Office: NMR
(409) 747-6801
Office: SOM
(409) 747-6801
Adm. Assist:
(409) 747-6800
Fax:
(409) 747-6850
Route: 1157
Mailing Address:
301 University Blvd.
Galveston, Texas
77555-1157
Location:
Room 2.114B
Dockside Bldg.
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Dr. David G. Gorenstein
O
ur work may be roughly divided into three main areas of structural biology research: (1) development and applications of NMR spectroscopy to
biological systems, (2) proteomics, and (3) drug design. We have been interested in the development of NMR spectroscopy to probe the detailed chemical structure and dynamics of biological molecules. Multinuclear NMR of enzyme complexes, nucleic acids, nucleic acid-drug complexes, and nucleic acid-protein complexes is being pursued.
Triple resonance, multidimensional NMR is carried out on a number of proteins and oligonucleotides such as our recently developed "thioaptamers". We are also using NMR to define the structure and dynamics of other proteins such as the domain 3 envelope protein of flaviviruses such as West Nile and dengue viruses.
We also have a major program oriented toward the combinatorial selection, rational design, synthesis and structural characterization of oligonucleotide analogues (especially monothiophosphate dithiophosphate analogues selected from large combinatorial libraries - "thioaptamers") and other agents directed toward viruses targeted for countermeasures to bioterrorism (this includes siRNA and thioaptamer oligonucleotides).
We have also spun-out several companies AptaMed, Inc. and AM Biotechnologies in Galveston, Texas that have licensed proprietary thioselection and phosphorothioate-modified oligonucleotide thioaptamer technology from UTMB originally developed in our laboratory. These efforts have been extensively expanded by DARPA, DHS and NIAID funding and are focused on the phosphoromonothioate and phosphorodithioate oligonucleotide thioaptamers targeting a wide range of biomolecules. Several of the thioaptamers are currently in pre-clinical development as therepeutics for infectious diseases such as West Nile virus and arenavirus hemorrhagic fevers. Our laboratory has also developed proprietary technology for high-throughput screening of bead-based combinatorial libraries of thioaptamers. This technology is being used with Sandia microfluidics chip technology to develop new POC proteomic diagnostics.
Sincerely,
David G. Gorenstein, Ph.D.
Charles Marc Pomerat Distinguished Professor of Biological Sciences
Associate Dean of Research, School of Medicine
dggorens@utmb.edu
Dr. David Gorenstein's Recent Publications (1998-2008)
2008
NMR Assignments of the Sylvatic Dengue 1 Virus Envelope Protein Domain III.
D. E. Volk, K. M. Anderson, S. H. A. Gandham, F. J. May, L. Li, David W. C. Beasley, A. D. T. Barrett and D. G. Gorenstein
Biomol. NMR Assigments, E-pub ahead of print (NIHMSID: NIHMS63470)
Bead-based Approaches to Develop Thioaptamers for Diagnostics and Therapeutics.
X. Yang, D. Beasley, J. Engelhardt, M. Shumbera, B. A. Luxon and D. G. Gorenstein
Phosphorus, Sulfur, and Silicon and the Related Elements 183(2):469-472, 2008.
Combinatorial selection of a single stranded DNA thioaptamer targeting TGF-beta-1 protein.
J. Kang, M. S. Lee, J. A. Copland, B. A. Luxon and D. G. Gorenstein
Bioorg. Med. Chem. Lett. 18(6):1835-1839, 2008.
Base-pairing Properties of the Oxidized Cytosine Derivative, 5-Hydroxy Uracil.
V. Thiviyanathan, A. Somasunderam, D. E. Volk, T.K. Hazra, S. Mitra and D. G. Gorenstein
Biochem. Biophys. Res. Commun. 366:752-757, 2008.
2007
Magnesium ion is an effective inhibitor of Escherichia coli to heparin.
J. Kang, M. S. Lee D. G. Gorenstein,
J. Microbiol. Methods 71(3):340-342, 2007.
Combinatorial Selection of a RNA Thioaptamer that binds to Venezuelan Equine Encephalitis Virus Capsid Protein.
J. Kang, M. S. Lee, S. J. Watowich and D. G. Gorenstein,
FEBS Lett. 581(13):2497-2502, 2007.
Ab initio base-pairing energies of an oxidized thymine product, 5-formyluracil,
with standard DNA bases at the BSSE-free DFT and MP2 theory levels.
D. E. Volk, V. Thiviyanathan, A. Somasunderam and D. G. Gorenstein,
Org. Biomol. Chem. 2007, 5(10), 1554-1558.
Application of RNase in the purification of RNA-binding proteins.
J. Kang, M. S. Lee and D. G. Gorenstein,
Anal. Biochem. 365(1):147-148, 2007.
(PMCID: PMC1933585)
NMR Assignments of the Yellow Fever Virus Envelope Protein Domain III
D. E. Volk, S. A. Gandham, F. J. May, A. Anderson, A. D. T. Barrett and D. G. Gorenstein.
Biomolecular NMR Assignments 1(1):49-50, 2007.
Structure of the Envelope Protein Domain III of Dengue-4 Virus
D. E. Volk, Y.-C. Lee, X. Li, V. Thiviyanathan, G. D. Gromowski, L. Li, A. Lamb, D. W. Beasley, A. D. T. Barrett and D. G. Gorenstein,
Virology 2007, 364(1), 147-154.
(PMCID: PMC1950219)
Thioaptamer Decoy Targeting AP-1 Proteins Influences
Cytokine Expression and the Outcome of Arenavirus Infections.
S. M. Fennewald, E. P. Scott, L. H. Zhang, J. F. Aronson, D. G. Gorenstein,
B. A. Luxon, R. E. Shope, D. W. C. Beasley and N. K. Herzog.
J. Gen. Virol. 2007, 88:981-990.
Combinatorial selection and delivery of thioaptamers.
V. Thiviyanathan, A. D. Somasunderam and D. G. Gorenstein
Biochem. Soc. Trans. 2007, 35:50-52.
Characterization of heparin-living bacteria interactions by chemiluminescence electrophoretic mobility shift assay.
J. Kang, M. S. Lee and D. G. Gorenstein
Anal. Biochem. 2007, 363(2):312-314.
(PMCID: PMC1987369)
Identification of Differentially Activated Cell-Signaling Networks
Associated with Pichinde Virus Pathogenesis Using Systems Kinomics.
G. C. Bowick, S. M. Fennewald, E. P. Scott, L. H. Zhang, B. L. Elsom,
J. F. Aronson, H. M. Spratt, B. A. Luxon, D. G. Gorenstein and N. K. Herzog.
Journal of Virology 2007, 81(4):1923-1933.
(PMCID: PMC1797588)
2006
Differential Signaling Networks Induced by Mild and Lethal
Hemorrhagic Fever Virus Infections.
G. C. Bowick, S. M. Fennewald, E. P. Scott, L. H. Zhang, B. L. Elsom,
J. F. Aronson, H. M. Spratt, B. A. Luxon, D. G. Gorenstein and N. K. Herzog.
Journal of Virology 2006, 80(20):10248-10252.
(PMCID: PMC1617297)
NMR Assignment of the Dengue 4 Virus Envelope Protein Domain III
D. E. Volk, Y.-C. Lee, X. Li, A. D. T. Barrett and D. G. Gorenstein,
Journal of Biomolecular NMR 2006, 36(suppl. 5):62.
Selection of Thioaptamers for Diagnostics and Therapeutics
X. Yang, H. Wang, D.W.C. Beasley, D. E. Volk, X. Zhao, B. A. Luxon,
L. O. Lomas, N. Herzog, J. F. Aronson, A.D.T. Barrett, J. F. Leary and D. G. Gorenstein
Annal. N. Y. Acad. Sci. 2006, 1082:116-119.
Ab Initio Base-pairing Energies of Uracil and 5-Hydroxy-Uracil with Standard DNA Bases at the BSSE-free DFT and MP2
Theory Levels
D. E. Volk, V. Thiviyanathan, A. Somasunderam and D. G. Gorenstein
Organic and Biomolecular Chemistry 2006, 4(9), 1741-1745.
Delivery of double-stranded DNA thioaptamers into HIV-1 infected cells for antiviral activity
M. R. Ferguson, D. R. Rojo, A. Somasunderam, V. Thiviyanathan, B. Ridley, X. Yang and D.G. Gorenstein
Biochem. Biophys. Res. Commun. 2006, 344(3), 792-797.
Identification of proteins bound to a thioaptamer probe on a proteomics array.
H. Wang, X. Yang, G. C. Bowick, N. K. Herzog, L. O. Lomas, B. A. Luxon and D. G. Gorenstein
Biochem. Biophys. Res. Commun. 2006 , 347(3), 586-593.
Structure of the Envelope Protein Domain III of Omsk Hemorrhagic Fever Virus.
D. E. Volk, L. Chavez, D. W. C. Beasley, A. D. T. Barrett, M. R. Holbrook and D. G. Gorenstein
Virology 2006, 351(1), 188-195.
Chemiluminescence-based electrophoretic mobility shift assay of
heparin-protein interactions.
J. Kang, M. S. Lee and D.G. Gorenstein
Analytical Biochemistry 2006 , 349(1), 156-158.
Chemiluminescence-based electrophoretic mobility shift assay of RNA-protein interactions:
Application to binding of viral capsid proteins to RNA.
J. Kang, M. S. Lee, S. J. Watowich and D.G. Gorenstein
Journal of Virological Methods 2006, 131(2), 155-159.
2005
Quantitative analysis of chemiluminescence signals using a
cooled charge-coupled device camera.
J. Kang, M. S. Lee and D.G. Gorenstein
Analytical Biochemistry 2005, 345(1), 66-71.
The enhancement of PCR amplification of
a random sequence DNA library
by DMSO and betaine: application to in vitro combinatorial selection of aptamers.
J. Kang, M. S. Lee and D.G. Gorenstein
Journal of Biochemical and Biophysical Methods 2005, 64(2), 147-151.
The effects of thiophosphate substitutions on native siRNA gene silencing.
Xheng-Yin Li, Haibo Mao, Deborah A. Kallick and David G. Gorenstein
Biochem. Biophys. Res. Commun. 2005 , 329(3), 1026-1030.
Combinatorial Selection, Inhibition and Antiviral Activity of DNA
Thioaptamers Targeting the RNase H Domain of HIV-1 Reverse Transcriptase.
A. Somasunderam, M. R. Ferguson, D. R. Rojo, V. Thiviyanathan, X. Li, W. A. O'Brien and D.G. Gorenstein
Biochemistry 2005 , 44(30), 10388-10395.
5-Hydroxy Uracil Can Form Stable Base Pairs With all
Four Bases in a DNA Duplex.
V. Thiviyanathan, A. Somasunderam, D.E. Volk, and D.G. Gorenstein
Chemical Communications. 2005(3) 400-402.
2004
TATA-Box Binding Protein Induces Structure in the
Recombinant Glucocorticoid Receptor AF1 Domain.
R. Kumar, D.E. Volk, J. Li, J.C. Lee, D.G. Gorenstein and E.B. Thompson
Proc. Nat. Acad. Sci. U.S.A. 2004, 101, 16425-16430.
(PMCID: PMC534534)
Progress in Thioaptamer Development
Xianbin Yang and David G. Gorenstein
Current Drug Targets 2004, 5, 705-715.
High-resolution structure of a picornaviral internal cis-acting RNA replication element (cre).
V. Thiviyanathan, Y. Yang, K. Kaluarachchi, R. Rijnbrand, D.G. Gorenstein and S. M. Lemon
Proc. Nat. Acad. Sci. U.S.A. 2004, 101, 12688-12693.
(PMCID: PMC515117)
Mutational and Structural Analysis of Stem-Loop IIIc of the Hepatitis C Virus and GB Virus B Internal Ribosome Entry Sites.
R. Rijnbrand, V. Thiviyanathan, K. Kaluarachchi, S. M. Lemon and D.G. Gorenstein
J. Mol. Biol. 2004, 343, 805-817.
Combinatorial Selection and Edited Combinatorial
Selection of Phosphorothioate Aptamers Targeting
Human Nuclear Factor-kappaB RelA/p50 and RelA/RelA.
S.E. Bassett, S. M. Fennewald, D. J. King, X. Li, N. K. Herzog, R. Shope, J. F. Aronson,
B. A. Luxon and D.G. Gorenstein
Biochemistry 2004, 43(28), 9105-9115.
Solution structure and antibody binding studies of the envelope protein domain III from the New York strain of West Nile virus.
D.E. Volk, D. W. C. Beasley, D. A. Kallick, M.R. Holbrook, A.D.T. Barrett and D. G. Gorenstein
J. Biol. Chem. 2004, 279, 38755-38761.
1H, 13C, and 15N resonance assignments
for domain III of the West Nile Virus envelope protein.
D.E. Volk, D. A. Kallick, M.R. Holbrook, D.W.C. Beasley, A.D.T. Barrett and D.G. Gorenstein
J. Biomol. NMR 2004, 29, 445-446.
NMR Structure of the Apo-S100P protein.
Y.-C. Lee, D.E. Volk, V. Thiviyanathan, Q. Kleerekoper, A.X. Gribenko, S. Zhang
D.G. Gorenstein, G. I. Makhatadze and B. A. Luxon.
J. Biomol. NMR 2004, 29, 399-402.
2003
Solution Structure of a Cis-Opened (10R)-N6-
Deoxyadenosine Adduct of
(9S,10R)-9,10-Epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene
in a DNA Duplex
D.E. Volk, V. Thiviyanathan, J.S. Rice, B.A. Luxon, J.H. Shah, H. Yagi, J.M. Sayer, D.M. Jerina, and D.G. Gorenstein
Biochemistry 2003, 42, 1410-1420.
Initiation of Repair of A:G Mismatches is
Modulated by Sequence Context
A.M. Sanchez, D.E. Volk, D.G. Gorenstein, and R.S. Lloyd
DNA Repair 2003, 2(8), 863-878.
Solution Structure, Dynamics and Thermodynamics of the
Native
State Ensemble of the Sem-5 C-terminal SH3 Domain
J.C. Ferreon, D.E. Volk, B.A. Luxon, D.G. Gorenstein and V.J. Hilser,
Biochemistry 2003, 42, 5582-5591.
Discrimination of components in atherosclerotic plaques from human carotid
endarterectomy specimens by magnetic resonance imaging ex vivo
J. Morrisett, W. Vick, R. Sharma, G. Lawrie, M. Reardon, E. Ezell,
J. Schwartz, G. Hunter, and D. Gorenstein
Magnetic Resonance Imaging 2003, 21, 465-474.
Immunofluorescence assay and
flow-cytometry selection of bead-bound aptamers
X. Yang, X. Li, T.W. Prow, L.M. Reece, S.E. Bassett, B.A. Luxon, N.K. Herzog,
J. Aronson, R.E. Shope, J.F. Leary and D.G. Gorenstein,
Nucleic Acids Research 2003 31, e54.
(PMCID: PMC156057)
Solution Structure of a DNA Duplex Containing 8-Hydroxy- 2'-Deoxyguanosine
Opposite Deoxyguanosine
V. Thiviyanathan, A. Somasunderam, T.K. Hazra, S. Mitra and D.G. Gorenstein,
Journal of Molecular Biology 2003, 325, 433-442.
2002
Design of Bloch-Siegert phase-shift self-compensated
pulses for HCN triple-resonance experiments
S. Zhang and D.G. Gorenstein,
Chemical Physics Letters 2002 362, 278-284.
Coherence Excitation with Phase-Incremented Pulses
in Nuclear Magnetic Resonance
S. Zhang and D.G. Gorenstein,
Journal of Magnetic Resonance 2002 154, 73-79.
Combinatorial Selection and Binding of Phosphorothioate
Aptamers Targeting Human NF-kB RelA(p65) and p50
D.J. King S.E. Bassett, X. Li, S.A. Fennewald, N.K. Herzog, B.A. Luxon, R.E. Shope and D.G. Gorenstein,
Biochemistry 2002 41, 9696-9706.
Construction and selection of bead-bound combinatorial
oligonucleoside phosphorothioate
and phosphorodithioate
aptamer libraries designed for rapid PCR-based sequencing
X. Yang S.E. Bassett, X. Li, B.A. Luxon, N.K. Herzog, R.E. Shope, J. Aronson, T.W. Prow,
J.F. Leary, R. Kirby, A.D. Ellington and D.G. Gorenstein,
Nucleic Acids Research 2002 30, e132.
(PMCID: PMC137987)
Structure of Hybrid Backbone Methylphosphonate DNA Heteroduplexes:
Effect of R and S Stereochemistry
V. Thiviyanathan, K.V. Vyazovkina, E.K. Gozansky, E Bichenchova,
T.V. Abramova, B.A. Luxon, A.V. Lebedev and D.G. Gorenstein,
Biochemistry 2002, 41, 827-838.
Suppression of Linearly Responsive Residual Water, an invited review
S. Zhang and D.G. Gorenstein,
Concepts in Magnetic Resonance 2002 14, 102-111.
Separation of Synthetic Oligonucleotide Dithioates
from Monothiophosphate Impurities by Anion-Exchange
Chromatography on a Mono-Q Column
X. Yang, R.P. Hodge, B.A. Luxon, R. Shope, and D.G. Gorenstein,
Analytical Biochemistry 2002 306, 92-99.
Solution structure and design of dithiophosphate backbone
aptamers targeting transcription factor NF-kappa B
D.E. Volk, X. Yang, S.M. Fennewald, D.J. King, S. Bassett,
S. Venkitachalam, N. Herzog, B.A. Luxon, and D.G. Gorenstein,
Bioorganic Chemistry 2002, 30, 396-419.
An ab initio study of phosphorothioate and phosphorodithioate interactions with sodium cation.
D.E. Volk, T.D. Power, D.G. Gorenstein and B.A. Luxon,
Tetrahedron Letters 2002, 43, 4443-4447.
2001
Potential Double-Flipping Mechanism by E. coli MutY.
P.G. House, D.E. Volk, V. Thiviyanathan, R.C. Manual, B.A. Luxon, D.G. Gorenstein, and R.S. Lloyd,
Progress in Nucleic Acid Research and Molecular Biology, 2001, 68, 349-364.
Cholera toxin-induced PGE2 activity is reduced by chemical reaction with L-histidine.
J.W. Peterson, D. King, E.L. Ezell, M. Rogers, D. Gessell, J. Hoffpauer, L. Reuss, A.K. Chopra and D. Gorenstein,
Biochimica et Biophysica Acta (BBA)- Molecular Basis of Disease 2001 1537, 27-41.
2000
NMR Evidence for Syn-Anti Interconversion of a Trans Opened (10R)-dA
Adduct of Benzo[a]pyrene (7S,8R)-Diol (9R,10S)-Epoxide in a DNA Duplex.
D.E. Volk, J.S. Rice, B.A. Luxon, H.J.C. Yeh, C. Liang, G. Xie, J.M. Sayer, D.M. Jerina, and D.G. Gorenstein,
Biochemistry 2000, 39, 14040-14053.
Structural Similarities between MutT and the C-Terminal Domain of MutY.
D.E. Volk, P.G. House,V. Thiviyanathan, B.A. Luxon, S. Zhang, R.S. Lloyd and D.G. Gorenstein,
Biochemistry (Accelerated Publication) 2000, 39, 7331-7336.
Solution Conformation of a Bulged Adenosine Base in an RNA Duplex by Relaxation Matrix Refinement
V. Thiviyanathan, A.B. Guliaev, N.B. Leontis and D.G. Gorenstein,
Journal of Molecular Biology : 2000, 300, 1143-1156
Enhanced Suppression of Residual Water in a "270" WET Sequence
S. Zhang, X. Yang and D.G. Gorenstein,
Journal of Magnetic Resonance : 2000, 143, 382-386
Adiabatic Decoupling Sidebands
S. Zhang and D.G. Gorenstein,
Journal of Magnetic Resonance : 2000, 144, 316-321
Synchronized Adiabatic Decoupling
S. Zhang and D.G. Gorenstein,
Journal of Magnetic Resonance : 2000, 147, 110-115
Solution Structure and Local Conformational Dynamics of Lac Operators by 2D NMR
K. Kaluarachchi, D.G. Gorenstein and B.A. Luxon,
Journal of Biomolecular Structure Dynamics : 2000, 11, 123-134
Absence of perilipin results in leanness
and reverses obesity in Lepr^(db/db) mice.
J. Martinez-Botas, J.B. Anderson, D. Tessier, A. Lapillonne,
B. H-J. Change, M.J. Quast, D.G. Gorenstein, K-H. Chen and L. Chan,
Nature Genetics 2000, 26, 474-479.
D.G. Gorenstein and B.A. Luxon, "31P NMR", in
Encyclopedia of Spectroscopy and Spectrometry ,
Eds., J. Lindon, G. Tanter and J. Holmes, pp 1735-1744, Acdemic Press (2000)
1999
1H, 13C, and 15N resonance assignments of the C-terminal
domain of MutY: An Adenine glycosylase active on G:A mismatches.
D.E. Volk, V. Thiviyanathan, P.G. House, R.S. Lloyd and D.G. Gorenstein,
J. Biomol. NMR: 1999, 14, 385-386
E. Gozanski, V. Thiviyanathan, B.A. Luxon and D.G. Gorenstein,
"Hybrid-Hybrid Matrix Method for 3D NOESY-NOESY Data Refinements", in
Modern Techniques in Protein NMR ,
N. Rama Krishna and L.J. Berliner, Eds., Plenum Press, Vol. 17, 163-199 (1999)
Multiple effective fields created by a periodic
irradiation of radiofrequency field in NMR.
S. Zhang and D.G. Gorenstein,
Chemical Physics Letters : 1999, 303, 587-592
"Best" Homonuclear Adiabatic Decoupling for 13C and
15N Double-Labeled Proteins
S. Zhang and D.G. Gorenstein,
Journal of Magnetic Resonance : 1999, 138, 281-287
Automated 2D NOESY Assignment and Structure Calculation
of Crambin(S22/I25) with
the Self-Correcting Distance Geometry Based NOAH/DIAMOD Programs
Y. Xu, J. Wu, D.G. Gorenstein and W. Braun,
Journal of Magnetic Resonance : 1999, 136, 76-85
Aptamers containing thymidine 3'-O-phosphorodithioates: Synthesis and Binding to Nuclear Factor-kB
X. Yang, S. Fennewald, B.A. Luxon, J. Aronson, N. Herzog and D.G. Gorenstein,
Bioorganic and Medicinal Chemistry Letters: 1999, 9, 3357-3362
Measurement of 3JH3'-P with Watergate
X. Yang, S. Zhang, B.A. Luxon, and D.G. Gorenstein,
NMR Newsletter: 1999, 495, 25-27
1998
Novel Combinatorial Selection of Phosphorothioate Oligonucleotide Aptamers
D.J. King, D.A. Ventura, A.R. Brasier and D.G. Gorenstein,
Biochemistry : 1998, 37, 16489-16493
Bloch-Siegert Shift Compensated and Cyclic Irradiation Sidebands Eliminated,
Double-Adiabatic
Homonuclear Decoupling for13C- and15N-Double-Labeled Proteins
S. Zhang and D.G. Gorenstein,
Journal of Magnetic Resonance : 1998, 132, 81-87
V. Thiviyanathan, N. Illangasekara, E. Gozanski, F. Zhu, N.B. Leontis, B.A. Luxon and D.G. Gorenstein,
"P-31 NOESY-NOESY Hybrid-Hybrid Matrix Refinement of a DNA Three-Way Junction",
American Chemical Society Symposium on Computational Biology, Series 682, in
Molecular Modeling of Nucleic Acids
(N.B. Leontis and J. SantaLucia, Jr., Eds., Chapter 10, pp 167-180 (1998)
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