A5103245552- dental development and anomalies
- Cleft Lip and Palate Research
- Developmental Biology and Gene Regulation
- Craniofacial Disorders and Treatments
- Oral and Maxillofacial Pathology
- Cancer-related gene regulation
- Telomeres, Telomerase, and Senescence
- Genetics, Aging, and Longevity in Model Organisms
- Dental materials and restorations
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Pluripotent Stem Cells Research
- Genomic variations and chromosomal abnormalities
- Renal and related cancers
- Genomics and Chromatin Dynamics
- Bone and Dental Protein Studies
- Wnt/β-catenin signaling in development and cancer
- Osteoarthritis Treatment and Mechanisms
- Neuroendocrine Tumor Research Advances
- Head and Neck Anomalies
- Chromatin Remodeling and Cancer
- Protein Tyrosine Phosphatases
- Neurobiology and Insect Physiology Research
- Sirtuins and Resveratrol in Medicine
- Hair Growth and Disorders
Centre for Life
2007-2020
Newcastle University
2007-2020
University of Newcastle Australia
2006
Brigham and Women's Hospital
1999-2002
Harvard University
1999-2002
Witten/Herdecke University
2002
Institute of Groundwater Ecology
1998
Eppendorf (Germany)
1992
Justus-Liebig-Universität Gießen
1992
University of Göttingen
1981
Aging is an inherently stochastic process, and its hallmark heterogeneity between organisms, cell types, clonal populations, even in identical environments. The replicative lifespan of primary human cells telomere dependent; however, not understood. We show that mitochondrial superoxide production increases with age fibroblasts despite adaptive UCP-2–dependent uncoupling. This dysfunction accompanied by compromised [Ca2+]i homeostasis other indicators a retrograde response senescent cells....
Telomerase is a ribonucleoprotein that counteracts telomere shortening and can immortalise human cells. There also evidence for telomere-independent survival function of telomerase. However, its mechanism not understood. We show here TERT, the catalytic subunit telomerase, protects fibroblasts against oxidative stress. While TERT maintains length under standard conditions, telomeres increased stress shorten as fast in cells without active This because reversibly excluded from nucleus dose-...
Msx2-deficient mice exhibit progressive hair loss, starting at P14 and followed by successive cycles of wavelike regrowth loss. During the cycle, Msx2 deficiency shortens anagen phase, but prolongs catagen telogen. shafts are structurally abnormal. Molecular analyses suggest a Bmp4/Bmp2/Msx2/Foxn1 acidic keratin pathway is involved. These abnormal hairs easily dislodged in implying precocious exogen. Deficiency helps to reveal distinctive skin domains on same mouse. Each domain...
Embryonic stem cells (ESCs) are capable of extended self-renewal and maintenance pluripotency even after many population doublings. This is supported by high levels telomerase activity enhanced antioxidant protection in ESCs, both which downregulated during differentiation. To examine the role for ESC differentiation, we overexpressed reverse transcriptase subunit (Tert) murine ESCs. Increased enhances ability Tert-overexpressing improves their resistance to apoptosis, increases...
The murine paired box-containing gene Pax1 is required for normal development of the vertebral column, sternum, and scapula. Previous studies have shown that three natural mouse mutants, undulated alleles, exhibit phenotypes different severity in these skeletal elements. Nevertheless, analyses not clarified whether semidominant Undulated short-tail ( Un s ) mutation, which complete locus deleted, represents a null allele. Moreover, classical mutants did allow conclusion with respect to...
Pax9 and Msx1 encode transcription factors that are known to be essential for the switch in odontogenic potential from epithelium mesenchyme. Multiple lines of evidence suggest these molecules play an important role maintenance mesenchymal Bmp4 expression, which ultimately drives morphogenesis dental organ. Here we demonstrate is able directly regulate expression interact with at protein level enhance its ability transactivate during tooth development. In addition, tested how a missense...
Abstract Objective To identify the genes up‐regulated by interleukin‐1 (IL‐1) in combination with oncostatin M (OSM) chondrocytes that may be involved mechanisms of cartilage repair and degradation. Methods Gene microarray real‐time polymerase chain reaction (PCR) experiments were performed using RNA from SW1353 primary human articular chondrocytes. Sections prepared murine joints, injected adenovirus vectors overexpressing IL‐1 and/or OSM, analyzed immunohistochemistry for selected...
Abstract Clinical and cytogenetic examinations were performed on eight unrelated infants with duplication of part the long arm chromosome 3. A review published cases shows a clinical syndrome characterized by statomotoric retardation, shortened life span, multiple congenital anomalies (MCA) abnormal head configuration, hypertrichosis, hypertelorism, ocular anomalies, anteverted nostrils, philtrum, maxillary prognathia, down turned corners mouth, highly arched or cleft palate, micrognathia,...
The variation in mandibular morphology of mammals reflects specialisations for different diets. Omnivorous and carnivorous posses large coronoid processes, while herbivorous have proportionally smaller or absent coronoids. This is correlated with the relative size temporalis muscle that forms an attachment to process. role this development unclear. By comparative developmental biology mouse knockout studies, we demonstrate here initiation growth are two independent being intrinsic ossifying...
Tooth morphogenesis involves patterning through the activity of epithelial signaling centers that, among other molecules, secrete Sonic hedgehog (Shh). While it is known that Shh responding cells need intact primary cilia for signal transduction, roles individual components tooth are poorly understood. The clinical features individuals with Ellis-van Creveld syndrome include various dental anomalies, and we show here absence cilial protein Evc in mice causes hypo- hyperplasia defects during...
PAX9 is a transcription factor of the PAX family characterized by DNA-binding paired domain. Previous studies have suggested potential role in squamous cell differentiation and carcinogenesis oro-oesophageal epithelium. However, its functional roles remain unclear. In this study, Pax9 deficiency mouse oesophagus promoted proliferation, delayed differentiation, altered global gene expression profile. Ethanol exposure downregulated human oesophageal epithelial cells vitro forestomach tongue...
Abstract Pax9 is required for the formation of a variety organs during mouse development. The function at postnatal stages unknown since homozygosity null allele ( lacZ ) causes neonatal lethality. Recently, we have generated hypomorphic allele, neo , which contains removable neomycin resistance cassette (neo) and loxP sites flanking first two exons . Here show that FLP‐mediated in vivo excision generates phenotypically normal flox mice. Crossing mice to PGK‐Cre leads efficient recombination...
In mammals, taste buds develop in different regions of the oral cavity. Small epithelial protrusions form fungiform papillae on ectoderm-derived dorsum tongue and contain one or few buds, while soft palate without distinct papilla structures. contrast, endoderm-derived circumvallate foliate located at back a large number buds. These cluster deep trenches, which are generated by intercalating period growth between initial placode formation conversion cells into sensory cells. How trench is...
The majority of mouse genes are estimated to undergo bidirectional transcription; however, their tissue-specific distribution patterns and physiological significance largely unknown. This is in part due the lack methodology routinely assess expression natural antisense transcripts (NATs) on a large scale. Here we tested whether commercial DNA arrays can be used monitor transcription kidney brain. We took advantage reversely annotated oligonucleotides U74 genome array from Affymetrix that...
Abstract Mutations in the gene encoding T‐box transcription factor TBX22 cause X‐linked cleft palate and ankyloglossia humans. Here we show that Tbx22 expression during facial palatal development is regulated by FGF BMP signaling. Our results demonstrate FGF8 induces early face while BMP4 represses thus restricts its expression. This regulation conserved between chicken mouse, although ‐expression patterns differ considerably these two species. We suggest species‐specific differences may...