The integrity of metabolic processes is critical for the function of every cell and tissue and determines normal body mass maintenance, blood glucose homeostasis, neurological function, and other fundamental systemic coordination. Aberrant physiological and biochemical mechanisms that compromise metabolic integrity create an imposing national economic burden through health care costs and are accordingly a significant area of emphasis in NIH programming priorities. Mentors focused on lipid transport and trafficking, macromolecular clearance in the liver, and impacts of perturbations to these functions on body mass regulation, fatty liver, and reproductive function naturally complement mentors examining molecular signaling and disease microenvironment.
Hewett University Professor of Chemistry
Research focus: Chromatographic-based immunoassays, biointeraction analysis.
- Postdoctoral, Mayo Clinic
- Ph.D. Iowa State University
- B.S. University of Wisconsin
Affinity-based separation of proteins or metabolites from a complex mixture is a powerful method for identifying and quantifying specific components. Such methods have additional utility for determining association constants and rate constants for protein-protein or protein-ligand interactions. Dr. Hage's laboratory has developed multiple novel and innovative methods for affinity separation and bioanalysis. For example, students have used heavy water labeling followed by protein digestion and mass spectrometry to characterize residues that preferentially react to immobilize the protein in specific conditions. The students relate the coupling through those residues to resultant activity of the protein, ensuring maximal conservation of function following immobilization. Ongoing projects in the Hage laboratory use this and other methods of chromatographic separation for forensics, immunoassays, hormone and drug detection and quantification, and other important applications.
Charles Bessey Professor, Chair of Biochemistry
Research focus: Fatty acid transport and trafficking in eukaryotes.
Fatty acids are critical nutritional macromolecules and essential structural precursors of cellular membranes and specific cell signals. Certain types of fatty acids promote disease progression, while others are considered health promoting. Dr. Black's research is focused on the mechanisms that regulate exogenous fatty acid import into the cell and direct their unique intracellular metabolic fates. These research efforts will define the roles of different classes of exogenously derived fatty acids in normal and lipotoxic conditions. At present, students in his laboratory are addressing the functions of fatty acid transport proteins (FATPs) in fatty acid homeostasis using high-resolution mass spectrometry to trace the metabolism of isotopically labeled exogenous fatty acids. His collaborations with the UNL College of Engineering have led to the implementation of Coherent Anti-Stokes Raman Scattering (CARS) microscopy to monitor trafficking and spatial distribution of isotopically labeled fatty acids.
Professor of Biochemistry
Research focus: High-throughput screens for fatty acid uptake inhibitors.
Inhibition of cellular fatty acid uptake from circulation is one strategy that may be successful in combating obesity, diabetes, and diseases such as non-alcoholic fatty liver disease (NAFLD). Dr.DiRusso's laboratory has identified five structural classes of fatty acid uptake inhibitors selected from bioactive chemical library screens and characterized their respective specificity andaffinity for the fatty acid transport proteins isoforms, as well as their efficacy in reducing cellular fatty acid uptake. In addition, her students have examined the effect of specific dietary fatty acid manipulation on the development of NAFLD in a mouse model that develops the disease due to elevated intracellular fatty acid synthesis in the liver. This work demonstrated that progression of the disease could be decelerated by dietary abundance of particular fatty acid classes. Dr. DiRusso's students are currently addressing the mechanistic basis of two lead fatty acid uptake inhibitors using cultured cells and mouse models of obesity and NAFLD.
Associate Professor of Biochemistry
Research focus: Liver endothelial scavenger receptor function; systemic clearance of heparin.
The liver is an absorptive organ with a highly specialized reticulated endothelium rich in a variety of cell surface scavenger receptors that clear circulating proteins, lipids, and other macromolecules. Dr. Harris has extensively characterized the stabilin class of receptors, due to its rapid and continuous endocytic clearance activity and strong affinity for heparin, heparin-like molecules, hyaluronan and other circulating glycosaminoglycans, as well as low-density lipoproteins and related ligands. Dr. Harris' laboratory has shown that stabilins have a critical role in heparin clearance, which has a strong biomedical impact because of the widespread use of heparin in many complex surgical procedures. Although a relatively new investigator, Dr. Harris has established strong collaborations to characterize the role of stabilins in clearing clinically relevant synthetic heparins.
Professor of Chemistry
Research focus: Nuclear magnetic resonance (NMR) metabolomics.
NMR identification and quantification of cellular metabolite profiles in the presence of a variety of external stimuli is a powerful approach to examine molecular mechanisms and pathway flux in normal and diseased cells, tissues, organs, or biofluids. NMR methods can also be applied to examine protein conformational transitions, map protein-ligand or protein-protein docking interactions, and determine association/dissociation constants for such interactions. Research in Dr. Powers' laboratory is oriented toward development, validation, and application of new metabolite analysis techniques to examine disease mechanisms in collaboration with many labs at UNL, UNMC, and elsewhere. Students in his laboratory are currently working on projects that use bioinformatics, structural biology, and functional genomics to examine molecular docking, biofilm formation, assessment of drug activity and potency during and following inhibitor treatments in infectious disease and cancer models, and several other biochemical and biological questions. Much of Dr. Powers' work is directed at metabolomic analysis of human diseases.
Assistant Professor of Biological Sciences.
Research focus: Lipid distribution and storage mechanisms.
- Ph.D. Michigan State University, 2004 (Biochemistry & Molecular Biology)
- B.S. University of Missouri, 1999 (Biochemistry)
Trafficking of lipids from the plasma membrane to subcellular organelles that process or store them is a critical process in membrane biogenesis and cell metabolism. Research in Dr. Riekhof's laboratory uses yeast as a model system to identify and manipulate components of lipid trafficking. Students in his laboratory are currently using the power of yeast genetics to define phospholipid synthesis and distribution pathways, which has broad implications in normal human metabolism and heart disease.
Associate Professor of Animal Science
Research focus: Steroid hormone signaling and metabolic effects on ovarian follicular development.
- B.A., Indiana University, IN, 1992, Microbiology
- M.S., University of Illinois, IL, 1996, Reproductive Endocrinology, Department of Molecular and Integrative Physiology
- Ph.D., University of Illinois, IL, 2000, Reproductive Endocrinology-Thesis: Estrogen Receptor Conformation: Modulation by Estrogen Response Elements, Department of Molecular and Integrative Physiology
- Post-doctorate, University of Pennsylvania, PA, 2000-2005, Center for Research on Reproduction and Women's Health
Reproductive efficiency is directly impacted by nutritional status and overall metabolic homeostasis, which are reflected in the normal development and maturation of ovarian follicles. The Wood laboratory is providing molecular insights into pathologies such as polycystic ovarian syndrome using an innovative bovine model that mimics progression of the human disease. Student projects in Dr. Wood's lab are also centered on defining the crosstalk among signal transduction pathways that mediate dietary control of steroid flux and the role of these pathways in regulating ovulatory response genes.