About

Marygorret Obonyo is an Associate Professor of Medicine at UC San Diego, specializing in gastric cancer research. Her work focuses on understanding the pathways and genes involved in Helicobacter-associated gastric cancer progression, with particular attention to the role of the immune microenvironment and inflammatory responses. She has contributed to the development of novel animal models to study gastric cancer, including murine models for Helicobacter-induced disease, and has investigated targeted therapies such as fluorescent antibodies for cancer detection and treatment. Her research also explores the molecular mechanisms underlying gastric carcinogenesis, including the TRIF-IFN-I pathway, MyD88-dependent mechanisms, and the impact of bacterial factors on host cell survival. She has been involved in projects examining the microbiome's contribution to gastric cancer, the immune response in gastric lesions, and innovative drug delivery systems against Helicobacter pylori infection. Her work aims to translate these findings into improved diagnostic and therapeutic strategies for gastric cancer.

Selected publications

• ASO Visual Abstract: Bright and Specific Targeting of Metastatic Lymph Nodes in Orthotopic Mouse Models of Gastric Cancer with a Fluorescent Anti-CEA Antibody

  Annals of Surgical Oncology · 2025-03-10

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• Repurposing Carfilzomib as a Promising Drug for Targeted Therapy in Gastric Cancer

  Cancers · 2025-10-24

  articleOpen accessSenior authorCorresponding

  Background/Objectives: Identifying novel targets to treat gastric cancer (GC) has become a focus of research in recent years. Our accelerated Helicobacter-induced gastric cancer mouse model allowed us to identify several differentially expressed genes (DEGs), including Psmb8 (proteasome subunit beta type 8, also called Lmp7), which was also found to be elevated in GC patient samples. PSMB8 encodes one of the immune subunits of the immunoproteasome, which has been associated with disease severity in multiple cancers. Methods: We identified carfilzomib from a public database as a potential drug targeting PSMB8; it effectively halts immunoproteasome activity, leading to apoptosis. We tested carfilzomib’s efficacy against gastric cancer by subcutaneously implanting nude mice with human gastric epithelial-derived tumors and treating them with carfilzomib, either alone or in combination with 5-fluorouracil (5-FU), a standard-of-care drug. The effectiveness of drug treatment was measured by tumor growth, cell proliferation, and apoptosis. Results: We observed that carfilzomib retarded tumor growth, inhibited cell proliferation, and induced apoptosis. Conclusions: These results strongly suggest that PSMB8 is a suitable candidate for targeted therapy. Moreover, with carfilzomib having robust anti-tumor activity, it has potential as a treatment option for cancers where high levels of PSMB8 are associated with poor overall survival.

  PublisherDOI

• Bright and Specific Targeting of Metastatic Lymph Nodes in Orthotopic Mouse Models of Gastric Cancer with a Fluorescent Anti-CEA Antibody

  Annals of Surgical Oncology · 2025-01-29 · 2 citations

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• A new locoregional mouse model of gastric cancer for identifying probes for fluorescence guided surgery

  Surgery · 2025-03-04 · 4 citations

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• Gastric cancer treatment target identified from an accelerated Helicobacter-induced gastric cancer mouse model

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-20

  preprintSenior authorCorresponding

  ABSTRACT Helicobacter pylori ( H. pylori ) infection and consequent inflammation leads to gastric cancer (GC). Despite the prevalence of this bacterium and availability of genomic data, targeted therapies for GC are still early in development. Previously in our accelerated Helicobacter -induced gastric cancer mouse model we identified several differentially expressed genes (DEGs), including PSMB8 (proteasome subunit beta type 8, also called LMP7); one of the immune subunits of the immunoproteasome, which has been associated with disease severity in multiple cancers. We observed elevated expression of PSMB8 in our accelerated gastric cancer model, in the human gastric cancer cell line (MKN45), and in gastric cancer patient samples. Moreover, we identified carfilzomib as a potential drug that targets PSMB8. Therefore, to test its efficacy against gastric cancer, nude mice were subcutaneously implanted with MKN45 derived tumors and treated with carfilzomib, alone or in combination with 5-fluorouracil (5-FU), the standard care drug. The effectiveness of drug treatment was measured by tumor growth, cell proliferation, and apoptosis. We observed that carfilzomib retarded tumor growth, inhibited cell proliferation and induced apoptosis. These results strongly suggest that carfilzomib has a robust anti-tumor activity and is a suitable drug candidate for targeted therapy in gastric cancer.

  PublisherDOI

• Tu1219: PROGRESSION TOWARDS GASTRIC ADENOCARCINOMA IS HINDERED IN THE ABSENCE OF TYPE I INTERFERON SIGNALING

  Gastroenterology · 2025-05-01

  articleSenior author
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• Protocol to establish an accelerated murine model for Helicobacter-induced gastric cancer

  STAR Protocols · 2024-09-01 · 2 citations

  articleOpen accessSenior authorCorresponding

  Helicobacter -induced gastric cancer progresses very slowly, even in animal models, making it difficult to study. Here, we present a protocol to establish an accelerated murine model for Helicobacter -induced gastric cancer. We describe steps for infecting mice with Helicobacter felis , harvesting gastric tissue, assessing disease severity by histopathologic scoring, and performing gene expression studies with RT-qPCR and RNA sequencing. The accelerated model shows rapid progression of the disease, with gastric precancerous lesions developing within 6 months post-infection with Helicobacter . For complete details on the use and execution of this protocol, please refer to Bali et al. 1 • Protocol for developing an accelerated gastric cancer model • Steps for performing mouse infections, tissue harvesting, and histology • Details for performing cDNA synthesis and RT-qPCR • Instructions for performing RNA sequencing and pathway enrichment Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Helicobacter -induced gastric cancer progresses very slowly, even in animal models, making it difficult to study. Here, we present a protocol to establish an accelerated murine model for Helicobacter -induced gastric cancer. We describe steps for infecting mice with Helicobacter felis , harvesting gastric tissue, assessing disease severity by histopathologic scoring, and performing gene expression studies with real-time RT-PCR and RNA sequencing. The accelerated model shows rapid progression of the disease, with gastric precancerous lesions developing within 6 months post-infection with Helicobacter .

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• ASO Visual Abstract: Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

  Annals of Surgical Oncology · 2024-07-16

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• Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

  Annals of Surgical Oncology · 2024-06-18 · 10 citations

  articleOpen access

  BACKGROUND: Gastric cancer poses a major diagnostic and therapeutic challenge as surgical resection provides the only opportunity for a cure. Specific labeling of gastric cancer could distinguish resectable and nonresectable disease and facilitate an R0 resection, which could improve survival. METHODS: Two patient-derived gastric cancer lines, KG8 and KG10, were established from surgical specimens of two patients who underwent gastrectomy for gastric adenocarcinoma. Harvested tumor fragments were implanted into the greater curvature of the stomach to establish patient-derived orthotopic xenograft (PDOX) models. M5A (humanized anti-CEA antibody) or IgG control antibodies were conjugated with the near-infrared dye IRDye800CW. Mice received 50 µg of M5A-IR800 or 50 µg of IgG-IR800 intravenously and were imaged after 72 hr. Fluorescence imaging was performed by using the LI-COR Pearl Imaging System. A tumor-to-background ratio (TBR) was calculated by dividing the mean fluorescence intensity of the tumor versus adjacent stomach tissue. RESULTS: M5A-IR800 administration resulted in bright labeling of both KG8 and K10 tumors. In the KG8 PDOX models, the TBR for M5A-IR800 was 5.85 (SE ± 1.64) compared with IgG-IR800 at 0.70 (SE ± 0.17). The K10 PDOX models had a TBR of 3.71 (SE ± 0.73) for M5A-IR800 compared with 0.66 (SE ± 0.12) for IgG-IR800. CONCLUSIONS: Humanized anti-CEA (M5A) antibodies conjugated to fluorescent dyes provide bright and specific labeling of gastric cancer PDOX models. This tumor-specific fluorescent antibody is a promising potential clinical tool to detect the extent of disease for the determination of resectability as well as to visualize tumor margins during gastric cancer resection.

  PublisherOA PDFDOI

• TRIF-IFN-I pathway in Helicobacter-induced gastric cancer in an accelerated murine disease model and patient biopsies

  iScience · 2024-03-08 · 7 citations

  articleOpen accessSenior author

  -infected patients and thus enable treatment prioritization of patients.

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