A5023506888- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Advanced Breast Cancer Therapies
- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Mathematical Biology Tumor Growth
- Genomics and Phylogenetic Studies
- Plant and animal studies
- Species Distribution and Climate Change
- Animal Ecology and Behavior Studies
- Ecology and Vegetation Dynamics Studies
- Cell Image Analysis Techniques
- Architecture and Computational Design
- Bioinformatics and Genomic Networks
- Design Education and Practice
- Immunotherapy and Immune Responses
- Ecosystem dynamics and resilience
- Ovarian cancer diagnosis and treatment
- Evolutionary Game Theory and Cooperation
- Immune cells in cancer
- Estrogen and related hormone effects
- Evolution and Genetic Dynamics
- Cancer-related molecular mechanisms research
- Lung Cancer Research Studies
- Marine and coastal ecosystems
City Of Hope National Medical Center
2020-2025
University of Utah
2018-2025
City of Hope
2021-2024
Beckman Research Institute
2021-2024
University of Sheffield
2014-2020
Arizona State University
2008-2011
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 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...
The interplay of positive and negative interactions between drug-sensitive resistant cells influences the effectiveness treatment in heterogeneous cancer cell populations. Here, we study estrogen receptor-positive breast lineages that are sensitive to ribociclib-induced cyclin-dependent kinase 4 6 (CDK4/6) inhibition. In mono- coculture, find grow compete more effectively absence treatment. During with ribociclib, survive proliferate better when grown together than monoculture, termed...
The recent description of potentially generic early warning signals is a promising development that may help conservationists to anticipate population's collapse prior its occurrence. So far, the majority such documented have been in highly controlled laboratory systems or theoretical models. Data from wild populations, however, are typically restricted both temporally and spatially due limited monitoring resources intrinsic ecological heterogeneity-limitations affect detectability signals,...
Abstract Fibroblast growth factors (FGFs) control various cellular functions through fibroblast factor receptor (FGFR) activation, including proliferation, differentiation, migration, and survival. FGFR amplification in ER + breast cancer patients correlate with poor prognosis, inhibitors are currently being tested clinical trials. By comparing three-dimensional spheroid of cells without FGFR1 amplification, our research discovered that FGF2 treatment can paradoxically decrease proliferation...
Abstract The rapid evolution of machine learning has led to a proliferation sophisticated models for predicting therapeutic responses in cancer. While many these show promise research, standards clinical evaluation and adoption are lacking. Here, we propose seven hallmarks by which predictive oncology can be assessed compared. These Data Relevance Actionability, Expressive Architecture, Standardized Benchmarking, Generalizability, Interpretability, Accessibility Reproducibility, Fairness....
Abstract Advanced estrogen receptor positive (ER+) breast cancers are typically treated with endocrine therapy (ET) plus cell cycle inhibitors (CCI); however, nearly 20% of these recur due to treatment resistance. Our previous study tumor intrinsic properties during CCI ET found that CCI-resistant cancer cells associated diminished immune-activating signals cytotoxic CD8+ T in part reduced interleukin-15 (IL-15) signaling, a potent immunostimulatory cytokine. This finding motivates our...
End stage breast cancer often presents with oligometastatic tumors and lacks effective treatment options. Previous studies leveraged post-mortem tissue procurement (also called rapid autopsy) programs to collect shortly after death for profiling by bulk whole exome sequencing (WES). This has revealed substantial heterogeneity in the genomes of metastatic estrogen receptor-positive (ER+) triple-negative cancers. In order understand both genotypes, transcriptional phenotypes, evolution these...
Abstract Estrogen receptor-positive breast cancer (ER+BC) represent about 70% of all cases. Approximately 30-50% ER+BCs eventually develop resistance to primary endocrine therapy and progress metastatic disease. The addition cyclin-dependent kinases 4 6 inhibitors (CDK4/6i) has improved disease control in advanced ER+BC. However, progression on CDK4/6i is common further research required fully understand overcome the mechanisms We performed single-cell RNA sequencing (scRNA-seq) temporal...
Abstract In early-stage estrogen receptor-positive (ER + ) breast cancer, resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) often involve a shift away from estrogen-driven proliferation. The nature source of compensatory growth signals driving cancer proliferation remain unknown but represent direct therapeutic targets resistant cells. By analyzing single-cell RNA-sequencing data serial biopsies patient tumors, we elucidated signaling pathways activated in ET...
The development of video-based monitoring methods allows for rapid, dynamic and accurate individuals or communities, compared to slower traditional methods, with far reaching ecological evolutionary applications. Large amounts data are generated using which can be effectively processed machine learning (ML) algorithms into meaningful information. ML uses user defined classes (e.g. species), derived from a subset (i.e. training data) video-observed quantitative features phenotypic variation),...
Abstract Intraspecific trait change, including altered behaviour or morphology, can drive temporal variation in interspecific interactions and population dynamics. In turn, species’ densities alter the strength direction of change. The resulting feedback between traits abundance permits a wide range community dynamics that would not be expected from ecological theories purely based on species abundances. Despite theoretical importance these interrelated processes, unambiguous experimental...
Significance Demonstrating asymmetric competition in natural systems is difficult, as the effect of large individuals on small ones has to be measured, and vice versa. Numerous experiments have quantified one side interaction, typically ones. Here, we demonstrate, using a long-term study guppies, that an individual’s performance depends its relative size, with being competitively dominant. Accurate prediction both mean variance body size was possible by models incorporating competition,...
Multiple aspects of the environment often change at same time, influencing populations directly by modifying their physiology, but also indirectly other interacting species. The impacts each environmental upon population dynamics are usually assumed be independent state environment, despite evidence individual level indicating that combined non‐additive. importance indirect effects mediated through community interactions has high uncertainty. We used experimental microcosms to determine...
Tumors are comprised of subpopulations cancer cells that harbor distinct genetic profiles and phenotypes evolve over time during treatment. By reconstructing the course evolution, we can understand acquisition malignant properties drive tumor progression. Unfortunately, recovering evolutionary relationships individual linked to their remains a difficult challenge. To address this need, have developed PhylinSic, method reconstructs phylogenetic among gene expression from single cell...
A time-series analysis of serum Cancer Antigen 125 (CA-125) levels was performed in 791 patients with high-grade serous ovarian cancer (HGSOC) from the Australian Ovarian Study to evaluate development chemoresistance and response therapy. To investigate better predict treatment effectiveness, we examined two traits: resistance (defined as rate CA-125 change when were treated therapy) aggressiveness not treated). We found that number lines increases, data-based increases (a decreased decay)....
Abstract The interplay of positive and negative interactions between drug sensitive resistant cells influences the effectiveness treatment in heterogeneous cancer cell populations. In a study isogenic estrogen receptor (ER+) breast lineages to ribociclib-induced CDK4/6 inhibition mono- co-culture, we find that grow compete more effectively absence treatment. During with ribociclib, survive proliferate better when grown together than monoculture, termed facilitation ecology. Both liquid...
Despite high response rates to initial chemotherapy, the majority of women diagnosed with High-Grade Serous Ovarian Cancer (HGSOC) ultimately develop drug resistance within 1-2 years treatment. We previously identified most common mechanism acquired in HGSOC date, transcriptional fusions involving ATP-binding cassette (ABC) transporter ABCB1, which has well established roles multidrug resistance. However, underlying biology fusion-positive cells, as how clonal interactions between...
Abstract Background Accurately determining changes in tumor size during therapy is essential to evaluating response or progression. However, individual imaging methodologies often poorly reflect pathologic and long-term treatment efficacy patients with estrogen receptor positive (ER+) early-stage breast cancer. Mathematical models that measure progression over time by integrating diverse measurement modalities are not currently used but could increase accuracy measuring provide biological...
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,...
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...