Staff member

Manuel Lozano Garcia

Staff member publications

Hall, Jocelin Isabel, Lozano, Manuel, Estrada-Petrocelli, Luis, Birring, Surinder, Turner, Richard, (2020). The present and future of cough counting tools Journal of Thoracic Disease 12, (9), 5207-5223

The widespread use of cough counting tools has, to date, been limited by a reliance on human input to determine cough frequency. However, over the last two decades advances in digital technology and audio capture have reduced this dependence. As a result, cough frequency is increasingly recognised as a measurable parameter of respiratory disease. Cough frequency is now the gold standard primary endpoint for trials of new treatments for chronic cough, has been investigated as a marker of infectiousness in tuberculosis (TB), and used to demonstrate recovery in exacerbations of chronic obstructive pulmonary disease (COPD). This review discusses the principles of automatic cough detection and summarises key currently and recently used cough counting technology in clinical research. It additionally makes some predictions on future directions in the field based on recent developments. It seems likely that newer approaches to signal processing, the adoption of techniques from automatic speech recognition, and the widespread ownership of mobile devices will help drive forward the development of real-time fully automated ambulatory cough frequency monitoring over the coming years. These changes should allow cough counting systems to transition from their current status as a niche research tool in chronic cough to a much more widely applicable method for assessing, investigating and understanding respiratory disease.

JTD Keywords: Cough, Cough monitor, Cough frequency

Navarro, S., Moleiro, V., Molina-Estevez, F. J., Lozano, M. L., Chinchon, R., Almarza, E., Quintana-Bustamante, O., Mostoslavsky, G., Maetzig, T., Galla, M., Heinz, N., Schiedlmeier, B., Torres, Y., Modlich, U., Samper, E., Río, P., Segovia, J. C., Raya, A., Güenechea, G., Izpisua-Belmonte, J. C., Bueren, J. A., (2014). Generation of iPSCs from genetically corrected Brca2 hypomorphic cells: Implications in cell reprogramming and stem cell therapy Stem Cells , 32, (2), 436-446

Fanconi anemia (FA) is a complex genetic disease associated with a defective DNA repair pathway known as the FA pathway. In contrast to many other FA proteins, BRCA2 participates downstream in this pathway and has a critical role in homology-directed recombination (HDR). In our current studies, we have observed an extremely low reprogramming efficiency in cells with a hypomorphic mutation in Brca2 (Brca2Δ27/Δ27), that was associated with increased apoptosis and defective generation of nuclear RAD51 foci during the reprogramming process. Gene complementation facilitated the generation of Brca2Δ27/Δ27 induced pluripotent stem cells (iPSCs) with a disease-free FA phenotype. Karyotype analyses and comparative genome hybridization arrays of complemented Brca2Δ27/Δ27 iPSCs showed, however, the presence of different genetic alterations in these cells, most of which were not evident in their parental Brca2 Δ27/Δ27 mouse embryonic fibroblasts. Gene-corrected Brca2Δ27/Δ27 iPSCs could be differentiated in vitro toward the hematopoietic lineage, although with a more limited efficacy than WT iPSCs or mouse embryonic stem cells, and did not engraft in irradiated Brca2Δ27/Δ27 recipients. Our results are consistent with previous studies proposing that HDR is critical for cell reprogramming and demonstrate that reprogramming defects characteristic of Brca2 mutant cells can be efficiently overcome by gene complementation. Finally, based on analysis of the phenotype, genetic stability, and hematopoietic differentiation potential of gene-corrected Brca2Δ27/Δ27 iPSCs, achievements and limitations in the application of current reprogramming approaches in hematopoietic stem cell therapy are also discussed.

JTD Keywords: Bone marrow aplasia, Cellular therapy, Fanconi anemia, Gene therapy, Hematopoietic stem cells, Induced pluripotent stem cells