Article
Biochemistry & Molecular Biology
Avina Rami, Lukasz Laczmanski, Jagoda Jackow-Nowicka, Joanna Jackow
Summary: A model for studying the development of RDEB-cSCC was established using cellular reprogramming and re-differentiation technology. RNA-seq analysis revealed distinct gene expression signatures and functional changes in RDEB-cSCC subjected to reprogramming and re-differentiation, offering a valuable tool to study cSCC and identify potential therapeutic targets for RDEB-cSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Dermatology
K. S. Subramaniam, M. N. Antoniou, J. A. McGrath, S. M. Lwin
Summary: Epidermolysis bullosa (EB) is a group of inherited skin disorders with debilitating consequences. Recessive dystrophic EB (RDEB) is especially severe and can lead to chronic wounds and squamous cell carcinoma. Advances in molecular genetics and biotechnology have paved the way for gene and cell-based therapies for EB, and RDEB has become the focus of clinical trials. There is a global effort involving academia, industry, and patient organizations to develop targeted therapeutics for EB. Dermatologists should familiarize themselves with gene therapy and its applications.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Editorial Material
Medicine, Research & Experimental
Christen L. Ebens
Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic blistering skin disease caused by biallelic mutations in the COL7A1 gene. Clinical manifestations include fragile skin, pain, itch, high metabolic demand, and dermal fibrosis.
EMBO MOLECULAR MEDICINE
(2021)
Article
Cell & Tissue Engineering
Julia Riedl, Michael Pickett-Leonard, Cindy Eide, Mark Andreas Kluth, Christoph Ganss, Natasha Y. Frank, Markus H. Frank, Christen L. Ebens, Jakub Tolar
Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, incurable skin disease caused by biallelic mutations in type VII collagen (C7), and advancements in treatment have been made by utilizing the immunomodulatory potential of mesenchymal stem cells (MSCs). A unique subset of skin-derived MSCs expressing ABCB5 have superior skin homing ability and may induce wound repair through increased expression of HOXA3 gene. Further exploration of the immunomodulatory mechanisms among MSC populations may have broader implications in regenerative medicine beyond RDEB treatment.
Article
Dermatology
Yasushi Kikuchi, Tomoki Tamakoshi, Ryuichi Ishida, Ryosuke Kobayashi, Shiho Mori, Akemi Ishida-Yamamoto, Manabu Fujimoto, Yasufumi Kaneda, Katsuto Tamai
Summary: In this study, researchers developed an ex vivo gene therapy for recessive dystrophic epidermolysis bullosa (RDEB) using autologous mesenchymal stromal cells (MSCs). The gene-modified MSCs were injected into mice with type VII collagen deficiency, leading to continuous and widespread expression of type VII collagen. The therapy showed successful application in both early blistering skin and advanced ulcerative lesions in the RDEB mouse model.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Christine Gretzmeier, Didier Pin, Johannes S. Kern, Mei Chen, David T. Woodley, Leena Bruckner-Tuderman, Mark P. de Souza, Alexander Nystroem
Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin disease characterized by skin blistering and fibrosis. This study found that intravenous administration of recombinant C7 can reduce fibrosis in RDEB patients, and this treatment method is well-tolerated in mice and dogs.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Dermatology
S. J. Robertson, C. Prodinger, L. Liu, C. Skilbeck, G. Petrof, A. E. Martinez, J. E. Mellerio, D. T. Greenblatt
Summary: The rare inversa subtype of recessive dystrophic epidermolysis bullosa (RDEB-I) is characterized by predominant intertriginous skin blistering and marked mucosal involvement. This study found a higher prevalence of otological complications in RDEB-I patients than previously reported, and presented the first case of cholesteatoma in RDEB-I. Bone-anchored hearing aids (BAHA) and middle ear implants (MEI) were identified as safe and effective treatment options for hearing loss in RDEB-I patients.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jose Bonafont, Angeles Mencia, Esteban Chacon-Solano, Wai Srifa, Sriram Vaidyanathan, Rosa Romano, Marta Garcia, Rosario Hervas-Salcedo, Laura Ugalde, Blanca Duarte, Matthew H. Porteus, Marcela Del Rio, Fernando Larcher, Rodolfo Murillas
Summary: This study presents a gene-editing approach using CRISPR-Cas9 system to achieve gene correction in different cell types, showing therapeutic potential for RDEB.
Review
Biochemistry & Molecular Biology
Grace Tartaglia, Qingqing Cao, Zachary M. Padron, Andrew P. South
Summary: RDEB is a devastating skin blistering disease caused by mutations in the C7 gene, leading to rapid fibrosis development, chronic wounds, and squamous cell carcinoma. It serves as a model for understanding the molecular basis of fibrosis and rapidly developing aggressive cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dermatology
Mohammad Reza Pourani, Hassan Vahidnezhad, Parvin Mansouri, Leila Youssefian, Azadeh Rakhshan, Behzad Hajimoradi, Fahimeh Abdollahimajd, Jouni Uitto
Summary: This case series reports the beneficial effects of losartan on RDEB as a potentially novel treatment. Losartan can improve the clinical features and severity of the disease, and enhance the quality of life for patients with RDEB.
DERMATOLOGIC THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Sung-Ah Hong, Song-Ee Kim, A-Young Lee, Gue-Ho Hwang, Jong Hoon Kim, Hiroaki Iwata, Soo-Chan Kim, Sangsu Bae, Sang Eun Lee
Summary: In this study, researchers identified and corrected pathogenic mutations in the COL7A1 gene using adenine base editors and prime editors in patients with recessive dystrophic epidermolysis bullosa (RDEB). The edited patient-derived skin equivalents showed positive outcomes in terms of C7 deposition and anchoring fibril formation, suggesting the feasibility of ex vivo gene editing as a potential treatment for RDEB.
Review
Dermatology
Leonie Huitema, Taylor Phillips, Vitali Alexeev, Olga Igoucheva
Summary: Hereditary epidermolysis bullosa is a mechanobullous skin fragility disorder characterized by skin blistering under mechanical stress, with no cure currently available. Recent data suggest systemic immunological defects in patients, particularly affecting antibacterial immunity.
EXPERIMENTAL DERMATOLOGY
(2021)
Article
Cell & Tissue Engineering
Camille Vincent, Nathalie Lefort, Mathieu Hamlin, Celine Banal, Alain Hovnanian, Araksya Izmiryan
Summary: This study investigated a rare genetic disease, Recessive Dystrophic Epidermolysis Bullosa (RDEB), caused by mutations in COL7A1 gene. Induced pluripotent stem cells (iPSCs) were generated from fibroblasts of RDEB patients carrying homozygous recurrent mutations in COL7A1. The pluripotent state of these cells was confirmed by the expression of stem cell markers. The capacity of RDEB iPSCs to differentiate into various cell types was demonstrated in vitro through embryoid body formation and analysis.
STEM CELL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Irina Gurevich, Pooja Agarwal, PeiPei Zhang, John A. Dolorito, Stacie Oliver, Henry Liu, Nicholas Reitze, Nikhil Sarma, Isin Sinem Bagci, Kunju Sridhar, Visesha Kakarla, Vamsi K. Yenamandra, Mark O'Malley, Marco Prisco, Sara F. Tufa, Douglas R. Keene, Andrew P. South, Suma M. Krishnan, M. Peter Marinkovich
Summary: This study evaluated the use of an engineered viral vector, B-VEC, for the treatment of recessive dystrophic epidermolysis bullosa (RDEB) patients with wounds. The results showed that B-VEC promotes wound healing and is well-tolerated.
Article
Biochemistry & Molecular Biology
Eijiro Akasaka, Hajime Nakano, Daisuke Sawamura
Summary: This study presented a novel method to test the consequences of mutations in DEB using COL7A1 mRNA extracted from PBMCs, accurately detecting the outcomes of specific COL7A1 mutations and identifying type VII collagen-expressing cells in PBMCs with similar surface markers as mesenchymal stem cells. These findings are expected to significantly contribute to genetic diagnoses and novel therapies for DEB.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Education, Scientific Disciplines
Jerica M. Berge, Kait Macheledt, Sophie Watson, Heather Dorr, Snigdha Pusalavidyasagar, Alicia Kunin-Batson, Rebekah Pratt, Sara L. Zimmer, Jakub Tolar, Amanda Termuhlen
Summary: This study describes the process of creating the Center for Women in Medicine and Science at the University of Minnesota Medical School, using a theory- and metric-driven approach. The study also shares four lessons learned from the development of the center and the outcomes achieved.
Article
Surgery
Kelly Walton, Kirsti Walker, Megan Riddle, Brent H. Koehn, Jordan Reff, Elizabeth M. Sagatys, Michael A. Linden, Joseph Pidala, Jongphil Kim, Marie C. Lee, John Kiluk, Jane Yuet Ching Hui, Sang Y. Yun, Yan Xing, Heather Stefanski, Harshani R. Lawrence, Nicholas J. Lawrence, Jakub Tolar, Claudio Anasetti, Bruce R. Blazar, Said M. Sebti, Brian C. Betts
Summary: AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable allo-inactivation. It reduces allograft invasion by limiting skin-homing CLA(+) donor T cells and suppresses pathogenic Th1 and Th17 cells while sparing regulatory T cells. Additionally, AJI-100 enhances human type 2 innate lymphoid cell responses for tissue repair by maintaining pSTAT5 levels and blocking interference by STAT3.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Dermatology
Courtney M. Popp, William C. Miller, Cindy R. Eide, Jakub Tolar
Summary: Three-dimensional bioprinting has the potential to revolutionize the treatment of skin wounds, especially for rare conditions like RDEB. Despite its therapeutic promise, there are technical challenges that need to be overcome before widespread implementation in clinical practice.
EXPERIMENTAL DERMATOLOGY
(2022)
Editorial Material
Dermatology
Helene Ragot, Alain Hovnanian
Summary: Drug repurposing has the potential to discover new treatments for diseases with high unmet medical needs. In this study, Lee et al. utilized transcriptomics and computational analysis to identify the phosphoinositide 3-kinase/protein kinase B/mTOR signaling pathway as central in treating epidermolysis bullosa simplex. A pilot study using a topical mTOR inhibitor showed marked improvement.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Endocrinology & Metabolism
Elizabeth Braunlin, Juan E. Abrahante, Ron McElmurry, Michael Evans, Miles Smith, Davis Seelig, M. Gerard O'Sullivan, Jakub Tolar, Chester B. Whitley, R. Scott McIvor
Summary: Adult immunocompetent C57Bl/6 MPSI male mice develop aortic insufficiency, dilated ascending aortas, and decreased cardiac function, which are not observed in immune incompetent NSG MPSI mice. RNA sequencing and histological staining results indicate that the upregulation of inflammasome pathway components and immune infiltration in the aorta are associated with these cardiac findings. The immune system plays an important role in these cardiac abnormalities.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Cameron Meyer-Mueller, Mark J. Osborn, Jakub Tolar, Christina Boull, Christen L. Ebens
Summary: Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by fragile skin. A recent study suggests that revertant mosaicism (RM), a phenomenon that corrects disease-causing mutations, could be a potential therapy for EB. RM cells provide a powerful autologous platform for therapy, avoiding the risks associated with gene therapy/editing. However, more research is needed to ensure the genomic integrity and long-term functionality of RM-derived cells.
Article
Dermatology
Elizabeth L. Thompson, Michael Pickett-Leonard, Megan J. Riddle, Weili Chen, Frank W. Albert, Jakub Tolar
Summary: Using CRISPR technology, researchers identified genes and pathways that can increase C7 expression, and found compounds that upregulate C7 expression, providing a new therapeutic approach for the treatment of dystrophic epidermolysis bullosa.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Colby J. Feser, Christopher J. Lees, Daniel T. Lammers, Megan J. Riddle, Jason R. Bingham, Matthew J. Eckert, Jakub Tolar, Mark J. Osborn
Summary: In this study, we developed an engineering method based on the CRISPR/Cas9 system to efficiently express single or multiple gene products in human cells. Our findings demonstrate the potential of CRISPR/Cas9 SAMs as an engineering advance that improves recombinant peptide production techniques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Dermatology
Julia A. Riedl, Megan Riddle, Lily Xia, Cindy Eide, Christina Boull, Christen L. Ebens, Jakub Tolar
Summary: This study investigates the phenotype of epidermal allograft cells in recessive dystrophic epidermolysis bullosa (RDEB) patients and identifies potential proinflammatory and fibroblast phenotypes related to the local environment of RDEB skin. The study also highlights the presence of myofibroblast popu-lation and inflammatory fibroblasts expressing profibrotic gene POSTN. These findings provide important insights and targets for future RDEB studies and treatments.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Genetics & Heredity
Kathleen Bogart, Amanda Hemmesch, Erica Barnes, Thomas Blissenbach, Arthur Beisang, Patti Engel
Summary: This research survey discovered that people in the United States with rare diseases have poor health-related quality of life and are highly stigmatized. Access to healthcare resources is challenging for many, with delays in diagnosis and common misdiagnoses being reported. Factors such as stigma, anxiety levels, length of the diagnostic process, physical function, and pain interference are major predictors of patient satisfaction among adults with rare diseases. Adults and children with rare diseases have significantly poorer health-related quality of life and higher levels of stigma compared to the US population norms. Predictors of anxiety and depression include stigma, fatigue, sleep disturbance, limited social participation, and the course of disease.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Dermatology
Justine Basset, Lucile Marchal, Alain Hovnanian
Summary: Pachyonychia congenita is a rare disorder characterized by painful palmoplantar keratoderma, and there is no standard treatment currently available. This study found that overexpression of EGFR ligands and EGFR signaling proteins is associated with PC lesions. Treatment with a drug targeting EGFR resulted in a significant reduction in pain and improvement in quality of life for patients with PC.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Multidisciplinary Sciences
William Miller, Charles Lewis Humphrey Pruett, William Stone, Cindy Eide, Megan Riddle, Courtney Popp, Matthew Yousefzadeh, Christopher Lees, Davis Seelig, Elizabeth Thompson, Harry Orr, Laura Niedernhofer, Jakub Tolar
Summary: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease that primarily affects the retina and cerebellum. This study found that SCA7 leads to the accumulation of senescent cells in the kidneys and cerebellum, which may contribute to the specific phenotype of the disease.
Article
Biotechnology & Applied Microbiology
Monica E. Neugebauer, Alvin Hsu, Mandana Arbab, Nicholas A. Krasnow, Amber N. McElroy, Smriti Pandey, Jordan L. Doman, Tony P. Huang, Aditya Raguram, Samagya Banskota, Gregory A. Newby, Jakub Tolar, Mark J. Osborn, David R. Liu
Summary: Improved cytosine base editors are generated by phage-assisted evolution of a deoxyadenosine deaminase, which exhibit small size, low off-target activity, and high on-target activity. These modified base editors have significant application potential in cell and gene editing.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Colby J. J. Feser, James M. M. Williams, Daniel T. T. Lammers, Jason R. R. Bingham, Matthew J. J. Eckert, Jakub Tolar, Mark J. J. Osborn
Summary: Recombinant engineering commonly uses plasmid-based gene templates for protein production, but faces challenges with post-translational modifications and large protein expression. Integration of CRISPR/Cas9-synergistic activator mediator (SAM) system into human cells enables robust gene expression and protein production. This study successfully integrated SAM system components into human cells and demonstrated their potential for targeted gene expression and modulation, with broad applications in recombinant engineering and transcriptional regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Christopher J. Sipe, Mitchell G. Kluesner, Samuel P. Bingea, Walker S. Lahr, Aneesha A. Andrew, Minjing Wang, Anthony P. DeFeo, Timothy L. Hinkel, Kanut Laoharawee, John E. Wagner, Margaret L. MacMillan, Gregory M. Vercellotti, Jakub Tolar, Mark J. Osborn, R. Scott McIvor, Beau R. Webber, Branden S. Moriarity
Summary: Fanconi anemia is a rare genetic disease characterized by a lack of genes essential for DNA repair. Researchers have used digital genome editing to correct the mutated genes in patient cells, resulting in phenotypic rescue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
