A5039098508- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Brain Metastases and Treatment
- Epigenetics and DNA Methylation
- Ocular Oncology and Treatments
- Cardiac tumors and thrombi
- Renal cell carcinoma treatment
- Extracellular vesicles in disease
- Radiomics and Machine Learning in Medical Imaging
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Tissue Engineering and Regenerative Medicine
- Nanoplatforms for cancer theranostics
- Immunotherapy and Immune Responses
- Cardiac Fibrosis and Remodeling
Michigan State University
2025
University of California, Los Angeles
2019-2023
UCLA Medical Center
2023
UCLA Health
2018-2022
ORCID
2021
Primary brain tumors, such as glioblastoma (GBM), are remarkably resistant to immunotherapy, even though pre-clinical models suggest effectiveness. To understand this better in patients, here we take advantage of our recent neoadjuvant treatment paradigm map the infiltrating immune cell landscape GBM and how is altered following PD-1 checkpoint blockade using high dimensional proteomics, single transcriptomics, quantitative multiplex immunofluorescence. Neoadjuvant increases T infiltration...
Abstract Loss of function the von Hippel-Lindau (VHL) tumor suppressor gene is a hallmark clear cell renal carcinoma (ccRCC). The importance heterogeneity in loss this has been under reported. To study impact intratumoral VHL observed human ccRCC, we engineered deletion four RCC models, including new primary line derived from an aggressive metastatic case. gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and exhibited increased motility but diminished...
In comparison with responses in recurrent glioblastoma (rGBM), the intracranial response of brain metastases (BrM) to immune checkpoint blockade (ICB) is less well studied. Here, we present an integrated single-cell RNA-Seq (scRNA-Seq) study 19 ICB-naive and 9 ICB-treated BrM samples from our own published data sets. We compared them previously scRNA-Seq rGBM found that ICB led more prominent T cell infiltration into than rGBM. These BrM-infiltrating cells exhibited a tumor-specific...
Abstract Primary brain tumors, such as glioblastoma (GBM), have been remarkably resistant to immunotherapy, even though pre-clinical models suggest effectiveness. To understand this better in patients, we took advantage of our recent neoadjuvant treatment paradigm map the infiltrating immune cell landscape GBM and how is altered following PD-1 checkpoint blockade using high dimensional proteomics, single transcriptomics, quantitative multiplex immunofluorescence. Neoadjuvant increased T...
The use of anti-PD-1 therapy, pembrolizumab, has shown minimal therapeutic effect as an adjuvant treatment in glioblastoma, but its efficacy a neoadjuvant recurrent glioblastoma setting yet to be established. Ivy Foundation Early Phase Clinical Trials’ Consortium conducted randomized, multi-institution I clinical trial evaluate the immune response and survival following therapy with pembrolizumab thirty patients recurrent, surgically resectable glioblastoma. Formalin-fixed paraffin embedded...
Abstract Background: The brain metastatic niche has been historically difficult to study and thus poorly understood. Although metastases portend high morbidity mortality, increasing evidence shown that immune checkpoint blockade (ICB) can confer long-lasting responses in patients. How ICB remodels the tumor microenvironment is still relatively unknown. Here, we examine of resected a cohort 19 patients pre-operatively treated with without using single-cell methods. Methods: Tumor tissue was...
Abstract BACKGROUND Current treatment modalities, including surgical resection, radiosurgery and immune checkpoint inhibitors, have improved local control rates of brain metastases, but overall prognosis is still poor. AIM: To investigate the microenvironment in metastases for better understanding failures. METHODS We identified 42 patients with melanoma (M), breast (B) lung (L) performed multiplex immunofluorescent staining markers (CD4, CD8, CD45, PD1, PD-L1) quantitative analysis HALO...
Abstract INTRODUCTION Neoadjuvant anti-PD1 therapy (neo-aPD1) was previously shown to significantly increase the survival of recurrent glioblastoma patients in a small randomized clinical trial. However, neo-aPD1 alone not curative so defining limitations and discovering where other immunotherapies can be used alongside is needed. METHODS To understand how immune cells tumor microenvironment change with neo-aPD1, we single-cell RNAsequencing analyze from 27 glioma (n = 105,143 cells) which 9...
Abstract Brain tumors reside in a modified microenvironment where inflammatory processes are heavily regulated. Nevertheless, our recent study showed significant immune infiltration recurrent glioblastoma (rGBM) treated with neoadjuvant PD-1 checkpoint blockade therapy. In comparison to GBM, the intracranial response of brain metastases (BrM) immunotherapy has been less well studied. To test this question, we investigated effect pre-surgical (ICB) on compartments BrM, using multiplex...
Abstract To study the impact of intratumoral VHL heterogeneity observed in patient ccRCC primary tumors, we engineered gene deletion three RCC models, including a new tumor cell line derived from an aggressive metastatic ccRCC. The gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and showed diminished proliferation tumorigenicity compared to parental, VHL-expressing (VHL+) cells. Renal tumors with either VHL+ or VHL-KO alone exhibit minimal potential....
Abstract In a small phase I clinical trial, neoadjuvant anti-PD-1 (neo-aPD1) improved survival in glioblastoma patients (GBM) and was associated with increased interferon-γ-related gene expression an decrease cell cycle-related the tumor. Despite this, neo-aPD1 not curative. To better understand how alters GBM tumor microenvironment to discover new therapeutic axes, we used CyTOF single-cell RNAsequencing analyze tumor-infiltrating immune populations of 70 patients, 20 whom had received...