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1,552 results on '"Morley, Michael"'

1. Tackling Regional Public Health Issues Using Mobile Health Technology: Event Report of an mHealth Hackathon in Thailand

Author

Pathanasethpong, Atipong, Soomlek, Chitsutha, Morley, Katharine, Morley, Michael, Polpinit, Pattarawit, Dagan, Alon, Weis, James W, and Celi, Leo Anthony

Subjects
Information technology, T58.5-58.64, Public aspects of medicine, RA1-1270
Abstract

Hackathons are intense, short, collaborative events focusing on solving real world problems through interdisciplinary teams. This is a report of the mHealth hackathon hosted by Khon Kaen University in collaboration with MIT Sana and faculty members from Harvard Medical School with the aim to improve health care delivery in the Northeast region of Thailand. Key health challenges, such as improving population health literacy, tracking disease trajectory and outcomes among rural communities, and supporting the workflow of overburdened frontline providers, were addressed using mHealth. Many modifications from the usual format of hackathon were made to tailor the event to the local context and culture, such as the process of recruiting participants and how teams were matched and formed. These modifications serve as good learning points for hosting future hackathons. There are also many lessons learned about how to achieve a fruitful collaboration despite cultural barriers, how to best provide mentorship to the participants, how to instill in the participants a sense of mission, and how to match the participants in a fair and efficient manner. This event showcases how interdisciplinary collaboration can produce results that are unattainable by any discipline alone and demonstrates that innovations are the fruits of collective wisdom of people from different fields of expertise who work together toward the same goals.

Published
2017
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4. k-SALSA: k-anonymous synthetic averaging of retinal images via local style alignment

Author

Jeon, Minkyu, Park, Hyeonjin, Kim, Hyunwoo J., Morley, Michael, and Cho, Hyunghoon

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Cryptography and Security
Abstract

The application of modern machine learning to retinal image analyses offers valuable insights into a broad range of human health conditions beyond ophthalmic diseases. Additionally, data sharing is key to fully realizing the potential of machine learning models by providing a rich and diverse collection of training data. However, the personally-identifying nature of retinal images, encompassing the unique vascular structure of each individual, often prevents this data from being shared openly. While prior works have explored image de-identification strategies based on synthetic averaging of images in other domains (e.g. facial images), existing techniques face difficulty in preserving both privacy and clinical utility in retinal images, as we demonstrate in our work. We therefore introduce k-SALSA, a generative adversarial network (GAN)-based framework for synthesizing retinal fundus images that summarize a given private dataset while satisfying the privacy notion of k-anonymity. k-SALSA brings together state-of-the-art techniques for training and inverting GANs to achieve practical performance on retinal images. Furthermore, k-SALSA leverages a new technique, called local style alignment, to generate a synthetic average that maximizes the retention of fine-grain visual patterns in the source images, thus improving the clinical utility of the generated images. On two benchmark datasets of diabetic retinopathy (EyePACS and APTOS), we demonstrate our improvement upon existing methods with respect to image fidelity, classification performance, and mitigation of membership inference attacks. Our work represents a step toward broader sharing of retinal images for scientific collaboration. Code is available at https://github.com/hcholab/k-salsa., Comment: European Conference on Computer Vision (ECCV), 2022

Published
2023
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7. Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.

Author

Murashige, Danielle, Jung, Jae, Neinast, Michael, Levin, Michael, Chu, Qingwei, Lambert, Jonathan, Garbincius, Joanne, Kim, Boa, Hoshino, Atsushi, Marti-Pamies, Ingrid, McDaid, Kendra, Shewale, Swapnil, Flam, Emily, Yang, Steven, Roberts, Emilia, Li, Li, Morley, Michael, Bedi, Kenneth, Hyman, Matthew, Frankel, David, Margulies, Kenneth, Assoian, Richard, Elrod, John, Rabinowitz, Joshua, Arany, Zoltan, and Jang, Cholsoon

Subjects
BCAA, Mendelian randomization, blood pressure, branched-chain amino acid, cardiac metabolism, cardiovascular metabolism, heart failure, hypertension, metabolomics, Humans, Blood Pressure, Amino Acids, Branched-Chain, Heart, Heart Failure, Energy Metabolism
Abstract

Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.

Published
2022

8. Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy.

Author

Murashige, Danielle, Yang, Yifan, Morley, Michael, Jung, Sunhee, Kantner, Daniel, Pepper, Hannah, Bedi, Kenneth, Brandimarto, Jeff, Prosser, Benjamin, Cappola, Thomas, Snyder, Nathaniel, Rabinowitz, Joshua, Margulies, Kenneth, Arany, Zolt, Flam, Emily, and Jang, Cholsoon

Abstract

Heart failure (HF) is a leading cause of mortality. Failing hearts undergo profound metabolic changes, but a comprehensive evaluation in humans is lacking. We integrate plasma and cardiac tissue metabolomics of 678 metabolites, genome-wide RNA-sequencing, and proteomic studies to examine metabolic status in 87 explanted human hearts from 39 patients with end-stage HF compared with 48 nonfailing donors. We confirm bioenergetic defects in human HF and reveal selective depletion of adenylate purines required for maintaining ATP levels. We observe substantial reductions in fatty acids and acylcarnitines in failing tissue, despite plasma elevations, suggesting defective import of fatty acids into cardiomyocytes. Glucose levels, in contrast, are elevated. Pyruvate dehydrogenase, which gates carbohydrate oxidation, is de-repressed, allowing increased lactate and pyruvate burning. Tricarboxylic acid cycle intermediates are significantly reduced. Finally, bioactive lipids are profoundly reprogrammed, with marked reductions in ceramides and elevations in lysoglycerophospholipids. These data unveil profound metabolic abnormalities in human failing hearts.

Published
2022

9. Genome-wide fetalization of enhancer architecture in heart disease

Author

Spurrell, Cailyn H, Barozzi, Iros, Kosicki, Michael, Mannion, Brandon J, Blow, Matthew J, Fukuda-Yuzawa, Yoko, Slaven, Neil, Afzal, Sarah Y, Akiyama, Jennifer A, Afzal, Veena, Tran, Stella, Plajzer-Frick, Ingrid, Novak, Catherine S, Kato, Momoe, Lee, Elizabeth A, Garvin, Tyler H, Pham, Quan T, Kronshage, Anne N, Lisgo, Steven, Bristow, James, Cappola, Thomas P, Morley, Michael P, Margulies, Kenneth B, Pennacchio, Len A, Dickel, Diane E, and Visel, Axel

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Pediatric, Cardiovascular, Human Genome, Rare Diseases, Heart Disease, 1.1 Normal biological development and functioning, Adult, Cardiomyopathy, Dilated, Enhancer Elements, Genetic, Epigenome, Epigenomics, Humans, Transcription Factors, CP: Molecular biology, RNA-seq, enhancers, fetalization, genomics, hIP-seq, heart disease, regulatory elements, transgenic assay, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the regulatory landscape in heart disease is unclear. Here, we use RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from up to 26 healthy controls, 18 individuals with idiopathic dilated cardiomyopathy (DCM), and five fetal hearts. Healthy individuals have a highly reproducible epigenomic landscape, consisting of more than 33,000 predicted heart enhancers. In contrast, we observe reproducible disease-associated changes in activity at 6,850 predicted heart enhancers. Combined analysis of adult and fetal samples reveals that the heart disease epigenome and transcriptome both acquire fetal-like characteristics, with 3,400 individual enhancers sharing fetal regulatory properties. We also provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of DCM etiology.

Published
2022

11. Human distal airways contain a multipotent secretory cell that can regenerate alveoli

Author

Basil, Maria C, Cardenas-Diaz, Fabian L, Kathiriya, Jaymin J, Morley, Michael P, Carl, Justine, Brumwell, Alexis N, Katzen, Jeremy, Slovik, Katherine J, Babu, Apoorva, Zhou, Su, Kremp, Madison M, McCauley, Katherine B, Li, Shanru, Planer, Joseph D, Hussain, Shah S, Liu, Xiaoming, Windmueller, Rebecca, Ying, Yun, Stewart, Kathleen M, Oyster, Michelle, Christie, Jason D, Diamond, Joshua M, Engelhardt, John F, Cantu, Edward, Rowe, Steven M, Kotton, Darrell N, Chapman, Harold A, and Morrisey, Edward E

Subjects
Lung, Stem Cell Research, Stem Cell Research - Embryonic - Non-Human, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Animals, Bronchioles, Cell Lineage, Ferrets, Humans, Mice, Multipotent Stem Cells, Pulmonary Alveoli, Pulmonary Disease, Chronic Obstructive, General Science & Technology
Abstract

The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.

Published
2022

12. Generation of human alveolar epithelial type I cells from pluripotent stem cells

Author

Burgess, Claire L., Huang, Jessie, Bawa, Pushpinder S., Alysandratos, Konstantinos-Dionysios, Minakin, Kasey, Ayers, Lauren J., Morley, Michael P., Babu, Apoorva, Villacorta-Martin, Carlos, Yampolskaya, Maria, Hinds, Anne, Thapa, Bibek R., Wang, Feiya, Matschulat, Adeline, Mehta, Pankaj, Morrisey, Edward E., Varelas, Xaralabos, and Kotton, Darrell N.

Published
2024
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13. Guided construction of single cell reference for human and mouse lung

Author

Guo, Minzhe, Morley, Michael P., Jiang, Cheng, Wu, Yixin, Li, Guangyuan, Du, Yina, Zhao, Shuyang, Wagner, Andrew, Cakar, Adnan Cihan, Kouril, Michal, Jin, Kang, Gaddis, Nathan, Kitzmiller, Joseph A., Stewart, Kathleen, Basil, Maria C., Lin, Susan M., Ying, Yun, Babu, Apoorva, Wikenheiser-Brokamp, Kathryn A., Mun, Kyu Shik, Naren, Anjaparavanda P., Clair, Geremy, Adkins, Joshua N., Pryhuber, Gloria S., Misra, Ravi S., Aronow, Bruce J., Tickle, Timothy L., Salomonis, Nathan, Sun, Xin, Morrisey, Edward E., Whitsett, Jeffrey A., and Xu, Yan

Published
2023
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14. TGF-[beta] controls alveolar type 1 epithelial cell plasticity and alveolar matrisome gene transcription in mice

Author

Callaway, Danielle A., Penkala, Ian J., Zhou, Su, Knowlton, Jonathan J., Cardenas-Diaz, Fabian, Babu, Apoorva, Morley, Michael P., Lopes, Mariana, Garcia, Benjamin A., and Morrisey, Edward E.

Subjects
Thermo Fisher Scientific Inc., Scientific equipment and supplies industry -- Genetic aspects, Dysplasia -- Genetic aspects, Integrins -- Genetic aspects, Transforming growth factors -- Genetic aspects, Genetic transcription -- Genetic aspects, Mice -- Genetic aspects, Infants (Premature), Health care industry
Abstract

Premature birth disrupts normal lung development and places infants at risk for bronchopulmonary dysplasia (BPD), a disease disrupting lung health throughout the life of an individual and that is increasing in incidence. The TGF-[beta] superfamily has been implicated in BPD pathogenesis, however, what cell lineage it impacts remains unclear. We show that TGFbr2 is critical for alveolar epithelial (AT1) cell fate maintenance and function. Loss of TGFbr2 in AT1 cells during late lung development leads to AT1-AT2 cell reprogramming and altered pulmonary architecture, which persists into adulthood. Restriction of fetal lung stretch and associated AT1 cell spreading through a model of oligohydramnios enhances AT1-AT2 reprogramming. Transcriptomic and proteomic analyses reveal the necessity of TGFbr2 expression in AT1 cells for extracellular matrix production. Moreover, TGF-[beta] signaling regulates integrin transcription to alter AT1 cell morphology, which further impacts ECM expression through changes in mechanotransduction. These data reveal the cell intrinsic necessity of TGF-[beta] signaling in maintaining AT1 cell fate and reveal this cell lineage as a major orchestrator of the alveolar matrisome., Introduction Bronchopulmonary dysplasia (BPD) is a lung disease that disproportionately affects infants born at less than 28 weeks gestation, the threshold for extreme prematurity (1). Despite multiple medical advances including [...]

Published
2024
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18. Pathogenic LMNA variants disrupt cardiac lamina-chromatin interactions and de-repress alternative fate genes

Author

Shah, Parisha P, Lv, Wenjian, Rhoades, Joshua H, Poleshko, Andrey, Abbey, Deepti, Caporizzo, Matthew A, Linares-Saldana, Ricardo, Heffler, Julie G, Sayed, Nazish, Thomas, Dilip, Wang, Qiaohong, Stanton, Liam J, Bedi, Kenneth, Morley, Michael P, Cappola, Thomas P, Owens, Anjali T, Margulies, Kenneth B, Frank, David B, Wu, Joseph C, Rader, Daniel J, Yang, Wenli, Prosser, Benjamin L, Musunuru, Kiran, and Jain, Rajan

Subjects
Cardiovascular, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research, Heart Disease, Genetics, Aetiology, 2.1 Biological and endogenous factors, Cardiomyopathy, Dilated, Chromatin, Humans, Induced Pluripotent Stem Cells, Lamin Type A, Mutation, Myocytes, Cardiac, genome organization, hiPSC, laminopathy, peripheral heterochromatin, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Pathogenic mutations in LAMIN A/C (LMNA) cause abnormal nuclear structure and laminopathies. These diseases have myriad tissue-specific phenotypes, including dilated cardiomyopathy (DCM), but how LMNA mutations result in tissue-restricted disease phenotypes remains unclear. We introduced LMNA mutations from individuals with DCM into human induced pluripotent stem cells (hiPSCs) and found that hiPSC-derived cardiomyocytes, in contrast to hepatocytes or adipocytes, exhibit aberrant nuclear morphology and specific disruptions in peripheral chromatin. Disrupted regions were enriched for transcriptionally active genes and regions with lower LAMIN B1 contact frequency. The lamina-chromatin interactions disrupted in mutant cardiomyocytes were enriched for genes associated with non-myocyte lineages and correlated with higher expression of those genes. Myocardium from individuals with LMNA variants similarly showed aberrant expression of non-myocyte pathways. We propose that the lamina network safeguards cellular identity and that pathogenic LMNA variants disrupt peripheral chromatin with specific epigenetic and molecular characteristics, causing misexpression of genes normally expressed in other cell types.

Published
2021

20. Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials

Author

Williams, David F., Beardsley, Sara, Bennett, Steven, Cantrill, Herbert, Chan-Tram, Carmen, Cheshier, Holly, Damato, Kathyrn, Davies, John, Dev, Sundeep, Enloe, Julianne, Follano, Gennaro, Gilbert, Peggy, Johnson, Jill, Jones, Tori, Mayleben, Lisa, Mittra, Robert, Moos, Martha, Neist, Ryan, Oestreich, Neal, Quiram, Polly, Ramsay, Robert, Ryan, Edwin, Schindeldecker, Stephanie, Snater, John, Steele, Trenise, Selders, Dwight, Tonsfeldt, Jessica, Valardi, Shelly, Fish, Gary Edd, Aguado, Hank A., Arceneaux, Sally, Arnwine, Jean, Bell, Kim, Bell, Tina, Boleman, Bob, Bradley, Patricia, Callanan, David, Coors, Lori, Creighton, Jodi, Crew, Timothy, Cummings, Kimberly, Dock, Christopher, Duignan, Karen, Fuller, Dwain, Gray, Keith, Hendrix, Betsy, Hesse, Nicholas, Jaramillo, Diana, Jost, Bradley, Lash, Sandy, Lonsdale, Laura, Mackens, Michael, Mutz, Karin, Potts, Michael, Sanchez, Brenda, Snyder, William, Solley, Wayne, Tarter, Carrie, Wang, Robert, Williams, Patrick, Perkins, Stephen L., Anderson, Nicholas, Arnold, Ann, Blais, Paul, Googe, Joseph, Higdon, Tina T., Hunt, Cecile, Johnson, Mary, Miller, James, Moore, Misty, Morris, Charity K., Morris, Christopher, Oelrich, Sarah, Oliver, Kristina, Seitz, Vicky, Whetstone, Jerry, Doft, Bernard H., Bedel, Jay, Bergren, Robert, Borthwick, Ann, Conrad, Paul, Fec, Amanda, Fulwylie, Christina, Ingram, Willia, Latham, Shawnique, Lester, Gina, Liu, Judy, Lobes, Louis, Lucko, Nicole M., Mechling, Holly, Merlotti, Lori, McBroom, Keith, Olsen, Karl, Puskas, Danielle, Rath, Pamela, Schmucker, Maria, Schueckler, Lynn, Schultz, Christina, Shultz, Heather, Steinberg, David, Vyas, Avni, Whale, Kim, Yeckel, Kimberly, Orth, David H., Arredondo, Linda S., Brown, Susan, Ciscato, Barbara J., Civantos, Joseph M., Figliulo, Celeste, Hasan, Sohail, Kosinski, Belinda, Muir, Dan, Nelson, Kiersten, Packo, Kirk, Pollack, John S., Rezaei, Kourous, Shelton, Gina, Townsend-Patrick, Shannya, Walsh, Marian, McDonald, H. Richard, Ansari, Nina, Bye, Amanda, Fu, Arthur D., Grout, Sean, Indermill, Chad, Johnson, Robert N., Jumper, J. Michael, Linares, Silvia, Lujan, Brandon J., Munden, Ames, Persons, Meredith, Rodriguez, Rosa, Rose, Jennifer M., Teske, Brandi, Urias, Yesmin, Young, Stephen, Dreyer, Richard F., Daniel, Howard, Connaughton, Michele, Handelman, Irvin, Hobbs, Stephen, Hoerner, Christine, Hudson, Dawn, Kopfer, Marcia, Lee, Michael, Lemley, Craig, Logan, Joe, Ma, Colin, Mallet, Christophe, Milliron, Amanda, Peters, Mark, Wohlsein, Harry, Pearlman, Joel A., Andrews, Margo, Bartlett, Melissa, Carlson, Nanette, Cox, Emily, Equi, Robert, Gonzalez, Marta, Griffin, Sophia, Hogue, Fran, Kennedy, Lance, Kryuchkov, Lana, Lopez, Carmen, Lopez, Danny, Luevano, Bertha, McKenna, Erin, Patel, Arun, Reed, Brian, Secor, Nyla, Sison, Iris R., Tsai, Tony, Varghis, Nina, Waller, Brooke, Wendel, Robert, Yebra, Reina, Roth, Daniel B., Deinzer, Jane, Fine, Howard, Green, Flory, Green, Stuart, Keyser, Bruce, Leff, Steven, Leviton, Amy, Martir, Amy, Mosenthine, Kristin, Muscle, Starr, Okoren, Linda, Parker, Sandy, Prenner, Jonathan, Price, Nancy, Rogers, Deana, Rosas, Linda, Schlosser, Alex, Studenko, Loretta, Tantum, Thea, Wheatley, Harold, Trese, Michael T., Aaberg, Thomas, Bezaire, Denis, Bridges, Craig, Bryant, Doug, Capone, Antonio, Coleman, Michelle, Consolo, Christina, Cook, Cindy, DuLong, Candice, Garretson, Bruce, Grooten, Tracy, Hammersley, Julie, Hassan, Tarek, Jessick, Heather, Jones, Nanette, Kinsman, Crystal, Krumlauf, Jennifer, Lewis, Sandy, Locke, Heather, Margherio, Alan, Markus, Debra, Marsh, Tanya, Neal, Serena, Noffke, Amy, Oh, Kean, Pence, Clarence, Preston, Lisa, Raphaelian, Paul, Regan, Virginia R., Roberts, Peter, Ruby, Alan, Sarrafizadeh, Ramin, Scherf, Marissa, Scott, Sarita, Sneed, Scott, Staples, Lisa, Terry, Brad, Trese, Matthew T., Videtich, Joan, Williams, George, Zajechowski, Mary, Joseph, Daniel P., Blinder, Kevin, Boyd, Lynda, Buckley, Sarah, Crow, Meaghan, Dinatale, Amanda, Engelbrecht, Nicholas, Forke, Bridget, Gabel, Dana, Grand, Gilbert, Grillion-Cerone, Jennifer, Holekamp, Nancy, Kelly, Charlotte, Nobel, Ginny, Pepple, Kelly, Raeber, Matt, Rao, P. Kumar, Ressel, Tammy, Schremp, Steven, Sgorlon, Merrilee, Shears, Shantia, Thomas, Matthew, Timma, Cathy, Vaughn, Annette, Walters, Carolyn, Weeks, Rhonda, Wehmeier, Jarrod, Wright, Tim, Berinstein, Daniel M., Ayyad, Aida, Barazi, Mohammed K., Bickhart, Erica, Brady, Tracey, Byank, Lisa, Cronise, Alysia, Denny, Vanessa, Dunn, Courtney, Flory, Michael, Frantz, Robert, Garfinkel, Richard A., Gilbert, William, Lai, Michael M., Melamud, Alexander, Newgen, Janine, Newton, Shamekia, Oliver, Debbie, Osman, Michael, Sanders, Reginald, von Fricken, Manfred, Dugel, Pravin, Arenas, Sandra, Balea, Gabe, Bartoli, Dayna, Bucci, John, Cornelius, Jennifer A., Dickens, Scheleen, Doherty, Don, Dunlap, Heather, Goldenberg, David, Jamal, Karim, Jimenez, Norma, Kavanagh, Nicole, Kunimoto, Derek, Martin, John, Miner, Jessica, Mobley, Sarah, Park, Donald, Quinlan, Edward, Sipperley, Jack, Slagle, Carol, Smith, Danielle, Yafchak, Miguelina, Yager, Rohana, Flaxel, Christina J., Bailey, Steven, Francis, Peter, Howell, Chris, Hwang, Thomas, Ira, Shirley, Klein, Michael, Lauer, Andreas, Liesegang, Teresa, Lundquist, Ann, Nolte, Sarah, Nolte, Susan K., Pickell, Scott, Pope, Susan, Rossi, Joseph, Schain, Mitchell, Steinkamp, Peter, Toomey, Maureen D., Vahrenwald, Debora, West, Kelly, Hubbard, Baker, Andelman, Stacey, Bergstrom, Chris, Brower, Judy, Cribbs, Blaine, Curtis, Linda, Dobbs, Jannah, DuBois, Lindreth, Gaultney, Jessica, Gibbs, Deborah, Jordan, Debora, Leef, Donna, Martin, Daniel F., Myles, Robert, Olsen, Timothy, Schwent, Bryan, Srivastava, Sunil, Waldron, Rhonda, Antoszyk, Andrew N., Balasubramaniam, Uma, Brooks, Danielle, Brown, Justin, Browning, David, Clark, Loraine, Ennis, Sarah, Held, Susannah, Helms, Jennifer V., Herby, Jenna, Karow, Angie, Leotaud, Pearl, Massimino, Caterina, McClain, Donna, McOwen, Michael, Mindel, Jennifer, Pereira, Candace, Pierce, Rachel, Powers, Michele, Price, Angela, Rohrer, Jason, Sanders, Jason, Avery, Robert L., Avery, Kelly, Basefsky, Jessica, Beckner, Liz, Castellarin, Alessandro, Couvillion, Stephen, Giust, Jack, Giust, Matthew, Nasir, Maan, Pieramici, Dante, Rabena, Melvin, Risard, Sarah, See, Robert, Smith, Jerry, Wan, Lisha, Bakri, Sophie J., Abu-Yaghi, Nakhleh, Barkmeier, Andrew, Berg, Karin, Burrington, Jean, Edwards, Albert, Goddard, Shannon, Howard, Shannon, Iezzi, Raymond, Lewison, Denise, Link, Thomas, McCannel, Colin A., Overend, Joan, Pach, John, Ruszczyk, Margaret, Shultz, Ryan, Stephan, Cindy, Vogen, Diane, Bradford, Reagan H., Jr., Bergman, Vanessa, Burris, Russ, Butt, Amanda, Daniels, Beth, Dwiggins, Connie, Fransen, Stephen, Guerrero, Tiffany, Haivala, Darin, Harris, Amy, Icks, Sonny, Kingsley, Ronald, Redden, Lena, Richmond, Rob, Ross, Brittany, White, Kammerin, Youngberg, Misty, Topping, Trexler M., Bennett, Steve, Chong, Sandy, Ciotti, Mary, Cleary, Tina, Corey, Emily, Donovan, Dennis, Frederick, Albert, Freese, Lesley, Graham, Margaret, Gud, Natalya, Howard, Taneika, Jones, Mike, Morley, Michael, Moses, Katie, Stone, Jen, Ty, Robin, Wiegand, Torsten, Williams, Lindsey, Winder, Beth, Awh, Carl C., Amonette, Michelle, Arrindell, Everton, Beck, Dena, Busbee, Brandon, Dilback, Amy, Downs, Sara, Guidry, Allison, Gutow, Gary, Hardin, Jackey, Hines, Sarah, Hutchins, Emily, LaCivita, Kim, Lester, Ashley, Malott, Larry, McCain, MaryAnn, Miracle, Jayme, Moffat, Kenneth, Palazzotta, Lacy, Robinson, Kelly, Sonkin, Peter, Travis, Alecia, Wallace, Roy Trent, Winters, Kelly J., Wray, Julia, Harris, April E., Bunnell, Mari, Crooks, Katrina, Fitzgerald, Rebecca, Javid, Cameron, Kew, Corin, Kill, Erica, Kline, Patricia, Kreienkamp, Janet, Martinez, Maricruz, Moore, Roy Ann, Saavedra, Egbert, Taylor, LuAnne, Walsh, Mark, Wilson, Larry, Ciulla, Thomas A., Coyle, Ellen, Harrington, Tonya, Harris, Charlotte, Hood, Cindi, Kerr, Ingrid, Maturi, Raj, Moore, Dawn, Morrow, Stephanie, Savage, Jennifer, Sink, Bethany, Steele, Tom, Thukral, Neelam, Wilburn, Janet, Walker, Joseph P., Banks, Jennifer, Ciampaglia, Debbie, Dyshanowitz, Danielle, Frederick, Jennifer, Ghuman, A. Tom, Grodin, Richard, Kiesel, Cheryl, Knips, Eileen, McCue, Jonathan, Ortiz, Maria, Peters, Crystal, Raskauskas, Paul, Schoeman, Etienne, Sharma, Ashish, Wing, Glenn, Youngblood, Rebecca, Chandra, Suresh R., Altaweel, Michael, Blodi, Barbara, Burke, Kathryn, Dietzman, Kristine A., Gottlieb, Justin, Knutson, Gene, Krolnik, Denise, Nork, T. Michael, Olson, Shelly, Peterson, John, Reed, Sandra, Soderling, Barbara, Somers, Guy, Stevens, Thomas, Wealti, Angela, Bearelly, Srilaxmi, Branchaud, Brenda, Bryant, Joyce W., Crowell, Sara, Fekrat, Sharon, Gammage, Merritt, Harrison, Cheala, Jones, Sarah, McClain, Noreen, McCuen, Brooks, Mruthyunjaya, Prithvi, Queen, Jeanne, Sarin, Neeru, Skalak, Cindy, Skelly, Marriner, Suner, Ivan, Tomany, Ronnie, Welch, Lauren, Park, Susanna S., Cassidy, Allison, Chandra, Karishma, Good, Idalew, Imson, Katrina, Sashi, Kaur, Metzler, Helen, Morse, Lawrence, Redenbo, Ellen, Salvador, Marisa, Telander, David, Thomas, Mark, Wallace, Cindy, Barr, Charles C., Battcher, Amanda, Bottorff, Michelle, Chasteen, Mary, Clark, Kelly, Denning, Diane, Schoen, Debra, Schultz, Amy, Tempel, Evie, Wheeler, Lisa, Whittington, Greg K., Stone, Thomas W., Blevins, Todd, Buck, Michelle, Cruz, Lynn, Heath, Wanda, Holcomb, Diana, Isernhagen, Rick, Kidd, Terri, Kitchens, John, Sears, Cathy, Slade, Ed, Van Arsdall, Jeanne, VanHoose, Brenda, Wolfe, Jenny, Wood, William, Zilis, John, Crooks, Carol, Disney, Larry, Liu, Mimi, Petty, Stephen, Sall, Sandra, Folk, James C., Aly, Tracy, Brotherton, Abby, Critser, Douglas, Hinz, Connie J., Karakas, Stefani, Kirschner, Valerie, Lester, Cheyanne, Montague, Cindy, Russell, Stephen, Stockman, Heather, Taylor, Barbara, Verdick, Randy, Walshire, Jean, Thompson, John T., Connell, Barbara, Constantine, Maryanth, Davis, John L., Jr., Gwen Holsapple, Hunter, Lisa, Lenane, C. Nicki, Mitchell, Robin, Russel, Leslie, Sjaarda, Raymond, Brown, David M., Benz, Matthew, Burns, Llewellyn, Carranza, JoLene G., Fish, Richard, Goates, Debra, Hay, Shayla, Jeffers, Theresa, Kegley, Eric, Kubecka, Dallas, McGilvra, Stacy, Richter, Beau, Sneed, Veronica, Stoever, Cary, Tellez, Isabell, Wong, Tien, Kim, Ivana, Andreoli, Christopher, Barresi, Leslie, Brett, Sarah, Callahan, Charlene, Capaccioli, Karen, Carli, William, Coppola, Matthew, Emmanuel, Nicholas, Evans, Claudia, Fagan, Anna, Grillo, Marcia, Head, John, Kieser, Troy, Lee, Elaine, Lord, Ursula, Miretsky, Edward, Palitsch, Kate, Petrin, Todd, Reader, Liz, Reznichenko, Svetlana, Robertson, Mary, Smith, Justin, Vavvas, Demetrios, Wells, John, Cahill, Cassie, Clark, W. Lloyd, Henry, Kayla, Johnson, David, Miller, Peggy, Oliver, LaDetrick, Spivey, Robbin, Swinford, Tiffany, Taylor, Mallie, Lambert, Michael, Chase, Kris, Fredrickson, Debbie, Khawly, Joseph, Lazarte, Valerie, Lowd, Donald, Miller, Pam, Willis, Arthur, Ferrone, Philip J., Almonte, Miguel, Arnott, Rachel, Aviles, Ingrid, Carbon, Sheri, Chitjian, Michael, DAmore, Kristen, Elliott, Christin, Fastenberg, David, Golub, Barry, Graham, Kenneth, Lavorna, AnnMarie, Murphy, Laura, Palomo, Amanda, Puglisi, Christina, Rhee, David, Romero, Juan, Rosenblatt, Brett, Salcedo, Glenda, Schlameuss, Marianne, Shakin, Eric, Sookhai, Vasanti, Kaiser, Richard, Affel, Elizabeth, Brown, Gary, Centinaro, Christina, Fine, Deborah, Fineman, Mitchell, Formoso, Michele, Garg, Sunir, Grande, Lisa, Herbert, Carolyn, Ho, Allen, Hsu, Jason, Jay, Maryann, Lavetsky, Lisa, Liebenbaum, Elaine, Maguire, Joseph, Monsonego, Julia, O’Connor, Lucia, Pierce, Lisa, Regillo, Carl, Rosario, Maria, Spirn, Marc, Vander, James, Walsh, Jennifer, Davidorf, Frederick H., Barnett, Amanda, Chang, Susie, Christoforidis, John, Elliott, Joy, Justice, Heather, Letson, Alan, McKinney, Kathryne, Perry, Jeri, Salerno, Jill A., Savage, Scott, Shelley, Stephen, Singerman, Lawrence J., Coney, Joseph, DuBois, John, DuBois, Kimberly, Greanoff, Gregg, Himmelman, Dianne, Ilc, Mary, McNamara, Elizabeth, Novak, Michael, Pendergast, Scott, Rath, Susan, Smith-Brewer, Sheila, Tanner, Vivian, Weiss, Diane E., Zegarra, Hernando, Halperin, Lawrence, Aramayo, Patricia, Dhalla, Mandeep, Fernandez, Brian, Fernandez, Cindy, Lopez, Jaclyn, Lopez, Monica, Mariano, Jamie, Murphy, Kellie, Sherley, Clifford, Veksler, Rita, Rahhal, Firas, Babikian, Razmig, Boyer, David, Hami, Sepideh, Kessinger, Jeff, Kurokouchi, Janet, Mukarram, Saba, Pachman, Sarah, Protacio, Eric, Sierra, Julio, Tabandeh, Homayoun, Zamboni, Adam, Elman, Michael, Belz, Jennifer, Butcher, Tammy, Cain, Theresa, Coffey, Teresa, Firestone, Dena, Gore, Nancy, Singletary, Pamela, Sotirakos, Peter, Starr, JoAnn, Meredith, Travis A., Barnhart, Cassandra J., Cantrell, Debra, Esquejo-Leon, RonaLyn, Houghton, Odette, Kaur, Harpreet, NDure, Fatoumatta, Glatzer, Ronald, Joffe, Leonard, Schindler, Reid, Xue, Katie, Hua, Peiying, Maguire, Maureen G., Daniel, Ebenezer, Jaffe, Glenn J., Grunwald, Juan E., and Ying, Gui-shuang

Published
2023
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23. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.

Author

Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjörnsson, Garðar, Fatemifar, Ghazaleh, Hedman, Åsa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Ärnlöv, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engström, Gunnar, Esko, Tõnu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, März, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Regeneron Genetics Center, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, and Stott, David J

Subjects
Regeneron Genetics Center, Humans, Atrial Fibrillation, Cardiomyopathies, Microfilament Proteins, Adaptor Proteins, Signal Transducing, Carrier Proteins, Muscle Proteins, Risk Factors, Case-Control Studies, Ventricular Function, Left, Cyclin-Dependent Kinase Inhibitor p21, Apoptosis Regulatory Proteins, Coronary Artery Disease, Heart Failure, Genome-Wide Association Study, Mendelian Randomization Analysis, Adaptor Proteins, Signal Transducing, Ventricular Function, Left
Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Published
2020

24. k-SALSA: k-Anonymous Synthetic Averaging of Retinal Images via Local Style Alignment

Author

Jeon, Minkyu, Park, Hyeonjin, Kim, Hyunwoo J., Morley, Michael, Cho, Hyunghoon, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Avidan, Shai, editor, Brostow, Gabriel, editor, Cissé, Moustapha, editor, Farinella, Giovanni Maria, editor, and Hassner, Tal, editor

Published
2022
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28. A longitudinal atlas of post-viral lung regeneration reveals persistent injury-associated cell states

Author

Niethamer, Terren K, primary, Planer, Joseph D, additional, Morley, Michael P, additional, Babu, Apoorva, additional, Basil, Maria C, additional, Cantu, Edward, additional, Frank, David B, additional, Diamond, Joshua M, additional, Nottingham, Ana N, additional, Li, Shanru, additional, Levin, Lillian I, additional, Zhou, Su, additional, and Morrisey, Edward E, additional

Published
2024
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29. Assessing Potential Bias from Metadata while Labeling Retinal Images Fundus Photographs for Diabetic Retinopathy: Preliminary Experience in the Multimodal Database of Retinal Images in Africa (MoDRIA) (Preprint)

Author

Arunga, Simon, primary, Morley, Katharine Elise, additional, Kwaga, Teddy, additional, Morley, Michael Gerard, additional, Nakayama, Luis Filipe, additional, Mwavu, Rogers, additional, Kaggwa, Fred, additional, Ssempiira, Julius, additional, Celi, Leo Anthony, additional, Haberer, Jessica, additional, and Obua, Celestino, additional

Published
2024
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32. Genome-Wide Fetalization of Enhancer Architecture in Heart Disease

Author

Spurrell, Cailyn, Barozzi, Iros, Mannion, Brandon, Blow, Matthew, Fukuda-Yuzawa, Yoko, Afzal, Sarah, Akiyama, Jennifer, Afzal, Veena, Tran, Stella, Plajzer-Frick, Ingrid, Novak, Catherine, Kato, Momoe, Lee, Elizabeth, Garvin, Tyler, Pham, Quan, Harrington, Anne, Lisgo, Steven, Bristow, James, Cappola, Thomas, Morley, Michael, Margulies, Kenneth, Pennacchio, Len, Dickel, Diane, and Visel, Axel

Subjects
Human Genome, Genetics, Rare Diseases, Heart Disease, Cardiovascular, 1.1 Normal biological development and functioning
Abstract

Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the genome-wide regulatory landscape in heart disease has remained obscure. Here we show that pervasive epigenomic changes occur in heart disease, with thousands of regulatory sequences reacquiring fetal-like chromatin signatures. We used RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from 18 healthy controls and 18 individuals with idiopathic dilated cardiomyopathy (DCM). Healthy individuals had a highly reproducible epigenomic landscape, consisting of more than 31,000 predicted heart enhancers. In contrast, we observed reproducible disease-associated gains or losses of activity at more than 7,500 predicted heart enhancers. Next, we profiled human fetal heart tissue by ChIP-seq and RNA-seq. Comparison with adult tissues revealed that the heart disease epigenome and transcrip-tome both shift toward a fetal-like state, with 3,400 individual enhancers sharing fetal regulatory properties. Our results demonstrate widespread epigenomic changes in DCM, and we provide a comprehensive data resource ( http://heart.lbl.gov ) for the mechanistic exploration of heart disease etiology.

Published
2019

33. Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure

Author

Cordero, Pablo, Parikh, Victoria N, Chin, Elizabeth T, Erbilgin, Ayca, Gloudemans, Michael J, Shang, Ching, Huang, Yong, Chang, Alex C, Smith, Kevin S, Dewey, Frederick, Zaleta, Kathia, Morley, Michael, Brandimarto, Jeff, Glazer, Nicole, Waggott, Daryl, Pavlovic, Aleksandra, Zhao, Mingming, Moravec, Christine S, Tang, WH Wilson, Skreen, Jamie, Malloy, Christine, Hannenhalli, Sridhar, Li, Hongzhe, Ritter, Scott, Li, Mingyao, Bernstein, Daniel, Connolly, Andrew, Hakonarson, Hakon, Lusis, Aldons J, Margulies, Kenneth B, Depaoli-Roach, Anna A, Montgomery, Stephen B, Wheeler, Matthew T, Cappola, Thomas, and Ashley, Euan A

Subjects
Biological Sciences, Genetics, Human Genome, Biotechnology, Heart Disease, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Animals, Benzeneacetamides, Cells, Cultured, Datasets as Topic, Disease Models, Animal, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Knockdown Techniques, Gene Regulatory Networks, Genome-Wide Association Study, Heart Failure, Humans, Male, Metabolic Networks and Pathways, Mice, Mice, Knockout, Middle Aged, Myocytes, Cardiac, Phosphoprotein Phosphatases, Primary Cell Culture, Pyridines, Quantitative Trait Loci, Rats, Rats, Sprague-Dawley, Sequence Analysis, RNA
Abstract

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure.

Published
2019

34. Genome-Wide Fetalization of Enhancer Architecture in Heart Disease

Author

Spurrell, Cailyn H, Barozzi, Iros, Mannion, Brandon J, Blow, Matthew J, Fukuda-Yuzawa, Yoko, Afzal, Sarah Y, Akiyama, Jennifer A, Afzal, Veena, Tran, Stella, Plajzer-Frick, Ingrid, Novak, Catherine S, Kato, Momoe, Lee, Elizabeth, Garvin, Tyler H, Pham, Quan T, Harrington, Anne N, Lisgo, Steven, Bristow, James, Cappola, Thomas P, Morley, Michael P, Margulies, Kenneth B, Pennacchio, Len A, Dickel, Diane E, and Visel, Axel

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Heart Disease, Rare Diseases, Human Genome, Cardiovascular, Underpinning research, 1.1 Normal biological development and functioning
Abstract

Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the genome-wide regulatory landscape in heart disease has remained obscure. Here we show that pervasive epigenomic changes occur in heart disease, with thousands of regulatory sequences reacquiring fetal-like chromatin signatures. We used RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from 18 healthy controls and 18 individuals with idiopathic dilated cardiomyopathy (DCM). Healthy individuals had a highly reproducible epigenomic landscape, consisting of more than 31,000 predicted heart enhancers. In contrast, we observed reproducible disease-associated gains or losses of activity at more than 7,500 predicted heart enhancers. Next, we profiled human fetal heart tissue by ChIP-seq and RNA-seq. Comparison with adult tissues revealed that the heart disease epigenome and transcrip-tome both shift toward a fetal-like state, with 3,400 individual enhancers sharing fetal regulatory properties. Our results demonstrate widespread epigenomic changes in DCM, and we provide a comprehensive data resource ( http://heart.lbl.gov ) for the mechanistic exploration of heart disease etiology.

Published
2019

37. Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure

Author

Levin, Michael G., Tsao, Noah L., Singhal, Pankhuri, Liu, Chang, Vy, Ha My T., Paranjpe, Ishan, Backman, Joshua D., Bellomo, Tiffany R., Bone, William P., Biddinger, Kiran J., Hui, Qin, Dikilitas, Ozan, Satterfield, Benjamin A., Yang, Yifan, Morley, Michael P., Bradford, Yuki, Burke, Megan, Reza, Nosheen, Charest, Brian, Judy, Renae L., Puckelwartz, Megan J., Hakonarson, Hakon, Khan, Atlas, Kottyan, Leah C., Kullo, Iftikhar, Luo, Yuan, McNally, Elizabeth M., Rasmussen-Torvik, Laura J., Day, Sharlene M., Do, Ron, Phillips, Lawrence S., Ellinor, Patrick T., Nadkarni, Girish N., Ritchie, Marylyn D., Arany, Zoltan, Cappola, Thomas P., Margulies, Kenneth B., Aragam, Krishna G., Haggerty, Christopher M., Joseph, Jacob, Sun, Yan V., Voight, Benjamin F., and Damrauer, Scott M.

Published
2022
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38. Investigating management practices and their impact on social value creation : a case study of social enterprises in North East England

Author

Morley, Michael and Robson, Andrew

Subjects
658.4, N200 Management studies
Abstract

The research presented explores links between key quality management practices and social impact creation within small to medium sized social enterprises (SMSEs). In particular, this study investigates workforce management and customer relationship management practices, and their perceived influence on social impact, whilst also considering the influence of external environmental factors. The research adopted a qualitative, single case study design, framing social enterprises in North east England as its unit of analysis. Within which, fourteen distinct social enterprises, and two sector experts represented sub units creating an embedded case study. The research identified three key findings following the template analysis procedure. Firstly, there are perceived links, both implicit, and explicit, between both practices discussed and the ability to provide social impact. Most notably through understanding and being able to respond to customer and stakeholder needs and creating positive working environments which offset resource constraints by increasing motivation. Secondly, the research suggests that where management practices may well be of benefit, such elements are often overshadowed by the availability of funding, especially when SMSEs are beholden to public sector contracts and institutional funders. Finally, the research builds upon current knowledge related to workforce management practices within SMSEs, where pro social motivations appear critical to workforce performance, even in more commercially focussed social enterprises. This research is unique as it begins to build a bridge between social enterprise and quality management discourse, showing the potential importance of practice to performance relationships to social value creation. Furthermore, research on social impact performance is yet to explore the collective importance of internal practices such as those mentioned.

Published
2018

40. Diversified boards and the achievement of environmental, social, and governance goals.

Author

Alawadi, Asma, Kakabadse, Nada, Morley, Michael, and Khan, Nadeem

Subjects
RESOURCE dependence theory, DIVERSITY in the workplace, SOCIAL goals, SOCIAL skills, ACHIEVEMENT
Abstract

We explore the impact of board resources arising from diverse board members on the achievement of environmental, social, and governance (ESG) goals. Employing resource dependence theory as our frame and drawing on qualitative data from 41 interviews with board directors of publicly traded and privately held companies in the United Arab Emirates (UAE), we identify three key mechanisms underpinning the achievement of ESG goals, namely, the leveraging of particular connections, the deployment of different resources, and the harnessing of a range of diversity types. We find that the use of social resources is often related to environmental concerns and occasionally social goals, but rarely governance issues. We also find that financial motivations often drive environmental issues, while many of the social resources that added value occurred in the public sector. Importantly, the combining of both skill and social resources, rather than relying on each alone, was seen to increase the likelihood of achieving ESG goals. Our findings also point to the importance of board diversity in accomplishing the board's ESG goals, most especially functional diversity. We propose that such functional diversity, along with resources in the form of social resources and skills, needs to feature more prominently in order to improve ESG performance and outcomes. We highlight the implications of our work, especially regarding the establishment of board diversity policies beyond gender alone. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Articulating scholarship in human resource management: Guidance for researchers.

Author

Budhwar, Pawan, Wood, Geoffrey, Chowdhury, Soumyadeb, Aguinis, Herman, Breslin, Dermot, Collings, David G., Cooke, Fang Lee, Darabi, Fariba, Eby, Lillian T., Martin, Ursula M., Morley, Michael J., Morris, Shad, Ren, Shuang, Saunders, Mark N. K., and Suddaby, Roy

Subjects
PERSONNEL management, RESEARCH personnel, RESEARCH methodology, SCHOLARLY method, EVIDENCE
Abstract

HRMJ is a business and management journal: we seek to publish excellent work that deals not simply with people and organisations, but with the management of people and the issues and tensions around the latter. As such, the journal is broadly multidisciplinary, the key focus being on advancing theory through empirical evidence, through consolidations and extensions of conceptual knowledge, through revisiting and extending existing theory, literature reviews, as well as the development of salient research methods. This extended editorial brings together a range of perspectives from and beyond the editorial team to advance understanding around developing work for publication. As such, it is intended not only to guide authors interested in publishing in HRMJ, but all with an interest in advancing their scholarly work. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction

Author

Macri, Vincenzo, Brody, Jennifer A, Arking, Dan E, Hucker, William J, Yin, Xiaoyan, Lin, Honghuang, Mills, Robert W, Sinner, Moritz F, Lubitz, Steven A, Liu, Ching-Ti, Morrison, Alanna C, Alonso, Alvaro, Li, Ning, Fedorov, Vadim V, Janssen, Paul M, Bis, Joshua C, Heckbert, Susan R, Dolmatova, Elena V, Lumley, Thomas, Sitlani, Colleen M, Cupples, L Adrienne, Pulit, Sara L, Newton-Cheh, Christopher, Barnard, John, Smith, Jonathan D, Van Wagoner, David R, Chung, Mina K, Vlahakes, Gus J, O'Donnell, Christopher J, Rotter, Jerome I, Margulies, Kenneth B, Morley, Michael P, Cappola, Thomas P, Benjamin, Emelia J, Muzny, Donna, Gibbs, Richard A, Jackson, Rebecca D, Magnani, Jared W, Herndon, Caroline N, Rich, Stephen S, Psaty, Bruce M, Milan, David J, Boerwinkle, Eric, Mohler, Peter J, Sotoodehnia, Nona, and Ellinor, Patrick T

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Heart Disease, Biotechnology, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Biophysical Phenomena, Electrocardiography, Genetic Association Studies, Haplotypes, Heart Conduction System, Humans, Ion Channel Gating, Mutation, Missense, NAV1.8 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Quantitative Trait Loci, atrial fibrillation, electrocardiography, haplotypes, Na plus channels, population genetics, Na+ channels, genetics, population, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BACKGROUND:Genetic variants at the SCN5A/SCN10A locus are strongly associated with electrocardiographic PR and QRS intervals. While SCN5A is the canonical cardiac sodium channel gene, the role of SCN10A in cardiac conduction is less well characterized. METHODS:We sequenced the SCN10A locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology. RESULTS:We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium (r  2=0.86) with each other to be the strongest signals for PR (rs10428132, β=-4.74, P=1.52×10-14) and QRS intervals (rs6599251, QRS β=-0.73; P=1.2×10-4), respectively. Although these variants were not associated with SCN5A or SCN10A expression in human atrial tissue (n=490), they were in high linkage disequilibrium (r  2≥0.72) with a common SCN10A missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%, P=0.03, and I962V+V1073A, 22.4±0.8%, P=0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%, P=0.03). CONCLUSIONS:Our findings suggest an association between genetic variation in SCN10A, the late sodium current, and alterations in cardiac conduction.

Published
2018

45. Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium

Author

McCauley, Katherine B, Alysandratos, Konstantinos-Dionysios, Jacob, Anjali, Hawkins, Finn, Caballero, Ignacio S, Vedaie, Marall, Yang, Wenli, Slovik, Katherine J, Morley, Michael, Carraro, Gianni, Kook, Seunghyi, Guttentag, Susan H, Stripp, Barry R, Morrisey, Edward E, and Kotton, Darrell N

Subjects
Lung, Stem Cell Research - Induced Pluripotent Stem Cell, Regenerative Medicine, Stem Cell Research, Stem Cell Research - Embryonic - Human, Respiratory, Animals, Cell Differentiation, Cell Line, Cell Lineage, Cell Plasticity, Epithelium, Gene Expression Profiling, Genes, Reporter, Humans, Induced Pluripotent Stem Cells, Kinetics, Mice, Secretoglobins, Sequence Analysis, RNA, Single-Cell Analysis, Solubility, Spheroids, Cellular, Time Factors, Transcriptome, Wnt Signaling Pathway, airway, alveoli, directed differentiation, lung epithelium, pluripotent stem cells, single-cell RNA sequencing, Biochemistry and Cell Biology, Clinical Sciences
Abstract

Lung epithelial lineages have been difficult to maintain in pure form in vitro, and lineage-specific reporters have proven invaluable for monitoring their emergence from cultured pluripotent stem cells (PSCs). However, reporter constructs for tracking proximal airway lineages generated from PSCs have not been previously available, limiting the characterization of these cells. Here, we engineer mouse and human PSC lines carrying airway secretory lineage reporters that facilitate the tracking, purification, and profiling of this lung subtype. Through bulk and single-cell-based global transcriptomic profiling, we find PSC-derived airway secretory cells are susceptible to phenotypic plasticity exemplified by the tendency to co-express both a proximal airway secretory program as well as an alveolar type 2 cell program, which can be minimized by inhibiting endogenous Wnt signaling. Our results provide global profiles of engineered lung cell fates, a guide for improving their directed differentiation, and a human model of the developing airway.

Published
2018

46. PDK4 Inhibits Cardiac Pyruvate Oxidation in Late Pregnancy

Author

Liu, Laura X, Rowe, Glenn C, Yang, Steven, Li, Jian, Damilano, Federico, Chan, Mun Chun, Lu, Wenyun, Jang, Cholsoon, Wada, Shogo, Morley, Michael, Hesse, Michael, Fleischmann, Bernd K, Rabinowitz, Joshua D, Das, Saumya, Rosenzweig, Anthony, and Arany, Zoltan

Subjects
Cardiovascular, Diabetes, Heart Disease, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Animals, Citric Acid Cycle, Fatty Acids, Female, Glucose, Lactic Acid, Mice, Mice, Inbred C57BL, Myocardium, Pregnancy, Progesterone, Protein Serine-Threonine Kinases, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Pyruvic Acid, glucose, heart, metabolism, mitochondria, pregnancy, progesterone, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

RationalePregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations, are not well understood.ObjectiveTo determine the mechanisms underlying cardiac substrate use during pregnancy.Methods and resultsWe use here 13C glucose, 13C lactate, and 13C fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid cycle, while reducing glucose and lactate oxidation. Mitochondrial quantity, morphology, and function do not seem altered. Insulin signaling seems intact, and the abundance and localization of the major fatty acid and glucose transporters, CD36 (cluster of differentiation 36) and GLUT4 (glucose transporter type 4), are also unchanged. Rather, we find that the pregnancy hormone progesterone induces PDK4 (pyruvate dehydrogenase kinase 4) in cardiomyocytes and that elevated PDK4 levels in late pregnancy lead to inhibition of PDH (pyruvate dehydrogenase) and pyruvate flux into the tricarboxylic acid cycle. Blocking PDK4 reverses the metabolic changes seen in hearts in late pregnancy.ConclusionsTaken together, these data indicate that the hormonal environment of late pregnancy promotes metabolic remodeling in the heart at the level of PDH, rather than at the level of insulin signaling.

Published
2017

47. Sex-Specific Effect of MTSS1 Downregulation on Dilated Cardiomyopathy

Author

Choe, Dongwook, primary, Burke, Megan, additional, Brandimarto, Jeffrey A, additional, Marti-Pamies, Ingrid, additional, Yob, Jaime, additional, Yang, Yifan, additional, Morley, Michael P, additional, Drivas, Theodore G., additional, Day, Sharlene, additional, Damrauer, Scott, additional, Wang, Xiao, additional, and Cappola, Thomas P, additional

Published
2024
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48. An injury-induced tissue niche shaped by mesenchymal plasticity coordinates the regenerative and disease response in the lung

Author

Jones, Dakota L., primary, Morley, Michael P., additional, Li, Xinyuan, additional, Ying, Yun, additional, Cardenas-Diaz, Fabian L., additional, Li, Shanru, additional, Zhou, Su, additional, Schaefer, Sarah E., additional, Chembazhi, Ullas V., additional, Nottingham, Ana, additional, Lin, Susan, additional, Cantu, Edward, additional, Diamond, Joshua M., additional, Basil, Maria C., additional, Vaughan, Andrew E., additional, and Morrisey, Edward E., additional

Published
2024
Full Text
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