Daniel Baker, Ph.D., Assistant Professor
 Department of Medicine

Dr. Baker's interests are focused on understanding the functional roles of phospholipid growth factors in homeostasis and disease. Lysophosphatidic acid (LPA) and sphingosine phosphate (S1P) are prototypic members of a class of bioactive lipids termed phospholipid growth factors. These compounds elicit profound cellular effects including stimulation of proliferation and motility, and prevention of apoptosis. These characteristics have lead many researchers to speculate central roles for these lipids in the initiation and progression of cardiovascular disease and cancer.

Mass spectrometry is exploited as the central tool in Dr. Baker's studies. He previously developed a stable-isotope dilution, liquid chromatography mass spectrometry assay for the direct quantitative analysis of individual LPA molecular species in biological fluids. This method has subsequently been applied to several research questions including analysis of the mechanisms underlying LPA production during platelet activation, evaluation of the utility of LPA as a marker of early ovarian cancer, and determination of LPA-mediated PPARg activation in the development of neointimal lesions.

Current projects in Dr. Baker's lab include identification of plasma proteins that interact with and modulate the activity of phospholipid growth factors in vivo. Photoaffinity labeling, 2-dimensional gel electrophoresis and mass spectrometry are being utilized to catalog these binding partners. A related project is designed to probe the specific interactions that govern the interactions between phospholipid growth factors and their specific G protein-coupled receptors. This project takes advantage of baculovirus protein expression, photoaffinity labeling, and mass spectrometry to map the hydrophobic binding pocket of these integral membrane receptors.

Future studies include analyzing the molecular species distribution and mechanism of formation of LPA in various lipoprotein fractions in plasma and serum; and developing a stable isotope dilution method for the quantitative analysis of S1P in biological fluids. If validated, this method will be applied to important research questions including the value of plasma S1P for the accurate prediction of coronary artery disease.

Recent Publications

Rother E, Brandl R, Baker DL, Tigyi G and Siess W. Inhibition of platelet activation induced by lysophosphatidic acid, mildly oxidized LDL and plaque lipid core by subtype-selective antagonists of lysophosphatidic acid receptors. Circulation 108: 741-747, 2003.

Baker DL, Morrison P, Miller B, Riely CA, Tolley B, Bonfrer JMG, Westermann AM, Moolenaar WH and Tigyi GJ. Lack of a Diagnostic Correlation Between Plasma Lysophosphatidic Acid Concentration and Ovarian Cancer. JAMA 287: 3081-3082, 2002.

Sano T, Baker DL, Wada A, Yatomi Y, Kobayashi T, Lgarashi Y and Tigyi GJ. Multiple mechanisms linked to platelet activation generate lysophosphatidic acid and sphingosine-1-phosphate in blood. J Biol Chem 277:21197-21206, 2002.

Yokoyama K, Baker DL, Virag T, Liliom K, Byun H, Tigyi G and Bittman R. Stereochemical properties of lysophosphatidic acid signaling and metabolism. Biochim Biophys Acta 1582: 296-309, 2001.

Sardar VM, Bautista DL, Fischer DJ, Yokoyama K, Nusser N, Virag T, Wang D, Baker DL, Tigyi G and Parrill AL. Molecular basis for lysophosphatidic acid receptor antagonist selectivity. Biochim Biophys Acta 1582:310-318, 2001.

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