A5046793239- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Immune cells in cancer
- Gene Regulatory Network Analysis
- Nanoparticle-Based Drug Delivery
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Epigenetics and DNA Methylation
- Biomarkers in Disease Mechanisms
- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Chemokine receptors and signaling
- Mathematical Biology Tumor Growth
- T-cell and B-cell Immunology
- RNA Research and Splicing
- Birth, Development, and Health
- Ferroptosis and cancer prognosis
- Wound Healing and Treatments
- Immunotherapy and Immune Responses
- Science, Research, and Medicine
- Immune responses and vaccinations
- Cellular Mechanics and Interactions
- Computational Drug Discovery Methods
University of Southern California
2019-2025
Southern California University for Professional Studies
2019-2024
University of California, Irvine
2016-2023
Tsinghua University
2023
University of Oxford
2015-2018
UC Irvine Health
2018
Imperial College London
2013-2017
StemCells (United States)
2017
Our knowledge of transcriptional heterogeneities in epithelial stem and progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance drive wound healing. Previous studies have probed heterogeneity potential, but a comprehensive dissection dynamics during differentiation lacking. Using single-cell RNA sequencing coupled with RNAScope fluorescence lifetime imaging, we identify three non-proliferative one proliferative state homeostatic skin that differ...
How stem cells give rise to epidermis is unclear despite the crucial role plays in barrier and appendage formation. Here we use single cell-RNA sequencing interrogate basal cell heterogeneity of human interfollicular find four spatially distinct populations at top bottom rete ridges transitional positions between suprabasal epidermal layers. Cell-cell communication modeling suggests that serve as signaling hubs maintain communication. Combining pseudotime, RNA velocity, cellular entropy...
Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in disease remains unclear. Here, we used single-cell transcriptomics determine molecular attributes dystrophic and healthy macrophages. We identified six clusters unexpectedly found that none corresponded traditional definitions M1 or M2 Rather, predominant macrophage signature was characterized by high expression fibrotic factors, galectin-3 (gal-3) osteopontin...
The use of single-cell transcriptomics has become a major approach to delineate cell subpopulations and the transitions between them. While various computational tools using different mathematical methods have been developed infer clusters, marker genes, lineage, none yet integrate these within framework perform multiple tasks coherently. Such coherence is critical for inference cell–cell communication, remaining challenge. Here, we present similarity matrix-based optimization data analysis...
Chronic inflammation is a serious risk factor for cancer; however, the routes from to cancer are poorly understood. On basis of processes implicated by frequently mutated genes associated with and in three organs (stomach, colon, liver) extracted Gene Expression Omnibus, The Cancer Genome Atlas, Ontology databases, we present multiscale model long-term evolutionary dynamics leading tumorigenesis. incorporates cross-talk among interactions on several scales, including responses DNA damage,...
Single-cell RNA-sequencing (scRNA-seq) offers unprecedented resolution for studying cellular decision-making processes. Robust inference of cell state transition paths and probabilities is an important yet challenging step in the analysis these data.Here we present scEpath, algorithm that calculates energy landscapes probabilistic directed graphs order to reconstruct developmental trajectories. We quantify landscape using 'single-cell energy' distance-based measures, find combination enables...
As our catalog of cell states expands, appropriate characterization these and the transitions between them is crucial. Here we discuss roles intermediate (ICSs) in this growing collection. We begin with definitions evidence for existence ICSs their relevance various tissues. then provide a list possible functions examples. Finally, describe means by which functional can be identified from single-cell data or predicted models.
In animal models,
Chronic myeloid leukemia (CML) is a blood disease that disrupts normal function of the hematopoietic system. Despite great progress made in terms molecular therapies for CML, there remain large gaps our understanding. By comparing mathematical models describe CML progression and etiology we sought to identify those provide best description dynamics their underlying mechanisms. Data two clinical outcomes--disease remission or relapse--are considered, investigate these using Bayesian inference...
Mechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem (MSC) is influenced by past mechanical dosing (memory), but mechanisms underlying this process have not yet been well defined. We to understand how memory affects specific decisions, such as differentiation MSCs into neurons, adipocytes, myocytes, osteoblasts. study a minimal gene regulatory network permissive multi-lineage MSC four fates. present continuous model that able...
The adult mammalian kidney has a complex, highly-branched collecting duct epithelium that arises as ureteric bud sidebranch from an epithelial tube known the nephric duct. Subsequent branching of to form tree is regulated by subcellular interactions between and population mesenchymal cells surround tips outgrowing branches. produce glial cell-line derived neurotrophic factor (GDNF), binds with RET receptors on surface stimulate several pathways in epithelium. Such are be prerequisite for...
The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions people with disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity other coronaviruses that infect humans allowed for rapid insight into mechanisms it uses human hosts, as well ways immune system can respond. Here, we contextualize SARS-CoV-2 among identify what is known be inferred about behavior once inside a host....
Abstract Increasing evidence links metabolism, protein synthesis, and growth signaling to impairments in the function of hematopoietic stem progenitor cells (HSPCs) during aging. The Lin28b/Hmga2 pathway controls tissue development, postnatal downregulation this limits self-renewal adult vs fetal (HSCs). Igf2bp2 is an RNA binding downstream Lin28b/Hmga2, which regulates messenger stability translation. role HSC aging unknown. In study, analysis wild-type knockout mice showed that oxidative...
Significance The canonical Wnt/β-catenin signaling pathway is important for essential cellular functions and implicated in many diseases. We introduce a new mathematical model that focuses on β-catenin degradation protein shuttling between compartments. compare our to others show all fit time-dependent experimental data. To evade this parameter problem, we use algebraic methods characterize features are independent of the choice values. find multiple responses Wnt feasible under certain...
Neural crest (NC) cells migrate throughout vertebrate embryos to give rise a huge variety of cell types, but when and where lineages emerge their regulation remain unclear. We have performed single-cell RNA sequencing (RNA-seq) cranial NC from the first pharyngeal arch in zebrafish over several stages during migration. Computational analysis combining pseudotime real-time data reveals that these adopt transitional state, becoming specified mid-migration, with lineage decisions being skeletal...
Abstract Myeloid-derived suppressor cells (MDSC) play a prominent role in the tumor microenvironment. A quantitative understanding of tumor–MDSC interactions that influence disease progression is critical, and currently lacking. We developed mathematical model metastatic growth immune-rich microenvironments. modeled tumor–immune dynamics with stochastic delay differential equations studied impact delays MDSC activation/recruitment on outcomes. In lung environment, when circulating level...
Biological systems exhibit complex dynamics that differential equations can often adeptly represent. Ordinary equation models are widespread; until recently their construction has required extensive prior knowledge of the system. Machine learning methods offer alternative means model construction: be learnt from data via discovery using sparse identification nonlinear (SINDy). However, SINDy struggles with realistic levels biological noise and is limited in its ability to incorporate We...
Abstract Most patients with breast cancer eventually succumb to disease due health complications caused by metastasis, the lungs being one of most common sites metastasis. Immune checkpoint inhibitors (ICIs) can reactivate T cells eliminate cells, but they have proved ineffective against metastatic on their own. Immunosuppressive myeloid in tumor microenvironment (TME), such as associated macrophages (TAMs) and myeloid-derived suppressor (MDSCs), are abundant tumors metastases, which inhibit...
Abstract Myeloid derived suppressor cells (MDSCs) are key players in an immune-suppressed tumor microenvironment (TME) and significantly contribute to immune checkpoint inhibition (ICI) resistance, making them favorable targets for cancer immunotherapy. Our group others have investigated MDSCs as a therapeutic sensitize the TME ICIs breast cancer. We reported that epigenetic reprogramming of by inhibiting histone deacetylases (HDACs) 1 3 with Entinostat decreases MDSC immunosuppressive...