A5027298635- T-cell and B-cell Immunology
- Neurobiology and Insect Physiology Research
- Invertebrate Immune Response Mechanisms
- Olfactory and Sensory Function Studies
- Monoclonal and Polyclonal Antibodies Research
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Animal Behavior and Reproduction
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Cancer Cells and Metastasis
- Evolution and Genetic Dynamics
- vaccines and immunoinformatics approaches
- Influenza Virus Research Studies
- Immunodeficiency and Autoimmune Disorders
- Radiomics and Machine Learning in Medical Imaging
- Gene expression and cancer classification
- Plant Disease Resistance and Genetics
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Biotin and Related Studies
- Insect and Arachnid Ecology and Behavior
California Institute of Technology
2021-2024
Howard Hughes Medical Institute
2023-2024
Stanford University
2016-2023
Chan Zuckerberg Initiative (United States)
2017-2023
Applied BioPhysics (United States)
2016-2020
Bioengineering Center
2020
The Gurdon Institute
2018
University of Cambridge
2018
Amherst College
2012-2017
University of Helsinki
2013
For more than 100 years, the fruit fly
Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth expansion to neighboring distal tissues. The study phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout mouse model Kras;Trp53(KP)-driven lung adenocarcinoma tracked tumor from single-transformed metastatic tumors at unprecedented...
Antibody memory protects humans from many diseases. Protective antibody responses require activation of transcriptional programs, cell proliferation, and production antigen-specific antibodies, but how these aspects the response are coordinated is poorly understood. We profile molecular cellular features to influenza vaccination by integrating single-cell transcriptomics, longitudinal repertoire sequencing, binding measurements. Single-cell profiling reveals a program B characterized CD11c...
Despite the vast diversity of antibody repertoire, infected individuals often mount responses to precisely same epitopes within antigens. The immunological mechanisms underpinning this phenomenon remain unknown. By mapping 376 immunodominant “public epitopes” at high resolution and characterizing several their cognate antibodies, we concluded that germline-encoded sequences in antibodies drive recurrent recognition. Systematic analysis antibody-antigen structures uncovered 18 human 21...
A system for programmable export of RNA molecules from living cells would enable both non-destructive monitoring cell dynamics and engineering capable delivering executable programs to other cells. We developed genetically encoded cellular exporters, inspired by viruses, that efficiently package secrete cargo mammalian within protective nanoparticles. Exporting sequencing barcodes enabled population with clonal resolution. Further, incorporating fusogens into the nanoparticles, we...
Antibody class switching is a feature of the adaptive immune system which enables diversification effector properties antibodies. Even though essential for mounting protective response to pathogens, in vivo patterns and lineage characteristics antibody have remained uncharacterized living humans. Here we comprehensively measured landscape human adult twins using repertoire sequencing. The map identifies how antibodies every are created delineates two-tiered hierarchy switch pathways. Using...
Recognition of environmental cues is essential for the survival all organisms. Transcriptional changes occur to enable generation and function neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes Drosophila olfactory- (ORNs), thermo-, hygro-sensory neurons at an early developmental adult stage using single-nucleus RNA sequencing. We discovered that ORNs maintain expression same olfactory receptors across development. Using...
Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with ability to recognize eliminate diverse pathogens. However, evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show population genetic signatures of evident lineages reveal how antibodies evolve somatically. We measured dynamics diversity responses five adults longitudinally before after...
Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained single-cell transcriptomes of
Natural cell death pathways such as apoptosis and pyroptosis play dual roles: they eliminate harmful cells modulate the immune system by dampening or stimulating inflammation. Synthetic protein circuits capable of triggering specific programs in target could similarly remove while appropriately modulating responses. However, actively influence their modes response to natural signals, making it challenging control modes. Here, we introduce naturally inspired "synpoptosis" that proteolytically...
Transposable elements (TEs) are ubiquitous genomic parasites that have prompted the evolution of genome defense systems restrict their activity. Repeat-induced point mutation (RIP) is a homology-dependent introduces C-to-T transition mutations in duplicated DNA sequences and thought to control proliferation selfish repetitive DNA. Here, we determine taxonomic distribution hypermutation patterns indicative RIP among basidiomycetes. We quantify particular di- trinucleotide target sites for...
Theory indicates that spatial scale and habitat configuration are fundamental for coevolutionary dynamics how diversity is maintained in host–pathogen interactions. Yet, we lack empirical data to translate the theory natural host–parasite systems. In this study, conduct a multiscale cross‐inoculation study using specialist wild plant pathogen Podosphaera plantaginis on its host Plantago lanceolata. We apply same sampling scheme region with highly fragmented (Åland) continuous (Saaremaa)...
Abstract The ubiquitous challenge from infectious disease has prompted the evolution of diverse host defenses, which can be divided into two broad classes: resistance (which limits pathogen growth and infection) tolerance does not limit infection, but instead reduces or offsets its negative fitness consequences). Resistance may provide equivalent short‐term benefits, have fundamentally different epidemiological consequences thus exhibit evolutionary behaviors. We consider in a spatially...
Transposable elements (TEs) are selfish, autonomously replicating DNA sequences that constitute a major component of eukaryotic genomes and contribute to genome evolution through their movement amplification. Many fungal genomes, including the anther-smut fungi in basidiomycete genus Microbotryum, have defense mechanisms, such as repeat-induced point mutation (RIP), which hypermutate repetitive limit TE activity. Little is known about how hypermutation affects tempo activity sequence...
The individual detection of human immunodeficiency virus (HIV) virions and resolution from extracellular vesicles (EVs) during analysis is a difficult challenge. Infectious enveloped nonviral EVs are released simultaneously by HIV-infected host cells, in addition to hybrid viral containing combinations HIV components but lacking replicative ability. Complicating the issue, both delimited lipid bilayer share similar size density. feature that distinguishes infectious genomic RNA (gRNA), which...
We combined single-cell transcriptomics and lineage tracing to understand fate choice in human B cells. Using the antibody sequences of cells, we tracked clones during vitro differentiation. Clonal analysis revealed a subset IgM+ cells which were more proliferative than other B-cell types. Whereas population adopted diverse states differentiation, had restricted set fates available them; there two times single-fate expected given population-level cell-type diversity. This implicated...
Abstract Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with ability to recognize eliminate diverse pathogens. However, evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show molecular signatures of evident lineages reveal how antibodies evolve somatically. We measured dynamics genetic diversity responses five adults longitudinally before...
SUMMARY Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth, expansion to neighboring distal tissues, therapeutic resistance. The study phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout mouse model Kras;Trp53 (KP)-driven lung adenocarcinoma which enabled us track tumor from single...
The ultimate function of a neuron is determined by both its physiology and connectivity, but the transcriptional regulatory mechanisms that coordinate these two features are not well understood 1–4 . Drosophila Olfactory receptor neurons (ORNs) provide an excellent system to investigate this question. As in mammals 5 , each ORN class defined expression single olfactory or unique combination thereof, which determines their odor responses, glomerulus axons target, how sensory signals...
Abstract Recognition of environmental cues is essential for the survival all organisms. Precise transcriptional changes occur to enable generation and function neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes Drosophila olfactory receptor neurons (ORNs), thermosensory hygrosensory from third antennal segment at an early developmental adult stage. We discovered that ORNs maintain expression same receptors across...
Abstract A key feature of cells is the capacity to activate new functional polarized domains contemporaneously pre-existing ones. How accomplish this not clear. Here, we show that in fission yeast inhibition cell polarity at growth required growth. This mediated by ERM-related factor Tea3, which antagonizes activation Rho-GTPase Cdc42 its co-factor Scd2. We demonstrate Tea3 acts a phosphorylation-dependent manner controlled PAK kinase Shk1 and that, like Scd2, direct substrate Shk1....
Abstract How a neuronal cell type is defined and how this relates to its transcriptome are still open questions. The Drosophila olfactory projection neurons (PNs) among the best-characterized types: Different PN classes target dendrites distinct glomeruli PNs of same class exhibit indistinguishable anatomical physiological properties. Using single-cell RNA-sequencing, we comprehensively characterized transcriptomes 40 unequivocally identified for 6 classes. We found new lineage-specific...