- About Us
- BPS Student Chapter
|William M. Baird (Chemical carcinogenesis)||Elisar Barbar (Motor proteins, NMR spectroscopy)||Joseph Beckman (Cell signaling, nitric oxide)|
|Balz Frei (Free radicals, atherosclerosis)||Michael Freitag (Epigenomics, gene silencing)||Adrian F. Gombart (vitamin D, innate immune response and aging)|
|Julie A. Greenwood (Cell adhesion)||Tory M. Hagen (Mitochondria, stress response mechanisms and aging)||David Hendrix (Bioinformatics and Computational Biophysics)|
|Victor L. Hsu (DNA & protein NMR spectroscopy)||Colin Johnson (Molecular mechanisms that underlie membrane fusion)||P. Andrew Karplus (Protein crystallography)|
|Philip N. McFadden (Cellular biosensors)||Ryan A. Mehl (Protein engineering, synthetic chemical biology)||Gary F. Merrill (Gene expression, cancer)|
|Afua Nyarko (Protein interactions)||Viviana I. Perez (Protein homeostasis, aging)||Weijian Zhang (Vascular biology, inflammation and atherosclerosis)|
|Chris Mathews (Nucleic acid enzymology)|
Polycyclic aromatic hydrocarbons are widespread environmental contaminants formed during incomplete combustion; some are potent carcinogens in experimental animals. Our laboratory is examining the relationship of various hydrocarbon metabolism pathways to the induction of biological effects. We are examining the role of induction of specific cytochrome P450 isozymes in the activation of different polycyclic aromatic hydrocarbons by Northen and Western blotting, the use of specific inhibitory antibodies and antisense oligonucleotides. After metabolic activation, hydrocarbons bind covalently to DNA, and these DNA interactions are involved in the induction of mutation. The role of specific metabolites of polycyclic aromatic hydrocarbons in the induction of biological effects is being investigated through analysis of the hydrocarbon-DNA adducts by high-performance liquid chromatography. In addition to activation and detoxification, the amount of hydrocarbon bound to specific genes in DNA can be affected by the sequence of the DNA, the structure of chromatin, and repair of the DNA adducts. The role of chromatin structure is being determined by the use of polyclonal antibodies to hydrocarbon-modified DNA. The repair of hydrocarbon-DNA adducts is being investigated in total genomic DNA and in specific genes through laser-induced cleavage and Southern blotting analysis and by LM-PCR techniques. We are also examining how hydrocarbon-DNA interactions affect the tumor suppressor gene P53, its signal transduction through P21 and how the cell cycle is arrested. These studies will help to determine how hydrocarbons are activated to carcinogenic forms and how they induce biological events.
The major research focus of my lab is the structural biology and assembly of cytoplasmic dynein, a principal motor for minus end directed transport along microtubules. Cytoplasmic dynein is a large protein complex composed of two globular heads joined by flexible stalk domains to a common base. The head and stalk domains comprise the heavy chain motor subunits (~530 kDa) which contain the microtubule binding sites and the hydrolytic ATP-binding sites required for force production. The base of the motor complex contains two 74 kDa intermediate chains, four light intermediate chains (52-61 kDa), and several light chains (10-25 kDa). By comparison to the multiplicity of kinesin heavy chain genes, the diversity of cytoplasmic dynein heavy chains is quite limited. This has fostered the hypothesis that the multiple functions of dynein are mediated through variations in the composition, modification, and interactions of the intermediate, light intermediate and light chains. The heterogeneity of these accessory subunits within the base of the motor complex could enable coupling of the dynein motor to a wide variety of intracellular cargoes. To understand this system, we use a 'ground up' approach, whereby the structure and dynamics of the individual proteins are examined first, then the interactions between subunits and cargo are characterized. We employ a variety of techniques primarily heteronuclear NMR and mass spectrometry to determine the three-dimensional structure of individual subunits and their complexes. Electrospray mass spectrometry and MALDI can give valuable information about structure and protein interactions using hydrogen isotope exchange techniques, limited proteolysis and chemical cross-linking. We hope that our work on dynein will lead to new methods for controlling certain diseases. The cancer drug Taxol, for example, is effective in preventing spindle formation in rapidly dividing cells; a complementary therapy would prevent transport of chromosomes by dynein along the spindle. Perhaps just as important, however, will be advances in our fundamental understanding of protein-protein interactions, molecular recognition, and the assembly of biologically important protein complexes.
A major research project in my laboratory is aimed at understanding how oxidative stress, superoxide dismutase, and zinc are involved in Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS). ALS is a dreadful disease caused by the unexplained death of motor neurons that control the movement of all voluntary muscles. We have only about 500,000 motor neurons at birth that cannot be replaced. Mutations in the antioxidant enzyme superoxide dismutase are the first identified cause of ALS. Our research indicates that the loss of zinc from superoxide dismutase is what causes motor neurons to die. We have shown that supporting cells in the spinal cord called astrocytes are key to understanding why the disease progresses. We are also investigating other dietary supplements, such as lipoic acid, acetyl-L-carnitine, and alpha-tocopherol, as possible means to slow the progression of ALS.The second major project in the laboratory focuses on the roles of nitric oxide, peroxynitrite, and nitrotyrosine in human disease. The major function of superoxide dismutase is to scavenge superoxide, which is an oxygen radical. Nitric oxide also has a “dark side” and, following reaction with superoxide to produce the powerful oxidant peroxynitrite, can promote oxidative and nitrative damage to blood vessels, skin, heart, lung, kidney, and brain.We are characterizing the role of peroxynitrite in injuring cells and how cells respond to this damage.
The research program in my laboratory is aimed at understanding the role of free radicals and inflammation in human chronic diseases, in particular atherosclerosis and cardiovascular disease, and the ameliorating effects of micronutrients, phytochemicals, and dietary supplements.Additional projects in the laboratory investigate the biological mechanisms and metabolic effects of flavonoids, the interactions of lipoic acid and ascorbic acid (vitamin C) in improving vitamin C body status and antioxidant defenses in humans, and the mechanisms of pharmacological doses of vitamin C in its potential cancer therapeutic effects.
We aim to understand how genome defense systems and epigenetic silencing phenomena shape and maintain eukaryotic genomes and "epigenomes". The epigenome is the sum of differential DNA or protein modifications that result in heritable chromatin states not encoded in the DNA sequence. Posttranslational modifications of chromatin proteins are now recognized to play an important role in all aspects of eukaryotic gene regulation. Evidence from cytological, biochemical and genetic studies suggests that transcriptionally silent "heterochromatin" is distinct from active "euchromatin" in both DNA composition and epigenetic modifications.
In many eukaryotes, heterochromatin is predominantly assembled from repeats of active or mutated transposable elements (TE) and thus appears to result from the action of genome defense and gene silencing systems. Extended, constitutive heterochromatic regions are associated with centromeres, telomeres and ribosomal DNA repeats, but short dispersed or facultative heterochromatic regions are common in many organisms. While heterochromatic regions have been assigned structural functions, e.g. as spindle attachment points during cell division, relatively little is known about their evolutionary roles.Centromeric DNA and its associated proteins undergo accelerated evolution, but the underlying mechanisms are unresolved. Closely related filamentous fungi (e.g., Neurospora crassa and Gibberella zeae, aka Fusarium graminearum) serve as excellent models to study the basis for this phenomenon because they exhibit strikingly different amounts and distribution of heterochromatic regions in their genomes. This variation may be caused by differences in the activity of genome defense and recombination processes.The development of novel immunological methods for both in vivo and in vitro studies of chromatin-associated molecules, microarray technology and the advent of high throughput genomics, allow us to ask questions about entire eukaryotic genomes. Four projects are underway: (1) Studies to elucidate epigenetic modifications and chromatin composition of centromeres, (2) mechanistic studies on a mutagenic genome defense system called "repeat-induced point mutation" (RIP); (3) deciphering transcriptional networks of light inducible genes in Neurospora, and (4) identification and characterization of small RNA species in fungi.
Our research is focused on understanding the regulation of antimicrobial peptide expression by the vitamin D pathway. When immune cells called macrophages encounter a pathogen and become activated, the vitamin D pathway is turned on, leading to the induction of the cathelicidin antimicrobial peptide if serum levels of vitamin D are sufficient. We have shown that this mechanism is conserved in humans and primates but not in other mammals. Therefore, we developed a transgenic mouse that carries the human cathelicidin gene. Using this model, we are testing the ability of vitamin D to protect against infection by influenza, Salmonella, and Mycobacterium tuberculosis. Vitamin D has been used to treat tuberculosis, and its deficiency is associated with increased risk of tuberculosis. This model will allow us to test the role of vitamin D and cathelicidin during initial infection, latency, and reactivation.Another focus of our research is to identify additional dietary compounds that regulate the expression of the cathelicidin gene. This gene is also induced by sodium butyrate and lithocholic acid, which functions through the vitamin D receptor. Nutrients that bind the vitamin D receptor may modulate the immune system by inducing the cathelicidin gene. We discovered that curcumin in curry modestly induces expression of the cathelicidin gene, which could protect the gut from infection. In collaboration with colleagues at Cedars-Sinai Medical Center, we discovered that vitamin B3 (niacin) boosts killing of methicillin-resistant Staphylococcus aureus (MRSA) by white blood cells, in part, by increasing cathelicidin levels. A small molecule library is being screened for regulators of the cathelicidin gene. The identification of new regulatory compounds may give clues as to how the gene is regulated in vivo and lead to the identification of other nutrients that can be used to boost the immune system.Finally, we are interested in determining the effect of vitamin D on the function of the innate immune system in the elderly. Aging is accompanied by low-grade, chronic, systemic inflammation, and vitamin D has important anti-inflammatory properties. We want to determine if sufficient levels of vitamin D will reduce the inflammatory phenotype. We also want to determine if reversing severe deficiency will raise cathelicidin protein levels in the blood, which may reduce mortality in kidney dialysis and sepsis patients.
The lab's interest in the regulation of cell adhesion and migration by phosphoinositide 3-kinase and its lipid product PtdIns (3,4,5)-P3 have led us to investigate the invasion of tumor cells in the brain. Glioblastoma, which accounts for 20% of all primary brain tumors and is the most malignant form of brain cancer, is a devastating diagnosis with a 5-year survival rate of less than 4%. Although the mechanisms responsible for the carcinogenesis and progression of glioblastoma tumors are unknown, several gene mutations have been identified in glioblastoma cells. For example, protein mutations resulting in overproduction of the lipid PtdIns (3,4,5)-P3 have been identified to play a key role in the migration and invasion of glioblastoma cells. Our preliminary results suggest that PtdIns (3,4,5)-P3 is an important regulator of calpain proteolysis. Calpain is a calcium-activated protease which cleaves several cytoskeletal adhesion proteins involved in cell motility and inhibition of calpain activity reduces tumor cell migration and invasion. The mechanisms regulating the proteolysis of proteins by calpain and the role of this posttranslational modification during migration are not clear. Understanding the function and regulation of calpain during the migration of tumor cells is expected to lead to the identification of new approaches for controlling cancer by targeting the activities of calpain.One of the most exciting accomplishments this past year was the development of a zebrafish model to study tumor cell dispersal in the brain.
Our research seeks to identify the mode of action of two “age-essential” micronutrients, lipoic acid (LA) and acetyl-Lcarnitine (ALCAR). This work is aligned with Dr. Pauling’s concept of “orthomolecular medicine”—varying the concentrations of substances normally present in the body to affect health. We are using LA and ALCAR as “keys” to unlock important mechanisms associated with the basic biology of aging, which may lead to effective therapies for a number of age-related diseases and enhance the quality of life. We found that ALCAR and LA improve two of the most important cellular lesions of aging: the inability to respond to oxidative and toxicological challenges and the loss of mitochondrial function. Feeding old rats LA markedly elevates both cellular ascorbic acid and glutathione levels and induces Phase II detoxification enzymes, which markedly decline with age. LA appears to improve stress-response mechanisms by activating a transcription factor, Nrf2, enabling it to again bind to DNA sequences called the “Antioxidant Response Element” (ARE) found in over 200 genes involved in protecting cells against oxidative and toxicological insults. We are currently exploring why these stress response mechanisms decline with age and are focusing on cellular signaling pathways that LA may induce to activate Nrf2-mediated gene expression.We found that ALCAR and LA, when fed to old rats, markedly improve many indices of mitochondrial decay. Mitochondria may be the “Achilles’ heel” of cellular aging because their dysfunction adversely affects conversion of dietary fuels into useful energy, dysregulates cellular calcium levels, increases oxidative stress, and limits tissue renewal. Our goal is to determine whether these age-essential micronutrients can improve human health by maintaining mitochondrial function.We are also interested in defining how LA and ALCAR improve such seemingly distinct aging lesions as mitochondrial decay and lost stress-response mechanisms. We have evidence that these compounds synergistically regulate the metabolism of an enigmatic class of biomolecules called sphingolipids, which may be involved in both the age-related loss of Nrf2-mediated gene expression and mitochondrial decay. Identification that sphingolipids are part of these aging deficits opens the possibility for new therapies to improve human healthspan.
The primary focus of our lab is to understand the structure, function and mechanisms of action of non-coding RNAs, both large and small. The past decade has seen the discovery of numerous non-coding RNAs whose function is largely unknown. We will employ structure prediction, genome-wide sequence analysis and deep sequencing data to uncover the roles of these molecules in gene regulation.In addition, our lab develops algorithms and computational approaches to understand many different areas of computational biology. Our lab develops and utilizes motif finding algorithms to understand how promoters and regulatory elements operate. We develop computational approaches, incorporating structural predictions and deep sequencing data, to discover new regulatory RNAs and their functions. We develop new methods of analysis for deep sequencing data to help understand the principles of transcription, which will include transcription initiation, transcriptional gene silencing, post-transcriptional gene silencing and Polymerase stalling/pausing.
Our laboratory is interested in studying the structural aspects of biomolecular recognition and interactions, especially in protein-nucleic acid complexes. These interactions account for many of the major cell functions such as the induction or repression of gene expression and the packaging of nucleic acids into other superstructures. The primary technique that we use is nuclear magnetic resonance (NMR) spectroscopy, which is uniquely suited for studying biomolecular structures at atomic resolution. We are studying both sequence-specific and nonspecific DNA-binding proteins and have been active in developing isotope-edited NMR strategies to obtain more accurate distance constraints for use in structure calculations, and to investigate the intrinsic flexibility of protein and DNA backbones. We utilize wild-type and mutant DNA-binding proteins to provide insights into which factors most affect protein stability and how DNA-binding is mediated. Another approach that we employ to better understand the molecular recognition of DNA is to determine the detailed structures of DNA-drug complexes. Certain antitumor agents bind to specific sequences of DNA, and we are investigating how modifications of these sites affects recognition, binding and activity. Finally, conformational changes associated with changes in the local solvent environment and the ability for certain protein sequences to fold into different structural elements is being studied using model peptides and intact proteins. The relationship between this phenomenon and protein interactions is being investigated.
Our research is focused on a family of proteins known as the ferlins, which help regulate membrane trafficking events and have been linked to several human pathologies. Specifically, work currently focuses on the muscle protein dysferlin, which is believed to catalyze fusion between the plasma membrane and intracellular vesicles in response to elevated calcium levels. Mutations in dysferlin have been implicated in several forms of muscular dystrophy, suggesting a key role for the protein in muscle physiology. Also of interest is otoferlin. Although still unclear, otoferlin may modulate the release of neurotransmitter and the encoding of sound in the brain. Mutations in otoferlin have been linked to deafness in human patients. We are currently characterizing both of these calcium sensing proteins in an attempt to understand the exact contributions of these proteins to membrane fusion, as well as the basis for why mutants in dysferlin and otoferlin result in muscular dystrophy and deafness.In addition, we are also interested in ferlin binding partners, with special focus on syntaxin and SNAP-25. These transmembrane proteins are members of the SNAREs, a family of proteins involved in nearly all intracellular membrane trafficking and exocytotic events. By using a combination of biochemical, biophysical, and spectroscopic approaches, we aim to understand the conformational changes that occur within these proteins that help accelerate fusion between lipid bilayers.Current experiments include the reconstitution of SNAREs, otoferlin and dysferlin into synthetic vesicles to study calcium triggered membrane fusion in vitro, as well as the use of fluorescence methods like FRET to monitor protein-protein and protein-lipid interactions, confocal imaging and immunofluorescence to visualize protein and lipid redistribution within cells after wounding.In addition, collaborative efforts to determine the structure of these proteins via X-ray and NMR are also planned.
Proteins play central roles in all aspects of biochemistry. In addition to the proteins that serve as enzymes catalyzing the reactions of metabolism, there are, among others, structural proteins, protein hormones, transport proteins, cell surface receptors and proteins involved in the regulation of DNA replication and transcription. A theme common to all classes of proteins is specific recognition and function through unique structure. To develop a better understanding of the mechanisms involved in the specificity of recognition and catalysis, we need detailed structural information. I am interested in using X-ray crystallography, complemented by protein chemistry, enzymology and theoretical approaches such as molecular dynamics, to obtain this detailed structural information. The protein structures we are working on are a diverse group. Proteins are chosen with the dual goal that their detailed study will lead to insights relevant for understanding the particular protein and to insights relevant to understanding general principles of protein structure, stability and function. Most projects being worked on are collaborative and current projects include the following: studies of flavoenzymes to investigate how the enzyme:flavin interactions influence the electronic structure of the flavin, and modulate its reactivity (e.g., ferredoxin reductases, glyceraldehyde-phosphate oxidase, and bacterial SsuE); studies to investigate the structural, functional and evolutionary relationships among peroxiredoxins and to probe their role in hydrogen peroxide signaling in eukaryotes; investigation into the mechanism of the iron-dependent enzyme cysteine dioxygenase important for cysteine catabolism and sulfur metabolism in mammals, and studies on the a series of related enzymes that catalyzes carbon-carbon bonds involved in ring closure reactions of 7-carbon phosphosugars. In addition to these studies we have an ongoing effort to use empirical studies of ultrahigh-resolution protein structures in the protein data bank to discover detailed features of protein structure that have not yet been recognized. In some cases this leads to fundamental shifts in how we understand the most basic characteristics of proteins, such as the planarity (or perhaps non-planarity) of the peptide bond or the common conformational building blocks from which structures are built. A recent accomplishment has been to characterize how protein covalent geometry varies with conformation. The variation is substantial and we have shown that taking it into account in crystallographic refinement protocol and in homology modeling does produce more accurate structures.
My laboratory is studying the responses of single-cells to environmental toxins. Our focus is on environmental toxins that cause long-lasting impairment of neurons weeks or even months after a person has been exposed to them. We have recently built a prototype biosensor device that quickly measures such toxins, hopefully before they can harm the nervous system. The device is based on a new idea -that neurotoxins can be measured by their interference with natural color changes in animal cells. Early tests of this idea proved successful, and so we are now learning all we can about the fundamental biology of color change in animals. Color changes in the skin of fish, amphibians and reptiles are accomplished through a mechanism that is conceptually similar to color changes taking place on a color computer monitor. In the skin, each "pixel" is in fact a single living cell called a chromatophore. The "video signal" that causes changes in the intensity of these living pixels is, in fact, the continually changing mixture of neurotransmitters and hormones that originate from a two-dimensional network of nerve endings and blood capillaries in the skin. Chromatophores change their color through enzyme-dependent movements of their colored subcellular organelles. We think that chromatophores are affected by neurotoxins because neurons use similar enzymatic machinery to carry materials over the long distance between the neuron's cell body and its distant processes.
The Mehl Lab uses genetic code expansion to site-specifically incorporate non-canonical amino acids (ncAAs) into proteins to advance the capabilities of biochemical studies and technological development with bio-molecules. The incorporation of ncAAs into proteins is a cornerstone of chemical biology and will likely be the next major building block for advancing both biotechnology and nanotechnology. The key advantage to genetic code expansion is that it allows proteins to be engineered with molecular control in living cells and in the fabrication of nanomaterials in. In order to engineer these proteins the concepts of synthetic biology are applied to alter protein translation. This reengineering of translation in vivo allows for precise incorporation of unique chemical functionality that can be used for chemical biology in vivo and in vitro as well as fabricating new materials.Our current research efforts center around four areas: (1) Genetic code expansion (2) developing polymer-protein hybrid materials, (3) determining the physiological effects of protein nitration and oxidation (4) developing catalyst-free in vivo bioorthogonal methods.
The thioredoxin system, consisting of the small redox-active protein thioredoxin and the large selenocysteine-containing enzyme thioredoxin reductase, has been implicated in several enzymatic and regulatory processes. For example: it can provide electrons for the enzymatic reduction of ribonucleotides, peroxides and sulfoxides; it can support target gene binding and activation by p53, NFkB and AP1; and it can restore oxidatively inactivated protein tyrosine phosphatases to the reduced and active state. Our laboratory uses genetic and biochemical approaches to study the biological roles of thioredoxin. Genetically, we use budding yeast and knockout mice to study the effects of deleting thioredoxin reductase on cancer rates, metabolism, transcription factor activity and cell signaling. Biochemically, we have developed methods for measuring the redox state of proteins and small molecules in vivo, and are using these methods to determine the real consequences of thioredoxin reductase ablation. Our results suggest thioredoxin reductase plays a physiological role in reducing protein disulfides, suppressing inflammation, and maintaining carbonyl homeostasis.
Drosophila Yorkie (Yki) and its vertebrate ortholog, Yes-associated protein (Yap), are transcription co-activator proteins that do not bind DNA directly, but instead utilize interactions with multiple DNA-binding partners to elevate transcription of growth-promoting and anti-apoptosis target genes. Their role as major effectors of cell growth and anti-apoptosis has been linked to tumor formation. Yki/Yap is a downstream regulatory target of the Hippo pathway, a highly conserved signaling pathway which is critical to the precise control of organ size. Activation of hippo signaling leads to phosphorylation of key serine residues, and promote protein-protein interactions that inhibit the transcription co-activator proteins. Hippo signaling also induces degradation of Yap by recruiting the E3 ubiquitin ligase SCFβ-RCP complex. Current research is primarily focused on protein-protein interactions that inhibit Yki by modulating its subcellular localization. We combine NMR solution structure and dynamics with thermodynamics and other biophysical techniques to investigate recognition specificity and how this leads to effective inhibition. The ultimate goal is to use this fundamental knowledge to design small molecules that can act as selective inhibitors and prevent tumorigenesis.
My primary research focus is investigation of the role of protein homeostasis in aging. Studies in mice, Drosophila and C. elegans suggest that activities associated with protein homeostasis decrease during aging. Previously in our laboratory, we found that the proteomes of long-lived species (i.e., little brown bat and naked mole rat) are more resistant to both urea-induced and heat-induced unfolding than that of shorter-lived bats or mice. We have also shown more robust maintenance of the proteasome and lower levels of ubiquitinated proteins in old (20-yr) naked mole rats when compared to old (3-yr) mice, suggesting that long-lived species might have evolved enhanced chaperone-like activities to preserve protein structure and prevent misfolding/aggregation. Using a comparative biology approach, my laboratory investigates the role of proteostasis in longevity by studying the three important processes that affect protein homeostasis: protein aggregation; protein folding (chaperones); and protein degradation.My second area of interest includes studies on dietary restriction and rapamycin. The rationale for this study is that both interventions extend lifespan in rodents, and previous data suggest that dietary restriction and rapamycin could be acting via similar mechanisms. To test this, I am developing a study that compares the lifespan of mice maintained under four conditions: ad libitum feeding; dietary restriction; ad libitum feeding plus rapamycin; dietary restriction plus rapamycin. If rapamycin and dietary restriction act via the same mechanism, the effects of dietary restriction and rapamycin on lifespan should not be additive. If this is found to be the case, it will have a big impact on the aging field. It will provide a better understanding of the aging process, spur the development of caloric restriction mimetics, and generate new insights regarding human aging.
Compelling evidence links oxidative stress and inflammation to major cardiovascular diseases (CVD), including atherosclerosis, hypertension, coronary heart disease, and stroke. While antioxidants and anti-inflammatories have been found to inhibit atherosclerosis in experimental animals, antioxidant vitamin trials to prevent or slow CVD in humans have been disappointing. The disparity between clinical trials and animal studies points to major gaps in our understanding of the effects and mechanisms of antioxidants in atherosclerotic vascular diseases in humans. Our long-term goal is to target oxidative stress and inflammation in humans to better understand their etiologic roles in atherosclerosis. The intracellular redox environment regulates endothelial cell function; an imbalance in this redox environment may cause upregulation of cellular adhesion molecules and pro-inflammatory and prothrombotic mediators, all of which promote atherosclerosis. We have found that lipoic acid affects redox-sensitive cellsignaling processes, transcription factors, and gene expression in endothelial and mononuclear cells, and exerts strong anti-inflammatory and anti-atherogenic effects in experimental animals. In collaboration with researchers at Oregon Health & Science University, we are currently testing whether lipoic acid supplementation reduces risk factors for the development of atherosclerosis in humans by attenuating oxidative stress and inflammation.
Some of the questions explored by Dr. Mathews and his 35 Ph.D. students, plus postdoctoral associates, research assistants, and undergraduates, included the following:
As he continues in semi-retirement, Dr. Mathews has served as lead author of the textbook Biochemistry, published in 2012 in its fourth edition. Currently he is completing work, with two coauthors, on Biochemistry: Concepts and Connections, scheduled for publication in late 2014. Also he serves on several journal editorial boards, and he continues to teach one or two courses per year.