A5036752445- Protist diversity and phylogeny
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Immune cells in cancer
- RNA and protein synthesis mechanisms
- Adipose Tissue and Metabolism
- Ubiquitin and proteasome pathways
- Burn Injury Management and Outcomes
- Fibroblast Growth Factor Research
- Cellular transport and secretion
- Wound Healing and Treatments
- RNA modifications and cancer
- Hepatitis C virus research
- Physiological and biochemical adaptations
- Hepatitis B Virus Studies
- Hormonal Regulation and Hypertension
- Immune Cell Function and Interaction
- Tendon Structure and Treatment
- Signaling Pathways in Disease
- Vitamin C and Antioxidants Research
- Parasites and Host Interactions
- Alkaline Phosphatase Research Studies
Harvard University
2011-2024
Broad Institute
2023-2024
Massachusetts Institute of Technology
2024
Boston Children's Hospital
2021-2024
Yale University
2014-2022
Howard Hughes Medical Institute
2011-2020
Center for Systems Biology
2011-2017
Peking University
2007
University of Washington
1990
There is a growing interest in understanding tissue organization, homeostasis, and inflammation. However, despite an abundance of data, the organizing principles biology remain poorly defined. Here, we present perspective on organization based relationships between cell types functions that they perform. We provide formal definition homeostasis as collection circuits regulate specific variables within environment, describe how functional tissues allows for maintenance both systemic...
Tissue repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, pathological state of excessive scarring. To pinpoint the dynamic mechanisms underlying it important understand principles cell circuits that carry out tissue repair. In this study, we establish cell-circuit framework for myofibroblast-macrophage circuit in wound healing, including accumulation scar-forming extracellular matrix. We find fibrosis results from multistability between...
Animal tissues comprise diverse cell types. However, the mechanisms controlling number of each type within tissue compartments remain poorly understood. Here, we report that different types utilize distinct strategies to control population numbers. Proliferation fibroblasts, stromal cells important for integrity, is limited by space availability. In contrast, proliferation macrophages, innate immune involved in defense, repair, and homeostasis, constrained growth factor Examination...
The transcriptional coactivator Yes-associated protein (Yap) promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene. Most oncogenes, however, require a combination of at least two signals to promote proliferation. In this study, we present evidence activation is insufficient growth in the otherwise normal tissue. Using mosaic mouse model, demonstrate overexpression fraction hepatocytes does not lead their clonal expansion, counterbalanced by increased...
Palatable foods (fat and sweet) induce hyperphagia, facilitate the development of obesity. Whether how overnutrition increases appetite through adipose-to-brain axis is unclear. O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation intracellular proteins at serine/threonine residues. Chronic dysregulation O-GlcNAc signaling contributes metabolic diseases. Here we show that adipocyte OGT essential for high fat diet-induced but dispensable...
Significance Many tissues in the body constantly turn over as cells divide and are replaced within weeks. Despite this turnover, able to keep proper ratios of their different cell types. How attain balance, called homeostasis, is unclear. Here we show that homeostasis can be achieved by circuits signal each other using diffusible signals. A key negative feedback loop stabilizes these endocytosis, a common feature biological signaling which takes up degrades molecule makes it survive. Thus,...
Differences in the phase of circadian clock contribute to heterogeneity inflammatory response macrophages.
Understanding chromatin function requires knowing the precise location of nucleosomes. MNase-seq methods have been widely applied to characterize nucleosome organization in vivo, but generally lack accuracy determine positions. Here we develop a computational approach leveraging digestion variability positions at base-pair resolution from data. We generate template as simple error model for how MNase affects mapping individual Applied both yeast and human cells, this analysis reveals that...
Although combinatorial regulation is a common feature in gene regulatory networks, how it evolves and affects network structure function not well understood. In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 Pho2 are required for induction survival during starvation. related human commensal C. glabrata, but dispensable only partially inducing PHO genes. Phylogenetic survey suggests that reduced dependence on evolved glabrata closely species. less...
Inflammation is an essential defense response but operates at the cost of normal functions. Whether and how negative impact inflammation monitored remains largely unknown. Acidification tissue microenvironment associated with inflammation. Here we investigated whether macrophages sense acidification to adjust inflammatory responses. We found that acidic pH restructured in a gene-specific manner. identified mammalian BRD4 as novel intracellular sensor. Acidic disrupts transcription...
Abstract Animal tissues are comprised of diverse cell types. However, the mechanisms controlling number each type within tissue compartments remain poorly understood. Here, we report that different types utilize distinct strategies to control population numbers. Proliferation fibroblasts, stromal cells important for integrity, is limited by space availability. In contrast, proliferation macrophages, innate immune involved in defense, repair, and homeostasis, constrained growth factor...
As a hepatitis B virus (HBV) envelope domain, preS plays significant roles in receptor recognition and viral infection. However, the regions critical for maintaining stable functional conformation of are still unclear require further investigation. In order to unravel these regions, serially truncated fragments were constructed expressed Escherichia coli. Their solubility, stability, secondary structure, affinity polyclonal antibodies hepatocytes examined. The results showed that amino acids...
Abstract In S. cerevisiae , the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are jointly required for induction of response genes survival in conditions. related human commensal pathogen C. glabrata is but dispensable phosphate-limited conditions only partially inducing genes. This reduced dependence on evolved closely species. orthologs that less dependent induce more when introduced into background, both binds to sites induces with expanded functional roles...
Abstract Background Hepatitis B virus (HBV) infection is a serious health problem worldwide. Treatment recommendation and response are mainly indicated by viral load, e antigen (HBeAg) seroconversion, ALT levels. The S (HBsAg) seroconversion much less frequent. Since HBeAg can be negative in the presence of high replication, preS (HBpreSAg) might useful indicator management chronic HBV infection. Results A new assay double antibody sandwich ELISA was established to detect antigens. Sera 104...
Abstract Tissue-repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, pathological state of excessive scarring. To pinpoint the dynamic mechanisms underlying it important understand principles cell circuits that carry out tissue-repair. In this study, we establish cell-circuit framework for myofibroblast-macrophage circuit in wound-healing, including accumulation scar-forming extracellular matrix. We find fibrosis results from multistability...