DAVID F. WILSON, Ph.D.

Professor of Biochemistry and Biophysics

Location: 901A Stellar-Chance Building
Tel: (215) 898-6382
Fax: (215) 573-3787
Email: wilsondf@mail.med.upenn.edu

Ph.D. Oregon State University (1964)

DESCRIPTION OF RESEARCH INTERESTS

Dr. Wilson's research interests can be divided into three areas:

Regulation of energy metabolism in vivo

Cells require a continuous supply of energy, as adenosine triphosphate, for survival and function. Restrictions in availability of substrates for oxidative phosphorylation, such as oxygen, or failure of the regulatory mechanisms leads to disruption of cellular and tissue function. The regulation of and interactions among metabolic pathways is being examined at all levels of organization, from isolated mitochondria to tissue in vivo. Dr. Wilson's particular interest is in the oxygen dependence of energy metabolism, with the related problems of oxygen delivery to tissue, oxygen sensing by tissue, and hypoxia induced cellular injury.

Tissue oxygenation, its regulation and pathology
(collab. with Dr. Sergei A. Vinogradov).

Dr. Wilson's group has pioneered an optical method for tissue oxygen measurement and imaging. This technique is based on oxygen dependent quenching of phosphorescence, and is currently being developed and applied to a wide range of physiological/biochemical problems. Phosphorescence quenching method is noninvasive and can provide quantitative oxygen measurements with high spatial and temporal resolution in both in vitro and in vivo systems. Measurement of oxygen by phosphorescence quenching can be implemented as both 2D and 3D imaging modalities. 3D oxygen imaging combines techniques from near infrared optical tomography with luminescence quenching and constitutes the most rigorously pursued project in the group. Phosphors that absorb and emit in either the visible or near infrared regions of the spectrum have been synthesized. New "protected" phosphors, based on porphyrin-dendrimers, are being developed specifically for in vivo applications. Some of these phosphors are suitable for oxygen imaging in surface tissue, while others allow for measurements through several cm of tissue. Phosphorescence lifetime instruments for oxygen measurements and imaging is being designed in Dr. Wilson's group, constructed and applied to measure oxygen in animal models of several clinically important pathologies, including diabetic retinopathy, tumors and some other diseased states.

The biochemical basis for neuronal injury in the brain due to hypoxic/ischemic insult and reperfusion
(collab. with Dr. Anna Pastuszko)

Phosphorescence quenching technique is being applied to quantify the degree of hypoxia in the brain during controlled hypoxic/ischemic insults. The metabolic consequences of these insults and the subsequent reperfusion period are being evaluated through their influence on: a) release, reuptake and metabolism of key neurotransmitters, particularly the catecholamines and glutamate; b) expression of different genes associated with cell adaptation and injury; and c) the activity of key enzymes in neurotransmitter metabolism. The group is studying the metabolism of the catecholamines and other neurotansmitters in the brain in vivo, and the influence of various natural and synthetic compounds on that metabolism. Among other techniques, in vivo microdialysis in combination with microbore HPLC detection are being used to continuously monitor neurotransmitter metabolism in the brain, allowing the drug induced metabolic alterations to be accurately evaluated. Regional distribution of the observed metabolic alterations within the brain is being compared to the sensitivity to ischemia/hypoxia-reperfusion injury of the region as indicated by neuronal necrosis, cellular apoptosis, expression of heat shock proteins, etc.

RECENT REPRESENTATIVE PUBLICATIONS:

1. Wilson, D.F., Vinogradov, S.A. (2003) Tissue oxygen measurements using phosphorescence quenching, in Handbook of Biomedical Fluorescence, Ch. 17, Ed.: Mycek, M.-A.; Pogue B. W., Marcel Dekker, New York.
   
2. Soloviev V.D., Wilson D.F., Vinogradov S.A. (2003) 3D phosphorescence lifetime imaging in turbid media: the forward problem. Applied Optic 42:113-123.
   
3. Dunphy, I., Vinogradov, S.A., Wilson, D.F. (2002) Oxyphor R2 and G2: new phosphors for measuring oxygen by oxygen dependent quenching of phosphorescence Anal. Biochem. 310:191-198.
   
4. Vinogradov, S.A., Fernandez-Seara, M.A., Dugan, B.W., Wilson, D.F. (2001) Frequency domain instrument for measuring phosphorescence lifetime distributions in heterogeneous samples. Rev. Sci. Instrum. 72:3396-3406.
   
5. Vinogradov, S.A., Lo, L.-W., Wilson, D.F. (1999) Dendritic polyglutamic porphyrins: probing porphyrin protection by oxygen dependent quenching of phosphorescence. Chem. Eur. J. 5:1388-1347.
   
6. Kuo, M.-F., Song, D., Murphy, S., Delivoria-Papadopoulos, M., Wilson, D.F., Pastuszko, A. (1998) Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of newborn piglets. Neurochem. Int. 32:281-289.
   
7. Vinogradov, S.A., Lo, L.-W., Jenkins, W.T., Evans, S.M., Koch, C., Wilson, D.F. (1996) Non-invasive imaging of the distribution of oxygen in tissue in vivo using near infrared phosphors. Biophys. J. 70:1609-1617.