A5004582329- Hair Growth and Disorders
- Microtubule and mitosis dynamics
- Skin and Cellular Biology Research
- Wnt/β-catenin signaling in development and cancer
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Renal and related cancers
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- 14-3-3 protein interactions
- Genetic and Kidney Cyst Diseases
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Hippo pathway signaling and YAP/TAZ
- Cancer and Skin Lesions
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- RNA regulation and disease
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Tissue Engineering and Regenerative Medicine
University of Michigan
2023-2025
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2016-2024
University of Cologne
2017-2024
Michigan United
2024
University Hospital Cologne
2016-2023
Memorial Sloan Kettering Cancer Center
2014-2020
Columbia University Irving Medical Center
2019
Kettering University
2011-2017
Columbia University
2003-2009
Developmental Studies Center
2009
Centrosomes are the microtubule-organizing centers of animal cells that organize interphase microtubules and mitotic spindles. Centrioles microtubule-based structures centrosomes, a defined set proteins, including spindle assembly defective-4 (SAS4) (CPAP/CENPJ), is required for centriole biogenesis. The biological functions centrioles centrosomes vary among animals, mammalian have not been genetically defined. Here we use null mutation in mouse Sas4 to define cellular developmental vivo....
Abstract Poised enhancers (PEs) represent a genetically distinct set of distal regulatory elements that control the expression major developmental genes. Before becoming activated in differentiating cells, PEs are already bookmarked pluripotent cells with unique chromatin and topological features could contribute to their privileged properties. However, since were originally characterized embryonic stem (ESC), it is currently unknown whether functionally conserved vivo. Here, we show 3D...
A key initial event in hair follicle morphogenesis is the localised thickening of skin epithelium to form a placode, partitioning future from interfollicular epidermis. Although many developmental signalling pathways are implicated morphogenesis,the role epidermal growth factor (EGF) and keratinocyte (KGF,also known as FGF7) receptors not defined. EGF receptor (EGFR) ligands have previously been shown inhibit developing follicles; however, underlying mechanisms characterised. Here we show...
Abstract While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that protein CSDE1 (cold shock domain containing E1) highly expressed hESCs to maintain their undifferentiated state prevent default neural fate. Notably, loss accelerates...
SAS-6 (SASS6) is essential for centriole formation in human cells and other organisms but its functions the mouse are unclear. Here, we report that Sass6 -mutant embryos lack centrioles, activate mitotic surveillance cell death pathway, arrest at mid-gestation. In contrast, not required embryonic stem (mESCs), to maintain architecture. Of note, centrioles appeared after just one day of culture blastocysts, from which mESCs derived. Conversely, number with centrosomes drastically decreased...
The esterification of alcohols such as sterols, diacylglycerols, and monoacylglycerols with fatty acids represents the formation both storage cytoprotective molecules. Conversely, overproduction these molecules is associated several disease pathologies, including atherosclerosis obesity. human acyl-CoA:diacylglycerol acyltransferase (DGAT) 2 gene superfamily comprises seven members, four which have been previously implicated in synthesis di- or triacylglycerol. remaining 3 members comprise...
Abstract The development of complex stratified epithelial barriers in mammals is initiated from single-layered epithelia. How stratification and fueled are still open questions. Previous studies on skin epidermal suggested a central role for perpendicular/asymmetric cell division orientation the basal keratinocyte progenitors. Here, we use centrosomes, that organize mitotic spindle, to test whether linked. Genetically ablating centrosomes developing epidermis leads activation p53-, 53BP1-...
The blueprints of developing organs are preset at the early stages embryogenesis. Transcriptional and epigenetic mechanisms proposed to developmental trajectories. However, we reveal that competence for future cardiac fate human embryonic stem cells (hESCs) is in pluripotency by a specialized mRNA translation circuit controlled RBPMS. RBPMS recruited active ribosomes hESCs control essential factors needed commitment program, including Wingless/Integrated (WNT) signaling. Consequently, loss...
Ectodermal appendage formation requires hedgehog (HH) signal reception, its conduction through the primary cilium and activation of Gli transcription factors (TF). How HH signalling induces cell-type-specific responses TF in stem cells (SCs) their ciliadependence remain open questions. Here, we use conditional mouse mutants to genetically dissect roles cilia mediators skin epithelium. Upon Gli2 depletion, hair follicle (HF) morphogenesis is delayed whereas sebaceous gland (SG) enhanced,...
Abstract: Desmogleins play critical roles in cell adhesion and skin blistering diseases, as they are the target antigens of autoimmune antibodies bacterial toxins. We recently cloned several novel members desmoglein gene family, bringing number desmogleins to four rat human genomes six mouse. Here, we have produced a monoclonal antibody cytoplasmic epitope Dsg4, assessed its specificity compared it existing Dsg1–3 antibodies. also demonstrated cross‐reactivity commercially available often...
Significance CTLs fight intracellular pathogens and cancer by forming a close cell–cell interaction, called the immunological synapse with an infected or transformed target cell then releasing toxic proteins directionally into synaptic space. Directional secretion is thought to depend on polarization of CTL centrosome position just beneath center synapse. We show here that lacking centrioles, which are core structural components centrosomes, unexpectedly retain capacity for polarized...
Abstract The mammalian epidermis is the first line of defense against external environmental challenges including dehydration. undergoes a highly intricate developmental program in utero, transforming from simple to complex stratified epithelium. During this process stratification and differentiation, epidermal keratinocytes express defined set structural proteins, mainly keratins, whose expression controlled by largely unknown mechanisms. In order identify novel factors contributing...
Significance Striatin-interacting phosphatases and kinases (STRIPAK) complexes can regulate the cytoskeleton cell migration in lines, but their roles vivo mammals are not known. Here, we show that mouse embryos lack striatin-interacting protein 1 (STRIP1), a core component of STRIPAK complexes, arrest at midgestation with striking morphological defects. Strip1 mutants trunk, both paraxial axial mesoderm fail to elongate along anterior–posterior body axis. Mesodermal cells from have defects...
Centrosomes, composed of two centrioles and pericentriolar material, organize mitotic spindles during cell division template cilia interphase. The first few divisions mouse development occur without centrioles, which form around embryonic day (E) 3. However, disruption centriole biogenesis in Sas-4 null mice leads to arrest E9. Centriole loss Sas-4-/- embryos causes prolonged mitosis p53-dependent death. Studies vitro discovered a similar USP28-, 53BP1-, surveillance pathway that cycle...