What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology

Bradford G. Hill, Brian P. Dranka, Shannon M. Bailey, Jack R. Lancaster Jr. and Victor M. Darley-Usmar

Bradford G. Hill

Current position: Assistant professor in the department of cardiovascular medicine at the University of Louisville in Kentucky

Education: Ph.D. in biochemistry in 2007 from the University of Louisville

Nonscientific interests: Spending time with my wife (Anne), my son (Lincoln), and my daughter (Ashlyn), baseball, reading, and hiking

My research interests largely focus on how bioenergetics regulate cardiovascular responses to stress. I became interested specifically in how nitric oxide (NO) controls bioenergetic function during my postdoctoral studies under Victor Darley-Usmar at the University of Alabama-Birmingham. I found it fascinating that NO-dependent regulation of respiration involves not only iron binding (i.e. at cytochrome c oxidase) but also the formation of NO-derived redox protein modifications. This has led me to examine how specific types of oxidant- and NO-derived protein modifications (e.g. protein glutathiolation and alkylation of proteins by reactive lipid species) regulate bioenergetic function and (patho)physiology.

Read Hill's article on page 19699.

Brian Dranka

Brian P. Dranka

Current position: Postdoctoral fellow at the department of biophysics at the Medical College of Wisconsin

Education: Ph.D. in molecular and cellular pathology in 2009 from the University of Alabama at Birmingham

Nonscientific interests: Distance running, gardening, and computer technology, especially where it intersects science.

My interest in the biochemistry of nitric oxide (NO) began when I joined the laboratory of Victor Darley-Usmar in 2005 as a graduate student. Building upon decades of research demonstrating that NO inhibits Cytochrome c Oxidase, we started a project to understand this interaction more completely. Studies published around that time suggested that NO impacts other mitochondrial processes, beyond the archetypal consumption of oxygen at Cytochrome c Oxidase. Through monitoring endothelial cell respiration, we demonstrated that mitochondria have decreased oxygen consumption following long-term NO exposure, even after removal of the NO. Our research has significant implications in cardiovascular disease where the endothelium is persistently exposed to NO.

Read Dranka's article on page 19699.

Shannon M. Bailey

Shannon M. Bailey

Current position: Associate professor at the department of environmental health sciences at the University of Alabama at Birmingham

Education: Ph.D. in pharmacology in 1996 from the University of Oklahoma Health Sciences Center

Nonscientific interests: Cooking, reading, kitty cats, and spending weekends watching movies and cheering the OU Sooners to victory with my wonderful husband, Hans

I began my scientific career while an undergraduate at the University of Oklahoma doing field work in the Puerto Rican rain forest during summer break. However, I quickly realized that mud, rain, and bugs weren't for me; whereas, the confines of an air-conditioned, bug-free lab were more suitable. My graduate studies were performed in the laboratory of Dr. Lester A. Reinke at The University of Oklahoma Health Sciences Center, working on the contribution of free radicals to hepatic ischemia-reperfusion injury. During this time, I focused on studying the role of the Kupffer cell in liver disease pathogenesis. After completing my Ph.D., I joined Dr. Carol C. Cunningham's laboratory at Wake Forest University School of Medicine to continue my training in liver disease pathogenesis with a focus on alcoholic liver disease. It was during my postdoc with Dr. Cunningham that I became interested in the role of mitochondrial dysfunction in liver disease, demonstrating that chronic alcohol consumption increases mitochondrial ROS production. Since joining the faculty at the University of Alabama at Birmingham, I have continued to work in the area of mitochondrial dysfunction in liver disease, focusing our work on alcohol and nonalcohol-mediated changes in the mitochondrial proteome as well as how the interaction between NO and mitochondria is altered in fatty liver diseases.

Read Bailey's article on page 19699.

Jack R. Lancaster Jr.

Jack R. Lancaster, Jr.

Current position: Professor at the department anesthesiology at the University of Alabama at Birmingham

Education: Ph.D. in biochemistry in 1974 from the University of Tennessee Center for the Health Sciences

Nonscientific interests: Golf, fossil collecting and fly fishing

I received my B.Sc. in chemistry from the University of Tennessee at Martin and my Ph.D. in biochemistry from the University of Tennessee Health Sciences Center at Memphis. I was trained as a postdoc at Cornell University (mentors Dr. Peter Hinkle and Dr. Efraim Racker) and at Duke University (mentor Dr. Henry Kamin). My first academic position (1980) was in the department of chemistry and biochemistry at Utah State University, where my research focused on bioenergetics and metalloenzyme-mediated electron transport and also the biological actions of nitrogen oxides. In 1992, I moved to the departments of surgery, anesthesiology and pharmacology at the University of Pittsburgh; in 1994, the department of physiology at Louisiana State University Health Sciences Center (New Orleans); and in 2002 the Center for Free Radical Biology at the University of Alabama-Birmingham, where I am the William A. Lell, M.D./Paul N. Samuelson, M.D. professor of anesthesiology with appointments in the departments of physiology and biophysics and environmental health sciences.

My first publication on nitric oxide was in 1979, dealing with the heme- and iron-sulfur-containing enzyme spinach nitrite reductase, which I demonstrated produces enzyme-bound NO as an intermediate. In 1983, I also proposed NO as an active participant in the mechanism of prevention of botulism by nitrite. I began research on NO in mammalian systems in 1989 with a collaboration with Dr. John Hibbs.

Read Lancaster's article on page 19699.

Victor M. Darley-Usmar

Victor M. Darley-Usmar

Current position: Director of the Center for Free Radical Biology and professor and vice chairman for research at the department of pathology for the University of Alabama at Birmingham

Education: Ph.D. in biological chemistry in 1980 from the University of Essex

Nonscientific interests: Playing piano, reading and gardening.

My research program is focused on redox cell signaling and molecular bioenergetics in the pathogenesis of human disease. I received my Ph.D. training from Dr. M.T. Wilson at the University of Essex and focused on the structure and function of cytochrome c oxidase. This involved isolating the enzyme from such exotic species as camels and sharks (not together). I continued my interest in mitochondrial proteins with Dr. R.A. Capaldi at the University of Oregon and was one of the first to use Western blotting to understand the molecular pathology of a mitochondrial myopathy. On returning to the U.K., I first became interested in the area of nitric oxide research in industry as a research scientist at Wellcome Research Laboratories in the U.K., where I worked on the interactions of nitric oxide with reactive oxygen species and mitochondria. Working with Salvador Moncada and Tony Schapira (Royal Free Hospital), we were one of the first teams to discover that nitric oxide can interact reversibly with cytochrome c oxidase and so control respiration. I left the U.K. in 1995 to join the Free Radical group at UAB led by Bruce Freeman. Currently, I am developing novel methods to assess the measurement of oxidative stress in mitochondria and defining how we determine the mitochondrial response to oxidative stress in the pathologies associated with bioenergetic dysfunction.

Read Darley-Usmar's article on page 19699.