Department Affiliation: Primary: Medicine, Division of Clinical Pharmacology; Secondary: Division of Allergy and Clinical Immunology
Secondary: Pharmacology and Molecular Sciences
Degree: Ph.D., Vanderbilt University School of Medicine
Rank: Associate Professor, Director of Mass Spectroscopy Laboratory
Telephone Number: 410-502-3879
Fax Number: 410-614-9978
E-mail address: whubbard@jhmi.edu
School of Medicine Address: 600 N. Wolfe Street, Osler 505, Baltimore, MD 21287-5554
Mass Spectroscopy Laboratory: Osler 520
Representative Publications:
Mass Spectrometry Instrumentation:
One Applied Biosystems-Sciex API4000 LC-MS/MS (Agilent 1100 series LC), Installation 11/2002
One Applied Biosystems-Sciex API5000 LC-MS/MS (Waters Acquity UPLC); Installation 8/2008
The combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrumentation in the laboratory is designed specifically for quantitation of small molecules with molecular weights less than 1000. The atmospheric pressure ionization capabilities include electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) and electron-capture APCI. Employing multiple reaction monitoring MRM) analysis, ions of both polarities (positive and negative), the detection limits range from <20 picomoles (<20 x 10-12 moles) to less than 50 femtomoles (<50 x 10-15 moles) injected on column with correlation coefficients (R2) > 0.98. The capabilities of the LC-MS/MS instrumentation for quantitation of small molecules are quite broad and not necessarily limited to the research interests stated below.
Research Interests:
The primary research interest of the laboratory is quantitative LC-MS/MS analysis employing MRM of small molecules. Specific applications include clinical and laboratory research such as: (1) pharmacokinetics and metabolism of agents employed for prevention and treatment of HIV/AIDS and other viral diseases; (2) lipid molecular species and their potential as diagnostic markers for use in newborn screening for leukodystrophies and other peroxisomal disorders (3) roles of lipids as mediators of signal transduction in cells and (4) role of lipids in pulmonary obstructive and inflammatory diseases.
- Giardiello, F.M., Yang, V.W., Hylind, L.M., Krush, A.J., Petersen, G.M., Trimbath, J.D., Piantidosi, S., Garrett, E., Geiman, D.E., Hubbard, W.C., Offerhaus, G.J., and Hamilton, S.R. Primary chemoprevention of familial polyposis with sulindac. N Engl J Med 346:1054-1059, 2002. Pub Med Reference
- Berdyshev, E.V., Gorshkova, I.A., Garcia, J.G.N., Natarajan, V. and Hubbard, W.C. Quantitative analysis of sphingoid base-1-phosphates as bisacetylated derivatives by liquid chromatography-tandem mass spectrometry. Anal Biochem 339:129-136, 2005. Pub Med Reference
- Petrache, I, Natarajan, V, Zhen, L, Medler, TR, Richter, AT, Cho, C, Hubbard, WC, Berdyshev, EV and Tuder, RM. Ceramide upregulation causes pulmonary cell apoptosis and emphysema. Nature Medicine 11:491-498, 2005. Pub Med Reference
- Li, J., Thorne, L.N., Punjabi, N.M., Sun, C.,-K., Schwartz, A.R., Smith, P.L., Marino, R.L., Rodriguez, A., Hubbard, W.C., O’Donnell, C.P., and Polotsky, V.Y. Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 97: 698-706, 2005. Pub Med Reference
- Berdyshev, E.V., Gorshkova, I.A., Usatyuk, P., Zhao, Y., Hubbard, W., and Natarajan, V. (2006) De novo biosynthesis of dihydrosphingosine-1-phosphate by sphingosine kinase 1 in mammalian cells. Cell Signaling 18:1779-1792, 2006. Pub Med Reference
- Hubbard, W.C., Moser, A.B., Tortorelli, S., Liu, A. and Moser, H. Combined liquid chromatography-tandem mass spectrometry as an analytical method for high throughput screening for X-linked adrenoleukodystrophy and other peroxisomal disorders: Preliminary findings. Molec Genet Metab 89:185-187, 2006. Pub Med Reference
- Georas, S.N., Berdyshev, E., Hubbard, W., Gorshkova, I. A., Usatyuk, P.V., Saatian, B., Myers, A.C., Williams, M. A., Xiao, H. Q. , Liu, M., and Natarajan,V. Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental challenge. Clin Exp Allergy 37:311-322, 2007. Pub Med Reference
- Boscom, A., Inman, D.M , Steele, M.R., Wu, G., Soto, I., Marsh-Armstrong, N., Hubbard, W.C., Calkins, D.J., Horner, P.J., and Vetter, M.L. Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. Invest Ophtham and Vis Sci 49:1437-1446, 2008. Pub Med Reference
- Yokoi, H., Choi, O.H., Hubbard, W., Lee, H.-S., Canning, B.J., Lee, H.H., Ryu, S.-D., von Gunten, S., Bickel, C.A., Hudson, S.A., MacGlashan, D.W., Jr., and Bochner, B.S. Inhibition of FCeRI-dependent mediator release and calcium flux from human mast cells by sialic-acid binding immunoglobulin-like lectin 8 engagement. J Allergy Clin Immunol 121: 499-505-2008. Pub Med Reference
- Medler, T. R., Petrusca, D. N., Lee, P. J., Hubbard, W. C., Berdyshev, E. V., Skirball, J., Kamocki, K., Schuchman, E., Tuder, R. M., and Petrache, I. Apoptotic sphingolipid signaling by ceramides in lung endothelian cells. Am J Respir Cell Mol Biol 38:639-646, 2008. Pub Med Reference
- Petrache, I., Medler, T.R., Richter, A.T., Kamocki, K., Chukwueke, U., Zhen, L., Gu, Y., Adamowicz, J., Schweitzer, K.S., Hubbard, W.C., Berdyshev, E.V., Lungarella, G., Tuder, R.M. Superoxide dismutase protects against apoptosis and alveolar enlargement induced by ceramide. Am J Physiol Lung Cell Molec Physiol (in press 4/25/2008). Pub Med Reference
Other graduate programs in which Dr. Hubbard participates: None
