Studies of the physiological functions of trace elements have become an exciting area of research in nutrition. Trace elements, in addition to their roles in metalloenzymes, regulate basic functions, such as protein synthesis, growth, and differentiation.
Our laboratory has been investigating mechanisms whereby gastrointestinal cell differentiation and proliferation may be mediated by neuropeptide Y (NPY) and peptide YY (PYY) secretion by receptosecretory and neurosecretory cells in response to specific luminal nutrients and signals originatin from the central nervous system (CNS).
Our primary research objective is to characterize the efficacy and mode of action of naturally occurring cancer protective agents in food. We have focused our attention on dietary vegetables of the Brassica genus, including cabbage, broccoli, and Brussels sprouts. It is now well established that diets rich in these vegetables are protective against hormone-dependent cancers.
Research in the Environmental Chemistry and Toxicology Laboratory emphasizes pesticide mode of action and metabolism. This information is important to optimize pesticide use, improve their selectivity and environmental characteristics, and minimize the hazards of exposure for humans, domestic animals and other non-target species.
Diet and Cancer: Anticancer Compounds in Soybean and Other Seeds. Epidemiological data support the link between consumption of plant foods and reduced incidence of cancer. In 2001, we reported for the first time the cancer preventive properties of a unique peptide in soy that we termed lunasin, demonstrating its efficacy in mammalian cells and a skin cancer mouse model against chemical carcinogens and oncogenes. Lunasin has now been found in barley, wheat, Solanum family, amaranth (the golden grain of the Aztecs in South and
Central America) and rye. These seeds are considered "healthy" and our findings serve to link seed consumption and reduced incidence of cancer. We are doing animal experiments to demonstrate further the efficacy of diet-administered lunasin against breast, prostate and colon cancer. We are also elucidating the way lunasin inhibits histone acetylation and retinoblastoma phosphorylation as molecular mechanisms by which lunasin disrupts carcinogenesis.
The intestinal tract is of major importance to human health: it is a key player in the digestion and absorption of nutrients; it plays a major role in providing a barrier between the environments outside and inside our bodies; and it contributes to immune function in several important ways. Maintenance of these functions may be lost with the onset of intestinal disease, or with any serious illness requiring the discontinuation of oral feeding.
Who studies metabolic regulation these days - the flow of metabolites through competing pathways, the anabolic and catabolic processes that determine tissue composition, adaptations to environmental stresses and how their failure leads to disease? It is our belief that the study of physiologic chemistry (metabolic regulation) can be seized by nutrition researchers interested in making fundamental contributions to biochemistry and medicine.
Our group has been searching for biologically active natural products which have potential application as antimicrobial agents, enzyme inhibitors, or insect control agents. Of particular interest to us are plant sources that have been used as foods or traditional medicines. A number of bioactive natural products have been isolated but only a few are of practical use.
As a dietetics practioner I have a special interest in diabetes, especially in developing and implementing effective dietary and exercise management strategies. I am a Certified Diabetes Educator and serve as secretary for the Chapter Presidents Council of the American Association of Diabetes Educators.
Retinoid Endocrinology and Metabolism Metabolism of retinol (vitamin A) produces the endocrine factor retinoic acid (RA). RA controls the differentiation programs of epithelial cells in the digestive tract, the respiratory system, skin, bone, the nervous system and the immune system. RA also promotes growth, reproduction (fertility, placental development, embryonic development), and resistance to and recovery from infection.
The major research efforts of my laboratory are in the area of bio-chemical nutrition and, in particular, metabolic control mechanisms. We investigate experimental nutrition problems at a basic molecular or cellular level to obtain a better understanding of factors that influence nutritional requirements and how this varies among the population and in various disease states.
The main focus of the laboratory is to elucidate the molecular mechanisms underlying the uptake of key metabolites into cells, with a particular emphasis on fatty acids. Cells use fatty acids as an energy source, for intracellular signaling, for anchoring proteins to the plasma membrane and for membrane biosynthesis. However, increased levels of intracellular fatty acid can be detrimental and have been directly linked to the development of type 2 (adult onset) diabetes. Our goal is to understand on a molecular level how fatty acids enter cells and how this process is regulated.
Adipocytes are highly specialized cells that play a crucial role in the energy balance most vertebrates by providing ability to synthesize and deposit fat during times of positive energy balance in preparation for periods of food deprivation. In modern society, however, excess adipose tissue leading to obesity is a major health problem. There is an increase in lipogenesis and storage of fat in adipose tissue causing hypertrophy.
Copper and Iron in Health and Disease
Copper and iron are vital mineral nutrientsrequired for the growth and development of mammalian organisms. However,these metals pose a dilemma for living systems. Their capacity to convert between oxidation states accounts for their essential role inmany proteins yet can lead to the generation of free radicalsor oxidative damage. These conflicting properties demand close regulationof copper and iron levels.
The long-term goal of my research is to elucidate mechanisms underlying regulation of energy homeostasis. Abnormal energy metabolism is associated with various diseases, including diabetes, obesity and cancer. My current studies will encompass fundamental investigation of physiological processes and novel approaches to therapeutic intervention. I will focus on a single regulatory pathway, glucocorticoid signaling, applying a combinatorial approach, including biochemistry, genetics, chemistry and physiology, to dissect its function in metabolic regulation.
For more than twenty years I have conducted research in the prevention of childhood obesity and have served as Principal Investigator of the longitudinal NHLBI Growth & Health Study, as well as the 5-state Fit WIC Child Obesity Intervention Study. I authored the American Public Health Association's resolution and action plan on childhood obesity which in 2001-02 was voted one of the top three priorities for the organization.
Dale E. Johnson
Dr. Johnson works for Chiron as Divisional Vice President for Drug Assessment and Development. In this position, he is responsible for preclinical research and development, including pharmacology, toxicology, pharmacokinetics, drug metabolism, experimental pathology, comparative medicine and translational medicine.
Genetic factors influencing plasma lipoprotein profiles and dietary responsiveness in humans. Metabolic behavior, physicochemical characteristics, and functional properties of low density lipoprotein (LDL) subclasses. Role of lipolytic enzymes and cell-surface receptors in lipoprotein metabolism. Gene-environment interactions underlying the cluster of coronary disease risk factors associated with small, dense LDL and insulin resistance.
The goal of our research is to understand how lipid transport and metabolism are regulated by molecular interactions between lipoproteins and cell surface receptors. Knowledge of the metabolic roles of apolipoprotein E (apoE) and the low density lipoprotein receptor (LDLR) is combined with available structural information in the design of an experimental strategy to dissect the determinants of a productive receptor-ligand interaction.
Genetic diseases, sickle cell disease and thalassemia, and the dietary condition of iron deficiency, all have side effects involving ferritin. Molecular properties of ferritin are being studied in transgenic models and with small numbers of human subjects to unravel clinical mysteries and achieve more individualized therapies for sickle cell diseases, thalassemia and iron deficiency. The Theil Molecular BioIron Group in CeBIC (Center for BioIron at CHORI) studies protein and mRNA biochemistry and iron nutrition.
George Wolf
The metabolism of vitamin A and its function in growth and differentiation, and as an anti-cancer agent. The conversion of beta-carotene to vitamin A. The history of vitamin A. My research interests are in respect to reviewing these topics for "Nutrition Reviews" and for historical work.
Although I am now emeritus, I continue to work in the Department, researching and writing on the history of ideas in nutrition. My book on the history of ideas about the need for protein in our diet was published in 1994. This is a subject with a long history, and it is educational for us to realize that intelligent, honest scientists have been able to hold dogmatic and quite diverse views on a subject so important for the evaluation of diet.
As a food microbiologist, I work on foodborne illness and the microbiological safety of our food and water supply (water is, after all, a major food and nutrient).Right now we are witnessing a revolution in food microbiology, as people devise faster and more specific methods for monitoring food and water.
Though the demand for nutrients increases significantly during pregnancy and lactation, very few women report eating more. We are interested in determining how pregnancy or lactation alters the mother's use of zinc, calcium, and energy to provide for fetal growth or milk synthesis.
Research & People 
