Linda C. McPhail, PhD

Professor, Biochemistry

Telephone: (336) 716-2621
Fax: (336) 716-7671

Email: lmcphail@wfubmc.edu

Education:

• Methodist College, BS, 1970
• Wake Forest University, PhD (Biochemistry), MS, 1973; PhD, 1976

Current Research:

The research in my laboratory is focused on elucidation of the molecular mechanisms involved in the activation of NADPH oxidase, the enzyme in neutrophils responsible for the generation of toxic oxygen radicals. The elicited production of oxygen radicals by neutrophils plays critical roles in both protection against microbial infections and in damage to tissue in a variety of diseases, including arthritis, stroke, atherosclerosis, neurodegenerative diseases, and myocardial infarction. Also, NADPH oxidase is a member of a newly discovered family of enzymes, found in many tissues and organisms, whose functions (still being elucidated) include regulation of cell proliferation, apoptosis, and redox signaling, which play roles in cancer and aging.  A mechanistic understanding of the regulation of NADPH oxidase could ultimately be used for design of therapeutic approaches to control the activity of this enzyme in these various disease situations. Mechanisms involved in NADPH oxidase activation include phosphorylation of component(s), activation of GTP-hydrolyzing proteins, binding of lipids to enzyme components, and assembly of the enzyme from various intracellular compartments to form an active complex. We are exploring these mechanisms in intact neutrophils and using mutagenesis of NADPH oxidase components for structure/function studies in both a cell-free reconstitution system and in transfectable cell lines. In addition, we are studying a disease called chronic granulomatous disease, which is caused by mutations in the genes that code for the neutrophil NADPH oxidase components and are developing new diagnostic assays to detect the disease.

Recent Publications:

Taylor, R. M., Foubert, T. R., Burritt, J. B., Baniulis, D., McPhail, L.C., and Jesaitis, A. J.:  Anionic amphiphile and phospholipid-induced conformational changes in human neutrophil flavocytochrome b observed by fluorescence resonance energy transfer.  Biochim. Biophys. Acta 1663:201-213 (2004).

Price MO, McPhail LC, Lambeth JD, Han CH, Knaus UG, Dinauer MC. Creation of a genetic system for analysis of the phagocyte respiratory burst: high-level reconstitution of the NADPH oxidase in a nonhematopoietic system. Blood. 2002 Apr 15;99(8):2653-61.

Sergeant S, Waite KA, Heravi J, McPhail LC. Phosphatidic acid regulates tyrosine phosphorylating activity in human neutrophils: enhancement of Fgr activity. J Biol Chem. 2001 Feb 16;276(7):4737-46.

Palicz A, Foubert TR, Jesaitis AJ, Marodi L, McPhail LC. Phosphatidic acid and diacylglycerol directly activate NADPH oxidase by interacting with enzyme components. J Biol Chem. 2001 Feb 2;276(5):3090-7.

Regier DS, Greene DG, Sergeant S, Jesaitis AJ, McPhail LC. Phosphorylation of p22phox is mediated by phospholipase D-dependent and -independent mechanisms. Correlation of NADPH oxidase activity and p22phox phosphorylation. J Biol Chem. 2000 Sep 15;275(37):28406-12.

Publications:
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine