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Your search keyword '"Flick, Leah M."' showing total 18 results
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18 results on '"Flick, Leah M."'

2. Immune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer

Author

Beckabir, Wolfgang, Zhou, Mi, Lee, Jin Seok, Vensko, Steven P., Woodcock, Mark G., Wang, Hsing-Hui, Wobker, Sara E., Atassi, Gatphan, Wilkinson, Alec D., Fowler, Kenneth, Flick, Leah M., Damrauer, Jeffrey S., Harrison, Michael R., McKinnon, Karen P., Rose, Tracy L., Milowsky, Matthew I., Serody, Jonathan S., Kim, William Y., and Vincent, Benjamin G.

Published
2024
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4. A BAFF/APRIL axis regulates obesogenic diet-driven weight gain

Author

Chan, Calvin C., Harley, Isaac T. W., Pfluger, Paul T., Trompette, Aurelien, Stankiewicz, Traci E., Allen, Jessica L., Moreno-Fernandez, Maria E., Damen, Michelle S. M. A., Oates, Jarren R., Alarcon, Pablo C., Doll, Jessica R., Flick, Matthew J., Flick, Leah M., Sanchez-Gurmaches, Joan, Mukherjee, Rajib, Karns, Rebekah, Helmrath, Michael, Inge, Thomas H., Weisberg, Stuart P., Pamp, Sünje J., Relman, David A., Seeley, Randy J., Tschöp, Matthias H., Karp, Christopher L., and Divanovic, Senad

Published
2021
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5. Differential colonization with segmented filamentous bacteria and Lactobacillus murinus do not drive divergent development of diet-induced obesity in C57BL/6 mice

Author

Harley, Isaac T.W., Giles, Daniel A., Pfluger, Paul T., Burgess, Stacey L., Walters, Stephanie, Hembree, Jazzminn, Raver, Christine, Rewerts, Cheryl L., Downey, Jordan, Flick, Leah M., Stankiewicz, Traci E., McAlees, Jaclyn W., Wills-Karp, Marsha, Balfour Sartor, R., Divanovic, Senad, Tschöp, Matthias H., and Karp, Christopher L.

Published
2013
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6. A BAFF/APRIL axis regulates obesogenic diet-driven weight gain

Author

Chan, Calvin C, Harley, Isaac T W, Pfluger, Paul T, Trompette, Aurelien, Stankiewicz, Traci E, Allen, Jessica L, Moreno-Fernandez, Maria E, Damen, Michelle S M A, Oates, Jarren R, Alarcon, Pablo C, Doll, Jessica R, Flick, Matthew J, Flick, Leah M, Sanchez-Gurmaches, Joan, Mukherjee, Rajib, Karns, Rebekah, Helmrath, Michael, Inge, Thomas H, Weisberg, Stuart P, Pamp, Sünje J, Relman, David A, Seeley, Randy J, Tschöp, Matthias H, Karp, Christopher L, Divanovic, Senad, Chan, Calvin C, Harley, Isaac T W, Pfluger, Paul T, Trompette, Aurelien, Stankiewicz, Traci E, Allen, Jessica L, Moreno-Fernandez, Maria E, Damen, Michelle S M A, Oates, Jarren R, Alarcon, Pablo C, Doll, Jessica R, Flick, Matthew J, Flick, Leah M, Sanchez-Gurmaches, Joan, Mukherjee, Rajib, Karns, Rebekah, Helmrath, Michael, Inge, Thomas H, Weisberg, Stuart P, Pamp, Sünje J, Relman, David A, Seeley, Randy J, Tschöp, Matthias H, Karp, Christopher L, and Divanovic, Senad

Abstract

The impact of immune mediators on weight homeostasis remains underdefined. Interrogation of resistance to diet-induced obesity in mice lacking a negative regulator of Toll-like receptor signaling serendipitously uncovered a role for B cell activating factor (BAFF). Here we show that overexpression of BAFF in multiple mouse models associates with protection from weight gain, approximating a log-linear dose response relation to BAFF concentrations. Gene expression analysis of BAFF-stimulated subcutaneous white adipocytes unveils upregulation of lipid metabolism pathways, with BAFF inducing white adipose tissue (WAT) lipolysis. Brown adipose tissue (BAT) from BAFF-overexpressing mice exhibits increased Ucp1 expression and BAFF promotes brown adipocyte respiration and in vivo energy expenditure. A proliferation-inducing ligand (APRIL), a BAFF homolog, similarly modulates WAT and BAT lipid handling. Genetic deletion of both BAFF and APRIL augments diet-induced obesity. Lastly, BAFF/APRIL effects are conserved in human adipocytes and higher BAFF/APRIL levels correlate with greater BMI decrease after bariatric surgery. Together, the BAFF/APRIL axis is a multifaceted immune regulator of weight gain and adipose tissue function.

Published
2021

8. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease

Author

Gu, YuanYuan, Harleys, Isaac T.W., Henderson, Lindsay B., Aronow, Bruce J., Vietor, Ilja, Huber, Lukas A., Harley, John B., Kilpatrick, Jeffrey R., Langefeld, Carl D., Williams, Adrienne H., Jegga, Anil G., Chen, Jing, Wills-Karp, Marsha, Arshads, S. Hasan, Ewart, Susan L., Thio, Chloe L., Flick, Leah M., Filippi, Marie-Dominique, Grimes, H. Leighton, Drumm, Mitchell L., Cutting, Garry R., Knowles, Michael R., and Karp, Christopher L.

Subjects
Cystic fibrosis -- Genetic aspects -- Research, Single nucleotide polymorphisms -- Health aspects -- Research -- Physiological aspects -- Genetic aspects, Membrane proteins -- Physiological aspects -- Genetic aspects -- Research -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Physiological aspects, Research, Genetic aspects, Health aspects
Abstract

Lung disease is the major cause of morbidity and mortality in cystic fibrosis, an autosomal recessive disease caused by mutations in CFTR. In cystic fibrosis, chronic infection and dysregulated neutrophilic inflammation lead to progressive airway destruction. The severity of cystic fibrosis lung disease has considerable heritability, independent of CFTR genotype (1). To identify genetic modifiers, here we performed a genome-wide single nucleotide polymorphism scan in one cohort of cystic fibrosis patients, replicating top candidates in an independent cohort. This approach identified IFRD1 as a modifier of cystic fibrosis lung disease severity. IFRD1 is a histone-deacetylase-dependent transcriptional co-regulator expressed during terminal neutrophil differentiation. Neutrophil, but not macrophages, from Ifrd1-deficient mice showed blunted effector function, associated with decreased NF-κB p65 transactivation. In vivo, IFRD1 deficiency caused delayed bacterial clearance from the airway, but also less inflammation and disease--a phenotype primarily dependent on haematopoietic cell expression, or lack of expression, of IFRD1. In humans, IFRD1 polymorphisms were significantly associated with variation in neutrophil effector function. These data indicate that IFRD1 modulates the pathogenesis of cystic fibrosis lung disease through the regulation of neutrophil effector function., Attention to the role of CFTR in regulating epithelial ion transport has failed to illuminate the path from gene to pathogenesis in cystic fibrosis (CF) lung disease. In CF, colonization [...]

Published
2009

10. Contributions of the Three CYP1 Monooxygenases to Pro-Inflammatory and Inflammation-Resolution Lipid Mediator Pathways

Author

Divanovic, Senad, primary, Dalli, Jesmond, additional, Jorge-Nebert, Lucia F., additional, Flick, Leah M., additional, Gálvez-Peralta, Marina, additional, Boespflug, Nicholas D., additional, Stankiewicz, Traci E., additional, Fitzgerald, Jonathan M., additional, Somarathna, Maheshika, additional, Karp, Christopher L., additional, Serhan, Charles N., additional, and Nebert, Daniel W., additional

Published
2013
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13. Cystic fibrosis and lipoxins

Author

Karp, Christopher L., primary, Flick, Leah M., additional, Yang, Rong, additional, Uddin, Jasim, additional, and Petasis, Nicos A., additional

Published
2005
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14. Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway

Author

Karp, Christopher L, primary, Flick, Leah M, additional, Park, Kiwon W, additional, Softic, Samir, additional, Greer, Todd M, additional, Keledjian, Raquel, additional, Yang, Rong, additional, Uddin, Jasim, additional, Guggino, William B, additional, Atabani, Sowsan F, additional, Belkaid, Yasmine, additional, Xu, Yan, additional, Whitsett, Jeffrey A, additional, Accurso, Frank J, additional, Wills-Karp, Marsha, additional, and Petasis, Nicos A, additional

Published
2004
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17. Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway.

Author

Flick, Leah M., Park, Kiwon W., Softic, Samir, Greer, Todd M., Keledjian, Raquel, Yang, Rong, Uddin, Jasim, Guggino, William B., Atabani, Sowsan F., Belkaid, Yasmine, Xu, Yan, Whitsett, Jeffrey A., Accurso, Frank J., Wills-Karp, Marsha, Petasis, Nicos A., and Karp, Christopher L.

Subjects
*LUNG diseases, *NEUTROPHILS, *INFLAMMATION, *CYSTIC fibrosis, *LIPOXINS, *ANTI-inflammatory agents, *LABORATORY mice, *AIRWAY (Anatomy), *PATHOLOGICAL physiology, *PATIENTS
Abstract

In cystic fibrosis, dysregulated neutrophilic inflammation and chronic infection lead to progressive destruction of the airways. The underlying mechanisms have remained unclear. Lipoxins are anti-inflammatory lipid mediators that modulate neutrophilic inflammation. We report here that lipoxin concentrations in airway fluid were significantly suppressed in patients with cystic fibrosis compared to patients with other inflammatory lung conditions. We also show that administration of a metabolically stable lipoxin analog in a mouse model of the chronic airway inflammation and infection associated with cystic fibrosis suppressed neutrophilic inflammation, decreased pulmonary bacterial burden and attenuated disease severity. These findings suggest that there is a pathophysiologically important defect in lipoxin-mediated anti-inflammatory activity in the cystic fibrosis lung and that lipoxins have therapeutic potential in this lethal autosomal disease. [ABSTRACT FROM AUTHOR]

Published
2004
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18. IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice

Author

Cappelletti, Monica, Softic, Samir, Kohli, Rohit, Karp, Christopher L., Divanovic, Senad, Sartor, R. Balfour, Flick, Leah M., Harley, Isaac T.W., Sheridan, Rachel, Xanthakos, Stavra A., Stankiewicz, Traci E., Steinbrecher, Kris A., and Giles, Daniel A.

Subjects
3. Good health
Abstract

Inflammation plays a central pathogenic role in the pernicious metabolic and end-organ sequelae of obesity. Among these sequelae, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the developed world. The twinned observations that obesity is associated with increased activation of the interleukin (IL)-17 axis and that this axis can regulate liver damage in diverse contexts prompted us to address the role of IL-17RA signaling in the progression of NAFLD. We further examined whether microbe-driven IL-17A regulated NAFLD development and progression. We show here that IL-17RA−/− mice respond to high-fat diet stress with significantly greater weight gain, visceral adiposity, and hepatic steatosis than wild-type controls. However, obesity-driven lipid accumulation was uncoupled from its end-organ consequences in IL-17RA−/− mice, which exhibited decreased steatohepatitis, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme expression, and hepatocellular damage. Neutralization of IL-17A significantly reduced obesity-driven hepatocellular damage in wild-type mice. Further, colonization of mice with segmented filamentous bacteria (SFB), a commensal that induces IL-17A production, exacerbated obesity-induced hepatocellular damage. In contrast, SFB depletion protected from obesity-induced hepatocellular damage. Conclusion: These data indicate that obesity-driven activation of the IL-17 axis is central to the development and progression of NAFLD to steatohepatitis and identify the IL-17 pathway as a novel therapeutic target in this condition. (Hepatology 2014;59:1830–1839)

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