Courtney Andersen studies the role of estrogen receptor-alpha in ovarian cancer.
Chris Barnes investigates the structural details by which transcription factor activity regulates RNA Polymerase II during the universal process of eukaryotic gene expression.
Soma Jobaggy studies nitrated fatty acid pharmacology and the antioxidant response in hypertensive end-organ damage.
Allison Nagle studies growth factor receptor signaling in breast cancer.
Adam C. Straub, PhD
Assistant Professor
E1254 Biomedical Science Tower
200 Lothrop Street, Pittsburgh, PA 15261

Email:
astraub@pitt.edu
Phone: 412-648-7097


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



Research Areas
Signal Transduction
Pharmacology of Cell and Organ Systems
Cardiovascular and Renal Pharmacology
Redox Pharmacology
Photo of Adam C. Straub, PhD

Our Focus

The overarching goal of the Straub laboratory is to investigate novel redox-controlled cell signaling mechanisms that regulate endothelial and smooth muscle cell biology and cell-cell communication in the microcirculation.  Our investigations focus on two important pathways: 1) the mechanisms by which endothelial cell expressed hemoglobin a regulates nitric oxide signaling in the blood vessel wall and 2) the mechanisms by which the intracellular nicotinamide phosphoribosyltransferase (NAMPT) pathway controls basic redox signaling functions in vascular cells. 

 

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.

 

NAD regulation and the NAMPT pathway in vascular physiology and disease

Nicotinamide adenine dinucleotide (NAD) is a fundamentally important molecule critical for many redox reactions in biology.  Interestingly, the regulation of NAD+ and NAD(H) is dependent on cell type, which are governed by multiple mechanisms. One mechanism that regulates NAD+ levels is NAMPT, also known as pre-B cell colony factor (PBEF) or visfatin.  Existing both as an extracellular and intracellular protein, NAMPT is a rate-limiting enzyme in the NAD+ biosynthesis pathway and is vital for embryonic development since homozygous knockout mice are embryonic lethal (Revollo et al, 2007).  The extracellular form of NAMPT stimulates both NAD+ and non-NAD+ signaling pathways in vascular cells, while intracellular NAD+ generated by NAMPT has been shown to regulate vascular cell longevity and protection against ischemia/reperfusion in the heart through a surtuin-1 dependent pathway (van der Veer et al 2007, Hsu et al, 2009).  Although it has been established that intracellular NAMPT can regulate NAD+ levels, the downstream signaling pathways relying on this enzyme with regards to resistance arterial tone regulation remains elusive.  Our goal is to better understand the role(s) of this enzyme in the microcirculation and in vascular biology in general.

http://www.straublab.pitt.edu/





Important Publications
Straub AC, AW Lohman, M Billaud, SR Johnstone, MY Lee, P Schoppee-Bortz, AK Best, ST Dwyer, L Columbus, B Gaston and BE Isakson.  Endothelial cell expression of hemoglobin alpha regulates nitric oxide signaling.  Nature 491:473-477, 2012.
Straub AC, M Billaud, SR Johnstone, AK Best, S Yemen, ST Dwyer, R Looft-Wilson, JJ Lysiak, B Gaston, LA Palmer and BE Isakson.  Compartmentalized connexin 43 S-nitrosylation/denitrosylation regulates heterocellular communication in the vessel wall.  Arterioscler Thromb Vasc Biol 31:399-407, 2011.
Billaud M, AW Lohman, AC Straub, R Looft-Wilson, SR Johnstone, CA Araj, AK Best, F Chekeni, K Ravichandran, S Penuela, D Laird and BE Isakson.  Pannexin 1 regulates alpha 1-adrenergic receptor-mediated vasoconstriction.  Circ Res 109:80-85, 2011.
Heberlein K, AC Straub, AK Best, RC Looft-Wilson and BE Isakson.  Plasminogen activator inhibitor-1 can regulate myoendothelial junction formation.  Circ Res 106:1092-1102, 2010.
Straub AC, KA Clark, MA Ross, AG Chandra, S Li, X Gao, PJ Pagano, DB Stolz and A Barchowsky.  Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH-oxidase generated superoxide.  J Clin Invest 118:3980-3989, 2008.
Straub AC, DB Stolz, MA Ross, A Hernandez-Zavala, NV Soucy, LR Klei and A Barchowsky.  Arsenic stimulates sinusoidal endothelial  cell capillarization and vessel remodeling in mouse liver.  Hepatology 45:205-212, 2007.

STUDENT NEWS


UPCOMING EVENTS
11/27/2017 8:30 AM Molecular Pharmacology Journal Club
Lloyd Harvey


11/30/2017 12:00 PM Pharmacology & Chemical Biology Seminar Series
Jeffrey L. Brodsky, Ph.D.


12/4/2017 8:30 AM Molecular Pharmacology Journal Club
Andrew Lamade


Pharmacology and Chemical Biology Event Calendar

Program Achievements

Molecular Pharmacology Graduate Program Ranked #2 in National Research Council Rankings

Molecular Pharmacology Graduate Program Ranked #2 in Faculty Scholarly Productivity Index


Outcomes:  Time to disseration, last five graduating clasess:  4.5 years, Completion Rate: 84.8%

Ranked #12 in National of Institute of Health funding of departments of Pharmacology

Ranked in the top 15 in funding for twenty consecutive years




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