma. Metabolites Abikenari, M., Nageeb, G., Ha, J. H., Sjoholm, M. A., Liu, J., Bergsneider, B., Valenzuela, J., Poe, J., Bog Cho, K., Verma, R., Wu, C., Sanker, V., Medikonda, R., Kim, L. H., Choi, J., Banu, M. A., Lim, M. 2026; 16 (3)

    Abstract

    Glioblastoma (GBM) is a universally fatal cancer for which the standard of care has remained largely unchanged for the last 20 years. Recent work has demonstrated that most therapeutic trials for GBM fail due to complex mechanisms of immunosuppression mediated by both the innate and adaptive immune systems. Various metabolic alterations in the tumor microenvironment help maintain this local and systemic immunosuppression, of which the axis of hypoxia-driven tryptophan degradation has garnered substantial attention over the last decade. This paper synthesizes a much-needed elucidation of the immunometabolic reshaping of glioma, myeloid, endothelial, and lymphoid cell lineages induced by hypoxia. The current paper critically evaluates the role of IDO1/TDO2-mediated breakdown of tryptophan and the consequent accumulation of kynurenine, a metabolite that triggers GCN2- and AHR-mediated CD8+ T-cell exhaustion and supports regulatory T-cell differentiation and expansion. Furthermore, we propose a synthesis of mechanistic evidence that establishes a role for the Trp-GCN2-ATF4-VEGFA axis in hypoxia-induced immunosuppression, supporting that pro-tumoral metabolic dysregulation is directly linked to angiogenesis. In GBM, hypoxia and tryptophan-kynurenine pathway dysregulation operate as an integrated metabolic circuit that drives widespread immunosuppression. These mechanisms can be captured by a metabolic signature shared across nearly every cell type in the GBM microenvironment. Drawing on recent spatial transcriptomic, metabolomic, and pharmacologic studies, we outline how this metabolic axis shapes disease biology and how it can be targeted to restore effective antitumor immunity.

    View details for DOI 10.3390/metabo16030185

    View details for PubMedID 41893336

    View details for PubMedCentralID PMC13028454

  • Automated Evaluation of Large Language Model Response Concordance with Human Specialist Responses on Physician-to-Physician eConsult Cases. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing Wu, D. J., Haredasht, F. N., Wu, D., Ravi, V., McCoy, L. G., Weng, Y., Chopra, K., Everett, S. S., Nageeb, G., Chen, W., Ma, S. P., Maharaj, S. K., Tran, J., Rosengaus, L., Giang, L., Jee, O., Goh, E., Chen, J. H. 2026; 31: 372-387

    Abstract

    Specialist consults in primary care and inpatient settings typically address complex clinical questions beyond standard guidelines. eConsults have been developed as a way for specialist physicians to review cases asynchronously and provide clinical answers without a formal patient encounter. Meanwhile, large language models (LLMs) have approached human-level performance on structured clinical tasks, but their real-world effectiveness requires evaluation, which is bottlenecked by time-intensive manual physician review. To address this, we evaluate two automated methods: LLM-as-judge and a decompose-thenverify framework that breaks down AI answers into verifiable claims against human eConsult responses. Using 40 real-world physician-to-physician eConsults, we compared AI-generated responses to human answers using both physician raters and automated tools. LLM-as-judge outperformed decompose-then-verify, achieving human-level concordance assessment with F1-score of 0.89 (95% CI: 0.750, 0.960) and Cohen's kappa of 0.75 (95% CI 0.47,0.90) , comparable to physician inter-rater agreement κ = 0.69-0.90 (95% CI 0.43-1.0).

    View details for DOI 10.1142/9789819824755_0026

    View details for PubMedID 41758154

  • When Central Tolerance Fails: Thymic Malignancies at the Intersection of Cancer Immunity and Autoimmunity. Cancers Abikenari, M., Choi, J., Enayati, I., Tucker, A., Bhatnagar, K., Chen, Y., Himic, V., Liu, J., Nageeb, G., Poe, J., Ong, S. J., Sanker, V., Diehl, M., Szeifert, V., Terasaki, A., Prolo, L. M., Engleman, E., Okwan-Duodu, D. 2026; 18 (5)

    Abstract

    Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good's syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk.

    View details for DOI 10.3390/cancers18050747

    View details for PubMedID 41827683

  • Nutritional Interventions in Osteoarthritis: Mechanisms, Clinical Evidence, and Translational Opportunities. Nutrients Patel, M., Betanzos, G., Troka, M., Modi, J., Nageeb, G., Kaye, A. D., Abd-Elsayed, A. 2026; 18 (2)

    Abstract

    Osteoarthritis (OA) is a leading cause of chronic pain worldwide. This is driven by progressive cartilage degradation, inflammation, oxidative stress, and metabolic dysfunction. Current pharmacologic interventions mostly lead to symptomatic relief without actually affecting disease progression. Thus, there is a growing interest in the development of new interventional methods. Our review seeks to synthesize preclinical, translational, and clinical evidence on the impact nutritional methods have on OA management. Whole-diet approaches, such as Mediterranean and plant-based, have been linked to reduced pain, increased physical function, and positive biomarker changes. Bioactive compounds, including curcumin, polyphenols, omega-3 fatty acids, and select herbal extracts, have shown anti-inflammatory, antioxidant, and chondroprotective effects via NF-κB, Nrf2, AMPK, and SIRT1 pathways. This review particularly focuses on plant-derived substances. Emerging nanoparticle technology with regard to advanced delivery systems shows initial promise in nutraceutical pharmacokinetics and tissue targeting. Overall, nutritional interventions are adjunct interventions to OA management. Although these are not full treatment replacements, dietary modifications and targeted nutraceutical strategies with improved delivery systems may lead to more preventive, personalized, and holistic OA management and care.

    View details for DOI 10.3390/nu18020244

    View details for PubMedID 41599857

    View details for PubMedCentralID PMC12844890

  • Risk-stratified management of ankylosing spondylitis-related spinal fractures-a meta-synthesis of contemporary surgical and nonsurgical strategies: a narrative review. Journal of spine surgery (Hong Kong) Abikenari, M. A., Yoo, K. H., Liu, J., Ha, J., Nageeb, G., Jain, B., Park, L., Hani, U., Veeravagu, A. 2025; 11 (4): 1095-1110

    Abstract

    Ankylosing spondylitis (AS) spinal fractures pose unique diagnostic and therapeutic challenges due to the altered biomechanics, rigid ankylosed spine, and risk for extensive neurologic injury. The optimal practice is not established with rising clinical occurrences. This article aims to review the current literature regarding diagnosis, classification, and operative and non-operative treatment paradigms of spinal fractures due to AS in adults and present a cohesive perspective to facilitate evidence-based clinical practice.A narrative systematic review was conducted on the basis of the PubMed database, including English-language papers from January 2000 to May 2025. Keywords included "AS", "spinal fracture", "vertebral trauma", "surgical management", and "neurological outcomes". Studies identified were evaluated based on clinical relevance, level of evidence, and representation of evolving concepts in diagnosis and management.The review discusses the specific biomechanical frailties of the ankylosed spine, recent classification methods like AO Spine and Denis classifications, and recent imaging modalities for diagnosis. It highlights operative decision-making approaches, posterior-only, anterior, and combination, in fracture morphology, neurologic status, and patient comorbidities. It discusses perioperative concerns such as positioning issues, blood loss, and complications like hardware failure and infection. Four summary tables provide insight into imaging preference, surgical interventions, outcomes, and complication profiles.Prompt diagnosis and personalized treatment of AS-related spinal fractures are essential to reducing morbidity and mortality. Emerging literature supports the use of posterior-only methods in selected cases, but highly context-specific surgical choices must remain. The review stresses the importance of prospective studies as a guide to standard treatment protocols and improved outcomes for this difficult patient group.

    View details for DOI 10.21037/jss-25-119

    View details for PubMedID 41509825

    View details for PubMedCentralID PMC12775638

  • Molecular and biophysical remodeling of the blood-brain barrier in glioblastoma: mechanistic drivers of tumor-neurovascular crosstalk FRONTIERS IN PHYSICS Abikenari, M., Sjoholm, M., Liu, J., Nageeb, G., Ha, J. H., Wu, J., Ren, A., Sayadi, J., Lim, J., Cho, K., Verma, R., Medikonda, R., Banu, M., Lim, M. 2025; 13

    View details for DOI 10.3389/fphy.2025.1723329

    View details for Web of Science ID 001651720600001

  • 'Time is brain': Enhancing stroke knowledge and emergency response readiness in seniors HEALTH EDUCATION JOURNAL Sadeghzadeh, S., Adu-Brimpong, J., Abikenari, M. A., Bhatia, A., Harary, P. M., Bhanot, P., Muller, R. K., Escalante, R., Schonfeld, E., Jain, B., Nageeb, G., Wu, A., Hsin, G. S., Vora, N., Dodd, R. L. 2025

    View details for DOI 10.1177/00178969251371488

    View details for Web of Science ID 001586652700001

  • Publicly Available Datasets for Artificial Intelligence in Neurosurgery: A Systematic Review. Journal of clinical medicine Chan, B., Kim, B., Schonfeld, E., Nageeb, G., Pant, A., Sjoholm, A., Medikonda, R., Hani, U., Veeravagu, A. 2025; 14 (16)

    Abstract

    Introduction: The advancement of artificial intelligence (AI) in neurosurgery is dependent on high quality, large, labeled datasets. Labeled neurosurgical datasets are rare, driven by the high expertise required for labeling neurosurgical data. A comprehensive resource overviewing available datasets for AI in neurosurgery is essential to identify areas for potential model building and areas of needed data construction. Methods: We conducted a systematic review according to PRISMA guidelines to identify publicly available neurosurgical datasets suitable for machine learning. A PubMed search on 8 February 2025, yielded 267 articles, of which 86 met inclusion criteria. Each study was reviewed to extract dataset characteristics, model development details, validation status, availability, and citation impact. Results: Among the 86 included studies, 83.7% focused on spine pathology, with tumor (3.5%), vascular (4.7%), and trauma (7.0%) comprising the remaining. The majority of datasets were image-based, particularly X-ray (37.2%), MRI (29.1%), and CT (20.9%). Label types included segmentation (36.0%), diagnosis (26.7%), and detection/localization (20.9%), with only 2.3% including outcome labels. While 97.7% of studies reported training a model, only 22.6% performed external validation, 20.2% shared code, and just 7.1% provided public applications. Accuracy was the most frequently reported performance metric, even for segmentation tasks, where only 60% of studies used the Dice score metric. Studies often lacked task-appropriate evaluation metrics. Conclusions: We conducted a systematic review to capture all publicly accessible datasets that can be applied to build AI models for neurosurgery. Current datasets are heavily skewed towards spine imaging and lack both clinical patient specific and outcomes information. Provided baseline models from these datasets are limited by poor external validation, lack of reproducibility, and reliance on suboptimal evaluation metrics. Future efforts should prioritize developing multi-institutional datasets with outcome labels, validated models, public access, and domain diversity to accelerate the safe and effective integration of AI into neurosurgical care.

    View details for DOI 10.3390/jcm14165674

    View details for PubMedID 40869500