- MicroRNA in disease regulation
- Invertebrate Immune Response Mechanisms
- Pancreatic function and diabetes
- Insect symbiosis and bacterial influences
- Single-cell and spatial transcriptomics
- Neurobiology and Insect Physiology Research
- Mosquito-borne diseases and control
- Genetics, Aging, and Longevity in Model Organisms
- Aquaculture disease management and microbiota
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Genetics and Neurodevelopmental Disorders
- Gene Regulatory Network Analysis
- Spaceflight effects on biology
- Phagocytosis and Immune Regulation
- Pancreatitis Pathology and Treatment
- Sphingolipid Metabolism and Signaling
- Extracellular vesicles in disease
- Genetics and Physical Performance
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Biomedical Text Mining and Ontologies
- Circular RNAs in diseases
- Bioinformatics and Genomic Networks
- FOXO transcription factor regulation
Harvard University
2018-2023
Boston VA Research Institute
2019-2023
Howard Hughes Medical Institute
2021-2022
Harvard University Press
2022
ORCID
2021
Max Delbrück Center
2011-2019
Institute of Bioinformatics
2007-2010
For more than 100 years, the fruit fly
Abstract We have developed NetPath as a resource of curated human signaling pathways. As an initial step, provides detailed maps number immune pathways, which include approximately 1,600 reactions annotated from the literature and more than 2,800 instances transcriptionally regulated genes - all linked to over 5,500 published articles. anticipate become consolidated for pathways that should enable systems biology approaches.
Studies of the adult Drosophila midgut have led to many insights in our understanding cell-type diversity, stem cell regeneration, tissue homeostasis, and fate decision. Advances single-cell RNA sequencing provide opportunities identify new types molecular features. We used characterize transcriptome epithelial cells identified 22 distinct clusters representing intestinal cells, enteroblasts, enteroendocrine (EEs), enterocytes. This unbiased approach recovered most known cells/enteroblast EE...
blood cells, called hemocytes, are classified into plasmatocytes, crystal and lamellocytes based on the expression of a few marker genes cell morphologies, which inadequate to classify complete hemocyte repertoire. Here, we used single-cell RNA sequencing (scRNA-seq) map hemocytes across different inflammatory conditions in larvae. We resolved plasmatocytes states involved cycle, antimicrobial response, metabolism together with identification intermediate states. Further, discovered rare...
Abstract The Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and mature hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis immunity. Three types hemocytes have characterized in gland: plasmatocytes, lamellocytes, crystal cells, which are analogous to vertebrate myeloid yet molecular underpinnings gland less investigated. Here, we use single-cell RNA sequencing comprehensively analyze heterogeneity developing discover...
Highlights•Silencing of miR-184 during insulin resistance promotes its target Ago2•Loss Ago2 blocks pancreatic β cell proliferation•Ago2 mediates the suppression Cadm1 by miR-375 in cell•Administration ketogenic diet to ob/ob mice rescues isletsSummaryPancreatic cells adapt compensate for increased metabolic demand resistance. Although microRNA pathway has an essential role proliferation, extent contribution is unclear. Here, we report that silenced islets insulin-resistant mouse models and...
Abstract The ability to obtain single cell transcriptomes for stable types and dynamic states is ushering in a new era biology. We created the Tabula Drosophilae , atlas of adult fruit fly which includes 580k cells from 15 individually dissected sexed tissues as well entire head body. Over 100 researchers community contributed annotations >250 distinct across all tissues. provide an in-depth analysis type-related gene signatures transcription factor markers, sexual dimorphism, whole...
miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of was underscored by the discovery that point mutations in gene led corneal/lens blinding disease. However, miR-184-related function vivo remained unclear. Here, we report knockout mouse model displayed increased p63 expression line with epidermal hyperplasia, while forced stem/progenitor cells enhanced Notch pathway and induced hypoplasia. In line, reduced clonogenicity accelerated differentiation...
Argonaute2 (Ago2) is an established component of the microRNA-induced silencing complex. Similar to miR-375 loss-of-function studies, inhibition Ago2 in pancreatic β-cell resulted enhanced insulin release underlining relationship between these two genes. Moreover, as most abundant microRNA endocrine cells, was also observed be enriched Ago2-associated complexes. Both and regulate secretome, by using quantitative mass spectrometry, we identified a set proteins or secretion "signatures "...
PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles Drosophila PDGF/VEGF-like factors (Pvfs). combine genetic approaches single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals the hepatocyte-like cells/oenocytes suppress lipid synthesis by activating Pi3K/Akt1/TOR signaling cascade oenocytes. Functionally, this axis regulates expansion...
With the advent of single-cell RNA sequencing (scRNA-seq) technologies, there has been a spike in studies involving scRNA-seq several tissues across diverse species including Drosophila. Although few databases exist for users to query genes interest within studies, search tools that enable find orthologous and their cell type-specific expression patterns are limited. Here, we built new database, DRscDB (https://www.flyrnai.org/tools/single_cell/web/), address this need. serves as...
IL-4-driven alternative macrophage activation and proliferation are characteristic features of both antihelminthic immune responses wound healing in contrast to classical activation, which primarily occurs during inflammatory responses. The signaling pathways defining the genome-wide microRNA expression profile as well cellular functions controlled by microRNAs largely unknown. Hence, current work we examined regulation function IL-4-regulated human mouse activation. We utilized...
Pancreatic β cells store insulin within secretory granules which undergo exocytosis upon elevation of blood glucose levels. Crinophagy and autophagy are instead responsible to deliver damaged or old acidic lysosomes for intracellular degradation. However, excessive consumption can impair cell function cause diabetes. Atp6ap2 is an essential accessory component the vacuolar ATPase required lysosomal degradative functions autophagy. Here, we show that Cre recombinase-mediated conditional...
Summary Drosophila blood cells, called hemocytes, are classified into plasmatocytes, crystal and lamellocytes based on the expression of a few marker genes cell morphologies, which inadequate to classify complete hemocyte repertoire. Here, we used single-cell RNA sequencing (scRNA-seq) map hemocytes across different inflammatory conditions in larvae. We resolved plasmatocytes states involved cycle, antimicrobial response, metabolism together with identification intermediate states. Further,...
SUMMARY Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis immunity. Three types mature hemocytes have characterized in gland: plasmatocytes, lamellocytes, crystal cells, which are analogous to vertebrate myeloid cells. Here, we used single-cell RNA sequencing comprehensively analyze heterogeneity developing discovered novel hemocyte types, stem-like prohemocytes,...
Studies on the adult Drosophila midgut have led many insights our understanding of cell type diversity, stem regeneration, tissue homeostasis and fate decision. Advances in scRNA-seq provide opportunities to identify new types molecular features. We used inDrop characterize transcriptome epithelial cells identified 12 distinct clusters representing intestinal (ISCs), enteroblasts (EBs), enteroendocrine (EEs), enterocytes (ECs). This unbiased approach recovered 90% known ISCs/EBs markers...
Abstract Studies of the adult Drosophila midgut have provided a number insights on cell type diversity, stem regeneration, tissue homeostasis and fate decision. Advances in single-cell RNA sequencing (scRNA-seq) provide opportunities to identify new types molecular features. We used inDrop characterize transcriptome epithelial cells identified 12 distinct clusters representing intestinal (ISCs), enteroblasts (EBs), enteroendocrine (EEs), enterocytes (ECs) from different regions, cardia. This...
Abstract Background To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role this compartment remains unclear. Objective The aim of study was to determine whether levels miRNAs abundant blood, neuroendocrine tissue-enriched miR-375, are altered response a glucose challenge. Design Twelve healthy males were recruited for an acute crossover that consisted two tests each following 8-hour fasting period. An...