A5074901217- Bone health and treatments
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- Bone Metabolism and Diseases
- Cell Adhesion Molecules Research
- Phagocytosis and Immune Regulation
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- Osteoarthritis Treatment and Mechanisms
- RNA modifications and cancer
- Connective tissue disorders research
- Cancer, Hypoxia, and Metabolism
- Bone health and osteoporosis research
- Cancer-related Molecular Pathways
- Kruppel-like factors research
- Erythrocyte Function and Pathophysiology
- Molecular Biology Techniques and Applications
- Hematological disorders and diagnostics
- Mesenchymal stem cell research
- Bone Tumor Diagnosis and Treatments
- Cytokine Signaling Pathways and Interactions
- Alkaline Phosphatase Research Studies
- Bone and Joint Diseases
- Cancer survivorship and care
Van Andel Institute
2018-2025
Memorial Sloan Kettering Cancer Center
2024
University of Michigan
2010-2019
Michigan United
2010
Apoptosis occurs at an extraordinary rate in the human body and effective clearance of dead cells (efferocytosis) is necessary to maintain homeostasis promote healing, yet contribution impact this process bone unclear. Bone formation requires that marrow stromal (BMSCs) differentiate into osteoblasts which direct matrix either become osteocytes, lining cells, or undergo apoptosis. A series experiments were performed identify regulators consequences macrophage efferocytosis apoptotic BMSCs...
Abstract Proteoglycan 4 (Prg4), known for its lubricating and protective actions in joints, is a strong candidate regulator of skeletal homeostasis parathyroid hormone (PTH) anabolism. Prg4 PTH-responsive gene bone liver. null mutant mice were used to investigate the impact proteoglycan on development, remodeling, PTH anabolic actions. Young wild-type administered intermittent PTH(1–34) or vehicle daily from 21 days. had decreased growth plate hypertrophic zones, trabecular bone, serum...
Parathyroid hormone (PTH) stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6) is upregulated by PTH and hematopoiesis. The purpose this investigation was to identify actions IL-6 in cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L), PTH, Flt-3L plus or vehicle control. alone increased adherent non-adherent cells. did not directly impact osteoclastic but acted concert further...
ABSTRACT Macrophages have established roles supporting bone formation. Despite their professional phagocytic nature, the role of macrophage phagocytosis in homeostasis is not well understood. Interestingly, apoptosis a pivotal feature cellular regulation and primary fate osteoblasts apoptosis. Efferocytosis (phagocytosis apoptotic cells) key physiologic process for many tissues, associated with expression osteoinductive factors. To test effects depletion compromised on bone, 16-week-old male...
ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development cancer. Conventionally, their biological functions have been associated regulating WNT signaling receptor ubiquitination degradation. However, our proteogenomic studies revealed EGFR as the most negatively correlated protein
ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development cancer. Conventionally, their biological functions have been associated regulating WNT signaling receptor ubiquitination degradation. However, our proteogenomic studies revealed EGFR as the protein most negatively correlated ZNRF3/RNF43 mRNA levels multiple human cancers. Through biochemical investigations, we demonstrate that interact via extracellular domains, leading to subsequent...
Ineffective oral wound healing is detrimental to patients' health-related quality of life. Delineating the cellular mechanisms involved in optimal will elicit better approaches treating patients with compromised healing. Osteal macrophages have recently emerged as important positive regulators bone turnover. The contributions long been studied, but their role osseous following tooth extraction less clear. Clodronate-loaded liposomes were used a tool deplete C57BL/6J mice and assess fill...
Proteoglycan 4 (PRG4), a critical protective factor in articular joints, is implicated hematopoietic progenitor cell expansion and megakaryopoiesis. PRG4 loss-of-function mutations result camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome, which characterized primarily by precocious joint failure. was identified as novel parathyroid hormone (PTH) responsiveness gene osteoblastic cells bone, investigated potential mediator of PTH actions on hematopoiesis. Sixteen-week-old...
A prolonged increase in proinflammatory cytokines is associated with osteoporotic and autoimmune bone loss and, conversely, anti-inflammatory pathways are protection against loss. Milk fat globule-epidermal growth factor (MFG-E)-8 a glycoprotein that proresolving, regulates apoptotic cell clearance, has been linked to disease skeletal homeostasis. The role of MFG-E8 the young vs. adult skeleton was determined mice deficient (KO). In vivo, trabecular similar MFG-E8KO wild-type (WT) at 6 16...
Abstract The activation of the Wnt/β‐catenin signaling pathway is critical for skeletal development but surprisingly little known about requirements specific frizzled (Fzd) receptors that recognize Wnt ligands. To define contributions individual Fzd proteins to osteoblast function, we profiled expression all 10 mammalian during calvarial differentiation. Expression Fzd4 was highly upregulated in vitro differentiation and therefore targeted further study. Mice lacking mature osteoblasts had...
ABSTRACT Frizzled 2 (FZD2) is a transmembrane Wnt receptor. We previously identified pathogenic human FZD2 variant in individuals with FZD2-associated autosomal dominant Robinow syndrome. The encoded protein premature stop and loss of 17 amino acids, including region the consensus dishevelled-binding sequence. To model this variant, we used zygote microinjection i-GONAD-based CRISPR/Cas9-mediated genome editing to generate mouse allelic series. Embryos mosaic for humanized Fzd2W553* knock-in...
Abstract Proteoglycan‐4 ( Prg4 ) protects synovial joints from arthropathic changes by mechanisms that are incompletely understood. Parathyroid hormone (PTH), known for its anabolic actions in bone, increases expression and has been reported to inhibit articular cartilage degeneration joints. To investigate the effect of PTH on cartilage, 16‐week‐old mutant wild‐type mice were treated with intermittent (1–34) or vehicle control daily six weeks. Analyses included histology knee joint,...
ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development cancer. Conventionally, their biological functions have been associated regulating WNT signaling receptor ubiquitination degradation. However, our proteogenomic studies revealed EGFR as the most negatively correlated protein ZNRF3/RNF43 mRNA levels multiple human cancers. Through biochemical investigations, we demonstrate that interact via extracellular domains, leading to subsequent...
ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development cancer. Conventionally, their biological functions have been associated regulating WNT signaling receptor ubiquitination degradation. However, our proteogenomic studies revealed EGFR as the most negatively correlated protein ZNRF3/RNF43 mRNA levels multiple human cancers. Through biochemical investigations, we demonstrate that interact via extracellular domains, leading to subsequent...
Abstract It is currently accepted that Wnt receptors, Frizzleds (Fzd), have high functional redundancy, making individual receptors challenging to target therapeutically. Specifically, Fzd2 believed be functionally redundant with Fzd1 and Fzd7, findings which were based largely on previously published global knockout mouse studies. Conversely, a model developed by the International Mouse Phenotype Consortium (IMPC) early embryonic lethal, suggesting critical for development. If deletion of...
Hypophosphatasia, the rare heritable disorder caused by TNAP enzyme mutations, presents wide-ranging severity of bone hypomineralization and skeletal abnormalities. Intermittent PTH (1-34) increased long volume in Alpl-/- mice but did not alter skull phenotype. may have therapeutic value for adults with deficiency-associated osteoporosis.Hypophosphatasia is mutations tissue non-specific alkaline phosphatase (TNAP) leading to deficiency. Individuals hypophosphatasia commonly present The...