A5008807217- Glioma Diagnosis and Treatment
- Medical Imaging and Pathology Studies
- Immune cells in cancer
- Brain Metastases and Treatment
- Meningioma and schwannoma management
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- CAR-T cell therapy research
- interferon and immune responses
- Nanoplatforms for cancer theranostics
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Cancer Research and Treatments
- Signaling Pathways in Disease
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Ocular Oncology and Treatments
Northwestern University
2021-2025
Neurological Surgery
2021-2025
Midwestern University
2025
Amiri Hospital
2025
Northwestern Medicine
2021-2024
Northwestern University
2024
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2023-2024
Manchester Academic Health Science Centre
2023
University of Manchester
2023
Saint Joseph University
2022
Aim: To ascertain the maximum tolerated dose (MTD)/maximum feasible (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. Patients & methods: In a first-in-human open-label, single-center, single-arm 3 + design Phase I clinical trial, eight patients were treated with until disease progression or unacceptable toxicities. Results: absence significant toxicity, MFD was identified to be 8 mg/kg. The most common adverse event grade 1 nausea diarrhea in 50% No...
Neutrophil (PMN) mobilization to sites of insult is critical for host defense and requires transendothelial migration (TEM). TEM involves several well-studied sequential adhesive interactions with vascular endothelial cells (ECs); however, what initiates or terminates this process not well-understood. Here we describe believe be a new mechanism where vessel associated macrophages (VAMs) through localized primed EC responses form ICAM-1 "hot spots", support PMN TEM. Using real-time intravital...
Abstract Sequential multiplex methodologies such as Akoya CODEX, Miltenyi MACSima, Rarecyte Orion, and others require modification of the antibodies by conjugation to an oligo or a specific fluorophore which means use off-the-shelf reagents is not possible. Modifications these are typically performed via reduction chemistry thus verification validation post-modification. Fixed panels therefore developed due various limitations including spectral overlap that creates unmixing issues, steric...
Abstract Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas limited to surgery and radiotherapy, systemic therapies remain ineffective or experimental. Resistance radiotherapy is in high-grade cell types signaling mechanisms that drive meningioma tumorigenesis resistance incompletely understood. Here, we report NOTCH3 drives find perivascular NOTCH3+ stem cells conserved across from humans, dogs, mice. Integrating single-cell transcriptomics...
STING agonists can reprogram the tumor microenvironment to induce immunological clearance within central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and Ivy Glioblastoma Atlas, expression was found in myeloid populations perivascular space. The agonist 8803 increased median survival multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% mice were cured. Ex vivo flow cytometry profiling during...
Abstract Background Glioblastoma is a highly aggressive brain cancer that resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in “cold” and immunotherapy-refractory cancers. Methods We evaluated the efficacy immune microenvironment phenotype of mouse analogue FcE-aCTLA-4 treatment-refractory preclinical models glioblastoma, both as monotherapy combination with doxorubicin delivered via low-intensity...
Activation of STING (
Understanding the spatial relationship and functional interaction of immune cells in glioblastoma (GBM) is critical for developing new therapeutics that overcome highly immunosuppressive tumor microenvironment. Our study showed B T form clusters within GBM microenvironment a 15-μm radius, suggesting could synapses GBM. However, GBM-infiltrating suppress activation CD8 + cells. To this immunosuppression, we leveraged B-cell functions by activating them with CD40 agonism, IFNγ, BAFF to...
Abstract Glioblastoma (GBM) remains a formidable challenge in neuro-oncology, characterized by heterogeneity and aggressive tumor growth. The identification of novel biomarkers therapeutic targets is crucial for advancing promising therapies. This study profiled patient-derived samples utilizing single-cell RNA sequencing proteomics platforms to uncover the upregulation glycoprotein non-metastatic melanoma protein B (GPNMB) cells, particularly post-treatment recurrent as well...
The glioblastoma tumor immune microenvironment (TIME) is an immunosuppressive barrier to therapy that encumbers responses checkpoint inhibition (ICI). Immunosuppressive cytokines, pro-tumor myeloid cells, and exhausted T-cells are hallmarks of the TIME. Here we integrate spatial single-cell analyses patient-matched human samples before after ICI with genetic, immunologic, single-cell, pharmacologic studies in preclinical models reveal interleukin-6 (IL-6) reprograms TIME sensitize mouse...
We report a case of Behçet syndrome in young male who presented with fever, oral and genital ulcerations weight loss. Investigations revealed elevated inflammatory markers extensive venous thrombosis the renal vein, inferior vena cava segmental subsegmental pulmonary embolisms. He was found to have an intracardiac thrombus right atrium nodules. diagnosed treated corticosteroids, azathioprine colchicine. underwent atrial extirpative surgery, he had patent foramen ovale, which closed....
Abstract Glioblastoma (GBM) is most common and aggressive primary brain tumor in adults, for which standard of care hasn’t changed twenty years. GBM associated macrophages (TAMCs), consisting infiltrating myeloid cells from the periphery resident microglia cells, are pro-tumorigenic, promoting growth. Fructose one abundant metabolites microenvironment (TME), as well healthy central nervous system (CNS). In CNS GBM, predominant expressors fructose transporter GLUT5. Mice lacking GLUT5...
Abstract Hedgehog signaling mediates embryologic development of the central nervous system and other tissues is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, most common primary brain tumor, exhibit activation in 6.5% cases, triggered recurrent mutations pathway mediators such as SMO . In this study, we find 35.6% meningiomas that lack previously known drivers acquired various types somatic structural variations affecting chromosomes 2q35...
Although myeloid-derived immune cells can be dispersed throughout the tumor microenvironment (TME), anti-tumor effector are confined to perivascular space. Here, we present a protocol quantify cell distribution from vasculature its glioma on sequential immunofluorescence multiplex images. We describe steps for staining, image generation, and storage. then detail procedures tissue, vessel, nuclei segmentation; phenotyping; data extraction; training using RStudio Spyder.
Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy harness potential immune system against cells. Our previous data showed that Bvax (B-cell-based vaccine) can induce responses in preclinical models GBM. In this study, we aim characterize antigenic reactivity BVax-derived antibodies evaluate their potential. We...
Tumor-associated macrophages and microglia (TAMs) are critical for tumor progression therapy resistance in glioblastoma (GBM), a type of incurable brain cancer. We previously identified lysyl oxidase (LOX) olfactomedin like-3 (OLFML3) as essential macrophage chemokines, respectively, GBM. Here, single-cell transcriptomics multiplex sequential immunofluorescence followed by functional studies demonstrate that negatively correlate with the GBM microenvironment. LOX inhibition PTEN-deficient...
BACKGROUND. Immune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not tumor microenvironment (TME), or analyzed via biopsies.
Meningiomas are the most common primary intracranial tumors