A5010605531- TGF-β signaling in diseases
- Bone Metabolism and Diseases
- Mesenchymal stem cell research
- Bone health and treatments
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- Hedgehog Signaling Pathway Studies
- Erythrocyte Function and Pathophysiology
- Oral and Maxillofacial Pathology
- NF-κB Signaling Pathways
- Parathyroid Disorders and Treatments
- Tissue Engineering and Regenerative Medicine
- Cancer-related gene regulation
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Fibroblast Growth Factor Research
- Developmental Biology and Gene Regulation
- Vitamin D Research Studies
- Kruppel-like factors research
- Tendon Structure and Treatment
- Magnesium in Health and Disease
- Heterotopic Ossification and Related Conditions
- Cytokine Signaling Pathways and Interactions
- Chemokine receptors and signaling
- Immunodeficiency and Autoimmune Disorders
Massachusetts General Hospital
2023
Harvard University
2017-2023
Harvard Stem Cell Institute
2020
Indian Institute of Technology Kanpur
2012-2020
Central Institute for Research on Buffaloes
2013
Mechanical forces are fundamental regulators of cell behaviors. However, molecular regulation mechanotransduction remain poorly understood. Here, we identified the mechanosensitive channels Piezo1 and Piezo2 as key force sensors required for bone development osteoblast differentiation. Loss Piezo1, or more severely Piezo1/2, in mesenchymal progenitor cells, led to multiple spontaneous fractures newborn mice due inhibition differentiation increased resorption. In addition, loss Piezo1/2...
Significance Understanding molecular and cellular mechanisms of rare genetic diseases provides invaluable insights into the human biology pathology both related common diseases. Fibrous dysplasia (FD) is a mosaic disease resulting from postzygotic activating mutations GNAS . The mouse models we created allowed us to precisely model FD by expressing Gα s mutation under control its endogenous locus. We found in our that up-regulated Wnt/β-catenin signaling resulted impaired differentiation...
Significance Understanding the cell origin and molecular mechanisms underlying rare genetic diseases provides invaluable insights into human biology pathology of not only but also related common disorders. Autosomal dominant hyper immunoglobulin-E syndrome (AD-HIES) or Job is a disease with skeletal defects resulting from mutations in STAT3 gene. We have modeled abnormality Syndrome by deleting Stat3 using cell-specific Cre lines. found that required osteoblast lineage cells for development...
BMP signaling pathway is critical for vertebrate development and tissue homeostasis. High-throughput molecular genetic screening may reveal novel players regulating response while chemical of modifiers have clinical significance. It therefore important to generate a cell-based tool execute such screens.We established responsive reporter cell line by stably integrating dual luciferase construct in the immortalized calvarial osteoblast cells isolated from tamoxifen inducible Bmp2; Bmp4 double...
Tendon injuries are common in race horses, and mesenchymal stem cells (MSCs) isolated from adult foetal tissue have been used for tendon regeneration. In the present study, we evaluated equine amniotic fluid (AF) as a source of MSCs standardised methodology markers their vitro tenogenic differentiation. Plastic-adherent colonies were 12 20 AF samples by day 6 after seeding 70-80% cell confluency was reached 17. These expressed surface [cluster differentiation (CD)73, CD90 CD105] reverse...
Low circulating phosphate (Pi) leads to rickets, characterized by expansion of the hypertrophic chondrocytes (HCs) in growth plate due impaired HC apoptosis. Studies HCs demonstrate that Pi activates Raf/MEK/ERK1/2 and mitochondrial apoptotic pathways. To determine how these pathways, a small-molecule screen was undertaken identify inhibitors Pi-induced ERK1/2 phosphorylation HCs. Vascular endothelial factor receptor 2 (VEGFR2) identified as target.
Abstract X-linked hypophosphatemia (XLH) is the most common form of hereditary hypophosphatemic rickets. The genetic basis for XLH loss function mutations in phosphate-regulating endopeptidase (PHEX), which leads to increased circulating fibroblast growth factor 23 (FGF23). This increase FGF23 impairs activation vitamin D and attenuates renal phosphate reabsorption, leading Previous studies have demonstrated that ablating Hyp mouse model hyperphosphatemia, high levels 1,25-dihydroxyvitamin...