Adam C. Straub, Ph.D.

  • Associate Professor
  • Department of Pharmacology and Chemical Biology

Education & Training

  • University of Virginia (Post-doc) 2013
  • University of Pittsburgh, 2008
  • Allegheny College, 2003

Research Interest Summary

Mechanism of cardiovascular redox regulation.

Research Categories

Research Interests

Our research program seeks to elucidate the chemistry, biology and translational impact of “redox switches” in the cardiovascular system. Our work has revealed that cytochrome b5 reductase 3 (CYB5R3) operates as a critical redox switch in the cardiovascular system by reducing substrates such heme and coenzyme Q to modulate reactive nitrogen and oxygen species and downstream signaling. The overarching goal of our research program is to fill four major gaps in our knowledge related to redox switches in the cardiovascular biology. Our projects will define the role(s) of the “other CYB5R” family members including CYB5R1, 2, 4, 5 and their functions in endothelial, smooth muscle and cardiomyocytes. While expressed in these cells types, there are few reports defining the function(s) of these enzymes in the cardiovascular system. Using new cell type specific knockouts of CYB5R1, 2, 4, 5, we will delineate the physiological and pathophysiological role(s) of these enzymes across endothelial, smooth muscle and cardiomyocytes and their potential function(s) in redox signaling. Second, we aim to establish novel client proteins for the CYB5R family of enzymes using an innovative “biopanning” approach. Utilizing a genetically modified soybean peroxidase coupled to CYB5R enzymes we will establish new binding partners, substrates and mechanisms for these reductases. Third, using large human data sets (i.e. n=8500 participants), we will assess if common genetic variants in CYB5R enzymes associates with diseases such as hypertension, sickle cell disease and heart failure. Mechanistic studies will determine functional impact of these variants on redox signaling pathways in cardiovascular cells. Forth, we will leverage the information gained from our studies on CYB5R3 to test if a new drug we developed called “NitroQ” and test if improves redox equilibrium and reverses hypertension, sickle cell disease and heart failure. Mechanistic studies will elucidate key targets and downstream signaling pathways influenced by NitroQ. Collectively, these fundamental basic, translational and therapeutic studies will provide a critical framework that will enable us to fill these major gaps in our knowledge and improve our understanding of redox switches in cardiovascular health and disease.

Representative Publications

Straub AC, Lohman AW, Billaud M, Johnstone SR, Lee MY, Schoppee-Bortz P, Best AK, Dwyer ST, Columbus L, Gaston B, Isakson BE.   Endothelial cell expression of hemoglobin α regulates nitric oxide signaling. Nature. 15;491(7424):473-7, 2012. PMCID: PMC3531883

Rahaman MM, Nguyen AT, Miller MP, Hahn SA, Sparacino-Watkins C, Jobbagy S, Carew NT, Cantu-Medellin N, Wood KC, Baty CJ, Schopfer FJ, Kelley EE, Gladwin MT, Martin E, Straub AC.  Cytochrome b5 reductase 3 modulates soluble guanylate cyclase redox state and cGMP signaling. Circulation Research, 2017 Jul 7; 121(2):137-148. PMCID: PMC5527687

Durgin BG, Hahn SA, Schmidt HM, Miller MP, Hafeez N, Mathar I, Freitag D, Sandner P, Straub AC. Loss of smooth muscle CYB5R3 amplifies angiotensin-II induced hypertension by increasing sGC heme oxidation. JCI Insight 2019 Oct 3;4 (19). PMCID: PMC31487266

Dosunmu-Ogunbi A, Yuan S, Reynolds M, Giordano L, Sanker S, Sullivan M, Stolz DB, Kaufman BA, Wood KC, Zhang Y, Shiva S, Nouraie SM, Straub AC. SOD2 V16A Amplifies Vascular Dysfunction in Sickle Cell Patients by Curtailing Mitochondria Complex IV Activity. Blood. 2021 Dec 27: blood.2021013350. PMID: 34958669.

Carew NT, Schmidt HM, Yuan S, Galley JC, Hall R, Altmann HM, Hahn SA, Miller MP, Wood KC, Gabris B, Stapleton MC, Hartwick S, Fazzari M, Wu YL, Trebak M, Kaufman BA, McTiernan CF, Schopfer FJ, Navas P, Thibodeau PH, McNamara DM, Salama G, Straub AC. Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death. J Clin Invest. 2022 Sep 15;132(18):e147120. doi: 10.1172/JCI147120. PMID: 36106636; PMCID: PMC9479700.

Full List of Publications