Victor Darley-Usmar (born in Worksop, Nottinghamshire, England in 1956) is a free-radical biologist and biochemist, the UAB Endowed Professor in Mitochondrial Medicine and Pathology at the University of Alabama at Birmingham. [1] Darley-Usmar also contributed to a book titled Microbes, Bugs & Wonder Drugs (by Fran Balkwill and Mic Rolph, with Victor Darley-Usmar), a science book written for young readers and their families. [2] [3]
Dr. Darley-Usmar got his B.Sc. from Essex University in Biochemistry in 1976, and followed that by getting a PhD from Essex University in 1980. He then did a postdoctoral fellowship at the University of Oregon from 1980-1983. Darley-Usmar then accepted a position as an Assistant Professor at the University of Tsukuba Medical School in Ibaraki, Japan, where he taught for 2 years. He then moved to Beckenham, Kent, England to be a Senior Biochemist at Wellcome Research Laboratories, where he stayed for 10 years. In 1995, he was recruited to University of Alabama at Birmingham, where he is now a professor. [4]
Darley-Usmar has held several leadership positions during his time at UAB. He has been the Graduate Program Director for the Department of Pathology, the Associate Dean for the Office of Post-Doctoral Education, the Chair of the Conflict of Interest Review Board, and has been the Interim Director for the Division of Molecular and Cellular Pathology twice. He is currently the Director of the Centre for Free Radical Biology and the Vice-Chair of Research for the Department of Pathology.
Darley-Usmar is also past President of the Society for Free Radical Biology and Medicine, [4] and is one of the two editors-in-chief of the journal Redox Biology. [1]
Among the most serious diseases that effect developed nations are those involving the cardiovascular system. Typical examples include atherosclerosis and the vascular complications of hypertension and diabetes. It is now known that this is mainly due to the production of free radicals and their interactions in the cells of the artery wall. The focus of Darley-Usmar's laboratory is to understand how the signaling pathways are altered in vascular disease and how free radicals play a part in this.
Two areas are of particular interest to Darley-Usmar. 1) Those involving oxidized lipoproteins and 2) the free radical signaling molecule nitric oxide. Nitric oxide is one of the beneficial free radicals in the artery wall and in a series of studies over the last few years he has been determining how it exerts protection over the vasculature. [6] Dr. Darley-Usmar is particularly interested in how the interaction of mitochondria with NO can modulate cell signaling. With an extensive network of collaborators at UAB and at other national and international institutions, he is defining the molecular events which control NO signaling pathways in the diseased vessel wall. Darley-Usmar's approach is to use his insight into the biochemistry of free radicals to understand events at the cellular level. Recently, he has found that NO activates a previously uncharacterized signaling pathway in the mitochondrion that increases synthesis of intracellular antioxidants in the cell in addition to directly inactivating damaging free radicals. His lab uses molecular biology, proteomics, and cellular approaches to address these problems.
Nitric oxide is a colorless gas with the formula NO. It is one of the principal oxides of nitrogen. Nitric oxide is a free radical, i.e., it has an unpaired electron, which is sometimes denoted by a dot in its chemical formula. Nitric oxide is also a heteronuclear diatomic molecule, a historic class that drew researches which spawned early modern theories of chemical bonding.
Protein disulfide isomerase, or PDI, is an enzyme in the endoplasmic reticulum (ER) in eukaryotes and the periplasm of bacteria that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold. This allows proteins to quickly find the correct arrangement of disulfide bonds in their fully folded state, and therefore the enzyme acts to catalyze protein folding.
The free radical theory of aging (FRTA) states that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. While a few free radicals such as melanin are not chemically reactive, most biologically relevant free radicals are highly reactive. For most biological structures, free radical damage is closely associated with oxidative damage. Antioxidants are reducing agents, and limit oxidative damage to biological structures by passivating them from free radicals.
Reactive oxygen species (ROS) are highly reactive chemical molecules formed due to the electron acceptability of O2. Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function.
Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, instead of signals leaving the nucleus, they are sent to the nucleus. In cell biology, this type of signaling typically occurs between the mitochondria or chloroplast and the nucleus. Signaling molecules from the mitochondria or chloroplast act on the nucleus to affect nuclear gene expression. In this regard, the chloroplast or mitochondria act as a sensor for internal external stimuli which activate a signaling pathway.
The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.
Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by reactive oxygen species (ROS) generated, e.g. O2− (superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.
Louis J. Ignarro is an American pharmacologist. For demonstrating the signaling properties of nitric oxide, he was co-recipient of the 1998 Nobel Prize in Physiology or Medicine with Robert F. Furchgott and Ferid Murad.
Marilyn Gist Farquhar was a pathologist and cellular biologist, Professor of Cellular and Molecular Medicine and Pathology, as well as the chair of the Department of Cellular and Molecular Medicine at the University of California, San Diego School of Medicine, who previously worked at Yale University from 1973 to 1990. She has won the E. B. Wilson Medal and the FASEB Excellence in Science Award. She was married to Nobel Laureate George Emil Palade from 1970 to his death in 2008. Her research focuses on control of intracellular membrane traffic and the molecular pathogenesis of auto immune kidney diseases. She has yielded a number of discoveries in basic biomedical research including: mechanisms of kidney disease, organization of functions that attach cells to one another, and mechanisms of secretions.
Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. This enzyme is one of three isoforms that synthesize nitric oxide (NO), a small gaseous and lipophilic molecule that participates in several biological processes. The other isoforms include neuronal nitric oxide synthase (nNOS), which is constitutively expressed in specific neurons of the brain and inducible nitric oxide synthase (iNOS), whose expression is typically induced in inflammatory diseases. eNOS is primarily responsible for the generation of NO in the vascular endothelium, a monolayer of flat cells lining the interior surface of blood vessels, at the interface between circulating blood in the lumen and the remainder of the vessel wall. NO produced by eNOS in the vascular endothelium plays crucial roles in regulating vascular tone, cellular proliferation, leukocyte adhesion, and platelet aggregation. Therefore, a functional eNOS is essential for a healthy cardiovascular system.
Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 (NOS2) and NADPH oxidase respectively. NOS2 is expressed primarily in macrophages after induction by cytokines and microbial products, notably interferon-gamma (IFN-γ) and lipopolysaccharide (LPS).
Henry Jay Forman is both Distinguished Professor Emeritus of Biochemistry at the University of California, Merced. and Research Professor Emeritus of Gerontology at the USC Leonard Davis School of Gerontology. He is a specialist in free radical biology and chemistry, antioxidant defense, and pioneered work in redox signaling including the mechanisms of induced resistance to oxidative stress.
Rafael Radi is an Uruguayan biochemist and biomedical scientist that has extensively worked to elucidate molecular mechanisms by which free radicals, oxidants and nitric oxide participate in human pathologies. In particular, he has made relevant contributions to unravel how the signal transducing free radical nitric oxide can evolve into toxic species via the formation of secondary nitric oxide-derived oxidants. His work has characterized reactions of oxidizing species with biological targets, the role of mitochondrial dysfunction is the alterations of cellular redox homeostasis and the impact of these biochemical processes in disease states. He has studied the actions of synthetic compounds in redox-based therapeutics, including in cardiovascular and neurodegenerative diseases. This work has also contributed to understand the redox biology of host cell interactions with intracellular pathogens and the impact in the control of infectious diseases. His seminal paper related to the biochemical actions of peroxynitrite, a potent oxidant and nucleophile formed secondary to the diffusion-controlled reaction of nitric oxide with superoxide radicals together with Joe S. Beckman, Kent Bush and Bruce A. Freeman in 1991 has been selected as a JBC Classics due to its influence in the field.
Katrina Miranda is an Associate Professor of Biochemistry at the University of Arizona. She works on nitric oxide and their role in diseases like breast cancer, stroke and chronic pain.
Jonathan Solomon Stamler is an English-born American physician and scientist. He is known for his discovery of protein S-nitrosylation, the addition of a nitric oxide (NO) group to cysteine residues in proteins, as a ubiquitous cellular signal to regulate enzymatic activity and other key protein functions in bacteria, plants and animals, and particularly in transporting NO on cysteines in hemoglobin as the third gas in the respiratory cycle.
The mitochondrial theory of aging has two varieties: free radical and non-free radical. The first is one of the variants of the free radical theory of aging. It was formulated by J. Michel in 1980 and was developed in the works of A. V. Linnan (1989). The second was proposed by A. N. Lobachev in 1978.
Thomas Kietzmann is a German physician and biochemist. He is a professor for biochemistry at the University of Oulu in Finland.
John B. Hibbs Jr. is an American physician-scientist and educator. He is Distinguished Professor Emeritus in the Department of Medicine at the University of Utah.