The major goal of this Program Project Grant (PPG) is to gain insight into the regulation of hypoxic adenosine responses in acute and chronic settings in order to advance novel adenosine-based therapies for the treatment of lung disease. The Project Leaders of this PPG have made substantial contributions to the understanding of adenosine signaling and the regulation of different injury processes, including acute and chronic lung disease. Furthermore, pharmaceutical companies are actively developing adenosine-based therapies to treat various disorders including lung disease. However, confusion over the beneficial and detrimental aspects of adenosine signaling has hindered these efforts. The experiments planned in the Component Projects of this PPG will address aspects of adenosine signaling in acute and chronic disease states with a focus on lung disease, and they will interact scientifically to understand organ and stage- specific aspects of adenosine signaling. It is hoped that the knowledge gained will help guide the development of specific adenosine-based therapies. However, we feel that this goal will be facilitated further by establishing mechanisms that promote interactions amongst the Project Research Teams, The Cores and Advisory Board Members. Thus, a major goal of this Administrative Core will be to provide administrative assistance to facilitate scheduled monthly meetings, Bi-Annual Project Leader Conferences, and a yearly PPG Scientific Retreat. These activities will focus on the exchange of data and ideas to understand the differences and similarities of the hypoxic adenosine response in different environments, and promote the importance of this pathway to the greater scientific community. Other goals of this Core include providing the administrative structure to assure the successful use of the Scientific Cores and the exchange of data and research material, monitor scientific progress of the Projects, address concerns, monitor compliance issues, and facilitate the presentation and publication of scientific results. By achieving these goals, this Administrative Core will contribute to the overall success and significance of this PPG.

Public Health Relevance

Acute and chronic lung diseases are the third leading cause of death behind cancer and cardiovascular disease. This is due in part to an incomplete understanding of injury responses in the lung. This Administrative Core is highly relevant to the betterment of human disease in that it will seek to facilitate interactions that are geared towards understanding novel mechanisms of lung disease that may lead to new treatments for these deadly lung disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL114457-05
Application #
9272007
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Aggarwal, Neil Raj
Project Start
Project End
2019-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
5
Fiscal Year
2017
Total Cost
$78,729
Indirect Cost
$27,309
Name
University of Texas Health Science Center Houston
Department
Type
Domestic Higher Education
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77030
Aherne, Carol M; Collins, Colm B; Rapp, Caroline R et al. (2018) Coordination of ENT2-dependent adenosine transport and signaling dampens mucosal inflammation. JCI Insight 3:
Mertens, Tinne C J; Hanmandlu, Ankit; Tu, Ly et al. (2018) Switching-Off Adora2b in Vascular Smooth Muscle Cells Halts the Development of Pulmonary Hypertension. Front Physiol 9:555
Bowser, Jessica L; Phan, Luan H; Eltzschig, Holger K (2018) The Hypoxia-Adenosine Link during Intestinal Inflammation. J Immunol 200:897-907
Lim, Grace; Facco, Francesca L; Nathan, Naveen et al. (2018) A Review of the Impact of Obstetric Anesthesia on Maternal and Neonatal Outcomes. Anesthesiology 129:192-215
Kiers, Dorien; Wielockx, Ben; Peters, Esther et al. (2018) Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation. EBioMedicine 33:144-156
Zhao, Shushan; Adebiyi, Morayo G; Zhang, Yujin et al. (2018) Sphingosine-1-phosphate receptor 1 mediates elevated IL-6 signaling to promote chronic inflammation and multitissue damage in sickle cell disease. FASEB J 32:2855-2865
Hadi, Tarik; Boytard, Ludovic; Silvestro, Michele et al. (2018) Macrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells. Nat Commun 9:5022
Yuan, Xiaoyi; Lee, Jae W; Bowser, Jessica L et al. (2018) Targeting Hypoxia Signaling for Perioperative Organ Injury. Anesth Analg 126:308-321
Liu, Hong; Adebiyi, Morayo; Liu, Rong Rong et al. (2018) Elevated ecto-5'-nucleotidase: a missing pathogenic factor and new therapeutic target for sickle cell disease. Blood Adv 2:1957-1968
Varadarajan, Supraja G; Kong, Jennifer H; Phan, Keith D et al. (2017) Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord. Neuron 94:790-799.e3

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