Adam Straub, PhD

Associate Professor, Department of Pharmacology and Chemical Biology
Director, Center for Microvascular Research
Principal Investigator and Scholar, Heart, Lung, Blood and Vascular Medicine Institute

astraub@pitt.edu  |  412-648-7097

Research Interests

Mechanisms of hemoglobin a-regulated nitric oxide signaling in endothelial cells
Nitric oxide (NO) signaling regulates arterial vascular reactivity in the microcirculation to control peripheral vascular resistance and thus blood pressure.  Recently, it was reported for the first time that hemoglobin a is expressed in arterial endothelial cells (ECs), where it is in complex with endothelial nitric oxide synthase (eNOS) (Straub et al., Nature 2012). It was demonstrated that endothelial hemoglobin a is enriched at the myoendothelial junction, the point where endothelial cells and smooth muscle cells make contact in resistance arteries and arterioles, where it regulates the effect of NO signaling on vascular reactivity.  Mechanistically, hemoglobin a heme iron in the Fe3+ state permits active NO signaling, and this signaling is shut off when hemoglobin a is reduced to the Fe2+ state by endothelial cytochrome B5 reductase 3 (CytB5R3).  These data reveal a novel paradigm by which the regulation of intracellular hemoglobin oxidation controls NOS signaling in non-erythroid cells. This paradigm may be relevant to a broad range of other somatic cells discovered to express hemoglobin (i.e. neurons, renal mesangial cells, macrophages, sympathetic nerves, hepatocytes, alveolar epithelial cells, and endometrial cells) and also known to express NOS isoforms. Our studies will be a direct outgrowth of this work, where we will focus on the molecular, cellular, and in vivo contribution of somatic hemoglobins and CytB5Rs as it pertains to vascular physiology and disease.

Redox regulation of soluble guanylate cyclase by cytochrome b5 reductase 3

Cardiovascular disease (CVD) is the leading cause of death in many developed countries.  Multiple pathophysiological conditions contribute to CVD, including systemic hypertension, atherosclerosis, stroke, and heart failure.  One of the key pathways dysregulated in CVD is the nitric oxide(NO)/soluble guanylate cyclase (sGC)/cGMP signal transduction pathway, which is critical for vascular health.  Loss of endothelial NO production and/or the inability of sGC to sense NO to contribute to CVD. sGC is a heme protein that can exist in the reduced, sensitive form (Fe2+) or in the oxidized, insensitive form (Fe3+), of which, the former binds NO to generate cGMP needed for vasorelaxation, anti-inflammatory actions, and anti-apoptosis signaling.   We recently discovered that cytochrome b5 reductase 3 as the first sGC heme iron reductase critical for maintaining sGC heme iron in the reduced, NO sensitive state (Rahaman, Nguyen et al Circ. Res. 2017) . Ongoing studies focus on systemic hypertension, sickle cell disease and heart failure and the role Cyb5R3 plays in cGMP signaling.  We are currently funded by the following grants:  NIH R01-HL 133864, R01-HL 128304 and a Bayer Sponsored research contract.

Education

B.S. (Biology), Allegheny College, 2003.

Ph.D. (Cardiovascular Toxicology), University of Pittsburgh Graduate School of Public Health, 2008.

Postdoctoral Research Fellow (Vascular Biology), University of Virginia School of Medicine, 2013.

Awards

2006- Kletei Prize for Excellence in Environmental Health, University of Pittsburgh

2006- National Environmental Public Health Student Award: Center for Disease Control

2008- Deans Day Award: Graduate School of Public Health-University of Pittsburgh

2008- Rosenkranz Award for Public Health Significance: University of Pittsburgh

2010- Pappenheimer Postdoctoral Award: Microcirculation Society

2011- Robert M. Berne Outstanding Trainee: University of Virginia

2013- Finalist for the Irvine H. Page Young Investigator Research Award,  ATVB American Heart Association

2017- Finalist for the Outstanding Early Career Investigator Award, BCVS, American Heart Association

2017- Recipient of the Harry Goldblatt Award for New Investigators, Council on Hypertension,  American Heart Association

2019- Recipient of the American Heart Association Established Investigator Award

2020- Recipient of the American Heart Association Mid- Career Research Award

Grants

Ongoing Research Support

R01 HL128304
NIH/NHLBI (07/2016-06/2021)
Adam C. Straub (Principal Investigator)
Project Title: Vascular Smooth Muscle and Blood Pressure Regulation by Cyb5R3.

R01 HL133864
NIH/NHLBI (09/2016-08/2020)
Adam C. Straub (Principal Investigator)
Project Title: Novel Role of Smooth Muscle B5 Reductase in Sickle Cell Disease.

R01 HL133864
NIH/NHLBI (07/2015-06/2017)
John Pacella (Principal Investigator): Straub (Co-I)
Project Title: Microbubble-Mediated Ultrasonic Therapy for Coronary Microvascular Obstruction.

P30 DK079307
NIH/NIDDK (08/2015-07/2017)
Tom Kleyman (Principal Investigator): Straub (Pilot award)
Project Title:  Pittsburgh Center for Kidney Research

Completed Research Support

AHA Grant-in Aid
American Heart Association (01/2016-07/2016)
Adam C. Straub (Principal Investigator)
*Declined after 6 months due to overlap with R01 HL128304
Project Title:  Cyb5R3 and Vascular Smooth Muscle Function

NIH Pathway to Independence Award, K99/R00 HL112904-02  (08/2013-07/2016) NIH/NHLBI)
Adam C. Straub (Principal Investigator)
Project Title: Mechanisms of intracellular NAMPT-regulated GSNOR in the vessel wall.

NIH F32HL103042
NIH/NHLBI (09/2010-09/2011)
Awarded in support of Adam C. Straub (Principal Investigator)
Mechanisms of compartmentalized nitric oxide signaling at the myoendothelial junction.

T32 HL7284
NIH/NHLBI (09/2008-08/2010)
Cardiovascular Training Grant Fellow
Brian Duling (Principal Investigator)
Mechanisms of nitric oxide signaling at the myoendothelial junction.

Grant Number: FP-91654201
EPA STAR Fellowship
(08/01/05-07/31/08) EPA
Awarded in support of Adam C. Straub (Principal Investigator)
Mechanism of arsenic-induced liver sinusoidal endothelial cell remodeling