A5024917310- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Microtubule and mitosis dynamics
- Biochemical and Molecular Research
- Advanced Breast Cancer Therapies
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- Neuroblastoma Research and Treatments
- Pancreatitis Pathology and Treatment
- Liver physiology and pathology
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Cancer Immunotherapy and Biomarkers
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- GDF15 and Related Biomarkers
- Immune cells in cancer
- Intraperitoneal and Appendiceal Malignancies
- Clusterin in disease pathology
- Neuroendocrine Tumor Research Advances
University of California, San Diego
2013-2025
Moores Cancer Center
2012-2024
UC San Diego Health System
2024
La Jolla Alcohol Research
2022
AntiCancer (United States)
2010-2012
Institute of Genetics and Developmental Biology
2012
University of Cincinnati Medical Center
2010
Cincinnati Children's Hospital Medical Center
2010
In-Q-Tel
2005
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with low 5-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kγ, key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved responsiveness standard-of-care chemotherapy in animal models PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming macrophages inhibits adaptive...
Mucinous neoplasms of the appendix (MNA) are rare tumors which may progress from benign to malignant disease with an aggressive biological behavior. MNA is often diagnosed after metastasis peritoneal surfaces resulting in mucinous carcinomatosis peritonei (MCP). Genetic alterations poorly characterized due its low incidence, hypo-cellularity MCPs, and a lack relevant pre-clinical models. As such, application targeted therapies this limited those developed for colorectal cancer not based on...
Early biomarkers and effective therapeutic strategies are desperately needed to treat pancreatic ductal adenocarcinoma (PDAC), which has a dismal 5-year patient survival rate. Here, we report that the novel tyrosine kinase PEAK1 is upregulated in human malignancies, including PDACs intraepithelial neoplasia (PanIN). Oncogenic KRas induced PEAK1-dependent amplification loop between Src, PEAK1, ErbB2 drive PDAC tumor growth metastasis vivo. Surprisingly, blockade of expression increased...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with low survival rate. Recently, new drugs that target KRASG12D, common mutation in PDAC, have been developed. We studied one of these compounds, MRTX1133, and found it was specific effective at nanomolar concentrations patient-derived organoid models cell lines harboring KRASG12D mutations. Treatment MRTX1133 upregulated the expression phosphorylation EGFR HER2, indicating inhibition ERBB signaling may potentiate antitumor...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked desmoplasia and drug resistance due, in part, to poor delivery extravascular tumor tissue. Here, we report that carcinoma-associated fibroblasts (CAFs) induce β5 integrin expression cells a TGF-β dependent manner, making them an efficient target for the tumor-penetrating peptide iRGD. The capacity of iRGD deliver conjugated co-injected payloads markedly suppressed when integrins are knocked out cells. Of note,...
The RON receptor tyrosine kinase is overexpressed in premalignant pancreatic intraepithelial neoplasia (PanIN) and the majority of cancers. In cells, an important K-Ras effector ligand can enhance migration/invasion apoptotic resistance. However, pathobiological significance overexpression cancers has yet to be fully established. this study, we demonstrate that signaling mediates a unique transcriptional program conserved between cultured cells derived from murine PanIN or human cancer grown...
The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed and stimulates invasive growth in pancreatic cancer cells, yet the mechanisms that underlie RON-mediated phenotypes remain poorly characterized. To better understand RON function we sought to identify novel interactants using multidimensional protein identification analysis. These studies revealed plectin, a large of spectrin superfamily, be interactant. Plectin multifunctional complexes with integrin-β4 (ITGB4)...
Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid cancers; thus, identifying more effective therapies is a major unmet need. In this study, we characterized super enhancer (SE) landscape human PDAC to identify drivers disease that might be targetable. This analysis revealed MICAL2 as enhancer-associated gene in PDAC, which encodes flavin monooxygenase induces actin depolymerization and indirectly promotes SRF transcription by modulating availability serum...
<p>Supplementary Figures and Tables legends.</p>
<div>Abstract<p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid cancers; thus, identifying more effective therapies is a major unmet need. In this study, we characterized super-enhancer (SE) landscape human PDAC to identify drivers disease that might be targetable. This analysis revealed <i>MICAL2</i> as an SE-associated gene in PDAC, which encodes flavin monooxygenase enzyme induces actin depolymerization and indirectly promotes serum...
<p>Supplementary Figures S1-S8</p>
Abstract Introduction: PDAC, characterized by fibroinflammatory stroma, involves cancer cell-microenvironment interactions driving progression and resistance. ChIP-seq on resected PDAC samples identified MICAL2 as a super-enhancer-associated gene involved in tumor progression. MICAL2, flavin monooxygenase, promotes actin depolymerization SRF transcription. This study evaluates how cells affects the microenvironment via IL1-a/p38 MAP kinase/STAT3 axis. Methods: AsPC-1 KPC-Shcontrol (ShCNT)...
This study used a unique xenogeneic breast cancer model to the effects of tumor cells and neighboring host upon each other in growth metastasis. It exploited species differences between interacting components determine how influenced vice versa. was found that gene expression profiles highly poorly metastatic clones from same human carcinoma changed differentially when were transferred vitro mammary gland. We describe novel sets genes, validated by human-specific probes, which induced 2...
Pancreatic cancer is an aggressive disease associated with a poor 5-year overall survival. Most patients are ineligible for surgery due to late diagnosis and treated primarily chemotherapy very limited success. relatively insensitive multiple factors, including reduced bioavailability of drugs tumor cells. One strategy improve drug efficacy toxicity the development antibody-drug conjugates (ADC), which have now been used successfully treat both solid liquid tumors. Here, we evaluate...
Gastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance emerged a major problem therefore, clinical efficacy of other drugs been investigated. Unfortunately, trials have failed to identify efficacious despite promising in vitro data pathological responses subcutaneous xenografts. We hypothesized that it was feasible develop orthotopic...