A5041670277- Cleft Lip and Palate Research
- TGF-β signaling in diseases
- dental development and anomalies
- Congenital heart defects research
- Glycosylation and Glycoproteins Research
- Neonatal Respiratory Health Research
- Lysosomal Storage Disorders Research
- Hedgehog Signaling Pathway Studies
- Cancer-related gene regulation
- Oral and Maxillofacial Pathology
- Chronic Myeloid Leukemia Treatments
- Craniofacial Disorders and Treatments
- Congenital Diaphragmatic Hernia Studies
- Connective tissue disorders research
- Cell Adhesion Molecules Research
- Renal and related cancers
- Acute Lymphoblastic Leukemia research
- Heterotopic Ossification and Related Conditions
- Cellular transport and secretion
- Tracheal and airway disorders
- Carbohydrate Chemistry and Synthesis
- Genetic and Kidney Cyst Diseases
- Protein Kinase Regulation and GTPase Signaling
- Bone Metabolism and Diseases
- Genetic Syndromes and Imprinting
University of Michigan–Ann Arbor
2016-2025
Material Sciences (United States)
2013-2020
The University of Texas Southwestern Medical Center
2017
Yale University
2017
University of North Carolina at Chapel Hill
2017
Southwestern Medical Center
2017
Gwangju Institute of Science and Technology
2017
Michigan United
2011-2013
Children's Hospital of Los Angeles
2002-2011
Organogenesis (United States)
2011
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive and profoundly disabling heterotopic ossification (HO). Here we show that fibro/adipogenic progenitors (FAPs) are major cell-of-origin of HO in an accurate genetic mouse model FOP (Acvr1 tnR206H ). Targeted expression the disease-causing type I bone morphogenetic protein (BMP) receptor, ACVR1(R206H), to FAPs recapitulates full spectrum observed patients. ACVR1(R206H)-expressing...
Cardiac neural crest cells are multipotent migratory that contribute to the formation of cardiac outflow tract and pharyngeal arch arteries. Neural crest-related developmental defects account for a large proportion congenital heart disorders. Recently, genetic bases some these disorders have been elucidated, signaling pathways required induction, migration differentiation emerged. Bone morphogenetic proteins comprise family secreted ligands implicated in numerous aspects organogenesis,...
The pathologic development of heterotopic ossification (HO) is well described in patients with extensive trauma or hyperactivating mutations the bone morphogenetic protein (BMP) receptor ACVR1. However, identification progenitor cells contributing to this process remains elusive. Here we show that connective tissue contribute a substantial amount HO anlagen caused by using postnatal, tamoxifen-inducible, scleraxis-lineage restricted reporter mice (Scx-creERT2/tdTomatofl/fl ). When...
Abstract Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification (HO). Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO. This study focuses on the ability collagen receptor, discoidin domain receptor 2 (DDR2), to regulate activity. As will be shown, induction formation by subcutaneous BMP2 implants is severely compromised in Ddr2...
Studies on transforming growth factor β3 (TGF-β3) deficient mice have shown that TGF-β3 plays a critical role in palatogenesis. These null mutant clefting of the secondary palate, caused by defect process fusion palatal shelves. A step mammalian is removal medial edge epithelial cells from midline seam and formation continuous mesenchyme. To determine more detail palatogenesis, we cultured wild-type control shelves an organ culture system. The fate was studied vitro using vital cell labeling...
Philadelphia chromosome-positive leukemias result from the fusion of BCR and ABL genes, which generates a functional chimeric molecule. The Abr protein is very similar to Bcr but lacks structural domain may influence its biological regulatory capabilities. Both have GTPase-activating (GAP) those found in other proteins that stimulate GTP hydrolysis by members Rho family GTP-binding proteins, as well region homology with guanine nucleotide dissociation-stimulating DBL oncogene product. We...
Cleft lip and palate syndromes are among the most common congenital malformations in humans. Mammalian palatogenesis is a complex process involving highly regulated interactions between epithelial mesenchymal cells of to permit correct positioning palatal shelves, remodeling extracellular matrix (ECM), subsequent fusion shelves. Here we show that several metalloproteinases (MMPs), including cell membrane-associated MMP (MT1-MMP) tissue inhibitor metalloproteinase-2 (TIMP-2) were expressed by...
BackgroundThe role of ß-catenin signaling in mesodermal lineage formation and differentiation has been elusive.MethodologyTo define the these processes, we used a Dermo1(Twist2)Cre/+ line to target floxed β-catenin allele, throughout embryonic mesenchyme. Strikingly, Dermo1Cre/+; β-cateninf/− conditional Knock Out embryos largely phenocopy Pitx1−/−/Pitx2−/− double knockout embryos, suggesting that mesenchyme depends mostly on PITX family transcription factors. We have dissected this...
Amniotes, regardless of genetic sex, develop two sets genital ducts: the Wolffian and Müllerian ducts. For normal sexual development to occur, one duct must differentiate into its corresponding organs, other regress. In mammals, differentiates male reproductive tract, mainly vasa deferentia, epididymides, seminal vesicles, whereas develops four components female oviducts, uterus, cervix, upper third vagina. males, fetal Leydig cells produce testosterone, which stimulates differentiation...
Implantation of a blastocyst in the uterus is multistep process tightly controlled by an intricate regulatory network interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands receptors are expressed pregnant mice, BMP2 has been shown to be key regulator implantation. In this study, we investigated roles BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy producing mice carrying conditional ablation Alk2 (Alk2 cKO mice). absence...
Goblet cell metaplasia and mucus overproduction contribute to the pathogenesis of chronic lung diseases, including asthma obstructive pulmonary disease (COPD). Notch signaling regulates fate decisions is crucial in controlling goblet differentiation gut epithelium. Little known, however, about how endogenous influences program that takes place postnatal lung. Using a combination genetic vitro approaches here we provide evidence novel role for restricting airway epithelium during period....
Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are members transforming factor family. There three TGF-ß isoforms–TGF- ß 1, 2, 3, each isoform showing unique expression pattern, suggesting they play distinct function during development repair. Previous studies reported an exclusive role for 3 in orofacial potent anti-scarring effect. However, TGF- excisional wound keratinocyte migration...
Although the importance of TGF-β superfamily signaling in craniofacial growth and patterning is well established, precise details its mechanisms are still poorly understood. This part because concentration studies on role Smad-dependent (so-called “canonical”) pathways relative to Smad-independent ones many biological processes. Here, we have addressed TGF-β-activated kinase 1 (Tak1, Map3k7), one key mediators (noncanonical) development, by deleting Tak1 specifically neural crest lineage....