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Article ; Online: Circadian rhythms in solid organ transplantation.

Patlin, Brielle H / Mok, Huram / Arra, Monaj / Haspel, Jeffrey A

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

2024

Abstract: Circadian rhythms are daily cycles in physiology that can affect medical interventions. This review considers how these rhythms may relate to solid organ transplantation. It begins by summarizing the mechanism for circadian rhythm generation known as the ...

Abstract	Circadian rhythms are daily cycles in physiology that can affect medical interventions. This review considers how these rhythms may relate to solid organ transplantation. It begins by summarizing the mechanism for circadian rhythm generation known as the molecular clock, and basic research connecting the clock to biological activities germane to organ acceptance. Next follows a review of clinical evidence relating time of day to adverse transplantation outcomes. The concluding section discusses knowledge gaps and practical areas where applying circadian biology might improve transplantation success.
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1062522-7
ISSN	1557-3117 ; 1053-2498
ISSN (online)	1557-3117
ISSN	1053-2498
DOI	10.1016/j.healun.2024.01.017
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Article ; Online: Circadian immunity from bench to bedside: a practical guide.

Mok, Huram / Ostendorf, Elaine / Ganninger, Alex / Adler, Avi J / Hazan, Guy / Haspel, Jeffrey A

The Journal of clinical investigation

2024 Volume 134, Issue 3

Abstract: The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping ...

Abstract	The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, an important clinical realization of immune function. Finally, we discuss practical steps to translate circadian immunity to the patient's bedside.
MeSH term(s)	Humans ; Circadian Rhythm ; Circadian Clocks ; Sleep ; Immune System
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI175706
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Article ; Online: Measuring Diurnal Rhythms in Autophagic and Proteasomal Flux.

Ryzhikov, Mikhail / Eubanks, Anna / Haspel, Jeffrey A

Journal of visualized experiments : JoVE

2019 , Issue 151

Abstract: Cells employ several methods for recycling unwanted proteins and other material, including lysosomal and non-lysosomal pathways. The main lysosome-dependent pathway is called autophagy, while the primary non-lysosomal method for protein catabolism is the ...

Abstract	Cells employ several methods for recycling unwanted proteins and other material, including lysosomal and non-lysosomal pathways. The main lysosome-dependent pathway is called autophagy, while the primary non-lysosomal method for protein catabolism is the ubiquitin-proteasome system. Recent studies in model organisms suggest that the activity of both autophagy and the ubiquitin-proteasome system is not constant across the day but instead varies according to a daily (circadian) rhythm. The ability to measure biological rhythms in protein turnover is important for understanding how cellular quality control is achieved and for understanding the dynamics of specific proteins of interest. Here we present a standardized protocol for quantifying autophagic and proteasomal flux in vivo that captures the circadian component of protein turnover. Our protocol includes details for mouse handling, tissue processing, fractionation, and autophagic flux quantification using mouse liver as the starting material.
MeSH term(s)	Animals ; Autophagy/physiology ; Circadian Rhythm ; Female ; Male ; Mice ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; Ubiquitin/metabolism
Chemical Substances	Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2019-09-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/60133
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Article ; Online: Why Lungs Keep Time: Circadian Rhythms and Lung Immunity.

Nosal, Charles / Ehlers, Anna / Haspel, Jeffrey A

Annual review of physiology

2019 Volume 82, Page(s) 391–412

Abstract: Circadian rhythms are daily cycles in biological function that are ubiquitous in nature. Understood as a means for organisms to anticipate daily environmental changes, circadian rhythms are also important for orchestrating complex biological processes ... ...

Abstract	Circadian rhythms are daily cycles in biological function that are ubiquitous in nature. Understood as a means for organisms to anticipate daily environmental changes, circadian rhythms are also important for orchestrating complex biological processes such as immunity. Nowhere is this more evident than in the respiratory system, where circadian rhythms in inflammatory lung disease have been appreciated since ancient times. In this focused review we examine how emerging research on circadian rhythms is being applied to the study of fundamental lung biology and respiratory disease. We begin with a general introduction to circadian rhythms and the molecular circadian clock that underpins them. We then focus on emerging data tying circadian clock function to immunologic activities within the respiratory system. We conclude by considering outstanding questions about biological timing in the lung and how a better command of chronobiology could inform our understanding of complex lung diseases.
MeSH term(s)	Animals ; Circadian Rhythm/physiology ; Humans ; Immunity/physiology ; Lung/immunology ; Lung/physiology ; Pneumonia/immunology ; Pneumonia/physiopathology
Language	English
Publishing date	2019-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	207933-1
ISSN	1545-1585 ; 0066-4278
ISSN (online)	1545-1585
ISSN	0066-4278
DOI	10.1146/annurev-physiol-021119-034602
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Article ; Online: Adventures in spacetime: circadian rhythms and the dynamics of protein catabolism.

Ryzhikov, Mikhail / Ehlers, Anna / Haspel, Jeffrey A

Autophagy

2019 Volume 15, Issue 6, Page(s) 1115–1116

Abstract: Circadian rhythms help cells to organize complex processes, but how they shape the kinetics of protein catabolism is unclear. In a recent paper, we employed proteomics to map daily biological rhythms in autophagic flux in mouse liver, and correlated ... ...

Abstract	Circadian rhythms help cells to organize complex processes, but how they shape the kinetics of protein catabolism is unclear. In a recent paper, we employed proteomics to map daily biological rhythms in autophagic flux in mouse liver, and correlated these rhythms with proteasome activity. We also explored the effect of inflammation caused by endotoxin on autophagy dynamics. Our data provide insight into how circadian rhythms serve as a framework for connecting the spatial, temporal, and metabolic aspects of autophagy at a system-wide level. Our observations also have implications for how to optimize autophagy-directed therapies in patients.
MeSH term(s)	Animals ; Autophagy ; Circadian Rhythm ; Humans ; Kinetics ; Mice ; Proteolysis ; Proteomics
Language	English
Publishing date	2019-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2019.1596498
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Article: Measuring diurnal rhythms in autophagic and proteasomal flux

Ryzhikov, Mikhail / Eubanks, Anna / Haspel, Jeffrey A

Journal of visualized experiments. 2019 Sept. 17, , no. 151

2019

Abstract	Cells employ several methods for recycling unwanted proteins and other material, including lysosomal and non-lysosomal pathways. The main lysosome-dependent pathway is called autophagy, while the primary non-lysosomal method for protein catabolism is the ubiquitin-proteasome system. Recent studies in model organisms suggest that the activity of both autophagy and the ubiquitin-proteasome system is not constant across the day but instead varies according to a daily (circadian) rhythm. The ability to measure biological rhythms in protein turnover is important for understanding how cellular quality control is achieved and for understanding the dynamics of specific proteins of interest. Here we present a standardized protocol for quantifying autophagic and proteasomal flux in vivo that captures the circadian component of protein turnover. Our protocol includes details for mouse handling, tissue processing, fractionation, and autophagic flux quantification using mouse liver as the starting material.
Keywords	animal models ; autophagy ; biological rhythms ; fractionation ; liver ; mice ; protein metabolism ; proteins ; quality control
Language	English
Dates of publication	2019-0917
Size	p. e60133.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/60133
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Nanoparticle targeting of neutrophil glycolysis prevents lung ischemia-reperfusion injury.

Liao, Fuyi / Scozzi, Davide / Zhou, Dequan / Maksimos, Mina / Diedrich, Camila / Cano, Marlene / Tague, Laneshia K / Liu, Zhyi / Haspel, Jeffrey A / Leonard, Jennifer M / Li, Wenjun / Krupnick, Alexander S / Wong, Brian W / Kreisel, Daniel / Azab, Abdel Kareem / Gelman, Andrew E

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2024

Abstract: Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this ... ...

Abstract	Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils. NP-Ly6G(2-DG)-treated neutrophils were unable to adapt to hypoglycemic conditions of the lung airspace environment as evident by the loss of demand-induced glycolysis, reductions in glycogen and ATP content, and an increased vulnerability to apoptosis. NP-Ly6G(2-DG) treatment inhibited pulmonary IRI following hilar occlusion and orthotopic lung transplantation. IRI protection was associated with less airspace neutrophil extracellular trap generation, reduced intragraft neutrophilia, and enhanced alveolar macrophage efferocytotic clearance of neutrophils. Collectively, our data show that pharmacologically targeting glycolysis in neutrophils inhibits their activation and survival leading to reduced pulmonary IRI.
Language	English
Publishing date	2024-03-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1016/j.ajt.2024.03.028
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Article ; Online: Biological rhythms in COVID-19 vaccine effectiveness in an observational cohort study of 1.5 million patients.

Hazan, Guy / Duek, Or A / Alapi, Hillel / Mok, Huram / Ganninger, Alex / Ostendorf, Elaine / Gierasch, Carrie / Chodick, Gabriel / Greenberg, David / Haspel, Jeffrey A

The Journal of clinical investigation

2023 Volume 133, Issue 11

Abstract: BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe ... ...

Abstract	BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on vaccination time, with lowest the rates associated with late morning to early afternoon and highest rates associated with evening vaccination. Vaccination timing remained significant after adjustment for patient age, sex, and comorbidities. Results were consistent in patients who received the basic 2-dose series and who received booster doses. The relationship between COVID-19 immunization time and breakthrough infections was sinusoidal, consistent with a biological rhythm that modifies vaccine effectiveness by 8.6%-25%. The benefits of daytime vaccination were concentrated in younger (<20 years old) and older patients (>50 years old). COVID-19-related hospitalizations varied significantly with the timing of the second booster dose, an intervention reserved for older and immunosuppressed patients (HR = 0.64, morning vs. evening; 95% CI, 0.43-0.97; P = 0.038).CONCLUSIONWe report a significant association between the time of COVID-19 vaccination and its effectiveness. This has implications for mass vaccination programs.FUNDINGNIH.
MeSH term(s)	Humans ; Child ; Young Adult ; Adult ; Middle Aged ; COVID-19 Vaccines ; COVID-19/epidemiology ; COVID-19/prevention & control ; BNT162 Vaccine ; Retrospective Studies ; Vaccine Efficacy ; Vaccination ; Cohort Studies ; Periodicity
Chemical Substances	COVID-19 Vaccines ; BNT162 Vaccine
Language	English
Publishing date	2023-06-01
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI167339
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Article ; Online: Long noncoding RNA FOXD3-AS1 regulates oxidative stress-induced apoptosis

Zhang, Duo / Lee, Heedoo / Haspel, Jeffrey A / Jin, Yang

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2017 Volume 31, Issue 10, Page(s) 4472–4481

Abstract: The function of most human long noncoding RNAs (lncRNAs) remains unclear. Our studies identified a highly up-regulated mammalian lncRNA, ...

Abstract	The function of most human long noncoding RNAs (lncRNAs) remains unclear. Our studies identified a highly up-regulated mammalian lncRNA,
MeSH term(s)	Animals ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Epithelial Cells/metabolism ; Forkhead Transcription Factors/genetics ; Gene Expression Regulation, Neoplastic ; Lung Neoplasms/genetics ; Mice, Inbred C57BL ; MicroRNAs/genetics ; Oxidative Stress/genetics ; RNA, Long Noncoding/genetics ; Repressor Proteins/genetics ; Up-Regulation
Chemical Substances	Forkhead Transcription Factors ; Foxd3 protein, mouse ; MicroRNAs ; Mirn150 microRNA, mouse ; RNA, Long Noncoding ; Repressor Proteins
Language	English
Publishing date	2017-06-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201700091R
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Article ; Online: Multi-organ phenotypes in mice lacking latent TGFβ binding protein 2 (LTBP2).

Bodmer, Nicholas K / Knutsen, Russell H / Roth, Robyn A / Castile, Ryan M / Brodt, Michael D / Gierasch, Carrie M / Broekelmann, Thomas J / Gibson, Mark A / Haspel, Jeffrey A / Lake, Spencer P / Koenitzer, Jeffrey R / Brody, Steven L / Silva, Matthew J / Mecham, Robert P / Ornitz, David M

Developmental dynamics : an official publication of the American Association of Anatomists

2023 Volume 253, Issue 2, Page(s) 233–254

Abstract: Background: Latent TGFβ binding protein-2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFβ, although it may interfere with the function of other LTBPs or interact with ... ...

Abstract	Background: Latent TGFβ binding protein-2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFβ, although it may interfere with the function of other LTBPs or interact with other signaling pathways. Results: Here, we investigate mice lacking Ltbp2 (Ltbp2 Conclusions: Analysis of these mice show that LTBP2 has complex effects on development through direct effects on the extracellular matrix (ECM) or on signaling pathways that are known to regulate the ECM.
MeSH term(s)	Animals ; Mice ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Extracellular Matrix/metabolism ; Phenotype ; Transforming Growth Factor beta/metabolism ; Protein Isoforms/metabolism ; Protein Binding
Chemical Substances	Carrier Proteins ; Transforming Growth Factor beta ; Protein Isoforms
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.651
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