A5012582399- Cleft Lip and Palate Research
- Craniofacial Disorders and Treatments
- Bone fractures and treatments
- Hedgehog Signaling Pathway Studies
- Morphological variations and asymmetry
- dental development and anomalies
- Developmental Biology and Gene Regulation
- Bone Metabolism and Diseases
- Osteoarthritis Treatment and Mechanisms
- Connective tissue disorders research
- Mesenchymal stem cell research
- Genetic and phenotypic traits in livestock
- Genetic Mapping and Diversity in Plants and Animals
- Cell Image Analysis Techniques
- Fibroblast Growth Factor Research
- Scoliosis diagnosis and treatment
- Congenital heart defects research
- Periodontal Regeneration and Treatments
- S100 Proteins and Annexins
- Bone health and osteoporosis research
- Bone and Dental Protein Studies
- Knee injuries and reconstruction techniques
- Molecular Biology Techniques and Applications
- Spine and Intervertebral Disc Pathology
- Protease and Inhibitor Mechanisms
University of California, San Francisco
2016-2025
San Francisco General Hospital
2012-2024
Orthopaedic Trauma Association
2010-2021
Charité - Universitätsmedizin Berlin
2016
Broad Center
2011
University of Calgary
2009
Stanford University
2005
Cornell University
1993-1999
Texas A&M University
1993
Fractures heal predominantly through the process of endochondral ossification. The classic model ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate transdifferentiate osteoblasts in growth plate during regeneration, yet mechanism(s) regulating this remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic at chondro-osseous border fracture callus,...
OBJECTIVES. Large facial infantile hemangiomas have higher rates of complications than small localized hemangiomas, more often require treatment, and can be associated with neurological, ophthalmologic, cardiac anomalies (PHACE syndrome). The anatomic patterns these are referred to as “segmental” despite a lack precise definitions. Our study aims define based on clinically observed patterns. secondary goal is relate the currently accepted developmental gain insight into hemangioma...
A fundamental set of patterning genes may define the global organization craniofacial region. One our goals has been to identify these basic and understand how they regulate outgrowth frontonasal process, which gives rise mid upper face. We identified a molecular boundary in process ectoderm, defined by juxtaposed domains Fibroblast growth factor 8 Sonic hedgehog,which presaged initial site outgrowth. Fate maps confirmed that this region later demarcated dorsoventral axis beak. Ectopic...
The goal of this work was to define cellular and molecular changes that occur during fracture healing as animals age. We compared the molecular, cellular, histological progression skeletal repair in juvenile (4 weeks old), middle-aged (6 months elderly (18 old) mice at 3, 5, 7, 10, 14, 21, 28, 35 days post-fracture, using a non-stabilized tibia model. Our analyses demonstrated there sharp decline potential between animals, while more subtle decrease apparent mice. By three after fracture,...
Vascular damage accompanying skeletal injury leads to an ischemic environment, and in clinical settings the extent of vascular is directly correlated with failure repair. However, exact mechanism(s) underlying ischemia-related defects bone healing are not well understood. To better understand mechanism facilitate development novel interventions treat fractures, a mouse model long fracture environment was created. Ischemia induced by femoral artery resection prior tibia fracture. Fractures...
One of the most perplexing questions in clinical genetics is why patients with identical gene mutations oftentimes exhibit radically different features. This inconsistency between genotype and phenotype illustrated malformation spectrum holoprosencephaly (HPE). Family members carrying sonic hedgehog (SHH) can a variety facial features ranging from cyclopia to subtle midline asymmetries. Such intrafamilial variability may arise environmental factors acting conjunction that collectively reduce...
SUMMARY Bone injury induces an inflammatory response that involves neutrophils, macrophages and other cells. The recruitment of cells to sites occurs in specific signaling pathways. CC chemokine receptor type 2 (CCR2) is crucial for recruiting macrophages, as well regulating osteoclast function. In this study, we examined fracture healing Ccr2−/− mice. We first demonstrated the expression Ccr2 transcripts filtration into calluses were most robust during early phases healing. then determined...
Interactions among the forebrain, neural crest and facial ectoderm regulate development of upper jaw. To examine these interactions, we activated Sonic hedgehog (SHH) pathway in brain. Beginning 72 hours after activation SHH pathway, growth within avian frontonasal process (FNP) was exaggerated lateral regions impaired medial regions. This pattern is similar to that mice superimposed a mammalian-like morphology on Jaw controlled by signals from ectodermal zone (FEZ), divergent morphologies...
ABSTRACT Although bone has great capacity for repair, there are a number of clinical situations (fracture non-unions, spinal fusions, revision arthroplasty, segmental defects) in which auto- or allografts attempt to augment regeneration by promoting osteogenesis. Critical failures associated with current grafting therapies include osteonecrosis and limited integration between graft host tissue. We speculated that the underlying problem techniques is they promote through direct Here we...
Extracellular matrix (ECM) remodeling is important during bone development and repair. Because metalloproteinase 13 (MMP13, collagenase-3) plays a role in long development, we have examined its adult skeletal In this study find that MMP13 expressed by hypertrophic chondrocytes osteoblasts the fracture callus. We demonstrate required for proper resorption of cartilage normal non-stabilized healing, which occurs via endochondral ossification. However, no difference callus strength was detected...
Abstract Age affects fracture repair; however, the underlying mechanisms are not well understood. The goal of this study was to assess effects that age has on vascularization during healing. Tibial fractures were created in juvenile (4‐week‐old), middle‐aged (6‐month‐old), and elderly (18‐month‐old) mice. length density surface blood vessels within calluses analyzed using stereology at 7 days after fracture. expression molecules regulate vascular invasion callus also compared among three...
Variation is an intrinsic feature of biological systems, yet developmental biology does not frequently address population-level phenomena. Sonic hedgehog (SHH) signaling activity in the vertebrate forebrain and face thought to contribute continuous variation morphology upper jaw, but despite its potential explanatory power, this idea has never been quantitatively assessed. Here, we test hypothesis with experimental design that explicitly focused on generation measurement multivariate shape,...
Abstract After bone injury, developmental processes such as endochondral and intramembranous ossification are recapitulated the skeleton regenerates. In contrast to development, skeletal healing involves inflammation. During early stages of a variety inflammatory cells infiltrate injured site, debride wound, stimulate repair process. Little is known about process during repair. this work, we examined effect pro‐inflammatory cytokine, Interleukin‐1 beta (IL‐1β), on osteoblast stem cell...
A central issue in biology concerns the presence, timing and nature of phylotypic periods development, but whether, when why species exhibit conserved morphologies remains unresolved. Here, we construct a developmental morphospace to show that amniote faces share period reduced shape variance convergent growth trajectories from prominence formation through fusion, after which phenotypic diversity sharply increases. We predict silico outcomes unoccupied morphospaces experimentally validate...