Dennis J. Stuehr,  PhD

Dennis J. Stuehr, PhD

Staff

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195

 

Our laboratory studies nitric oxide (NO) biosynthesis in mammals. NO is made by an enzyme named NO synthase, and is involved in many aspects of cell function and disease, including signal transduction in the brain, control of blood pressure and heart rate, gastric motility, oxygen delivery, immunologic destruction of tumor cells and microbes, infertility, impotence, and stroke. We study how NO biosynthesis takes place at the molecular level and how it is regulated, and also study the impact of NO synthesis on certain aspects of cells and tissues. Our interests include the NO synthase enzyme chemistry, understanding how the enzyme’s protein structure relates to its function, and learning how other cellular proteins can interact with NO synthase to control its activity. We are also studying how NO regulates heme insertion into cellular proteins, and how protein nitration, which is a downstream consequence of NO production, takes place in cells, is regulated, and how it may control protein functions in cells and tissues.


Glyceraldehyde-3-phosphate dehydrogenase is a chaperone that allocates labile heme in cells.

Sweeny EA, Singh AB, Chakravarti R, Martinez-Guzman O, Saini A, Haque MM, Garee G, Dans PD, Hannibal L, Reddi AR, Stuehr DJ.

J Biol Chem. 2018 Sep 14;293(37):14557-14568. doi: 10.1074/jbc.RA118.004169. Epub 2018 Jul 16.

PMID:

30012884

Hsp90 chaperones hemoglobin maturation in erythroid and nonerythroid cells.

Ghosh A, Garee G, Sweeny EA, Nakamura Y, Stuehr DJ.

Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):E1117-E1126. doi: 10.1073/pnas.1717993115. Epub 2018 Jan 22.

PMID:

29358373

Tetrahydrobiopterin redox cycling in nitric oxide synthase: evidence supports a through-heme electron delivery.

Ramasamy S, Haque MM, Gangoda M, Stuehr DJ.

FEBS J. 2016 Dec;283(24):4491-4501. doi: 10.1111/febs.13933. Epub 2016 Nov 18.

PMID:

27760279

Soluble guanylate cyclase as an alternative target for bronchodilator therapy in asthma.

Ghosh A, Koziol-White CJ, Asosingh K, Cheng G, Ruple L, Groneberg D, Friebe A, Comhair SA, Stasch JP, Panettieri RA Jr, Aronica MA, Erzurum SC, Stuehr DJ.

Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):E2355-62. doi: 10.1073/pnas.1524398113. Epub 2016 Apr 11.

PMID:

27071111

Regulation of sGC via hsp90, Cellular Heme, sGC Agonists, and NO: New Pathways and Clinical Perspectives.

Ghosh A, Stuehr DJ.

Antioxid Redox Signal. 2017 Feb 1;26(4):182-190. doi: 10.1089/ars.2016.6690. Epub 2016 May 2.

PMID:

26983679

Single-molecule spectroscopy reveals how calmodulin activates NO synthase by controlling its conformational fluctuation dynamics.

He Y, Haque MM, Stuehr DJ, Lu HP.

Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11835-40. doi: 10.1073/pnas.1508829112. Epub 2015 Aug 26.

PMID:

26311846