A5023323282- Cellular Mechanics and Interactions
- Inflammatory Bowel Disease
- Liver Disease Diagnosis and Treatment
- Gene Regulatory Network Analysis
- Liver physiology and pathology
- 3D Printing in Biomedical Research
- Hippo pathway signaling and YAP/TAZ
- Diet, Metabolism, and Disease
- Wound Healing and Treatments
- Cardiac Fibrosis and Remodeling
- Single-cell and spatial transcriptomics
- Burn Injury Management and Outcomes
- Microscopic Colitis
- Genetics, Aging, and Longevity in Model Organisms
- Fibroblast Growth Factor Research
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Reproductive Biology and Fertility
- Galectins and Cancer Biology
- Receptor Mechanisms and Signaling
- Advanced Glycation End Products research
- VLSI and FPGA Design Techniques
- Erythrocyte Function and Pathophysiology
- Caveolin-1 and cellular processes
- Tissue Engineering and Regenerative Medicine
Yale University
2022-2025
Hebrew University of Jerusalem
2024
Broad Institute
2020-2023
Massachusetts Institute of Technology
2020-2023
Weizmann Institute of Science
2014-2021
Advanced hepatic fibrosis, driven by the activation of stellate cells (HSCs), affects millions worldwide and is strongest predictor mortality in nonalcoholic steatohepatitis (NASH); however, there are no approved antifibrotic therapies. To identify drug targets, we integrated progressive transcriptomic morphological responses that accompany HSC advanced disease using single-nucleus RNA sequencing tissue clearing a robust murine NASH model. In found an autocrine signaling circuit emerged was...
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...
Many sensory systems in cells and organisms share a recurring property called fold-change detection (FCD). FCD describes system whose dynamics – including amplitude response time are determined only by the relative change input signal, rather than its absolute change. entails two important features exact adaptation Weber–Fechner law. Systems with include bacterial eukaryotic chemotaxis, signaling pathways mammalian such as NF-κB, Wnt Tgf-β, organismal vision, hearing olfaction. Here, we...
Age-related diseases such as cancer, cardiovascular disease, kidney failure, and osteoarthritis have universal features: Their incidence rises exponentially with age a slope of 6-8% per year decreases at very old ages. There is no conceptual model which explains these features in so many diverse terms single shared biological factor. Here, we develop model, test it using nationwide medical record dataset on the nearly 1000 over 50 million life-years, provide resource. The accumulation...
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...
Most cell types in multicellular organisms can perform multiple functions. However, not all functions be optimally performed simultaneously by the same cells. Functions incompatible at level of individual cells population level, where divide labor and specialize different Division arise due to instruction tissue environment or through self-organization. Here, we develop a computational framework investigate contribution these mechanisms division within cell-type population. By optimizing...
Highlights•Multi-tasking theory explains continuum gene-expression within a cell type•Enterocytes show 1D expression and trade-off between three tasks•Hepatocytes 3D four complexes of liver tasks•Spatial zonation task-specialist cells arises from task-performance gradientsSummarySingle-cell gene reveals the diversity differentiated type. Often, same type patterns. The origin such patterns is unclear. To address this, we develop to understand how provides division labor in tissue which...
Two central biophysical laws describe sensory responses to input signals. One is a logarithmic relationship between and output, the other power law relationship. These are sometimes called Weber-Fechner Stevens law, respectively. The two found in wide variety of human systems including hearing, vision, taste, weight perception; they also occur cells stimuli. However mechanistic origin these not fully understood. To address this, we consider class biological circuits exhibiting property...
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,...
Networks are fundamental for our understanding of complex systems. The study networks has uncovered common principles that underlie the behavior vastly different fields study, including physics, biology, sociology, and engineering. One these is existence network motifs—small recurrent patterns can provide certain features important specific network. However, it remains unclear how motifs joined in real to make larger circuits what properties emerge from interactions between motifs. Here, we...
Abstract Fibrosis is a broad pathology of excessive scarring with substantial medical implications. The fibrotic scar produced by myofibroblasts that interact macrophages. complex process involving thousands factors, therefore, to better understand fibrosis and develop new therapeutic approaches, it necessary simplify clarify the underlying concepts. Recently, we described mathematical model for macrophage-myofibroblast cell circuit, predicting two types - hot abundant macrophages...
Understanding the tradeoffs faced by organisms is a major goal of evolutionary biology. One main approaches for identifying these Pareto task inference (ParTI). Two recent papers claim that results obtained in ParTI studies are spurious due to phylogenetic dependence (Mikami T, Iwasaki W. 2021. The flipping t-ratio test: phylogenetically informed assessment theory phenotypic evolution. Methods Ecol Evol. 12(4):696-706) or hypothetical p-hacking and population-structure concerns (Sun M, Zhang...
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...
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...
During embryogenesis, homogenous groups of cells self-organize into stereotypic spatial and temporal patterns that make up tissues organs. These emergent are controlled by transcription factors secreted signals regulate cellular fate behaviors through intracellular regulatory circuits cell-cell communication circuits. However, the principles these how their properties combined to provide spatio-temporal remain unclear. Here we develop a framework explore building-block developmental...
Abstract Most cell types in multicellular organisms can perform multiple functions. However, not all functions be optimally performed simultaneously by the same cells. Functions incompatible at level of individual cells population level, where divide labor and specialize different Division arise due to instruction tissue environment or through self-organization. Here, we develop a computational framework investigate contribution these mechanisms division within cell-type population. By...
Abstract Identification of early processes leading to complex tissue pathologies, such as inflammatory bowel diseases, poses a major scientific and clinical challenge that is imperative for improved diagnosis treatment. Most studies inflammation onset focus on cellular signaling molecules, while overlooking the environment in which they take place, continuously remodeled extracellular matrix. In this study, we used colitis models investigating extracellular-matrix dynamics during disease...