A5086983885- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- PI3K/AKT/mTOR signaling in cancer
- Immune cells in cancer
- Microtubule and mitosis dynamics
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Planetary Science and Exploration
- Protein Degradation and Inhibitors
- Lung Cancer Research Studies
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Pharmacogenetics and Drug Metabolism
- Reproductive tract infections research
- Spacecraft and Cryogenic Technologies
- Estrogen and related hormone effects
- Histone Deacetylase Inhibitors Research
- Soil Moisture and Remote Sensing
- S100 Proteins and Annexins
City Of Hope National Medical Center
2020-2025
City of Hope
2021-2024
Beckman Research Institute
2022-2024
Langley Research Center
1993-2021
University of Pittsburgh
2016
Massachusetts Institute of Technology
2016
Amgen (United States)
2014-2016
University of Washington
1989
Traditional in vitro human liver cell culture models lose key hepatic functions such as metabolic activity during short-term culture. Advanced three-dimensional (3D) coculture platforms offer the potential for extended hepatocyte functionality and allow study of more complex biologic interactions, which can improve refine drug safety evaluations. Here, we use a perfusion flow 3D microreactor platform cryopreserved primary hepatocytes Kupffer cells to regulation cytochrome P450 3A4 isoform...
Significance The evolution of peripheral immune cell abundance and signaling over time, as well how these cells interact with the tumor, may impact a cancer patient’s response to therapy. By developing an ecological population model, we provide evidence dynamic predator–prey-like relationship between circulating tumor size in patients that respond immunotherapy. This is not found either are nonresponsive immunotherapy or during chemotherapy. Single-cell RNA sequencing serial blood samples...
Abstract The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection factors driving heterogeneity before and through adaptation to treatment, we profile single-cell RNA-sequencing (scRNA-seq) transcriptomes HGSOC tumors collected longitudinally during therapy. We analyze scRNA-seq data from two independent patient cohorts reveal that driven by three archetypal phenotypes, defined as oncogenic...
Abstract Immune evasion by cancer cells involves reshaping the tumor microenvironment (TME) via communication with non-malignant cells. However, resistance-promoting interactions during treatment remain lesser known. Here we examine composition, communication, and phenotypes of tumor-associated in serial biopsies from stage II III high-risk estrogen receptor positive (ER+ ) breast cancers patients receiving endocrine therapy (letrozole) as single agent or combination ribociclib, a...
CDK4/6 inhibitors such as ribociclib are becoming widely used targeted therapies in hormone-receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. However, cancers can advance due to drug resistance, a problem which tumor heterogeneity and evolution key features.Ribociclib-resistant HR+/HER2- CAMA-1 cancer cells were generated through long-term treatment. Characterization of sensitive resistant performed using RNA sequencing whole exome sequencing....
Previously, we identified three loci affecting HDL-cholesterol levels in a screen for ENU-induced mutations mice and discovered two mutated genes. We sought to identify the third gene further characterize mouse phenotype.We engaged, DNA sequencing, expression profiling, western blotting, lipoprotein characterization, metabolomics assessment, histology electron microscopy tissues.We as Ampd2, liver isoform of AMP Deaminase (Ampd), central component energy purine metabolism pathways. The...
Cancer cell phenotypes evolve during a tumor's treatment. In some cases, tumor cells acquire cancer stem cell-like (CSL) traits such as resistance to chemotherapy and diminished differentiation; therefore, targeting these may be therapeutically beneficial. this study we show that in progressive estrogen receptor positive (ER+) metastatic breast tumors, resistant subclones emerge following have increased CSL abundance. Further, vitro organoid growth of ER+ patient also shows treatment leads...
The mTOR inhibitor, everolimus, is an important clinical management component of metastatic ER+ breast cancer (BC). However, most patients develop resistance and progress on therapy, highlighting the need to discover strategies that increase inhibitor effectiveness. We developed BC cell lines, sensitive or resistant discovered combination treatment ONC201/TIC10 with everolimus inhibited growth in 2D/3D vitro studies. confirmed increased therapeutic response primary patient cells progressing...
NASA’s Artemis program will send astronauts to the lunar surface for extended mission durations throughout 2030s, with a focus on sustainability and extensibility Mars exploration. However, NASA must place more emphasis protecting both crew exploration systems if they hope achieve long-duration surface. It is now reasonable excavation, construction, autonomy technologies significant level of protection that was not viable architectures date. The Lunar Safe Haven (LSH) proposed protect...
Endocrine therapy remains the primary treatment choice for ER+ breast cancers. However, most advanced cancers ultimately develop resistance to endocrine. This acquired endocrine is often driven by activation of PI3K/AKT/mTOR signaling pathway. Everolimus, a drug that targets and inhibits mTOR complex has been shown improve clinical outcomes in metastatic there are no biomarkers currently available guide use everolimus clinic progressive patients, where multiple therapeutic options available....
Abstract Breast cancer is the most common malignancy in women and estrogen receptor positive (ER+) breast cancers represent nearly 75% of all tumors. Everolimus, an mTORC1 inhibitor, combination with exemestane has been approved for patients metastatic ER+ cancer. However, many eventually develop resistance to everolimus leads poor survival outcomes. Characterizing everolimus-resistant cells can reveal targetable molecular phenotypes that lead new therapeutic targets. In this study, we...
Tumor heterogeneity is a significant factor influencing cancer treatment effectiveness and can arise from genetic, epigenetic, phenotypic variations among cells. Understanding how tumor impacts evolution therapy response lead to more effective treatments improved patient outcomes. Traditional bulk genomic approaches fail provide insights into cellular-level events, whereas single-cell RNA sequencing (scRNA-seq) offers transcriptomic analysis at the individual cell level, advancing our...
Abstract Metastatic breast cancers show variable clinical responses due to inherent heterogeneity, both within tumors and among patients. Studies mainly examine molecular diversity across different patients' genetic variance a single tumor. Yet, the variability multiple or metastases in patient remains underexplored. Our study investigates this intrapatient examining cell tumor evolution from source metastatic cancer. In warm procurement trial involving 6 patients with multi-site tumors,...
Chemotherapy remains a commonly used and important treatment option for metastatic breast cancer. A majority of ER+ cancer patients ultimately develop resistance to chemotherapy, resulting in disease progression. We hypothesized that an "evolutionary double-bind", where with one drug improves the response different agent, would improve effectiveness durability responses chemotherapy. This approach exploits vulnerabilities acquired mechanisms. Evolutionary models can be refractory identify...
Abstract Cancer cells evolve, acquire resistance to therapy and change their environment. One mechanism involves altering communication with non-malignant in the tumor microenvironment (TME). By corrupting signals for growth survival, evolving cancer can engineer a pro-tumor TME. However, specific interactions between malignant that predispose drug changes during treatment remain widely unknown. Here we examine composition, communication, phenotypic diversity of tumor-associated cell...
Abstract Background CDK4/6 inhibitors such as ribociclib are becoming widely used targeted therapies in hormone-receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. However, cancers can advance due to drug resistance, a problem which tumor heterogeneity and evolution key features. Methods Ribociclib-resistant HR+/HER2-CAMA-1 cancer cells were generated through long-term treatment. Characterization of sensitive resistant performed using RNA...
Abstract Background Cancer cell phenotypes evolve over the course of a tumor’s treatment. The that emerge and disappear time will be specific to each drug regimen type cancer. Chemotherapy remains one most common effective treatments for metastatic breast cancer patients; however, resistance chemotherapy inevitably emerges. treatment regimens are not designed target emerging chemo-resistance, despite its clear importance in progressive This study focuses on finding sequential strategies...
Abstract The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To uncover phenotypic changes associated with resistance, we profiled single-cell RNA-sequencing (scRNA-seq) transcriptomes HGSOC tumors collected longitudinally during patient treatment. Analysis scRNA-seq data from two independent cohorts revealed that driven by three core archetypal phenotypes, defined as oncogenic tasks describe the majority...