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23 results on '"Twaroski, Kirk"'

3. Impaired Mitochondrial and Metabolic Function of Fibroblasts Derived from Patients with Recessive Dystrophic and Junctional Epidermolysis Bullosa

Author

Ilona Tietzova, Twaroski, Kirk R., Eide, Cindy R., Ostrander, Julie H., Peter Crawford, and Jakub Tolar

Subjects
fractal dimension, mitochondria, integumentary system, fibroblasts, lcsh:Dermatology, cellular bioenergetics, epidermolysis bullosa, lcsh:RL1-803
Abstract

Background: Recessive dystrophic epidermolysis bullosa (RDEB) and junctional EB (JEB) are inherited disorders characterised by fragility and blistering of epithelial tissues leading to pain, pruritus, and adherent scarring. The severity and chronic nature of the resultant skin wounds significantly reduces quality and length of life. Current therapies primarily consist of protective bandaging and nutritional supplementation; there is no cure for these disorders. Although the skin fragility results from a lack of C7 protein (RDEB) and laminin-332 (JEB), other serious aspects of these disorders, such as inflammation that interferes with healing and aggressive squamous cell carcinoma, have not been completely elucidated. Recent research has suggested that mitochondrial function plays a significant role in skin healing. Objective: To evaluate how mitochondrial function differs in patients with RDEB and JEB. Method: The energy status of RDEB and JEB patient-derived fibroblasts was determined by Seahorse analysis and metabolite production. The energetics and overall morphology of RDEB and JEB patient-derived fibroblasts were assayed as a measure of metabolic stress. Results: EB patient-derived fibroblasts showed impaired oxidative phosphorylation with concomitant compensation by glycolysis. Morphological parameters were altered in RDEB and JEB fibroblasts compared with controls. Conclusion: This is the first study to describe changes in mitochondrial energy metabolism, metabolic profile, and mitochondrial morphology of EB patients.

Published
2020
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12. ATXN1-CIC Complex Is the Primary Driver of Cerebellar Pathology in Spinocerebellar Ataxia Type 1 through a Gain-of-Function Mechanism

Author

Rousseaux, Maxime W.C., primary, Tschumperlin, Tyler, additional, Lu, Hsiang-Chih, additional, Lackey, Elizabeth P., additional, Bondar, Vitaliy V., additional, Wan, Ying-Wooi, additional, Tan, Qiumin, additional, Adamski, Carolyn J., additional, Friedrich, Jillian, additional, Twaroski, Kirk, additional, Chen, Weili, additional, Tolar, Jakub, additional, Henzler, Christine, additional, Sharma, Ajay, additional, Bajić, Aleksandar, additional, Lin, Tao, additional, Duvick, Lisa, additional, Liu, Zhandong, additional, Sillitoe, Roy V., additional, Zoghbi, Huda Y., additional, and Orr, Harry T., additional

Published
2018
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13. Rapid DNA replication origin licensing protects stem cell pluripotency

Author

Matson, Jacob Peter, primary, Dumitru, Raluca, additional, Coryell, Philip, additional, Baxley, Ryan M, additional, Chen, Weili, additional, Twaroski, Kirk, additional, Webber, Beau R, additional, Tolar, Jakub, additional, Bielinsky, Anja-Katrin, additional, Purvis, Jeremy E, additional, and Cook, Jeanette Gowen, additional

Published
2017
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18. CRISPR/Cas9-based genetic correction for recessive dystrophic epidermolysis bullosa

Author

Webber, Beau R, primary, Osborn, Mark J, additional, McElroy, Amber N, additional, Twaroski, Kirk, additional, Lonetree, Cara-lin, additional, DeFeo, Anthony P, additional, Xia, Lily, additional, Eide, Cindy, additional, Lees, Christopher J, additional, McElmurry, Ron T, additional, Riddle, Megan J, additional, Kim, Chong Jai, additional, Patel, Dharmeshkumar D, additional, Blazar, Bruce R, additional, and Tolar, Jakub, additional

Published
2016
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21. Inside out: regenerative medicine for recessive dystrophic epidermolysis bullosa

Author

Vanden Oever, Michael, Twaroski, Kirk, Osborn, Mark J, Wagner, John E, and Tolar, Jakub

Abstract

Epidermolysis bullosa is classified as a genodermatosis, an inherited genetic skin disorder that results in severe, chronic skin blistering with painful and life-threatening complications. Although there is currently no cure for epidermolysis bullosa, concurrent advances in gene and stem cell therapies are converging toward combinatorial therapies that hold the promise of clinically meaningful and lifelong improvement. Recent studies using hematopoietic stem cells and mesenchymal stromal/stem cells to treat epidermolysis bullosa have demonstrated the potential for sustained, effective management of the most severe cases. Furthermore, advances in the use of gene therapy and gene-editing techniques, coupled with the development of induced pluripotent stem cells from patients with epidermolysis bullosa, allow for autologous therapies derived from a renewable population of cells that are patient-specific. Here we describe emerging treatments for epidermolysis bullosa and other genodermatoses, along with a discussion of their benefits and limitations as effective therapies.

Published
2018
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22. Rapid DNA replication origin licensing protects stem cell pluripotency

Author

Chen, Weili, Baxley, Ryan M., Purvis, Jeremy E., Twaroski, Kirk, Dumitru, Raluca, Bielinsky, Anja-Katrin, Webber, Beau R., Matson, Jacob Peter, Cook, Jeanette Gowen, Coryell, Philip, and Tolar, Jakub

Subjects
3. Good health
Abstract

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 G1 length varies widely among cell types. Using quantitative single-cell analyses, we found that pluripotent stem cells with naturally short G1 phases load MCM much faster than their isogenic differentiated counterparts with long G1 phases. During the earliest stages of differentiation toward all lineages, MCM loading slows concurrently with G1 lengthening, revealing developmental control of MCM loading. In contrast, ectopic Cyclin E overproduction uncouples short G1 from fast MCM loading. Rapid licensing in stem cells is caused by accumulation of the MCM loading protein, Cdt1. Prematurely slowing MCM loading in pluripotent cells not only lengthens G1 but also accelerates differentiation. Thus, rapid origin licensing is an intrinsic characteristic of stem cells that contributes to pluripotency maintenance.

23. HNF4A Regulates the Formation of Hepatic Progenitor Cells from Human iPSC-Derived Endoderm by Facilitating Efficient Recruitment of RNA Pol II.

Author

DeLaForest, Ann, Di Furio, Francesca, Jing, Ran, Ludwig-Kubinski, Amy, Twaroski, Kirk, Urick, Amanda, Pulakanti, Kirthi, Rao, Sridhar, and Duncan, Stephen A.

Subjects
HEPATOCYTE nuclear factors, LIVER cells, ENDODERM, PROGENITOR cells, RNA polymerase II, INDUCED pluripotent stem cells
Abstract

Elucidating the molecular basis of cell differentiation will advance our understanding of organ development and disease. We have previously established a protocol that efficiently produces cells with hepatocyte characteristics from human induced pluripotent stem cells. We previously used this cell differentiation model to identify the transcription factor hepatocyte nuclear factor 4 α (HNF4A) as being essential during the transition of the endoderm to a hepatic fate. Here, we sought to define the molecular mechanisms through which HNF4A controls this process. By combining HNF4A chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) analyses at the onset of hepatic progenitor cell formation with transcriptome data collected during early stages of differentiation, we identified genes whose expression is directly dependent upon HNF4A. By examining the dynamic changes that occur at the promoters of these HNF4A targets we reveal that HNF4A is essential for recruitment of RNA polymerase (RNA pol) II to genes that are characteristically expressed as the hepatic progenitors differentiate from the endoderm. [ABSTRACT FROM AUTHOR]

Published
2019
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