R. William Caldwell, PhD
706-267-4631 |
Research & Education Building,CB 3622 Officephone icon: 706-721-3383/706-267-4631 Members of the Lab |
We are investigating interactions of nitric oxide synthases and arginases, which compete for their shared substrate, L-arginine. Alterations in their expression or activity of either enzyme can determine the levels of the other’s products. Inhibition or absence of arginase in the vasculature augments blood flow by increasing NO production. Inhibition/absence of arginase in immune cells results in inflammatory phenotypes. Our studies utilize specific gene and tissue knockouts of arginase 1 and 2 in animal models of diabetes, obesity, hypertension and stroke.
1965 BS in Applied Biology/Chemistry Georgia Institute of Technology
1969 PhD in Pharmacology Emory University
1969-1972 Walter Reed Army Institute for Research U.S. Army, Captain
2015 - Present Rehired - Professor of Pharmacology & Toxicology Medical College of Georgia, Augusta University, Augusta, GA.
1988 - 2014 Professor and Chair of Pharmacology & Toxicology Medical College of Georgia, Augusta University, Augusta, GA.
1972 - 1987 Assistant thru full Professor of Pharmacology University of Tennessee Center for Health Science (UTCHS)
1987 Fogarty Senior International Fellow Centre de Biochimie-CNRS; Nice, France
1986 Assistant Vice Chancellor of Research Services (Acting) UTCHS - Memphis
Abdelrahman AA, Bunch KL, Sandow PV, Cheng PN, Caldwell RB, Caldwell RW. Systemic Administration of Pegylated Arginase-1 Attenuates the Progression of Diabetic Retinopathy. Cells 2022 Sep 16;11(18):2890.doi:10.3390/ 11182890.PMID:36139465
Fouda AY, Xu Z, Suwanpradid J, Rojas M, Shosha E, Lemtalsi T, Patel C, Xing J, Zaidi SA, Zhi W, Stansfield BK, Cheng PN, Narayanan SP, Caldwell RW*, Caldwell RB. Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair. Cell Death Dis. 2022 Aug 29;13(8):745. doi:10.1038 /s41419-022-05196-8.PMID: 36038541
Fouda AY, Eldahshan W, Xu Z, Lemtalsi T, Shosha E, Zaidi SA, Abdelrahman AA, Cheng PN, Narayanan SP, Caldwell RW, Caldwell RB. Preclinical investigation of Pegylated arginase 1 as a treatment for retina and brain injury. Exp Neurol. 2022 Feb;348:113923. doi: 10.1016/j.expneurol.2021.113923. 34780773
Caldwell RW, Rodriguez PC, Toque HA, Narayanan SP, Caldwell RB. Arginase: A Multifaceted Enzyme Important in Health and Disease. Physiol Rev. 2018 Apr 1;98(2):641-665. doi: 10.1152/physrev.00037.2016.
Bhatta A, Yao L, Xu Z, Toque HA, Chen J, Atawia RT, Fouda AY, Bagi Z, Lucas R, Caldwell RB, Caldwell RW. Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1. Cardiovasc Res. 2017 Nov 1;113(13):1664-1676. doi: 10.1093/cvr/cvx164.PMID: 29048462
Caldwell RB, Toque HA, Narayanan SP, Caldwell RW. Arginase: an old enzyme with new tricks. Trends Pharmacol Sci. 2015 Jun;36(6):395-405. doi: 10.1016/ j.tips.2015.03.006. PMID: 25930708
Yao L, Chandra S, Toque HA, Bhatta A, Rojas M, Caldwell RB, Caldwell RW. Prevention of diabetes-induced arginase activation and vascular dysfunction by Rho kinase (ROCK) knockout. Cardiovasc Res. 2013 Mar 1;97(3):509-19. doi: 10.1093/cvr/cvs371. PMID: 23250919
Chandra S, Romero MJ, Shatanawi A, Alkilany AM, Caldwell RB, Caldwell RW. Oxidative species increase arginase activity in endothelial cells through the RhoA/Rho kinase pathway.Br J Pharmacol. 2012 Jan;165(2):506-19. doi: 10.1111/j.1476-5381.2011. PMID: 21740411
Shatanawi A, Romero MJ, Iddings JA, Chandra S, Umapathy NS, Verin AD, Caldwell RB, Caldwell RW. Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway. Am J Physiol Cell Physiol. 2011 May;300(5):C1181-92. doi: 10.1152/ajpcell.00328.2010. PMID: 21289285
Caldwell RB, Zhang W, Romero MJ, Caldwell RW. Vascular dysfunction in retinopathy-an emerging role for arginase. Brain Res Bull. 2010 Feb 15;81(2-3):303-9. doi: 10.1016/ j.brainresbull.2009.08.025.PMID: 19737603 .
Romero MJ, Platt DH, Tawfik HE, Labazi M, El-Remessy AB, Bartoli M, Caldwell RB, Caldwell RW. Diabetes-induced coronary vascular dysfunction involves increased arginase activity. Circ Res. 2008 Jan 4;102(1):95-102. doi:10.1161/CIRCRESAHA. 107.155028. PMID: 17967788
Tawfik HE, El-Remessy AB, Matragoon S, Ma G, Caldwell RB, Caldwell RW. Simvastatin improves diabetes-induced coronary endothelial dysfunction. J Pharmacol Exp Ther. 2006 Oct; 319(1):386-95. doi: 10.1124/jpet.106.106823. PMID: 16849625
Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res. 2008 Jul;27(4):331-71. doi: 10.1016/j.preteyeres.2008.05.001. PMID: 18653375