Billy W. Day, Ph.D.
Professor
Department of Pharmaceutical Sciences,
School of Pharmacy
Department
of Chemistry
Department
of Environmental & Occupational Health
Department
of Computational & Systems Biology
Clinical & Translational Sciences Institute
Director
Proteomics
Core Lab, Schools of the Health Sciences
Medicinal Chemistry, Drug Discovery Institute
University
of Pittsburgh
10017 BST3, 3501 Fifth Avenue,
Pittsburgh, PA 15213
Telephone: (412) 648-9706, FAX: (412)
383-5298, Internet: bday@pitt.edu
Education
B.S., 1982, Oklahoma City University, Chemistry and Biology
(double major)
Ph.D., 1988, University of Oklahoma, Medicinal
Chemistry
Post-doc, 1988-91, Massachusetts Institute of Technology, Chemistry
and Toxicology
Research Interests
My group's major research interest is
the study of the chemical and molecular mechanisms of antitumor agents. We apply
a variety of techniques and approaches to these studies, including
computational chemistry (2D- and 3D-QSAR, macromolecular modeling), synthetic
chemistry (design and preparation of novel agents, their radio- and stable
isotope-labeled forms, photoaffinity probes), analytical chemistry (GC- and
LC-MS, NMR), metabolism studies (microsomal and cells in culture),
bioanalytical methods, and the use of human carcinoma cells and normal human
epithelial cells in culture. One of our major interests is agents that target
microtubules. Lead compounds are the microtubule stabilizers (+)-discodermolide
and (-)-dictyostatin (E. Hamel, D.P. Curran, J.L. Eiseman, A. Vogt), and the
tubulin assembly inhibitors pironetin and the tubulysins (S.G. Nelson, P. Wipf,
A. Vogt). Other molecular targets for which we are pursuing small molecule
inhibitors and more mechanistic information include the molecular motor dynein
(D.P. Curran, P. Wipf, K. Brummond, D. DeFranco, R.B. Vallee, P.A. Johnston),
the estrogen receptors (P. Wipf, M. Nichols, W. Xie), chaperone proteins (P.
Wipf, J.L. Brodsky), dual specificity phosphatases (M. Tsang, A.
Vogt), p53/MDMx interactions (A. Doemling), HIV-1 protein/host protein interactions (T.E. Smithgall), histone deacetylases (N.A. Hukriede) and topoisomerase II (J.C. Yalowich).
We also have a major interest in the molecular dosimetry of carcinogens. We are particularly interested in defining the chemistry of protein adducts made by the electrophilic forms of these agents. Ongoing projects in this area include one aimed at determining the relative contributions of reactive nitrogen and oxygen species in cell injury (V.E. Kagan, J.C. Yalowich, N. Gorbunov, J. Atkins, M.P. Fink). We have developed isotope dilution GC- and LC-MS methods for quantitation of protein alterations, and have studied the interactions of nitric oxide with hemoproteins by ESR and LC-MS. The second is use of isotope dilution MS methods for quantitation of protein adducts of metabolically activated aromatic amines.
We provide the home for the Proteomics
Core Lab of the Schools of the Health Sciences. Ongoing proteomics projects in
the Day lab include a study of nuclear matrix proteins in normal vs. cancerous
breast (J.J. Latimer, S.G. Grant) and the influence of altered levels of
stathmin on microtubule stabilizer sensitivity (M.A. Jordan). Difference 2D
gels, solution-phase isoelectric focusing, MALDI-TOF-MS, MALDI-TOF/TOF-MS/MS,
micro- and nano-MDLC separations for LC-MALDI, LC-ESI-TOF-MS, MDLC-ESI-ion
trap-MS^n, LC-ESI-LIT-Orbitrap-MS/MS and LC-ESI/MALDI-hQh-ICR FT-MS analyses are
available on a cost-recovery or collaborative basis.
Selected Recent Publications
Vollmer, L.L., Jimenez, M., Camarco, D.P., Zhu, W., Daghestani, H.N., Balachandran, R., Reese, C.E., Lazo, J.S., Hukriede, N.A., Curran, D.P., Day, B.W. A simplified synthesis of novel dictyostatin analogs with in vitro activity against epothilone B resistant cells and antiangiogenic activity in zebrafish embryos. Molecular Cancer Therapeutics 2011, 10, 1-13.
Osman, S., Waud, W.R., Gorman, G.S., Day, B.W., Koide, K. Evaluation of FR901464 analogues in vitro and in vivo. MedChemComm 2011, 2, 38-43.
Balasubramani, M., Nakao, C., Uechi, G.T., Cardamone, J., Kamath, K., Leslie, K.L., Balachandran, R., Wilson, L., Day, B.W., Jordan, M.A. Characterization and detection of cellular and proteomic alterations in stable stathmin-overexpressing, taxol-resistant BT549 breast cancer cells using offgel IEF/PAGE difference gel electrophoresis. Mutation Research - Genetic Toxicology and Environmental Mutagenesis 2011, 722, 154-164.
Daghestani, H.N., Day, B.W. Theory and applications of surface plasmon resonance, resonant mirror, resonant waveguide grating, and dual polarization interferometry biosensors. Sensors 2010, 10, 9630-9646.
Cherra, S.J. III, Kulich, S.M., Uechi, G.T., Balasubramani, M., Mountzouris, J., Day, B.W., Chu, C.T. Regulation of the autophagy protein LC3 by phosphorylation. Journal of Cell Biology 2010, 190, 533-539.
Zhu, W., Jimenez, M., Jung,, W.-H., Camarco, D.P., Balachandran, R., Vogt, A., Day, B.W., Curran, D.P. Streamlined syntheses of (-)-dictyostatin, 25,26-dihydro-16-desmethyldictyostatin, and 6-epi-25,26-dihydro-16-desmethyldictyostatin. Journal of the American Chemical Society 2010, 132, 9175-9187.
Vogt, A., Codore, H., Day, B.W., Hukriede, N.A., Tsang, M. Development of automated imaging and analysis for zebrafish chemical screens. Journal of Visualized Experiments 2010, Jun 24;(40). pii:1900. doi:10.3791/1900. PMID: 20297785
de Groh, E.D., Swanheart, L.M., Cosentino, C.C., Jackson, R.L., Dai, W., Kitchens, C.A., Day, B.W., Smithgall, T.E., Hukriede, N.A. Inhibition of histone deacetylase expands the renal progenitor cell population. Journal of the American Society of Nephrology 2010, 21, in press.
Lakshman, M.K., Singh, M.K., Parrish, D., Balachandran, R., Day, B.W. Azide-tetrazole equilibrium of C-6 azidopurine nucleosides and their ligation reactions with alkynes. Journal of Organic Chemistry 2010, 75, 2461-2473.
You, Z., Gao, H., Gao, J., Shin, P. H., Day, B. W., Wang, Y. A functionalizable polyester with free hydroxyl groups and tunable physicochemical and biological properties. Biomaterials 2010, 31, 3129-3138.
Beckner, M. E., Fellows-Mayle, W., Zhang, Z., Agostino, N. R., Kant, J. A., Day, B. W., Pollack, I. F. Identification of ATP Citrate Lyase as a positive regulator of glycolytic function in glioblastomas. International Journal of Cancer 2010, 126, 2282-2295.
Emert-Sedlak, L., Kodama, T., E. C., Lerner, Dai, W., Foster, C., Day, B. W., Lazo, J. S., Smithgall, T. E. Chemical library screens targeting an HIV-1 accessory factor/host cell kinase complex identify novel anti-retroviral compounds. ACS Chemical Biology 2009, 4, 939-947.
Fan, Y., Schreiber, E. M., Day, B. W. Human liver microsomomal metabolism of (+)-discodermolide. Journal of Natural Products 2009, 72, 1748-1754.
Albert, B. J., McPherson, P. A., O'Brien, K., Czaicki, N. L., DeStefino, V., Li, M., Osman, S., Day, B. W., Grabowski, P. J., Moore, M., Vogt, A., Koide, K. Meayamycin inhibits pre-mRNA splicing and exhibits picomolar activity against multidrug resistant cells. Molecular Cancer Therapeutics 2009, 8, 2308-2318.
Daghestani, H. D., Fernig, D. G., Day, B. W. Evaluation of biosensor surfaces for detection of microtubule perturbation. Biosensors and Bioelectronics 2009, 24, 136-141.
Molina, G., Vogt, A., Bakan, A., Dai, W., de Olivera, P. Q., Smithgall, T., Bahar, I., Lazo, J. S., Day, B. W., Tsang, M. An allosteric inhibitor of Dusp6, identified from a zebrafish chemical screen, expands cardiac progenitors and heart size. Nature Chemical Biology 2009, 5, 680-687.
Gao, X., Kuruba, R., Day, B. W., Achary, D. K., Liu, D., Li, S. Polyhydroxylalkyleneamines: a class of hydrophilic cationic polymer-based gene transfer agents. Journal of Controlled Release 2009, 137, 38-45.
Brummond, K.M., Mao, S., Shinde, S.N., Johnston, P.J., Day, B. W. Design and synthesis of a library of tetracyclic hydroazulenoisoindoles. Journal of Combinatorial Chemistry 2009, 11, 486-494.
Sarachine, M. J., Janjic, J. M., Wipf, P., Day, B. W. Biphenyl C-cyclopropylalkylamides: new scaffolds for targeting estrogen receptor beta. Bioorganic & Medicinal Chemistry Letters 2009, 19, 2404-2408.
Chiang, A. N., Valderramos, J.-C., Balachandran, R., Chovatiya, R. J., Mead, B. P., Schneider, C. X., Bell, S. L., Klein, M. G., Huryn, D. M., Chen, X. S., Day, B. W., Fidock, D. A., Wipf, P., Brodsky, J. L. Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorganic & Medicinal Chemistry 2009, 17, 1527-1533.
Tierno, M. B., Petrik, B., Graham, T. H., Wipf, P., Xu, F., Saunders, W., Kitchens, C. A., Raccor, B. S., Balachandran, R., Day, B. W., Stout, J. R., Walczak, C. E., Ducruet, A. P., Hindman, C. E., Lazo, J. S. Microtubule binding and disruption and induction of premature senescence by disorazole C1. Journal of Pharmacology & Experimental Therapeutics 2009, 328, 715-722.
Su, Y., Fu, C., Ishikawa, S., Stella, A., Kojima, M., Shitoh, K., Schreiber, E. M., Day, B. W., Liu, B. APC is essential for targeting phosphorylated beta-catenin to the SCF(b-TrCP) ubiquitin ligase. Molecular Cell 2008, 32, 652-661.
Dietrich,
D. R. , O'Brien, E., Heussner, A.H., Gramatte', T., Runkel, M., Rumpf, S., Day, B.W. Propiverine-induced accumulation of nuclear and cytosolic protein in F344 rat kidneys: Isolation and identification of the accumulating protein. Toxicology & Applied Pharmacology 2008, 233, 411-419.
Eiseman, J. L.,
Bai. L., Jung, W.-H., Moura-Letts, G., Day, B. W., Curran, D. P. Improved synthesis of 6-epi-dictyostatin and antitumor efficacy in mice
bearing MDA-MB231 human breast cancer xenografts. Journal of Medicinal
Chemistry 2008, 51, 6650-6653.
Gibson, F.,
Anderson, L., Babnigg, G., Baker, M., Berth, M., Binz, P.-A., Borthwick, A.,
Phil Cash, P., Day, B. W., Friedman, D. B., Garland, D., Gutstein, H. B.,
Hoogland, C., Jones, N. A., Jones, A. R., Khan, A., Klose, J., Lamond, A. I.,
Lemkin, P. F., Lilley, K. S., Minden, J., Morris, N. J., Paton, N. W., Pisano,
M. R., Prime, J. E., Rabilloud, T., Stead, D. A., Taylor, C. F., Voshol, H.,
Wipat, A. Guidelines for reporting the use of gel electrophoresis in
proteomics. Nature Biotechnology 2008, 26, 863-864.
Thomas, C.
A., Grant, S. G.,
Pflug, B. R.,
Getzenberg, R. H., Day, B. W. Z-1,1-Dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane
induces concentration-dependent growth inhibition, apoptosis and upregulation
of apoptotic genes in TRAMP cells. Urologic Oncology 2008,
25, 378-385.
Kangani, C. O., Day, B.
W. Mild, efficient Friedel-Crafts acylation from carboxylic acids using cyanuric
chloride and AlCl3. Organic Letters 2008,
25, 378-385.
Wright, C. M.,
Chovatiya, R. J., Jameson, N.E., Turner, D. M., Zhu, G., Werner, S., Huryn,
D.M., Pipas, J. M., Day, B. W., Wipf, P., Brodsky, J. L. Pyrimidinone-peptoid hybrid molecules with distinct effects on
molecular chaperone function and cell proliferation. Bioorganic &
Medicinal Chemistry 2008, 16,
3291-3301.
Raccor, B. S., Vogt, A., Sikorski, R. P., Madiraju, C., Balachandran, R., Montgomery, K., Shin, Y., Fukui, Y., Jung, W.-H., Curran, D. P., Day, B. W. Cell-based and biochemical
structure-activity analyses of analogues of the microtubule stabilizer
dictyostatin. Molecular Pharmacology 2008, 73,
718-726.
Balachandran, R., Hopkins, T. D., Thomas, C.A., Wipf, P., Day, B.
W. Tubulin-perturbing naphthoquinone spiroketals. Chemical Biology &
Drug Design 2008, 71, 117-124.
Kangani, C. O., Day, B.
W., Kelley, D. E. Controlled conversion of phenylacetic acids to phenylacetonitriles
or benzonitriles using bis(2-methoxyethyl)aminosulfur trifluoride. Tetrahedron
Letters 2008, 49,
914-918.
Shin, Y.,
Fournier, J.-H., Brückner, A., Madiraju, C., Balachandran, R., Raccor, B. S.,
Edler, M. C., Hamel, E., Sikorski, R. P., Vogt, A., Day, B. W., Curran, D.P. Synthesis and biological evaluation of
(–)-dictyostatin and stereoisomers. Tetrahedron 2007, 63, 8537-8562.
Wang, Z., McPherson, P.
A., Raccor, B. S., Balachandran, R., Zhu, G., Day, B. W., Vogt, A., Wipf, P.
Structure-activity and high-content imaging analyses of novel tubulysins. Chemical
Biology & Drug Design 2007, 70,
75-86.
Jung, W.-H., Harrison, C., Shin, Y.,
Fournier, J.-H., Balachandran, R., Raccor, B. S., Sikorski, R. P., Vogt, A.,
Curran D. P., Day, B. W. Total
synthesis and biological evaluation of C16 analogs of (-)-dictyostatin. Journal
of Medicinal Chemistry
2007, 50, 2951-2966.
Elamin, A. H., Day, B. W.,
Yao, J. K. Unraveling complexity by integrative biological investigation. In Fatty
Acids and Oxidative Stress in Neuropsychiatric Disorders (Reddy, R. and Yao, J. K., eds.) Nova Science
Publishers, Inc., New York. 2007, 237-268.
Wipf, P., Gong, H., Janjic, J. M., Li, S.,
Day, B. W., Xie, W.
New opportunities for pregnane X receptor (PXR) targeting in drug development.
Lessons from enantio- and species-specific PXR ligands Identified from a
discovery library of amino acid analogues. Mini-Reviews in
Medicinal Chemistry 2007, 7, 617-625.
Heussner, A. H., Moeller, I., Day, B. W., Dietrich, D. R., O'Brien, E. Production and characterization of monoclonal antibodies against ochratoxin B. Food and Chemical Toxicology 2007,
45, 827-833.
Escobar, P. A., Olivero, O. A., Wade, N.
A., Abrams, E. J., Nesel, C. J., Ness, R. B., Day, R. D., Day, B. W., Meng, Q.,
O'Neill, J. P., Walker, D. M., Poirier, M. C., Walker, V. E., Bigbee, W. L.
Genotoxicity assessed by the comet and GPA assays following in vitro exposure
of human lymphoblastoid cells (H9) or perinatal exposure of mother-child pairs
to AZT or AZT-3TC. Environmental and Molecular Mutagenesis 2007,
48, 330-343.
Buey, R. M., Calvo, E., Barasoain, I.,
Pineda, O., Edler, M. C., Matesanz, R., Cerezo, G., Vanderwal, C. D., Day, B.
W., Sorensen, E. J., Lopez, J. A., Andreu, J. M., Hamel, E., Diaz, J. F.
Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding
sites. Nature Chemical Biology 2007, 3 117-125.
Hamel, E., Day, B. W., Miller, J. J.,
Jung, M. K., Northcote, P. T., Ghosh, A. K., Curran, D. P., Cushman, M.,
Nicolaou, K. C., Paterson, I., Sorensen, E. J. Synergistic effects of
peloruside and laulimalide with taxoid site drugs, but not with each other, on
tubulin assembly. Molecular Pharmacology 2006, 70,
1555-1564.
Beckner, M.E., Zhang, Z., Agostino, N.
R., Day, B. W., Pollack, I. F. Albumin marks pseudopodia of astrocytoma cells
responding to hepatocyte growth factor or serum. Laboratory Investigation 2006, 86, 1103-1114.
Kangani, C. O., Kelley, D. E., Day, B.
W. One-pot direct synthesis of oxazolines, benzoxazoles, and oxadiazoles from
carboxylic acids using the Deoxo-Fluor reagent. Tetrahedron Letters 2006, 47,
6497-6499.
Kangani, C. O., Kelley, D. E., Day, B.
W. One-pot synthesis of aldehydes or ketones from carboxylic acids via in
situ generation of
Weinreb amides using the Deoxo-Fluor reagent. Tetrahedron Letters 2006, 47,
6289-6292.
Fan, Y., Schreiber, E. M., Giorgianni,
A., Yalowich, J.
C., Day, B. W. Myeloperoxidase-catalyzed metabolism of etoposide to its
quinone and glutathione adduct forms in HL60 cells. Chemical Research in
Toxicology 2006, 19, 937-943.
Atkins, J. L., Day, B. W., Handrigan,
M. T., Zhang, Z., Pamnani, M. B., Gorbunov, N. V. Brisk production of nitric
oxide and associated formation of S-nitrosothiols in early hemorrhage. Journal of
Applied Physiology 2006, 100, 1267-1277.
Zhu, G., Yang, F., Balachandran, R.,
Hook, P., Vallee,
R. B., Curran, D. P., Day, B. W. Synthesis and biological evaluation of
purealin and analogues as cytoplasmic dynein heavy chain inhibitors. Journal
of Medicinal Chemistry 2006, 49, 2063-2076.
Gong, H., Singh, S. V., Singh, S. P.,
Mu, Y., Saini, S. P. S., Toma, D. Ren, S., Kagan,
V. E., Day, B. W. Zimniak, P., Xie, W. Orphan nuclear receptor PXR sensitizes
oxidative stress responses in transgenic mice and cancerous cells. Molecular
Endocrinology 2006, 20, 279-290.
Balasubramani, M., Day, B. W., Schoen,
R. E., Getzenberg, R. H. Altered expression and localization of creatine kinase
B, heterogenous nuclear ribonucleoprotein F and high mobility group box 1
protein in the nuclear matrix associated with colon cancer. Cancer Research, 66, 763-769.
Fukui, Y., Bruckner, A.M., Shin, Y.,
Balachandran, R., Day, B.W., Curran, D.P. Fluorous mixture synthesis of
(-)-dictyostatin and three stereoisomers. Organic Letters 2006, 301-304.
Khanday, F. A., Yamamori, T.,
Mattagajasingh, I., Zhang, Z., Bugayenko, A., Naqvi, A., Santhanam, L., Nabi, N.,
Kasuno, K., Day, B. W., Irani, K. Rac1 leads to phosphorylation-dependent
increase in stability of the p66shc adaptor protein: role in Rac1-induced
oxidative stress. Molecular Biology of the Cell 2006, 17, 122-129.
Giuliano, K. A., Cheung, W. S., Curran,
D. P., Day, B. W., Kassick, A. J., Lazo, J. S., Nelson, S. G.
Brisson, M., Nguyen, T., Wipf, P.,
Joo, B., Day, B. W., Skoko, J. S., Schreiber, E. M., Foster, C., Bansal, P.,
Lazo, J. S. Redox regulation of Cdc25B by cell active quinolinediones. Molecular
Pharmacology 2005, 68, 1810-1820.
Madiraju, C., Edler, M.C., Hamel, E.,
Raccor, B. S., Balachandran, R., Zhu, G.,Giuliano, K. A., Vogt, A., Shin, Y.,
Fournier, J.-H., Fukui, Y., Bruckner, A. M., Curran, D. P., Day, B.W. Tubulin
assembly, taxoid site binding and cellular effects of the
microtubule-stabilizing agent dictyostatin. Biochemistry 2005, 44,
15053-15063.
Nguyen, T. L., McGrath, C., Hermone, A.
R., Burnett, J. C., Zaharevitz, D. W., Day, B. W., Wipf, P., Hamel, E., Gussio,
R. A common pharmacophore for a diverse set of colchicine site inhibitors using
a structure-based approach. Journal of Medicinal Chemistry 2005, 48,
6107-6116 [correction p. 7917].
Shin, Y., Fournier, J. H.,
Balachandran, R., Madiraju, C., Raccor, B. S., Zhu, G., Edler, M. C., Hamel,
E., Day, B. W., Curran, D. P. Synthesis and biological evaluation of
(-)-16-normethyldictyostatin: a potent analog of (-)-dictyostatin. Organic Letters 2005, 7,
2873-2876.
Mu, Y., Stephenson, C. R. J., Kendall,
C., Saini, S. P. S., Toma, D., Ren, S., Cai, H., Strom, S. C., Day, B. W.,
Wipf, P., Xie, W. A pregnane X receptor agonist with unique species-dependent
stereoselectivity and its implications in drug development. Molecular
Pharmacology 2005, 68, 403-413.
Keohavong,
P., Xi, L., Day, R. D., Zhang, L., Grant, S. G., Day, B. W., Ness, R. B.,
Bigbee, W. L. HPRT
gene alterations in umbilical cord blood T-lymphocytes in newborns of mothers
exposed to tobacco smoke during pregnancy. Mutation Research 2005, 572, 156-166.
Wipf,
P., Coleman, C. M. Iyer, P. S., Fodor, M. D., Shafer, Y. A., Janjic, J. M.,
Stephenson, C. R. J., Kendall, C., Day, B. W. Microwave-assisted 'libraries
from libraries' approach toward the synthesis of allyl- and C-cyclopropylalkylamides. Journal of
Combinatorial Chemistry 2005, 7, 322-330.
Beckner,
M.E., Chen, X., An, J., Day, B.W., Pollack, I.F. Proteomic characterization of
harvested pseudopodia with differential gel electrophoresis and specific
antibodies. Laboratory Investigation 2005, 85, 316-327.
Cunningham,
S. L., Cunningham, A. R., Day, B. W. CoMFA, HQSAR and molecular docking studies
of butitaxel analogues with beta-tubulin. Journal of Molecular Modeling 2005, 11, 157-164.
Janjic,
J. M., Mu, Y., Kendall, C., Stephenson,
C. R. J., Balachandran, R., Raccor, B. S., Lu, Y., Zhu, G., Xie, W., Wipf, P.,
Day, B. W. New antiestrogens from a library screen of homoallylic amides,
allylic amides and C-cyclopropylalkylamides.
Bioorganic & Medicinal Chemistry 2005, 13, 157-164.
Fewell, S. W., Smith, C. M., Lyon, M.
A., Dumitrescu T. P., Wipf, P., Day, B. W., Brodsky, J. L. Small molecule modulators of
endogenous and co-chaperone-stimulated Hsp70 ATPase activity. Journal of
Biological Chemistry 2004, 279, 1131-1140.
Cheng, P., Kanterewicz, B., Hershberger, P. A., McCarty, K. S.,
Jr., Day, B. W., Nichols,
M. Inhibition of estrogen receptor
{alpha}-mediated transcription by antiestrogenic
1,1-dichloro-2,2,3-triarylcyclopropanes. Molecular Pharmacology 2004, 66,
972-977.
Wipf, P., Reeves, J. T., Day, B. W.
Chemistry and biology of curacin A.Current Pharmaceutical Design 2004, 10, 1417-1437.
Cunningham,
A. R., Cunningham, S. L., Day, B. W. Identification of structural components
associated with cytostatic activity in MCF-7 but not in MDA-MB231 cells. Bioorganic
& Medicinal Chemistry 2003, 11, 5249-5258.
Balachandran, R.,
Welsh, M. J., Day, B. W. Altered levels and regulation of stathmin in
paclitaxel-resistant ovarian cancer cells. Oncogene 2003, 22, 8924-8930.
Minguez, J. M., Kim,
S.-Y., Giuliano, K. G., Balachandran, R., Madiraju, C., Day, B. W., Curran, D.
P. Synthesis and biological assessment of simplified analogs of the potent
microtubule stabilizer (+)-discodermolide. Bioorganic & Medicinal
Chemistry
2003,
11,
3335-3357.
Choy, N., Shin, Y.,
Nguyen, P.-Q., Curran, D. P., Balachandran, R., Madiraju, C., Day, B. W.
Simplified discodermolide analogs: synthesis and biological evaluation of
4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as
microtubule-stabilizing agents. Journal of Medicinal Chemistry 2003, 46, 2846-2864.
Minguez, J. M.,
Giuliano, K. A., Balachandran, R., Curran, D. P., Day, B. W. Synthesis and high
content cell-based profiling of simplified analogues of the microtubule
stabilizer (+)-discodermolide. Molecular Cancer Therapeutics 2002, 1, 1305-1313.
Shin, Y., Choy, N.,
Turner, T. R., Balachandran, R., Madiraju, C., Day, B. W., Curran, D. P.
Discodermolide/Dictyostatin hybrids: synthesis and biological evaluation. Organic
Letters 2002, 4, 4443-4446.
Vogt, A., Pestell, K.
E., Day, B. W., Lazo, J. S., Wipf, P. The antisignaling agent
SC-{alpha,alpha,delta}9,
4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl)-2-decanoylaminobutyric
acid, is a structurally unique phospholipid analogue with Phospholipase C inhibitory
activity. Molecular Cancer Therapeutics 2002, 1, 885-892.
Day, B. W., Kangani,
C. O., Avor, K. S. Convenient syntheses of (2R,3S,4R)-3-(tert-butyldimethylsilanyloxy)-2,4-dimethyl-5-oxopentanoic
acid methoxymethylamide from methacrolein. Preparation of C1-C7 and C17-C24
fragments of (+)-discodermolide. Tetrahedron: Asymmetry 2002, 13, 1161-1165.
Wipf, P., Reeves, J.
T., Balachandran, R., Day, B. W. Synthesis and biological evaluation of
structurally highly modified analogues of the antimitotic natural product
curacin A. Journal of Medicinal Chemistry 2002, 45, 1901-1917.
Razzaghi, H., Day, B.
W., McClure, R. J., Kamboh, M. I. Structure-function analysis of D9N and N291S
mutations in human lipoprotein lipase using molecular modeling. Journal of
Molecular Graphics and Modeling 2001, 19, 487-494.
Hasinoff, B. B.,
Chee, G.-L., Day, B. W., Avor, K. S., Barnabe', N., Thampatty, P., Yalowich, J.
C. Synthesis and biological evaluation of a photoaffinity etoposide probe. Bioorganic
& Medicinal Chemistry 2001, 9, 1765-1771.
Fewell, S. W., Day,
B. W., Brodsky, J. L. Identification of an inhibitor of hsc70-mediated protein
translocation and ATP hydrolysis. Journal of Biological Chemistry 2001, 276, 910-914.
Zayas-Rivera, B.,
Zhang, L., Grant, S. G., Keohavong, P., Day, B. W. Mutational spectrum of N-hydroxy-N-acetyl-4-aminobiphenyl at exon 3
of the HPRT
gene. Biomarkers 2001, 6, 262-273.
Kozusko, F., Chen,
P.-H., Grant, S. G., Day, B. W., Panetta, J. C. A mathematical model of in vitro
cancer cell growth and treatment with the antimitotic agent curacin A. Mathematical
Biosciences
2001,
170,
1-16.
Lazo, J. S., Tamura,
K., Vogt, A., Jung, J. K., Rodriguez, S., Balachandran, R., Day, B. W., Wipf,
P. Antimitotic actions of a novel analog of the fungal metabolite palmarumycin
CP1. Journal of Pharmacology and Experimental Therapeutics 2001, 296, 364-371.
Balachandran, R.,
Grant, S. G., Welsh, M. J., Day, B. W. Z-1,1-Dichloro-2,3-diphenylcyclopropanes
block human prostate carcinoma cell proliferation, inhibit prostate-specific
antigen expression, and initiate apoptosis. Prostate 2000, 45, 277-288.
Wipf, P., Reeves, J.
T., Balachandran, R., Giuliano, K. A., Hamel, E., Day, B. W. Synthesis and
biological evaluation of a focused mixture library of analogs of the potent
antimitotic marine natural product curacin A. Journal of the American
Chemical Society 2000, 122, 9391-9395.
Day, B. W. Mutants
yield a pharmacophore model for the tubulin paclitaxel site. Trends in
Pharmacological Sciences 2000, 21, 321-323.
Goldman, R., Day, B.
W., Carver, T. A., Mauthe, R. J., Turtletaub, K. W., Shields, P. G.
Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic
anhydride and accelerator mass spectrometry. Chemico-Biological Interactions 2000, 126, 171-183.
Gorbunov, N. V.,
Pogue-Geile, K. L., Epperly, M. W., Bigbee, W. L., Draviam, R., Day, B. W.,
Wald, N., Watkins, S. L., Greenberger, J. S. Activation of the nitric oxide
synthase 2 pathway in the response of bone marrow stromal cells to high doses
of ionizing radiation. Radiation Research 2000, 154, 73-86.
Research and Core
Lab Personnel
Research
Associates/Staff Scientists/Research Professors:
Jielu Zhao, Ph.D., synthetic chemistry
Prema Iyer, Ph.D., synthetic chemistry
Lee McDermott,
Ph.D., synthetic chemistry
Emanuel M. Schreiber,
Ph.D., proteomics
Manimalha
Balasubramani, Ph.D., manager of the proteomics core lab
Guy Uechi, Ph.D.,
proteomics
Yuchen Lu, Ph.D. proteomics
Technical
Specialists:
John Cardamone, M.S.,
proteomics
Ph.D. Students:
Wanli Pu (working
on synthesis of microtubule stabilizers)
Dan Brody (working on synthesis of microtubule stabilizers) Honors: 2010 American Chemical Society Medicinal Chemistry Predoctoral Fellow
Amy Grote (working
on synthesis of microtubule stabilizers)
Sara Smith (working
on metabolism of microtubule stabilizers)
Tim Pouland (working on small molecule perturbogens of cytoplasmic dynein)
Undergraduates:
Katherine Adams (synthetic chem)
James Burrows (biochem)
Kerry Moore (synthetic chem)
Nathan Pancoast (biochem)
Amanda Gavin
(synthetic chem)
Matthew Dello Buono (proteomics)
Former Graduate Students:
Hikmat N. Daghestani, Ph.D., Structural Biol. - graduated 2010
Present Position: Postdoctoral Fellow, University of Michigan
Dissertation: Biophysical and pharmacological characterization of cytoplasmic dynein heavy
chain 1
Miranda J. Sarachine, Ph.D., Mol. Pharmacol. - graduated 2009
Present Position: Postdoctoral Fellow, Lawrence Livermore National Lab
Dissertation: Roles of the estrogen receptors and the nuclear matrix in breast cancer development and tamoxifen resistance
Yumin Song, M.S., Pharm. Sci. - graduated 2009
Thesis: Proteomic changes induced by knockdown of stathmin in BT549 breast cancer cell lines
Brianne Raccor,
Ph.D., Chemistry - graduated 2008
Present Position: Postdoctoral Fellow, School of Pharmacy, University of
Washington
Dissertation: Mechanisms
and kinetics of microtubule perturbing agents
Guangyu Zhu, Ph.D.,
Chemistry - graduated 2007
Present Position: Postdoctoral Fellow, Dept. Chemistry, Massachusetts
Institute of Technology
Dissertation: Cell-based
and biochemical screens for small-molecule inhibitors of dynein and HSP70
Zhe (Jenny) Zhang,
Ph.D., Pharm. Sci. - graduated 2007
Present Position: Postdoctoral Fellow, Dept. Biochemistry, Univ.
Missouri-Columbia
Dissertation: Targeted
functional proteomics to study protein post-translational modification and
protein-protein interactions
Yun Fan, Ph.D.,
Pharm. Sci. - graduated 2007
Present Position: Postodoctoral Fellow, Georgetown Univ.
Dissertation: In vitro
metabolism of three anticancer agents
Jelena Janjic, Ph.D., Pharm. Sci. - graduated
2005
Present Position: Assistant Professor, Department of Pharmaceutical Sciences, Duquesne University (formerly,
Postdoctoral Fellow, The Scripps Research Institute, then Research Biologist, Carnegie Mellon University)
Dissertation: Design, synthesis and biological evaluation of new agents
targeting estrogen receptor-alpha and -beta
Charitha Madiraju, Ph.D., Pharm. Sci. - graduated
2005
Present Position: Postdoctoral Fellow, Burnham Institute (formerly,
Postdoctoral Fellow, Ordway Research Institute)
Thesis: Pharmacological and structure-activity relationship
evaluation of microtubule stabilizing agents
Ying Lu, M.S., Chemistry –
graduated 2005
Present Position: Staff Scientist, Rangos Research Center, Childrens
Hospital of Pittsburgh, Pittsburgh, PA
Dissertation: Bioanalytical chemistry of microtubule stabilizers
Catherine A. Thomas, Ph.D., Environ. Occup. Health -
graduated 2004
Present Position: Staff Scientist, Dept. Immunology and Center for Vaccine
Research, University of Pittsburgh (formerly, Postdoctoral
Fellow, Dept. Urology, University of Pittsburgh)
Dissertation: Multiple screening techniques: a way to develop
chemical-animal models
Susana Felix-Delano,
Ph.D., Environ. Occup. Health - graduated 2002
Present Position: Staff Scientist, Los Alamos National Laboratory
Dissertation: High resolution genotyping of Clostridium
botulinum strains using amplified fragment linked polymorphism (AFLP)
analysis
Pao-Hsiu (Tracy)
Chen, Ph.D., Environ. Occup. Health - graduated 2001
Present Position: Program
Analyst, Anticonvulsant Screening Program, Technology Development Cluster, NIH/NINDS (formerly, Research
Associate, Department of Surgery, University of Pittsburgh, then Manager and
Scientist, Toxicogenomics, Gene Logic, Inc.)
Dissertation: Mechanisms of curacin A-induced cell toxicity
Beatriz Zayas-Rivera,
Ph.D., Environ. Occup. Health - graduated 1998
Present
Position: Associate Professor, Universidad Metropolitana, San Juan, Puerto
Rico (formerly, Postdoctoral Fellow, Dept. Obstetrics and Gynecology,
Magee-Womens Research Institute, then Postdoctoral Fellow, Division of
Bioengineering and Environmental Health, MIT)
Dissertation: Elucidation of cellular and mutational effects of
4-aminobiphenyl and metabolites
Judy Facey, M.S.,
Environ. Occup. Health - graduated 1998
Present Position: Scientist, U.S. EPA
Thesis: Profiles of tamoxifen metabolite adduction at exon 3 of the HPRT
gene
Bryon Petersen,
Ph.D., Environ. Occup. Health (joint supervision with G. Michalopoulos) -
graduated 1996
Present Position:
Associate Professor, Dept. Pathology, Immunology & Laboratory Medicine,
Univ. Florida (formerly Res. Asst. Prof., Dept. Radiation Oncology, Univ.
Pittsburgh)
Dissertation: Hepatic stem cells and growth factor regulation in
regenerating liver following toxin injury
Ernst ter Haar, Ph.D.
Environ. Occup. Health - graduated 1995
Present position: Research
Fellow I, Vertex
Pharmaceuticals, Cambridge, MA (formerly: Postdoctoral Fellow, Dept. Cell
Biology, Harvard Medical School)
Dissertation: Computational and biochemical analysis of three novel
anti-cancer drugs: Z-1,1-dichloro-2,3-diphenylcyclopropane, Z-chlorochalcone
and (+)-discodermolide
Donna L. Wilson, M.S.
Environ. Occup. Health - graduated 1993
Present position: Ph.D. student, Dept. Environmental and Occupational
Health, Univ. Pittsburgh
Thesis: Studies to characterize the binding site(s) of toluene
diisocyanate with human serum albumin
Charles F. Brehm,
M.S. Environ. Occup. Health - graduated 1993
Present position: Safety Manager, Michael Baker Jr, Inc.
Thesis: A proposed method to assess worker exposure to creosote: passive
dermal dosimetry and biological monitoring
Lisa K. Ryan, Ph.D.
Environ. Occup. Health - graduated 1992
Present
position: Assistant Professor, Dept. Oral Biology, UMDNJ (formerly,
Postdoctoral Fellow, Pulmonary Division, Harvard Medical School, then Senior
Scientist and ORD Regional Scientist (Region II) for the Environmental
Protection Agency)
Dissertation: The role of endotoxin and tumor necrosis factor in acute
pulmonary inflammation to inhaled cotton dust
Former Postdocs and Staff:
Sastry S.
Jonnalagadda, Ph.D. (1994-1995), synthetic chemistry
Present Position: unknown
Clara E. Mota-Nelson,
Ph.D. (1996-1997), synthetic chemistry
Present Position: Senior Scientist, PPG Industries, Inc.
Kwasi S. Avor, Ph.D.
(1998-2000), synthetic chemistry
Unfortunately, we lost this good friend and scientist when he passed away in
2004; he was at that time Senior Scientist at TransTech Pharmaceuticals,
Inc.
Cyrous O. Kangani,
Ph.D. (2000-2002), synthetic chemistry
Present Position: AstaTech, Inc.
Elisa Bellei, Ph.D.
(2004-2005), proteomics
Present Position: Dipartimento di Scienze Biomediche, Facolti di
Medicina e Chirurgia, Universiti di Modena e Reggio Emilia, Modena, Italy
Soumitra Basu,
Ph.D. (2004-2005), proteomics (core lab manager)
Present Position: Assistant Professor, Department of Chemistry, Kent
State University
Ashraf Elamin, Ph.D.
(2004-2006), proteomics
Present Position: Dept. Chemistry and Biochemistry, California State
University Long Beach
Weixiang Dai, Ph.D.
(2006-2007), synthetic chemistry
Present Position: Mylan Pharmaceuticals, Inc.
Tamanna Sultana, Ph.D.
(2005-2008), proteomics
Present Position: Bioinformatics Analysis Core, University of
Pittsburgh
Vasiliy Korotchenko, Ph.D. (2008-2010), synthetic chemistry
Present Position: Staff Chemist, Walter Reed Army Institute of Research