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541 results on '"Blau, Helen M."'

5. Spatial compartmentalization of signaling imparts source-specific functions on secreted factors

Author

Groppa, Elena, Martini, Paolo, Derakhshan, Nima, Theret, Marine, Ritso, Morten, Tung, Lin Wei, Wang, Yu Xin, Soliman, Hesham, Hamer, Mark Stephen, Stankiewicz, Laura, Eisner, Christine, Erwan, Le Nevé, Chang, Chihkai, Yi, Lin, Yuan, Jack H., Kong, Sunny, Weng, Curtis, Adams, Josephine, Chang, Lucas, Peng, Anne, Blau, Helen M., Romualdi, Chiara, and Rossi, Fabio M.V.

Published
2023
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9. Multiparameter analysis of timelapse imaging reveals kinetics of megakaryocytic erythroid progenitor clonal expansion and differentiation

Author

Scanlon, Vanessa M., Thompson, Evrett N., Lawton, Betty R., Kochugaeva, Maria, Ta, Kevinminh, Mayday, Madeline Y., Xavier-Ferrucio, Juliana, Kang, Elaine, Eskow, Nicole M., Lu, Yi-Chien, Kwon, Nayoung, Laumas, Anisha, Cenci, Matthew, Lawrence, Kalyani, Barden, Katie, Larsuel, Shannon T., Reed, Fiona E., Peña-Carmona, Gabriela, Ubbelohde, Ashley, Lee, June P., Boobalan, Shakthi, Oppong, Yvette, Anderson, Rachel, Maynard, Colby, Sahirul, Kaylie, Lajeune, Callista, Ivathraya, Varsha, Addy, Tiffany, Sanchez, Patricia, Holbrook, Colin, Van Ho, Andrew Tri, Duncan, James S., Blau, Helen M., Levchenko, Andre, and Krause, Diane S.

Published
2022
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12. Increased tissue stiffness triggers contractile dysfunction and telomere shortening in dystrophic cardiomyocytes

Author

Chang, Alex C.Y., Pardon, Gaspard, Chang, Andrew C.H., Wu, Haodi, Ong, Sang-Ging, Eguchi, Asuka, Ancel, Sara, Holbrook, Colin, Ramunas, John, Ribeiro, Alexandre J.S., LaGory, Edward L., Wang, Honghui, Koleckar, Kassie, Giaccia, Amato, Mack, David L., Childers, Martin K., Denning, Chris, Day, John W., Wu, Joseph C., Pruitt, Beth L., and Blau, Helen M.

Published
2021
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14. Neuromuscular impairment at different stages of human sarcopenia.

Author

Sarto, Fabio, Franchi, Martino V., McPhee, Jamie S., Stashuk, Daniel W., Paganini, Matteo, Monti, Elena, Rossi, Maira, Sirago, Giuseppe, Zampieri, Sandra, Motanova, Evgeniia S., Valli, Giacomo, Moro, Tatiana, Paoli, Antonio, Bottinelli, Roberto, Pellegrino, Maria A., De Vito, Giuseppe, Blau, Helen M., and Narici, Marco V.

Published
2024
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17. Hydrogel biomaterials that stiffen and soften on demand reveal that skeletal muscle stem cells harbor a mechanical memory.

Author

Madl, Christopher M., Yu Xin Wang, Holbrook, Colin A., Shiqi Su, Xuechen Shi, Byfield, Fitzroy J., Wicki, Gwendoline, Flaig, Iris A., and Blau, Helen M.

Subjects
YAP signaling proteins, ECTOPIC tissue, GUANOSINE triphosphate, DUCHENNE muscular dystrophy, TISSUE mechanics
Abstract

Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis. MuSCs are known to lose their regenerative potential if cultured on stiff plastic substrates. We sought to determine whether MuSCs harbor a memory of their past microenvironment and if it can be overcome. We tested MuSCs in situ using dynamic hydrogel biomaterials that soften or stiffen on demand in response to light and found that freshly isolated MuSCs develop a persistent memory of substrate stiffness characterized by loss of proliferative progenitors within the first three days of culture on stiff substrates. MuSCs cultured on soft hydrogels had altered cytoskeletal organization and activity of Rho and Rac guanosine triphosphate hydrolase (GTPase) and Yes-associated protein mechanotransduction pathways compared to those on stiff hydrogels. Pharmacologic inhibition identified RhoA activation as responsible for the mechanical memory phenotype, and single-cell RNA sequencing revealed a molecular signature of the mechanical memory. These studies highlight that microenvironmental stiffness regulates MuSC fate and leads to MuSC dysfunction that is not readily reversed by changing stiffness. Our results suggest that stiffness can be circumvented by targeting downstream signaling pathways to overcome stem cell dysfunction in aged and disease states with aberrant fibrotic tissue mechanics. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Telomere shortening is a hallmark of genetic cardiomyopathies

Author

Chang, Alex C. Y., Chang, Andrew C. H., Kirillova, Anna, Sasagawa, Koki, Su, Willis, Weber, Gerhard, Lin, Jue, Termglinchan, Vittavat, Karakikes, Ioannis, Seeger, Timon, Dainis, Alexandra M., Hinson, John T., Seidman, Jonathan, Seidman, Christine E., Day, John W., Ashley, Euan, Wu, Joseph C., and Blau, Helen M.

Published
2018

40. Long telomeres protect against age-dependent cardiac disease caused by NOTCH1 haploinsufficiency

Author

Theodoris, Christina V., Mourkioti, Foteini, Huang, Yu, Ranade, Sanjeev S., Liu, Lei, Blau, Helen M., and Srivastava, Deepak

Subjects
Research, Genetic aspects, Calcification (Physiology) -- Research, Telomeres -- Research, Cardiovascular diseases -- Genetic aspects -- Research
Abstract

Introduction Use of animal models to investigate age-dependent diseases in humans typically requires long-term aging. Furthermore, human diseases caused by genetic haploinsufficiency often fail to be modeled at any age [...], Diseases caused by gene haploinsufficiency in humans commonly lack a phenotype in mice that are heterozygous for the orthologous factor, impeding the study of complex phenotypes and critically limiting the discovery of therapeutics. Laboratory mice have longer telomeres relative to humans, potentially protecting against age-related disease caused by haploinsufficiency. Here, we demonstrate that telomere shortening in NOTCH1-haploinsufficient mice is sufficient to elicit age-dependent cardiovascular disease involving premature calcification of the aortic valve, a phenotype that closely mimics human disease caused by NOTCH1 haploinsufficiency. Furthermore, progressive telomere shortening correlated with severity of disease, causing cardiac valve and septal disease in the neonate that was similar to the range of valve disease observed within human families. Genes that were dysregulated due to NOTCH1 haploinsufficiency in mice with shortened telomeres were concordant with proosteoblast and proinflammatory gene network alterations in human NOTCH1 heterozygous endothelial cells. These dysregulated genes were enriched for telomere-contacting promoters, suggesting a potential mechanism for telomere-dependent regulation of homeostatic gene expression. These findings reveal a critical role for telomere length in a mouse model of age-dependent human disease and provide an in vivo model in which to test therapeutic candidates targeting the progression of aortic valve disease.

Published
2017
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41. An objective comparison of cell-tracking algorithms

Author

Ulman, Vladimír, Maška, Martin, Magnusson, Klas E G, Ronneberger, Olaf, Haubold, Carsten, Harder, Nathalie, Matula, Pavel, Matula, Petr, Svoboda, David, Radojevic, Miroslav, Smal, Ihor, Rohr, Karl, Jaldén, Joakim, Blau, Helen M, Dzyubachyk, Oleh, Lelieveldt, Boudewijn, Xiao, Pengdong, Li, Yuexiang, Cho, Siu-Yeung, Dufour, Alexandre C, Olivo-Marin, Jean-Christophe, Reyes-Aldasoro, Constantino C, Solis-Lemus, Jose A, Bensch, Robert, Brox, Thomas, Stegmaier, Johannes, Mikut, Ralf, Wolf, Steffen, Hamprecht, Fred A, Esteves, Tiago, Quelhas, Pedro, Demirel, Ömer, Malmström, Lars, Jug, Florian, Tomancak, Pavel, Meijering, Erik, Muñoz-Barrutia, Arrate, Kozubek, Michal, and Ortiz-de-Solorzano, Carlos

Published
2017
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44. Regeneration of neuromuscular synapses after acute and chronic denervation by inhibiting the gerozyme 15-prostaglandin dehydrogenase.

Author

Bakooshli, Mohsen A., Wang, Yu Xin, Monti, Elena, Su, Shiqi, Kraft, Peggy, Nalbandian, Minas, Alexandrova, Ludmila, Wheeler, Joshua R., Vogel, Hannes, and Blau, Helen M.

Subjects
DENERVATION, NERVOUS system regeneration, NEUROMUSCULAR diseases, SCIATIC nerve injuries, PERIPHERAL nervous system, CONNECTIN
Abstract

To date, there are no approved treatments for the diminished strength and paralysis that result from the loss of peripheral nerve function due to trauma, heritable neuromuscular diseases, or aging. Here, we showed that denervation resulting from transection of the sciatic nerve triggered a marked increase in the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle in mice, providing evidence that injury drives early expression of this aging-associated enzyme or gerozyme. Treating mice with a small-molecule inhibitor of 15-PGDH promoted regeneration of motor axons and formation of neuromuscular synapses leading to an acceleration in recovery of force after an acute nerve crush injury. In aged mice with chronic denervation of muscles, treatment with the 15-PGDH inhibitor increased motor neuron viability and restored neuromuscular junctions and function. These presynaptic changes synergized with previously reported muscle tissue remodeling to result in a marked increase in the strength of aged muscles. We further found that 15-PGDH aggregates defined the target fibers that are histopathologic hallmarks of human neurogenic myopathies, suggesting that the gerozyme may be involved in their etiology. Our data suggest that inhibition of 15-PGDH may constitute a therapeutic strategy to physiologically boost prostaglandin E2, restore neuromuscular connectivity, and promote recovery of strength after acute or chronic denervation due to injury, disease, or aging. Editor's summary: Skeletal muscle denervation, which can occur because of disease, trauma or disuse, results in muscle weakness and atrophy, with no available treatments to promote axon regeneration or to restore neuromuscular junctions (NMJs). Here, Bakooshli, Wang, and colleagues found that 15-prostaglandin dehydrogenase (15-PGDH), which accumulates with age and promotes muscle atrophy, markedly increased in denervated mouse myofibers and aggregated in 'target fibers, hallmarks of chronic nerve damage in human myogenic neuropathies. In a mouse model of sciatic nerve crush injury, small molecule inhibition of 15-PGDH promoted motor axon regeneration and NMJ restoration, leading to improvement in muscle force 14 days after injury. In aged mice, treatment improved NMJ number and morphology and elicited a pro-regenerative response in motor neurons, suggesting that 15-PGDH may be a therapeutic target for neuromuscular recovery after denervation. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Published
2023
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47. Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity

Author

Burridge, Paul W., Li, Yong Fuga, Matsa, Elena, Wu, Haodi, Ong, Sang-Ging, Sharma, Arun, Holmstrom, Alexandra, Chang, Alex C., Coronado, Michael J., Ebert, Antje D., Knowles, Joshua W., Telli, Melinda L., Witteles, Ronald M., Blau, Helen M., Bernstein, Daniel, Altman, Russ B., and Wu, Joseph C.

Subjects
Drug therapy, Complications and side effects, Development and progression, Patient outcomes, Methods, Doxorubicin -- Complications and side effects, Cardiovascular diseases -- Development and progression, Breast cancer -- Drug therapy, Stem cell transplantation -- Methods -- Patient outcomes, Stem cells -- Transplantation
Abstract

The anthracycline doxorubicin (trade name Adriamycin) was first introduced in the 1960s and remains one of the most effective and commonly used antineoplastic drugs (1). Despite the advent of targeted [...], Doxorubicin is an anthracycline chemotherapy agent effective in treating a wide range of malignancies, but it causes a dose-related cardiotoxicity that can lead to heart failure in a subset of patients. At present, it is not possible to predict which patients will be affected by doxorubicin-induced cardiotoxicity (DIC). Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate the predilection to DIC of individual patients at the cellular level. hiPSC-CMs derived from individuals with breast cancer who experienced DIC were consistently more sensitive to doxorubicin toxicity than hiPSC-CMs from patients who did not experience DIC, with decreased cell viability, impaired mitochondrial and metabolic function, impaired calcium handling, decreased antioxidant pathway activity, and increased reactive oxygen species production. Taken together, our data indicate that hiPSC-CMs are a suitable platform to identify and characterize the genetic basis and molecular mechanisms of DIC.

Published
2016

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