A5008665039- Esophageal Cancer Research and Treatment
- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Screening and Detection
- Pancreatic and Hepatic Oncology Research
- Cell Adhesion Molecules Research
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- Inflammatory mediators and NSAID effects
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Advanced Biosensing Techniques and Applications
- Renal and related cancers
- Immune Cell Function and Interaction
- Renal cell carcinoma treatment
- Salivary Gland Tumors Diagnosis and Treatment
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- Acute Lymphoblastic Leukemia research
- Cancer-related Molecular Pathways
- Neuroblastoma Research and Treatments
- Molecular Biology Techniques and Applications
The University of Texas MD Anderson Cancer Center
2016-2025
Scripps MD Anderson Cancer Center
2020-2024
Leukemia Research Foundation
2013-2023
Anderson University - South Carolina
2023
University of Michigan–Ann Arbor
2021
Roche (United States)
2021
Duke Medical Center
2021
Center for Devices and Radiological Health
2021
United States Food and Drug Administration
2021
Office of Science
2021
Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, phase 2 trials are ongoing glioblastoma (GBM). Previous reports have suggested that responses more frequent patients with tumors express PD-L1; however, this been disputed. At issue is validation PD-L1 biomarker assays prognostic impact. Using immunohistochemical analysis, we measured incidence expression 94 GBM. We...
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with an immunosuppressive microenvironment that is resistant to most therapies. IL17 involved in pancreatic tumorigenesis, but its role invasive PDAC undetermined. We hypothesized triggers and sustains immunosuppression. inhibited IL17/IL17RA signaling using pharmacological genetic strategies alongside mass cytometry multiplex immunofluorescence techniques. uncovered recruits neutrophils, neutrophil extracellular traps...
Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) induce immunosuppression. report that GSC-derived (GDEs) have predilection for monocytes, precursor macrophages. The GDEs traverse monocyte cytoplasm, cause reorganization actin cytoskeleton, skew monocytes toward suppresive M2 phenotype, programmed...
Exosome cargoes are highly varied and include proteins, small RNAs, genomic DNA (gDNA). The presence of gDNA suggests that different intracellular compartments contribute to exosome loading, resulting in distinct subpopulations. However, the loading other nuclear contents into exosomes (nExo) remains poorly understood. Here, we identify relationship between cancer cell micronuclei (MN), which markers instability, nExo formation. Imaging flow cytometry analyses reveal 10% derived from cells...
Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all deaths. Nevertheless, 15% patients diagnosed with advanced HGSC survive more than 10 years. The elucidation predictive markers these long-term survivors (LTS) could help identify therapeutic targets the disease, and thus improve patient survival rates. To investigate stromal heterogeneity tumor microenvironment (TME) in cancer, we used spatial transcriptomics to generate spatially resolved...
Abstract Inactivating TP53 mutations leads to a loss of function p53, but can also often result in oncogenic gain-of-function (GOF) mutant p53 (mutp53) proteins which promotes tumor development and progression. The GOF activities are well documented, the mechanisms involved remain poorly understood. Here, we study mutp53 interactome find that by targeting minichromosome maintenance complex components (MCMs), predisposes cells replication stress chromosomal instability (CIN), leading...
Natural killer (NK) cells are important mediators of anti-tumor immunity and active against several hematologic malignancies, including multiple myeloma (MM). Umbilical cord blood (CB) is a promising source allogeneic NK but large scale ex vivo expansion required for generation clinically relevant CB-derived (CB-NK) cell doses. Here we describe novel strategy expanding from cryopreserved CB units using artificial antigen presenting feeder (aAPC) in gas permeable culture system. After 14...
Understanding the unique phenotypes and complex signaling pathways of leukemia stem cells (LSCs) will provide insights druggable targets that can be used to eradicate acute myeloid (AML). Current work on AML LSCs is limited by number parameters conventional flow cytometry (FCM) analyze because cell autofluorescence fluorescent dye spectral overlap. Single-cell mass (CyTOF) substitutes rare earth elements for fluorophores label antibodies, which allows measurements up 120 in single without...
The pathogenesis of acute myeloid leukemia (AML) involves serial acquisition mutations controlling several cellular processes, requiring combination therapies affecting key downstream survival nodes in order to treat the disease effectively. BCL2 selective inhibitor venetoclax has potent anti-leukemia efficacy; however, resistance can occur due its inability inhibit MCL1, which is stabilized by MAPK pathway. In this study, we aimed determine efficacy concomitant targeting and pathways MEK1/2...
The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC), which is the most lethal gynecologic malignancy, not well understood. Here, we perform comprehensive multi-platform omics analyses, including integrated analysis, immune monitoring on primary metastatic sites from highly clinically annotated HGSC samples based a laparoscopic triage algorithm patients who underwent complete gross resection (R0) or received neoadjuvant chemotherapy (NACT) with excellent poor...
Pancreatic ductal adenocarcinoma (PDAC) is therapeutically recalcitrant and metastatic. Partial epithelial to mesenchymal transition (EMT) associated with metastasis; however, a causal connection needs further unraveling. Here, we use single-cell RNA sequencing genetic mouse models identify the functional roles of partial EMT stabilization in PDAC growth metastasis. A global expression signature identifies ∼50 cancer cell clusters spanning epithelial-mesenchymal continuum both human murine...
Vaccination against COVID-19 is critical for immuno-compromised individuals, including patients with cancer. Systemic reactogenicity, a manifestation of the innate immune response to vaccines, occurs in up 69% following vaccination RNA-based vaccines. Tumor regression can occur an intense immune-inflammatory and novel strategies treat cancer rely on manipulating host system. Here, we report spontaneous metastatic salivary gland myoepithelial carcinoma patient who experienced grade 3 systemic...
Abstract Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. CD74 (sCD74) has been identified sera inflammatory diseases and implicated their pathophysiology; however, few relevant data are available the context cancer. Here we assessed composition production mechanisms, as well clinical significance biological properties, sCD74 melanoma. Serum levels were significantly elevated advanced melanoma patients compared with normal healthy donors, high...
Inflammatory breast cancer (IBC), the most aggressive subtype, is driven by an immunosuppressive tumor microenvironment (TME). Current treatments for IBC have limited efficacy. In a clinical trial (NCT01036087), anti-EGFR antibody combined with neoadjuvant chemotherapy produced highest pathological complete response rate ever reported in patients having triple-negative receptor status. We determined molecular and immunological mechanisms behind this superior outcome. Using novel humanized...
Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are bona fide precursor lesions pancreatic ductal adenocarcinoma (PDAC). The most common subtype IPMNs harbors a gastric foveolar-type epithelium, and these low-grade harbingers with high-grade dysplasia cancer. molecular underpinning differentiation in is unknown, although identifying drivers this indolent phenotype might enable opportunities for intercepting progression to IPMN We conducted spatial transcriptomics on cohort...
Abstract Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated sera of most newly diagnosed acute myeloid leukemia (AML) patients, complex interplay AML remains insufficiently understood. We aim to characterize these interactions through comprehensive bulk single-cell approaches bone marrow patients. identify monocytic as having unique microenvironment characterized by...
Most platforms used for the molecular reconstruction of tumor–immune microenvironment (TIME) a solid tumor fail to explore spatial context three-dimensional (3D) space at single-cell resolution, and thus lack information about cell–cell or cell–extracellular matrix (ECM) interactions. To address this issue, pipeline which integrated multiplex spatially resolved multi-omics was developed identify crosstalk signaling networks among various cell types ECM in 3D TIME two FFPE (formalin-fixed...
Abstract Purpose: Wnt/β-catenin signaling is required for leukemic stem cell function. FLT3 mutations are frequently observed in acute myeloid leukemia (AML). Anomalous increases β-catenin nuclear localization and transcriptional activity. tyrosine kinase inhibitors (TKI) used clinically to treat FLT3-mutated AML patients, but with limited efficacy. We investigated the antileukemia activity of combined inhibition FLT3-mutant AML. Experimental Design: was inhibited by β-catenin/CBP antagonist...