University of Virginia Health System

My research interests center on understanding the biochemical, physical chemical, and thermodynamic pathways by which one portion of a biological organism transfers information to other portions of the same organism. This interest has spawned research at the level of whole organisms, at the cellular level and at the molecular level. At the molecular and cellular levels my research interest pertains to understanding the relationships between thermodynamics, dynamics and structural changes within biological macromolecule and how these can transfer information to other portions of the macromolecular structure and modify the physiological functioning. Of particular interest are the molecular mechanisms of cooperativity. I am currently involved in experimental and theoretical studies on several systems, including the the molecular mechanisms by which human hemoglobin binds oxygen and other ligands. The human hemoglobin system provides a unique opportunity for detailed analysis into the question of correlating structural and thermodynamic information at the molecular level. I am formulating a series of thermodynamic models which include the effects of subunit dissociation and ligand binding. Results of analyses on experimental data provide important new insights into the general problem of correlating thermodynamic and structural information, the underlying mechanisms of cooperativity, and the phenomena of ligand-linked polymerization processes. On the whole organism level I am studying the information transfer capabilities and properties of human serum hormones. We have developed a number of mathematical and statistical procedures which allow us to analyzes the temporal nature of the secretion of single hormone and the simultaneous secretion of multiple hormones. We anticipate that an understanding of the temporal nature of the secretion of these hormones will lead to a better understanding of the function of these hormones and the interaction between hormones in humans. Recently, in collaboration with Joseph Lakowicz of the Center for Fluorescence Spectroscopy at the University of Maryland I have been developing the mathematical methods needed for fluorescence lifetime imaging (FLIM). This method is conceptually analogous to MRI but uses fluorescence lifetime as the imaged parameter. This method should allow investigators to use most fluorescent dyes to image spatial information in real time within a single cell. Also, in collaboration with Michelle Lampl of the Anthropology Department of Emory University I have been developing methods to mathematically model the patterns of saltatory growth in children.