- Research Assistant Professor, Department of Periodontics
- Associate Member of the Graduate Faculty, Graduate College
- Cancer BiologyVirologyBio-engineering
Education & Career
- National Autonomous University of Mexico, B.Sc., Biology, 1988
- University of Maryland at College Park, PhD, Biochemistry, 1995
- Rutgers University, Postdoctoral Fellow, Protein Chemistry and Enzymology, 1998
- University of Medicine and Dentistry of New Jersey, Research Associate, 2001
Proteolytic enzymes, like the serine proteases, play a central role in the maintenance of physiological homeostasis. Complex networks of serine proteases are controlled by serpins, a family of proteins that inhibit serine proteases. We conduct research on the biochemistry of the regulation by serpins of two serine protease networks of great medical relevance.
Proprotein convertases (PCs) are a family of intracellular and pericellular serine proteases that are key regulators of cell growth, proliferation and differentiation, and are naturally inhibited by serpins. PCs are important therapeutic targets and diagnostic markers in cancer. Important viral and bacterial pathogens exploit PCs in order to perform their infectious cycle. We study PC specificity in the mechanism of activation of the human papilloma virus, and focus on the high cancer-risk HPV16 and HPV18 serotypes. We seek to engineer serpins for the selective inhibition of PCs.
Clotting factors of the blood coagulation cascade are serine proteases regulated by the heparin-dependent serpin antithrombin. We study the mechanism of heparin induced activation of antithrombin and the structural elements that determine specificity for the inhibition of clotting factors by antithrombin. We seek to engineer anticoagulant serpins for the heparin-independent inhibition of clotting factors.
Most of my published work can be accessed at MyBibliography through the following link:
Izaguirre G, Arciniega M, Quezada AG. (2019) Specific and selective inhibitors of proprotein convertases engineered by transferring serpin B8 reactive-site and exosite determinants of reactivity to the serpin α1PDX. Biochemistry. 58:1679-1688.
Richard B, Swanson R, Izaguirre G, and Olson ST. (2018) Cooperative interactions of three hotspot heparin binding residues are critical for allosteric activation of antithrombin by heparin. Biochemistry 57:2211-2226.
Richard B, Swanson R, Izaguirre G, and Olson ST. (2018) Cooperative interactions of three hotspot heparin binding residues are critical for allosteric activation of antithrombin by heparin. Biochemistry March 21, doi: 10.1021/acs.biochem.8b00216.
Aguila S, Izaguirre G, Martínez-Martínez I, Vicente V, Olson ST, and Corral J (2017) Disease-causing mutations in the serpin antithrombin reveal a key domain critical for inhibiting protease activities. Journal of Biological Chemistry 292:16513-16520
Roth R, Swanson R, Izaguirre G, Bock SC, Gettins PG, and Olson ST (2016) Saturation mutagenesis of the antithrombin reactive center loop P14 residue supports a three-step mechanism of heparin allosteric activation involving intermediates and fully activated states. Journal of Biological Chemistry 290:28020-28036
Schwartz J. Lathe A, Liu T, Belmonte M, and Izaguirre G (2015) Dose related effect of Actinomycete extracts, tobacco derived carcinogens and nicotine on human papillomavirus 16 entry into epithelium. Journal of Cancer Studies and Therapy 2(1):1-15
Schwartz J, Munaretto A, Bagchi S, Crowe D, and Izaguirre G (2015) Inhibition of EGFR suppresses ethyl alcohol and tobacco cell effects on growth of human oral keratinocytes and human papilloma 16 entry as a function of furin. Journal of Cancer Therapy 6:90-108
Izaguirre G, Aguila S, Qi L, Swanson R, Roth R, Rezaie AR, Gettins PG, and Olson ST (2014) Conformational activation of antithrombin by heparin involves an altered exosite interaction with protease. Journal of Biological Chemistry 289:34040-34064
Schwartz J, Izaguirre G, Pavlova S, Sroussi H, Lu Y, et al. (2014) Alcohol Treatment of Oral Streptococcus Spp. Increased the Entry of Human Papillomavirus Type 16 into Non-Malignant and Oral Squamous Cell Carcinoma Cells. Journal of Oral Biology 1(1):12
Dementiev A, Swanson R, Roth R, Isetti G, Izaguirre G, Olson ST, and Gettins, PG (2013) The allosteric mechanism of activation of antithrombin as an inhibitor of factor IXa and factor Xa heparin-independent full activation through mutations adjacent to helix D. Journal of Biological Chemistry 288:33611-33619
Maddur AA, Swanson R, Izaguirre G, Gettins PG, and Olson ST (2013) Kinetic intermediates en route to the final serpin-protease complex. Studies of complexes of a1-protease inhibitor with trypsin. Journal of Biological Chemistry 288:32020-32035
Izaguirre G, Qi L, Lima M, and Olson ST (2013) Identification of serpin determinants of specificity and selectivity for furin inhibition through studies of a1-PDX (a1-proteinase inhibitor Portland)-serpin B8 and furin active-site loop chimeras. Journal of Biological Chemistry 288:21802-21814
Olson ST, Richard B, Izaguirre G, Schedin-Weiss S, and Gettins PG (2010) Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases. A paradigm for understanding proteinase regulation by serpin family protein proteinase inhibitors. Biochimie 92:1587-1596
Izaguirre G, Rezaie AR, and Olson ST (2009) Engineering functional antithrombin exosites in alpha 1-proteinase inhibitor that specifically promote the inhibition of factor Xa and factor IXa. Journal of Biological Chemistry 248:1550-1558
Richard B, Swanson R, Schedin-Weiss S, Ramirez B, Izaguirre G, Gettins PG, and Olson ST (2008) Characterization of the conformational alterations, reduced anticoagulant activity, and enhanced antiangiogenic activity of prelatent antithrombin. Journal of Biological Chemistry 283:14417-14429
Izaguirre G, Swanson R, Raja SM, Rezaie AR, and Olson ST (2007) Mechanism by which exosites promote the inhibition of blood coagulation proteases by heparin-activated antithrombin. Journal of Biological Chemistry 282:33609-33622
Izaguirre G, and Olson ST (2006) Residues Tyr253 and Glu255 in strand 3 of beta-sheet C of antithrombin are key determinants of an exosite made accessible by heparin activation to promote rapid inhibition of factors Xa and IXa. Journal of Biological Chemistry 281:13424-13432
Zhang Z, Izaguirre G, Lin SY, Lee HY, Schaefer E, and Haimovich B (2004) The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by Src kinases, affects cell spreading. Molecular Biology of the Cell 15:4234-4247
Izaguirre G, Zhang W, Swanson R, Bedsted T, and Olson ST (2003) Localization of an antithrombin exosite that promotes rapid inhibition of factors Xa and IXa dependent on heparin activation of the serpin. Journal of Biological Chemistry 278:51433-51440
Izaguirre G, Pietruszko R, Cho S, and MacKerell Jr A (2001) Human aldehyde dehydrogenase catalytic activity and structural interactions with coenzyme analogs. Journal of Biomolecular Structure & Dynamics 19:429-447
Izaguirre G, Aguirre L, Hu Y, Lee HY, Schlaefer D, Aneskievich B., and Haimovich B (2001) The cytoskeletal /non-muscle isoform of a-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase. Journal of Biological Chemistry 276:28676-28685
Izaguirre G, Aguirre L, Ji P, Aneskievich B, and Haimovich B (1999) Tyrosine phosphorylation of alpha-actinin in activated platelets. Journal of Biological Chemistry 274:37012-37020
Ambroziak W, Izaguirre G, and Pietruszko R (1999) Metabolism of retinaldehyde and other aldehydes in soluble extracts of human liver and kidney. Journal of Biological Chemistry 274:33366-33373
Ambroziak W, Izaguirre G, Abriola D, Chern MK, and Pietruszko R (1999) Metabolism of retinaldehyde by human liver and kidney. Advances in Experimental Medicine and Biology 463:205-211
Pietruszko R, Abriola DP, Izaguirre G, Kikonyogo A, Dryjanski M and Ambroziak W (1999) Aldehyde inhibitors of aldehyde dehydrogenases. Advances in Experimental Medicine and Biology 463:79-87
Paul LK, Izaguirre G, and Hansen JN (1999) Studies of the subtilin leader peptide as a translocation signal in Escherichia coli K12. FEMS Microbiology Letters 176:45-50
Izaguirre G, Kikonyogo A, and Pietruszko R (1998) Methylglyoxal as substrate and inhibitor of human aldehyde dehydrogenase: comparison among isozymes. Comparative Biochemistry and Physiology 119B:747-54
Izaguirre G, Kikonyogo A, and Pietruszko R (1997) Tissue distribution of human aldehyde dehydrogenase E3. Comparison of enzyme activity with E3 protein and mRNA distribution. Comparative Biochemistry and Physiology 118B:59-64
Pietruszko R, Chern M, Kikonyogo A, and Izaguirre G (1997) Human aldehyde dehydrogenase E3, further characterization. Advances in Experimental Medicine and Biology 414:243-252
Izaguirre G, and Hansen JN (1997) Use of alkaline phosphatase as a reporter to study the role of the subtilin leader segment in the post-translational modifications and secretion of subtilin in Bacillus subtilis 168. Applied and Environmental Microbiology 63:3965-3971