A5070465805- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Gene expression and cancer classification
- Reproductive System and Pregnancy
- Extracellular vesicles in disease
- Gene Regulatory Network Analysis
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Epigenetics and DNA Methylation
- COVID-19 Clinical Research Studies
- Spectroscopy and Quantum Chemical Studies
- Endometriosis Research and Treatment
- Protein Structure and Dynamics
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
- RNA Research and Splicing
- Health, Environment, Cognitive Aging
- Uterine Myomas and Treatments
- Cancer-related Molecular Pathways
- Demographic Trends and Gender Preferences
- Optical Polarization and Ellipsometry
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
Carnegie Mellon University
2023-2024
Wellcome Sanger Institute
2016-2022
North-Western State Medical University named after I.I. Mechnikov
2020
Babraham Institute
2015-2017
University of Edinburgh
2011
Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T B lymphocyte antigen receptor analyses over 780,000 peripheral mononuclear from a cross-sectional cohort 130 patients with varying severities COVID-19. identified expansion nonclassical monocytes expressing complement transcripts (CD16
Abstract The endometrium, the mucosal lining of uterus, undergoes dynamic changes throughout menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps human uterus three-dimensional endometrial organoid cultures. dissect signaling pathways that determine cell fate epithelial lineages lumenal glandular microenvironments. Our benchmark organoids reveals states regulating differentiation secretory ciliated both vivo vitro. In vitro...
Transformative technologies are enabling the construction of three dimensional (3D) maps tissues with unprecedented spatial and molecular resolution. Over next seven years, NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping human body at single-cell resolution by supporting technology development, data acquisition, detailed mapping. HuBMAP will integrate its efforts other funding agencies, programs,...
Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries
The PI3K signaling pathway regulates cell growth and movement is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, latter producing PI(3,4)P2. PTEN tumor suppressor thought to function primarily as a 3-phosphatase, limiting activation of this pathway. Here we show that also functions PI(3,4)P2 both vitro vivo. major phosphatase Mcf10a cytosol, loss INPP4B, known 4-phosphatase, leads synergistic...
Abstract Using single-cell RNA-seq (scRNA-seq), the full transcriptome of individual cells can be acquired, enabling a quantitative cell-type characterisation based on expression profiles. However, due to large variability in gene expression, identifying cell types remains challenging. We present Single-Cell Consensus Clustering (SC3), tool for unsupervised clustering scRNA-seq data. SC3 achieves high accuracy and robustness by consistently integrating different solutions through consensus...
Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced function, molecular basis which largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation old HSCs carrying p53 signature indicative decline alongside pro-proliferative JAK/STAT signaling. To investigate relationship between signaling, challenged with constitutively active form JAK2 (V617F) observed an expansion p53-positive in mice. Our results reveal cellular...
As the cost of single-cell RNA-seq experiments has decreased, an increasing number datasets are now available. Combining newly generated and publicly accessible is challenging due to non-biological signals, commonly known as batch effects. Although there several computational methods available that can remove effects, evaluating which method performs best not straightforward. Here, we present BatchBench (https://github.com/cellgeni/batchbench), a modular flexible pipeline for comparing...
Abstract Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance ample phenotypic expressivity in CVID suggest participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for are uniquely valuable studying contribution epigenetics to disease. Here, we generate a single-cell epigenomics transcriptomics census...
Abstract In the last decade, single cell RNAseq (scRNAseq) datasets have grown in size from a to millions of cells. Due its high dimensionality, it is not always feasible visualize scRNAseq data and share scientific report or an article publication format. Recently, many interactive analysis visualization tools been developed address this issue facilitate knowledge transfer community. study, we review several currently available benchmark subset that allows on web with others. We consider...
Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance translational repression and subcellular location expression during B lymphocyte activation DNA damage response. Cytoplasmic RNA granules are formed upon cell with mitogens, including stress that contain binding Tia1. Tia1 binds to a subset transcripts involved in stress, p53 mRNA, controls silencing granule localization. promotes relocation translation part due dissociation...
Abstract The endometrium, the mucosal lining of uterus, undergoes dynamic changes throughout menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps human uterus 3D endometrial organoid cultures. dissect signalling pathways that determine cell fate epithelial lineages lumenal glandular microenvironments. Our benchmark organoids highlights common regulating differentiation secretory ciliated lineage vivo vitro . show downregulation WNT or...
Abstract The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling over 800,000 peripheral blood mononuclear cells from a cohort 130 patients COVID-19. Our cohort, three UK centres, spans spectrum clinical presentations disease...
PIP3 is synthesized by the Class I PI3Ks and regulates complex cell responses, such as growth migration. Signals that drive long-term reshaping of phenotypes are difficult to resolve because feedback networks operate over extended times. PIP3-dependent modulation mRNA accumulation clearly important in this process but poorly understood. We have quantified genome-wide mRNA-landscape non-transformed, breast epithelium-derived MCF10a cells its response acute regulation EGF, presence or absence...
Abstract Single-cell RNA-seq (scRNA-seq) is widely used to investigate the composition of complex tissues 1–9 since technology allows researchers define cell-types using unsupervised clustering transcriptome 8,10 . However, due differences in experimental methods and computational analyses, it often challenging directly compare cells identified two different experiments. Here, we present scmap ( http://bioconductor.org/packages/scmap ), a method for projecting from scRNA-seq experiment onto...
Biological membranes are complex environments whose physico-chemical properties of utmost importance for the understanding many crucial biological processes. Much attention has been given in literature to description along z-axis perpendicular membrane. Here, we instead consider lateral dynamics lipids and peripheral proteins due their electrostatic interaction. Previously, constructed a Monte Carlo automaton capable simulating mutual diffusive charged associated positively peptides. derive...
Abstract As the cost of single-cell RNA-seq experiments has decreased, an increasing number datasets are now available. Combining newly generated and publicly accessible is challenging due to non-biological signals, commonly known as batch effects. Although there several computational methods available that can remove effects, evaluating which method performs best not straightforward. Here we present BatchBench ( https://github.com/cellgeni/batchbench ), a modular flexible pipeline for...