A5025727183- Skin and Cellular Biology Research
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Liver physiology and pathology
- RNA Interference and Gene Delivery
- Dermatological and Skeletal Disorders
- Biomedical Ethics and Regulation
- Cellular Mechanics and Interactions
- Pancreatic function and diabetes
- DNA Repair Mechanisms
- Cell Adhesion Molecules Research
- RNA regulation and disease
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Silk-based biomaterials and applications
- Viral Infectious Diseases and Gene Expression in Insects
- Bone Metabolism and Diseases
- Epigenetics and DNA Methylation
- Nitric Oxide and Endothelin Effects
- 14-3-3 protein interactions
- Bone and Dental Protein Studies
- Autoimmune Bullous Skin Diseases
- Virus-based gene therapy research
- Genetic Neurodegenerative Diseases
- Tissue Engineering and Regenerative Medicine
University of Minnesota
2016-2021
Stem Cell Institute
2019
Medical College of Wisconsin
2012-2018
Twin Cities Orthopedics
2018
Complete and robust human genome duplication requires loading minichromosome maintenance (MCM) helicase complexes at many DNA replication origins, an essential process termed origin licensing. Licensing is restricted to G1 phase of the cell cycle, but length varies widely among types. Using quantitative single-cell analyses, we found that pluripotent stem cells with naturally short phases load MCM much faster than their isogenic differentiated counterparts long phases. During earliest stages...
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe disorder caused by mutations to the COL7A1 gene that deactivate production of structural protein essential for skin integrity. Haematopoietic cell transplantation can ameliorate some symptoms; however, significant side effects from allogeneic transplant procedure occur and unresponsive areas blistering persist. Therefore, we employed genome editing in patient-derived cells create an autologous platform multilineage engineering...
Gene editing with CRISPR/Cas9 is revolutionizing biotechnology and medical research, yet affordable, efficient, tailorable delivery systems are urgently needed to advance translation. Herein, a series of monodisperse amphiphilic block polymers poly[ethylene oxide-b-2-(dimethylamino) ethyl methacrylate-b-n-butyl methacrylate] (PEO-b-PDMAEMA-b-PnBMA) that housed three PEO lengths (2, 5, 10 kDa) variant lacking (PDMAEMA-b-PnBMA) were synthesized via controlled radical polymerization assembled...
When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. We proposed that homogeneous populations could be generated by fluorescence-activated sorting (FACS). Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes. Analyses the expression profiles during differentiation iPSCs revealed SLC10A1, CLRN3, and AADAC were highly enriched final stages...
Elucidating the molecular basis of cell differentiation will advance our understanding organ development and disease. We have previously established a protocol that efficiently produces cells with hepatocyte characteristics from human induced pluripotent stem cells. used this model to identify transcription factor nuclear 4 α (HNF4A) as being essential during transition endoderm hepatic fate. Here, we sought define mechanisms through which HNF4A controls process. By combining chromatin...
Fibroblast growth factors (FGFs) are required to specify hepatic fate within the definitive endoderm through activation of FGF receptors (FGFRs). While signaling pathways involved in specification well understood, mechanisms which FGFs induce character ill defined. Here we report identification genes whose expression is directly regulated by FGFR activity during transition from progenitor cell. The immediate early that were identified include those encoding transcription factors, and...
Revertant mosaicism has been described previously in recessive dystrophic epidermolysis bullosa (RDEB), manifesting as regions of skin with normal mechanical and biological characteristics. Here we report the discovery revertant dermal fibroblasts, unique that all other documented cases occur epidermal keratinocytes. To determine cause found a patient RDEB from isolated keratinocytes fibroblasts blister mosaic regions. Skin biopsies were taken RDEB. Allele identification was confirmed type...
Background Tat-interactive protein 60 (Tip60) is a member of the MYST family histone acetyltransferases. Studies using cultured cells have shown that Tip60 has various functions including DNA repair, apoptosis and cell-cycle regulation. We globally ablated gene (Htatip), observing Tip60-null embryos die at blastocyst stage (Hu et al. Dev.Dyn.238:2912;2009). Although adult heterozygous (Tip60+/−) mice reproduce normally without haploinsufficient phenotype, stress caused by Myc over-expression...
Fast, efficient, and inexpensive methods for delivering functional nucleic acids to primary human cell types are needed advance regenerative medicine therapies. Plasmid-based gene editing (such as with CRISPR-Cas9) can require the delivery of plasmids that large (∼9.5–13 kbp) in comparison common reporter (∼5–8 kbp). To develop more efficient plasmid vehicles, we investigated effect size on transfection dermal fibroblasts (HDFs) induced pluripotent stem cells (iPSCs) using a heparin-treated...
Osteoclasts are hematopoietic stem cell-derived multinucleated cells necessary for bone remodeling and resorption. TCIRG1 encodes a protein that is an adenosine triphosphate (ATP)-dependent vacuolar proton pump required this process. Recessive loss-of-function mutations in both copies of gene lead to impairment osteoclast function, with increased density, skeletal mass, early mortality.We isolated fibroblasts from patient the compound heterozygous c.1549G>A (p.517D>N) c.2236C>T (p.746Q>X),...
Squamous cell carcinoma (SCC) develops in more than 80% of individuals with the skin blistering disorder recessive dystrophic epidermolysis bullosa (RDEB). In contrast UV-induced SCC, RDEB-SCC results from damage and has a high proliferative metastatic rate 5-year survival near zero. Our objective is to determine mechanisms underlying increased tendencies RDEB-SCC. cultured lines were treated RDEB non-RDEB fibroblast conditioned media assayed for migration invasion without small molecule...
ABSTRACT Complete and robust human genome duplication requires loading MCM helicase complexes at many DNA replication origins, an essential process termed origin licensing. Licensing is restricted to G1 phase of the cell cycle, but length varies widely among types. Using quantitative single analyses we found that pluripotent stem cells with naturally short phases load much faster than their isogenic differentiated counterparts long phases. During earliest stages differentiation towards all...
Background: Recessive dystrophic epidermolysis bullosa (RDEB) and junctional EB (JEB) are inherited disorders characterised by fragility blistering of epithelial tissues leading to pain, pruritus, adherent scarring. The severity chronic nature the resultant skin wounds significantly reduces quality length life. Current therapies primarily consist protective bandaging nutritional supplementation; there is no cure for these disorders. Although results from a lack C7 protein laminin-332 (JEB),...