A5051791164- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Esophageal and GI Pathology
- Chemical Reactions and Isotopes
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Esophageal Cancer Research and Treatment
- 3D Printing in Biomedical Research
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Caveolin-1 and cellular processes
- CRISPR and Genetic Engineering
- Mathematical Biology Tumor Growth
- Gastrointestinal Tumor Research and Treatment
Mission Bio (United States)
2025
The University of Texas MD Anderson Cancer Center
2018-2024
The University of Texas Health Science Center at Houston
2019-2024
Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, KRAS mutations accelerate tumor development mouse models. We report that long after its complete resolution, transient inflammatory event primes epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such...
Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Here, studying clonal evolution tumor cells derived from pancreatic tumors, we demonstrate that in vitro cultures vivo are maintained by a common set tumorigenic can be used establish replica (CRTs), large cohorts animals bearing with identical composition. Using CRTs conduct quantitative assessments adaptive responses therapeutics, uncovered multitude...
To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with without goblet cells.Barrett's esophagus is associated increased risk adenocarcinoma (EAC), but appropriate histologic definition Barrett's debated. Intestinal (IM) defined by presence cells whereas nongoblet cell (NGM) lacks cells. Both have been implicated EAC this controversial. Although IM known to harbor changes EAC, little about NGM. We hypothesized that if NGM infer...
Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay clonal lineages dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted replica tumors to trace dynamics unperturbed expansion and dissemination. This model revealed multifaceted nature growth, with rapid changes in fitness leading continuous reshuffling architecture alternating dominance...
Abstract Somatic mutation has been implicated in many aspects of cancer such as susceptibility, diagnosis, prognosis, drug response and tumor progress. Detection somatic is wide interest research. The rapid advances next generation sequencing (NGS) technologies have transformed For example, the Ion AmpliSeq™ technology enables selective amplification 10s to 1000s target sequences a single multiplexed PCR meshes seamlessly with semiconductor platform. Ampliseq™ Comprehensive Cancer Panel...
Abstract Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay clonal lineages dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically-implanted replica tumors to trace dynamics unperturbed expansion and dissemination. This model revealed multifaceted nature growth, with rapid changes in fitness leading continuous reshuffling architecture alternating...
Abstract The lack of suitable experimental approaches to investigate and model functional heterogeneity in vivo has had a profound negative impact on our understanding how affects the response immunotherapy. To bridge this technological gap, we leverage new platform that visualizes spatial architecture subclones microenvironments. study heterogeneous populations cells their clonal dynamics vivo, performed barcode lineage tracing with next-generation sequencing analysis. It allows...
Abstract Tumor evolution and adaptation, especially in response to therapy, are well-established concepts clinical oncology a major causes of treatment failure. The inability current experimental models, including genetically engineered mouse inform on the breadth functional heterogeneity within human tumors has substantially limited our understanding tumor architecture under perturbations such as pharmacologic treatments with profound negative impact cancer drug discovery research, where...
Abstract Tumors are comprised of heterogenous populations tumor cells that rely on both glycolysis and oxidative phosphorylation (OXPHOS) for bioenergy synthetic processes in support cell proliferation. Over the past few years, we others have reported there is a subpopulation tumors resistant to standard care treatment or targeted therapies, these so-called persistent possess stem like properties. Of note, elevated levels mitochondria dependent OXPHOS survival. We previously disclosed...
Abstract Intrinsic and adaptive drug-resistance mechanisms allow human tumors to evade treatment through the demonstrated expansion of treatment-resistant clones. Thus, are complex, dynamic ecosystems wherein populations cells harboring both founder clones unique, subclonal mutations coexist progressively evolve. Modeling this functional heterogeneity can uncover critical contributions distinct tumor cell sub-populations toward identifying rational drug combinations. Here, studying clonal...
Abstract A major barrier to achieving durable remission and definitive cure in oncology patients is the emergence of tumor resistance, a common outcome different disease types independent from therapeutic approach undertaken. Patients with pancreatic ductal adenocarcinoma (PDAC) continue have poor prognosis despite concerted efforts advance new drugs clinic. One reason for this, PDAC other tumors, that tumors are constantly adapting evolving response external perturbations. To better...
Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Modeling the functional heterogeneity can unmask critical contributions distinct tumor cell sub-populations toward identifying rational drug combinations. Here, studying clonal evolution cells derived from pancreatic tumors, we demonstrate that in vitro adherent cultures vivo are maintained by a common set long term self-renewing tumorigenic be used...
Abstract Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Modeling the functional heterogeneity can unmask critical contributions distinct tumor cell sub-populations toward identifying rational drug combinations. Here, studying clonal evolution cells derived from pancreatic tumors, we demonstrate that in vitro adherent cultures vivo are maintained by a common set long term self-renewing tumorigenic be...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an incurable disease characterized by poor survival, dense desmoplastic stroma and activating mutations in KRAS (<90%). These tumors are highly complex ecosystems composed of molecularly distinct sub-populations that exhibit a spectrum genetic features associated phenotypes. Despite recent advances the transcriptomic characterization PDAC into at least two tumor subtypes, this alone has been insufficient to define more specific...