Education

B.S.E-Biomedical Engineering	1981 - 1985	University of Iowa, USA
Ph. D-Biochemistry	1986 - 1992	University of Iowa, USA

Biography

Dr. Gloria Borgstahl is from Dubuque, Iowa and graduated from Hempstead High School in 1981.  She then went all the way to Iowa City for her degree in Biomedical Engineering in 1985 and Ph.D. in Biochemistry in 1992.  During graduate school she learned protein X-ray crystallography with Dr. Arthur Arnone and was one of the first recipients of the NIH BioCATs doctoral fellowship.  She moved to the San Diego area to learn time-resolved crystallography and other structural biology methods during a postdoctoral fellowship at The Scripps Research Institute.  After a brief postdoctoral fellowship at Los Alamos National Laboratory she became an Assistant Professor of Chemistry at the University of Toledo.  She developed an independent research program involving protein crystal quality, defense mechanisms against reactive oxygen species and in double-strand break repair.  In 2002 she was happily recruited to Omaha, Nebraska where she continues these research programs at the Eppley Institute for Research in Cancer and Allied Diseases on the campus of the University of Nebraska Medical Center.  She is also a courtesy faculty member in the Department of Biochemistry and Molecular Biology and the Department of Pharmaceutical Sciences; as well as, a member of the NCI-designated Fred & Pamela Buffet Cancer Center.

Dr. Borgstahl uses the tools of X-ray crystallography to "see" what biological macromolecules look like and to understand the molecular basis of the chemistry of life. Many avenues of research are under exploration, with an emphasis on DNA repair, cellular motility, and collaborations within the Cancer Center to directly visualize cancer-related macromolecules. For example, her research on homologous recombination-based double-stranded DNA break repair has focused on understanding the structural basis for HR and searching for therapeutics for breast, ovarian and pancreatic cancer based on the synthetic lethality of the RAD52 repair pathway with the BRCA1/BRCA2/PALB2 pathway. Specifically her research has concentrated on human Replication protein A (RPA), the ubiquitous, single-stranded DNA-binding protein and complexes formed with the DNA repair factors RAD51 and RAD52. This research has led to three different crystal structures of the full-length RPA heterodimer, composed of the RPA14 and RPA32 subunits, several biophysical publications on the RAD52:RPA complex, along with research on regulation by posttranslational modifications and ongoing screening efforts to inhibit the RAD52:RPA complex. The laboratory has also had a long-standing interest in oxidative damage, and has determined several structures to contribute to the understanding of the enzymatic mechanism of superoxide dismutases. Another project includes an innovative research program in cellular motility that will provide new tools to macromolecular crystallographers for structure determination from modulated crystals employing the four-dimensional superspace approach, and will also provide unique structural information for the actin filament.  This work is supported by ACS, DHHS, NRI, NIH, NSF MCB, NSF CNIC and NASA.

Research Interest

• Protein Crystallography, Cancer, Biochemistry, DNA Metabolism, Modulated Crystals

Scientific Activities

• American Crystallographic Association (ACA) 1988 - present
• American Association for the Advancement of Science (AAAS) 1989 – present
• American Association for Cancer Research (AACR) 2004-present American Chemical Society (ACS) 1996 - present
• American Society for Biochemistry and Molecular Biology (ASBMB) 1998 – present The Biophysical Society 2006 – present
• The University of Nebraska, Graduate Faculty, Full Member 2002 - present

Publications

1. Borgstahl, G. E. O., Parge, H. E., Hickey, M. J., Beyer, W. F., Hallewell, R. A. and Tainer, J. A.* “The Structure of Human Manganese Superoxide Dismutase Reveals a Novel Tetrameric Interface of Two 4-helix Bundles”, Cell, 71, 107-118 (1992). Citations:  243
2. Borgstahl, G. E. O., Rogers, P. H. and Arnone, A.* “The 1.9 Å Structure of Deoxy- Hemoglobin: Analysis of the Partitioning of Quaternary-associated and Ligand-induced Changes in Tertiary Structure”, J. Mol. Biol., 236, 831-843 (1994). Citations:  26
3. Borgstahl, G. E. O., Rogers, P. H. and Arnone, A.* “The 1.8 Å Structure of Carbonmonoxy- Hemoglobin: Characterization of the R-like Quaternary Structure”, J. Mol. Biol., 236, 817-830 (1994). Citations: 41
4. Baca M., Borgstahl, G. E. O., Boissinot, M., Burke, P. M., Williams, D. R., Slater, K. A. and Getzoff, E. D.* “Complete Chemical Structure of Photoactive Yellow Protein: Novel Thioester-linked 4-Hydroxycinnamyl Chromophore and Photocycle Chemistry”, Biochemistry, 33, 14369-14377 (1994). Citations: 218
5. Borgstahl, G. E. O., Williams, D. R. and Getzoff, E. D.* “The 1.4 Å Structure of Photoactive Yellow Protein, a Cytosolic Photoreceptor: Unusual Fold, Active Site and Chromophore”, Biochemistry, 34, 6278-6287 (1995).  Citations: 326
6. Borgstahl, G. E. O., Parge, H. E., Hickey, M. J., Johnson, M. J., Boissinot, M., Hallewell, R. A., Lepock, J. R., Cabelli, D. E. and Tainer, J. A.* “Human Mitochondrial Manganese Superoxide Dismutase Polymorphic Variant Ile58Thr Reduces Activity by Destabilizing the Tetrameric Interface”, Biochemistry, 35, 4287-4297 (1996). Citations: 90
7. Ren, Z., Ng, K., Borgstahl, G. E. O., Getzoff, E. D. and Moffat, K.* “Quantitative Analysis of Time-resolved Laue Diffraction Patterns”, J. Appl. Cryst. 29, 246-260 (1996). Citations: 13
8. Genick, U.K.#, Borgstahl, G.E.O.#, Ng, K., Ren, Z., Pradervand, C., Burke, P.M., Srajer, V., Teng, T.Y., Schildkamp, W., McRee, D.E., Moffat, K. and Getzoff, E.D.* "Millisecond Time-Resolved  Laue  Crystallography:  Structure  of  a  Protein  Photocycle  Intermediate", Science, 275, 1471-1475 (1997) #Equal contribution. Citations: 287
9. Guan, Y., Hickey, M. J., Borgstahl, G. E. O., Hallewell, R. A., Lepock, J. R., O’Connor, D. Hsieh, Y. Nick, H. S. Silverman, D. N. and Tainer, J. A.* “Crystal Structure of Y34F Mutant Human Mitochondrial Manganese Superoxide Dismutase and the Functional Role of Tyrosine 34”, Biochemistry 37, 4722-4730 (1998).  Citations: 77
10. Garlitz, J. A., Summers, C. A., Flowers II, R. A. and Borgstahl, G. E. O.* “Ethylammonium Nitrate: A Protein Crystallization Reagent” Acta Cryst. D55, 2037-2038 (1999). Citations: 29
11. Borgstahl, G. E. O.*, Pokross, M., Chehab, R., Sekher, A. and Snell, E. H. “Cryo-trapping the Six-Coordinate, Distorted-Octahedral Active Site of Manganese Superoxide Dismutase” Mol. Biol. 296, 951-960 (2000). Citations: 44
12. Lovelace, J. Snell, E. H., Pokross, M., Aravai, A. S., Nielsen, C., Xuong N.-H., Bellamy, H. and Borgstahl, G. E. O.* “BEAM-ish: a graphical user interface for the physical characterization of macromolecular crystals” J. Appl. Cryst. 33, 1187-1188 (2000). Citations: 3
13. Bellamy, H. D., Snell, E. H., Lovelace, J., Pokross, M. and Borgstahl, G. E. O.* “The High Mosaicity Illusion: Revealing the True Physical Characteristics of Macromolecular Crystals” Acta Cryst. D56, 986-995 (2000). Citations: 25
14. Habel, J. E., Ohren, J. F. and Borgstahl, G. E. O.* “Dynamic light scattering analysis of full-length, human RPA14/32 dimer: purification crystallization and self-association” Acta Cryst. D57, 254-259 (2001). Citations: 15
15. Snell, E. H.*, Judge, R. A., Crawford, L., Pusey, M. L., Sporteillo, M., Todd, P. Bellamy, H. Lovelace, J., Cossanto, J. M. and Borgstahl, G. E., O. “Biochemical and X-ray Mosaicity Analysis of Impurity Doped Microgravity and Ground-grown Lysozyme Crystals” Crystal Growth & Design 1, 151-158 (2001). Citations: 26
16. Ranatunga, W., Jackson, D., Lloyd, J. A., Forget, A. L., Knight, K. L. and Borgstahl, G. E. O.* “Human Rad52 Exhibits Two Modes of Self-association” J. Biol. Chem. 276, 15876-15880 (2001). Accepted without revision. Citations: 35
17. Ranatunga, W., Jackson, D., Flowers II, R. A. and Borgstahl, G. E. O.* “Human Rad52 Protein Has Extreme Thermal Stability” Biochemistry 40, 8557-8562 (2001). Citations: 5
18. Borgstahl,  G.  E.  O.*,  Vahedi-Faridi,  A.,  Bellamy,  H.  and  Snell,  E.  “A  Test  of Macromolecular Crystallization in Microgravity: Large, Well-ordered Insulin Crystals” Acta Cryst. D57, 1204-1207 (2001). Citations: 43
19. Jackson, D., Dhar, K., Wahl, J. K., Wold, M. S. and Borgstahl, G. E. O.*  “Evidence for Cross-talk Between RPA70 and RPA32 in Binding Human Rad52” J. Mol. Biol. 321, 133-148 (2002). Citations: 33
20. Vahedi-Faridi, A., Porta, J. and Borgstahl, G. E. O. * “Improved Three-dimensional Growth of Manganese Superoxide Dismutase Crystals on the International Space Station” Acta Cryst. D59, 385-388 (2003). Citations: 8
21. Lovelace, J and Borgstahl, G. E. O.* “BEAM-ish 2.0: a graphical user interface for the physical characterization of macromolecular crystals” J. Appl. Cryst. 36, 1101-1102, (2003). Citations: 3
22. Vahedi-Faridi, A., Lovelace, J. Bellamy, H. D., Snell, E. H. and  Borgstahl, G. E. O.* “Physical and structural studies on the cryocooling of insulin crystals” Acta Cryst. D59, 2169-2182 (2003). Citations: 10
23. Lovelace, J., Narayan, K., Chik, J., Bellamy, H. D., Snell, E. H., Lindberg, U., Schutt, C., and Borgstahl, G. E. O.* “Imaging modulated reflections from a semi-crystalline state of profilin:actin crystals” J. Appl. Cryst. 37, 327-330 (2004). Citations: 2
24. Lovelace, J., Soares, A., Bellamy, H. D., Sweet, B., Snell, E. S., and Borgstahl, G. E. O.* “First results of digital topography applied to macromolecular crystals” J. Appl. Cryst, 37, 481-485 (2004). Citations: 7
25. Nachon, F.*, Asojo, O. A., Borgstahl, G. E. O., Masson, P., and Lockridge, O. “Role of water in aging of human butyrylcholinesterase inhibited by echothiophate. The crystal structure suggests two alternative mechanisms of aging.” Biochemistry 44, 1154-1162 (2005). Citations: 52
26. Asojo, O. A.*, Goud, G., Dhar, K. Loukas, A., Zhan, B., Deumic, V., Liu, S., Borgstahl, G.O., Hotez, P. “X-ray structure of Na-ASP-2, a PR-1 protein from the nematode parasite Necator americanus and a vaccine antigen for human hookworm infection” J. Mol. Biol. 346, 801-814 (2005). Citations: 52
27. Lovelace, J., Murphy, C., Bellamy, H. D., Pahl, R., Brister, K., and Borgstahl, G. E. O.* “Advances in Automated Digital Topography for Characterizing Imperfections in Protein Crystals” J. Appl. Cryst. 38, 512-519 (2005). Citations: 6
28. Lovelace, J. J., Murphy, C. R., Brister, K., Pahl, R., Borgstahl, G. E. O.* “Tracking Reflections through Cryogenic cooling with Topography” J. Appl. Cryst. 39, 425-432 (2006). Citations: 11
29. Lovelace, J. J., Borgstahl, G. E. O.* “Ripple: A Program to Collect and Analyze Digital Topographic Sequences” J. Appl. Cryst. 39, 466-467 (2006). Citations: 2
30. Porta, J., Kolar, C, Kozmin, S. G., Pavlov, Y. I., Borgstahl, G. E. O.* “Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase” Acta Cryst. F. 62, 1076-1081 (2006). Citations: 4
31. Yikilmaz, E., Porta, J., Vahedi-Faridi, A. V., Grove, L., Bronshteyn, Y., Brunold, T., Borgstahl G. E. O. and Miller, A. F.* “How can a single second sphere amino acid change cause reduction midpoint potential changes of hundreds of mV?” J. Am. Chem. Society. 129, 9927-9940 (2007). Citations: 24
32. Juers, D. H., Lovelace, J., Bellamy, H. D., Snell, E. H., Matthews, B. W.*, and Borgstahl, G.O. “Reversibility in cryocooling crystals of E. coli β-galactosidase” Acta Cryst. D63, 1139-1153 (2007). Citations: 3
33. Deng, X., Habel, J. E., Kabaleeswaran, V., Snell, E. H., Wold, M.S., and Borgstahl, G. E. O.* ” Structure of the full-length, human RPA14/32 complex gives insights into the mechanism of DNA binding and complex formation” J Mol. Biol. 374, 865-876 (2007). Citations: 19
34. Kellezi, A., Kieken, F., Grosely, R., Borgstahl, G. E. O., and Sorgen, P. L.* “Purification of the Connexin43 Carboxyl Terminus attached to the 4th Transmembrane Domain” Protein Expression and Purification 59, 215-222 (2008). Citations: 2
35. Lovelace, J. J., Murphy, C. R., Narayan, K., Schutt, C. E., Lindberg, U., Svensson, C., Winn, M., and Borgstahl, G. E. O.* “Protein Crystals Can Be Incommensurately Modulated” J. Appl. Cryst. 41, 600-605 (2008). Citations: 7
36. Deng, X., Prakash, A., Dhar, K., Baia, G. S., Kolar, C., Oakley, G. G. and Borgstahl, G. E. O.* “Human Replication Protein A-Rad52-ssDNA Complex: Stoichiometry and Evidence for Strand Transfer Regulation by Phosphorylation” Biochemistry 48, 6633-6643 (2009). Citations: 10
37. Stepchenkova, E. I., Tarakhovskaya, E. R., Spitler, K., Frahm, C., Menezes, M. R., Simone, P.D., Kolar, C., Marky, L. A., Borgstahl, G. E. O., and Youri I. Pavlov* “Functional study of human ITPA P32T representing polymorphism associated with drug sensitivity” J. Mol. Biol. 392, 602-613 (2009). Citations: 17
38. Kemp, M. G., Mason, A. C., Carreira, A., Reardon, J. T., Haring, S. J., Borgstahl, G. E. O., Kowalczykowski, S. C., Sancar, A. and Wold, M. S.* “An alternative form of RPA (aRPA) expressed in normal human tissues supports DNA repair” J. Biol. Chem. 285, 4788-4797 (2010).
39. Lovelace, J. J., Winn, M. D. and Borgstahl, G. E. O.* “Simulation of Modulated Reflections” J. Appl. Cryst. 43, 285-292 (2010).
40. Porta, J, Vahedi-Faridi, A. and Borgstahl, G. E. O.* “Structural analysis of peroxide-soaked MnSOD crystals reveals side-on binding of peroxide to active site manganese” J. Mol. Biol. 399, 377-384 (2010).
41. Lovelace, J. J. and Borgstahl, G. E. O.* “The Use of Orthogonal Projection to Visualize Mosaic Domains from Topographic Data Collected on Protein Crystals” J. Appl. Cryst. 43, 907-912 (2010).
42. Bao, B., Pestinger,V., Hassan, Y. I., Borgstahl, G. E. O., Kolar, C. and Zempleni, J.* “Holocarboxylase synthetase is a chromatin protein and interacts directly with histone H3 to mediate biotinylation of K9 and K18” J. Nutr. Biochem. 22, 470-475 (2011).
43. Filenko, N. A. Kolar, C., West, J. T., Abbie Smith, S., Hassan, Y. I., Borgstahl, G. E. O., Zempleni, J. and Lyubchenko, Y. I.* “The Role of Histone H4 Biotinylation in the Structure of Nucleosomes” Plos One 6, e16299 (2011).
44. Prakash, A., Natarajan, A., Marky, L. A., Ouellette, M. M. and Borgstahl, G. E. O.* “Identification of the DNA binding domains of human Replication Protein A that recognize G-quadruplex DNA” J. Nucleic Acids 2011, Article ID 896947, 14 pages (2011).
45. Prakash, A., Kieken, F., Marky, L. A., and Borgstahl, G. E. O.* “Stabilization of a G-quadruplex from unfolding by Replication Protein A using potassium and the porphyrin TMPyP4” J. Nucleic Acids 2011, Article ID 529828, 13 pages (2011).
46. Porta, J., Lovelace, J.J., Schreurs, A.M.M., Loes Kroon-Batenburg, L. and Borgstahl, G. E. O.* “Processing incommensurately modulated protein diffraction data with EVAL15”, Acta Cryst. D 67, 628-638 (2011).
47. Lada, A. G., Waisertreiger, I. S.-R., Grabow, C. E., Prakash, A., Borgstahl, G. E. O, Rogozin, I. B., and Pavlov, Y. I. * “Replication protein A (RPA) hampers the processive action of APOBEC3G cytosine deaminase on single-stranded DNA” PLoS ONE 6, e24848 (2011).
48. Porta, J. C. and Borgstahl, G. E. O.* “Structural basis for profilin-mediated actin nucleotide exchange” J. Mol. Biol. 418, 103-116 (2012).
49. Kumar, E. A. Yuan, Z., Palermo, N. Y., Dong, L., Ahmad, G., Lokesh, G.L., Kolar, C., Kizhake, S., Borgstahl, G. E. O., Band, H., and Natarajan, A.* “Peptide truncation leads to a twist and an unusual increase in affinity for Cbl tyrosine kinase binding domain” J. Med. Chem. 55, 3583-3597 (2012).
50. Mohapatra, B., Ahmad, G., Nadeau, S., Zutshi, N., An, W., Scheffee, S., Dong, L., Feng, D., Goetz, B., Arya, P., Baily, T.A., Palermo, N., Borgstahl, G. E. O., Natarajan, A., Raja, S., Naramura, M., Band, V., Band, H.* “Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases” Molecular Cell Research (2012) 1833, 122-139. Review.
51. Nadeau, S., An, W., Palermo, N., Feng, D., Ahmad, G., Dong, L., Borgstahl, G.E.O., Natarajan, A., Naramura, M., Band, V., and Band, H. “Oncogenic signaling by leukemia-associated mutant Cbl proteins” Biochemistry & Analytical Biochemistry 6, 7921 (2012) Review.
52. Simone, P., Struble, L. R, Kellezi, A., Brown, C. A., Grabow, C. E., Khutsishvili, I., Marky, A., Pavlov, Y. I. and Borgstahl, G. E. O. “The human ITPA polymorphic variant P32T is destabilized by the unpacking of the hydrophobic core” J. Structural. Biol. 182, 197-208(2013).
53. Lovelace, J.J., Simone, P.D., Petricek, V., and Borgstahl, G.E.O. “Simulation of modulated protein crystal structure and diffraction data in a supercell and in superspace” Acta Crystallogr D 69, 1062-72 (2013).
54. Kumar, Eric; Chen, Qianyi; Kizhake, Smitha; Kolar, Carol; Kang, Myungshim; Chang, Chia-en; Borgstahl, Gloria; Natarajan, Amarnath “The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides” Scientific Reports 3, 1639-45 (2013)
55. Simone, P., Pavlov, Y. I., and Borgstahl, G. E. O. “ITPA: Roles in Nucleotide Pool Maintenance, Disease, and Pharmacogenetics” Mutation Research 753, 131-46 (2013). REVIEW NIHMS 522523
56. Borgstahl, G. E. O., Brader, K., Mosel, A., Liu, S., Kremmer, E., Goettsch, K.A., Kolar, C., Nasheuer, H.P., Oakley, G.G., “Interplay of DNA damage and cell cycle signaling at the level of human Replication Protein A” DNA Repair 21, 12-23 (2014).
57. Choi, K. H., Lakamp-Hawley, A. S., Kolar, C., Yan, Y., Borgstahl, G. E. O., Ouellette, M. “The OB-fold domain 1 of human POT1 recognizes both telomeric and non-telomeric DNA motifs” Biochimie 115:17-27 (2015).