Allan Doctor, M.D.

Pediatric Critical Care Medicine
Associate Professor
Biochemistry and Molecular Biophysics

Biochemistry, Biophysics, and Structural Biology Program

  • 314-454-2527

  • 314-286-1291

  • 314-361-0733

  • 8208

  • McDonnell Pediatric Research Building 5220-3 room 5102



  • blood flow, hypoxia, membrane proteins, nitric oxide, redox processes, vascular biology

  • Mechanism by which erythrocytes exert hypoxia-responsive control of regional blood flow

Research Abstract:

My research program is focused upon the novel role of erythrocyte based signaling in matching regional blood flow to metabolic need. The RBC transport portfolio is newly appreciated to include 3 gases (O2, CO2, NO), and RBCs appear to serve as vascular control elements by exerting O2 - responsive control over the bioavailability of vasoactive effectors in plasma. My lab explores the biochemical and molecular events critical to this process.

Our fundamental working paradigm is that RBCs serve as a regulatory node in hypoxia- and redox- responsive signaling by either quenching or initiating thiol-based transfers of nitric oxide (NO) groups (transnitrosation reactions) that cascade through plasma and subcellular compartments in response to alterations in tissue O2 tension. These low mass S-nitrosothiols participate in hyper-acute regulation of vascular tone as well as modulate inflammatory signaling and the gene-regulatory response to hypoxia in vessels. The proposed mechanism within RBCs is that Hb conformational transition appears to govern thiol-based transactions between NO equivalents and RBCs in the microcirculation. Specifically: R-state Hb quenches, and T-state Hb deploys, net NO bioactivity. Thus coupling the release and capture of NO by RBCs to tissue O2 gradients subserves the matching of NO bioactivity to perfusion sufficiency. Notably, it appears that disordered NO flux in RBCs may subvert physiologic and cellular controls. Since transnitrosation signaling appears designed to tune physiologic responses to O2 gradients and local redox signatures in the microcirculation, this process is therefore particularly vulnerable to disruption during periods of sustained hypoxia or oxidative stress. Unmasking disruption in erythrocytic nitrosative signaling may provide mechanistic insight into the perfusion insufficiency and maladaptive physiologic and cellular responses in the microcirculation that characterize many forms of critical illness, and thus – inform novel therapies for these conditions. Query is modeled on many levels from isolated proteins - cell culture - isolated organ - whole mouse - to studies in humans.

Selected Publications:

Rogers SC, Said A, Corcuera D, McLaughlin D, Kell P, Doctor A. Hypoxia limits antioxidant capacity in red blood cells by altering glycolytic pathway dominance. FASEB J. 2009 Sep;23(9):3159-70. Epub 2009 May 5.

Palmer L, Doctor A, Chhabra P, Sheram ML, Laubach VE, Zigler M, Macdonald T, and Gaston B. Role of S-Nitrosothiol signaling in hypoxia-associated disease. J Clin Invest 2007 117:2592-2601.

Bin J, Doctor A, Lindner J, Henderson E, Le D, Leong-Poi H, Fisher N, Christiansen J, Kaul S. Effects of nitroglycerin on erythrocyte rheology and oxygen unloading: microvascular mechanisms in relieving myocardial ischemia. Circulation 2006 113:2502-2508.

Gaston B, Singel D, Doctor A, Stamler JS. S-nitrosothiol signaling in respiratory biology. Am J Respir Crit Care Med 2006 173:1186-1193.

McMahon TJ, Doctor A. Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin. Proc Am Thorac Soc 2006 3:153-160.

Last Updated: 8/3/2011 3:45:50 PM

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