Staff information

Biography

Dr. Tom Squier joined the Biological Sciences Division in January 2002, after leaving a tenured position in the Department of Molecular Biosciences at the University of Kansas. With an established background in the field of calcium homeostasis and transport in biological systems, he has expanded this research emphasis to participate in the growth of multidisciplinary biological research at the Laboratory, making major contributions to staff, program, and business development. A particular current focus is the development of a multi-disciplinary team of investigators that are creating the necessary technologies and approaches for understanding how cells adapt to changes in their environment. This team brings together novel organic synthesis strategies with spectroscopy and microbial cell biology to address fundamental technological limitations in analysis of proteins in living cells. This project is now developing the next generation of fluorescent probes for biological studies, Multiuse Affinity Probes (MAPs). MAPs promise a revolutionary strategy for labeling specific proteins within living cells, permitting both the analysis of protein dynamics in vivo, and allowing the rapid isolation of the proteins and the molecular machines with which they interact.

Research Interests

• Aging and cardiac muscles
• Structural changes involving calmodulin during aging
• Single-protein dynamics of target binding by calmodulin
• Regulatory mechanisms of secretory phospholipases A2
• Structural analogs of sadenosylmethionine

Education and Credentials

• Postdoc, Biophysics, University of Maryland, 1988-1990
• Postdoc, Biochemistry, University of Maryland, 1985-1988
• Ph.D., Biochemistry, University of Minnesota, 1985
• A.B., Biology/Chemistry, Oberlin College, 1979

Affiliations and Professional Service

• American Chemical Society
• Biophysical Society
• Society for Free Radicals and Medicine
• New York Academy of Sciences
• American Society for Biochemistry and Molecular Biology

Awards and Recognitions

• Adjunct Professor of Biology, Washington State University
• Ad-hoc Reviewer, National Institutes of Health (CCHF and NCI) 2004-present
• Reviewer, American Heart Association (Cell Function and Metabolism) 2004-present
• Reviewer, American Heart Association (Cellular Physiology) 2000-2004
• Ad-hoc Reviewer, National Institutes of Health (BBCB) 2000
• Editorial Board Member, Frontiers in Biosciences 1998-2003
• Postdoctoral Fellowship from National Institutes of Health 1988-1990
• Postdoctoral Fellowship from American Heart Association 1985-1988

PNNL Publications

2013

• Fu N, Y Xiong, and TC Squier. 2013. "Optimized Design and Synthesis of Cell Permeable Biarsenical Cyanine Probe for Imaging Tagged Cytosolic Bacterial Proteins ." Bioconjugate Chemistry 24(2):251-259.  doi:10.1021/bc300619m
• Fu N, D Su, JR Cort, B Chen, Y Xiong, W Qian, A Konopka, DJ Bigelow, and TC Squier. 2013. "Synthesis and Application of an Environmentally Insensitive Cy3-Based Arsenical Fluorescent Probe to Identify Adaptive Microbial Responses Involving Proximal Dithiol Oxidation." Journal of the American Chemical Society 135(9):3567-3575.  doi:10.1021/ja3117284
• Reback ML, B Ginovska-Pangovska, MH Ho, A Jain, TC Squier, S Raugei, JA Roberts, and WJ Shaw. 2013. "The Role of a Dipeptide Outer-Coordination Sphere on H2 -Production Catalysts: Influence on Catalytic Rates and Electron Transfer." Chemistry - A European Journal 19(6):1928-1941.  doi:10.1002/chem.201202849

2012

• Fu N, Y Xiong, and TC Squier. 2012. "Synthesis of a Targeted Biarsenical Cy3-Cy5 Affinity Probe for Superresolution Fluorescence Imaging." Journal of the American Chemical Society 134(45):18530-18533.  doi:10.1021/JA308503x
• Smith DMA, TP Straatsma, and TC Squier. 2012. "Retention of Conformational Entropy upon Calmodulin Binding to Target Peptides is Driven by Transient Salt Bridges." Biophysical Journal 103(7):1576-1584.  doi:10.1016/j.bpj.2012.08.037
• Jin H, Y Zhang, GW Buchko, SM Varnum, H Robinson, TC Squier, and PE Long. 2012. "Structure Determination and Functional Analysis of a Chromate Reductase from Gluconacetobacter hansenii." PLoS One 7(8):Article No. e42432.  doi:10.1371/journal.pone.0042432
• Smith DMA, Y Xiong, TP Straatsma, KM Rosso, and TC Squier. 2012. "Force Field Development and Molecular Dynamics of [NiFe] Hydrogenase." Journal of Chemical Theory and Computation 8(6):2103-2114.  doi:10.1021/ct300185u

2011

• Xiong Y, B Chen, L Shi, JK Fredrickson, DJ Bigelow, and TC Squier. 2011. "Targeted Protein Degradation of Outer Membrane Decaheme Cytochrome MtrC Metal Reductase in Shewanella oneidensis MR-1 Measured Using Biarsenical Probe CrAsH-EDT2." Biochemistry 50(45):9738-9751.  doi:10.1021/bi200602f
• Smallwood HS, D Lopez-Ferrer, and TC Squier. 2011. "Aging Enhances the Production of Reactive Oxygen Species and Bactericidal Activity in Peritoneal Macrophages by Upregulating Classical Activation Pathways." Biochemistry 50(45):9911-9922.  doi:10.1021/bi2011866
• Bigelow DJ, and TC Squier. 2011. "Thioredoxin-dependent Redox Regulation of Cellular Signaling and Stress Response through Reversible Oxidation of Methionines." Molecular Biosystems 7(7):2101-2109.  doi:10.1039/C1MB05081H
• Shi L, SM Belchik, AE Plymale, SM Heald, A Dohnalkova, K Sybirna, H Bottin, TC Squier, JM Zachara, and JK Fredrickson. 2011. "Purification and Characterization of [NiFe]-Hydrogenase of Shewanella oneidensis MR-1." Applied and Environmental Microbiology 77(16):5584-5590. 

2010

• Lourette NM, HS Smallwood, S Wu, EW Robinson, TC Squier, RD Smith, and L Pasa-Tolic. 2010. "A Top-Down LC-FTICR MS-Based Strategy for Characterizing Oxidized Calmodulin in Activated Macrophages ." Journal of the American Society for Mass Spectrometry 21(6):930-939. 
• Khor HK, ME Jacoby, TC Squier, GC Chu, and D Chelius. 2010. "Identification of Methionine Sulfoxide Diastereomers in Immunoglobulin Gamma Antibodies Using Methionine Sulfoxide Reductase enzymes." mAbs 2(3):299-308.  doi:10.4161/mabs.2.3.11755

2009

• Smallwood HS, D Lopez Ferrer, PE Eberlein, DJ Watson, and TC Squier. 2009. "Calmodulin Mediates DNA Repair Pathways Involving H2AX in Response to Low-Dose Radiation Exposure of RAW 264.7 Macrophages." Chemical Research in Toxicology 22(3):460-470. 
• Chen L, Q Yao, TA Soares, TC Squier, and DJ Bigelow. 2009. "Phospholamban Modulates the Functional Coupling between Nucleotide Domains in Ca-ATPase Oligomeric Complexes in Cardiac Sarcoplasmic Reticulum ." Biochemistry 48(11):2411-2421. 
• Lopez-Ferrer D, KK Hixson, HS Smallwood, TC Squier, K Petritis, and RD Smith. 2009. "Evaluation of a High Intensity Focused Ultrasound-Immobilized Trypsin Digestion and 18 O-Labeling Method for Quantitative Proteomics." Analytical Chemistry 81(15):6272-6277. 
• Yan P, T Wang, GJ Newton, TV Knyushko, Y Xiong, DJ Bigelow, TC Squier, and MU Mayer. 2009. "A Targeted Releasable Affinity Probe (TRAP) for In Vivo Photo-Crosslinking." Chembiochem 10(9):1507-1518.  doi:10.1002/cbic.200900029

2008

• Jones EM, TC Squier, and CA Sacksteder. 2008. "An Altered Mode of Calcium coordination in methionine-oxidized calmodulin." Biophysical Journal 95(11):5268-5280.  doi:10.1529/biophysj.108.139634
• Boschek CB, H Sun, DJ Bigelow, and TC Squier. 2008. "Different Conformational Switches Underlie the Calmodulin-Dependent Modulation of Caclium Pumps and Channels." Biochemistry 47(6):1640-1651.  doi:10.1021/bi701987n
• Boschek CB, TE Jones, HS Smallwood, TC Squier, and DJ Bigelow. 2008. "Loss of the Calmodulin-Dependent Inhibition of RyR1 Calcium Release Channel Upon Oxidation of Methionines in Calmodulin." Biochemistry 47(1):131-142.  doi:10.1021/bi701352w
• Chen B, D Lowry, MU Mayer, and TC Squier. 2008. "Helix A Stabilization Precedes Amino-terminal Lobe Activation upon Calcium Binding to Calmodulin." Biochemistry 47(35):9220-9226. 
• Chen B, JE Mahaney, MU Mayer, DJ Bigelow, and TC Squier. 2008. "Concerted but Noncooperative Activation of Nucleotide and Actuator Domains of the Ca-ATPase Upon Calcium Binding." Biochemistry 47(47):12448-12456.  doi:10.1021/bi8014289

2007

• Boschek CB, TC Squier, and DJ Bigelow. 2007. "Disruption of Interdomain Interactions Upon Partial Calcium Occupancy of Calmodulin ." Biochemistry 46(15):4580-4588. 
• Boschek CB, TE Jones, TC Squier, and DJ Bigelow. 2007. "Calcium Occupancy of N-terminal Sites within Calmodulin Induces Inhibition of the Ryanodine Receptor Calcium Release Channel." Biochemistry 46(37):10621-10628.  doi:10.1021/bi700655h
• Cao H, Y Xiong, T Wang, B Chen, TC Squier, and MU Mayer. 2007. "A Red Cy3-Based Biarsenical Fluorescent Probe Targeted to a Complementary Binding Peptide." Journal of the American Chemical Society 129(28):8672-8673.  doi:10.1021/ja070003c
• Cao H, Y Xiong, T Wang, B Chen, TC Squier, and MU Mayer. 2007. "A Red Cy3-Based Biarsenical Fluorescent Probe Targeted to a Complementary Binding Peptide." Journal of the American Chemical Society 129:8672-73.  doi:10.1021/ja070003c
• Chen B, H Cao, P Yan, MU Mayer, and TC Squier. 2007. "Identification of an Orthogonal Peptide Binding Motif for Biarsenical Multiuse Affinity Probes ." Bioconjugate Chemistry 18(4):1259-1265.  doi:10.1021/bc0603900
• Chen B, LM Markillie, Y Xiong, MU Mayer, and TC Squier. 2007. "Increased Catalytic Efficiency Following Gene Fusion of Bifunctional Methionine Sulfoxide Reductase Enzymes from Shewanella oneidensis." Biochemistry 46(49):14153-14161.  doi:10.1021/bi701151t
• Shi L, TC Squier, JM Zachara, and JK Fredrickson. 2007. "Respiration of metal (hydr)oxides by Shewanella and Geobacter: a key role for multihaem c-type cytochromes." Molecular Microbiology 65(1):12-20.  doi:10.1111/j.1365-2958.2007.05783.x
• Smallwood HS, NM Lourette, CB Boschek, DJ Bigelow, RD Smith, L Pasa-Tolic, and TC Squier. 2007. "Identification of a Denitrase Activity Against Calmodulin in Activated Macrophages Using High-Field Liquid Chromatography - FTICR Mass Spectrometry." Biochemistry 46(37):10498-10505. 
• Stenoien DL, TV Knyushko, MP Londono, L Opresko, MU Mayer, ST Brady, TC Squier, and DJ Bigelow. 2007. "Cellular Trafficking of Phospholamban and Formation of Functional Sarcoplasmic Reticulum During Myocyte DIfferentiation." American Journal of Physiology. Cell Physiology 292(6):C2084-2094.  doi:10.1152/ajpcell.00523.2006
• Verma S, Y Xiong, MU Mayer, and TC Squier. 2007. " Remodeling of Bacterial RNA Polymerase Supramolecular Complex in Response to Environmental Conditions." Biochemistry 46(11):3023-3035.  doi:10.1021/bi0621157
• Wang T, P Yan, TC Squier, and MU Mayer. 2007. "Prospecting the Proteome: Identification of Naturally Occurring Binding Motifs for Biarsenical Probes." Chembiochem 8(16):1937-40.  doi:10.1002/cbic.200700209

2006

• Cao H, B Chen, TC Squier, and MU Mayer. 2006. "CrAsH: A Biarsenical Multi-use Affinity Probe with low non-specific fluorescence." Chemical Communications (24):2601-2603.  doi:10.1039/b602699k
• Smallwood HS, L Shi, and TC Squier. 2006. "Increases in Calmodulin Abundance and Stabilization of Activated iNOS Mediate Bacterial Killing in RAW 264.7 Macrophages." Biochemistry 45(32):9717-9726.  doi:10.1021/bi060485p
• Squier TC. 2006. "Redox modulation of cellular metabolism through targeted degradation of signaling proteins by the proteasome." Antioxidants & Redox Signaling 8(1-2):217-228. 
• Xiong Y, B Chen, HS Smallwood, RJ Urbauer, LM Markillie, NA Galeva, TD Williams, and TC Squier. 2006. " High-Affinity and Cooperative Binding of Oxidized Calmodulin by Methionine Sulfoxide Reductase." Biochemistry 45(49):14642-14654.  doi:10.1021/bi0612465
• Bigelow DJ, and TC Squier. 2006. "Coil-to-Helix Transition within Phospholamban Underlies Release of Ca-ATPase Inhibition in Response to ß-Adrenergic Signaling." Current Enzyme Inhibition 2(1):19-27.  doi:10.2174/157340806775473508
• Sacksteder CA, W Qian, TV Knyushko, HH Wang, MH Chin, G Lacan, WP Melega, DG Camp, II, RD Smith, DJ Smith, TC Squier, and DJ Bigelow. 2006. "Endogenously Nitrated Proteins in Mouse Brain: Links To Neurodegenerative Disease ." Biochemistry 45(26):8009-8022.  doi:10.1021/bi060474w
• Sacksteder CA, JE Whittier, Y Xiong, J Li, NA Galeva, ME Jacoby, SO Purvine, TD Williams, MC Rechsteiner, DJ Bigelow, and TC Squier. 2006. "Tertiary Structural Rearrangements upon Oxidation of Methionine145 in Calmodulin Promotes Targeted Proteasomal Degradation." Biophysical Journal 91(4):1480-1493. 
• Shi L, B Chen, Z Wang, DA Elias, MU Mayer, YA Gorby, S Ni, BH Lower, DW Kennedy, DS Wunschel, HM Mottaz, MJ Marshall, EA Hill, AS Beliaev, JM Zachara, JK Fredrickson, and TC Squier. 2006. "Isolation of a High-Affinity Functional Protein Complex between OmcA and MtrC: Two Outer Membrane Decaheme c-type Cytochromes of Shewanella oneidensis MR-1 ." Journal of Bacteriology 188(13):4705-4714.  doi:10.1128/JB.01966-05
• Shi L, JN Adkins, JR Coleman, AA Schepmoes, A Dohnalkova, HM Mottaz, AD Norbeck, SO Purvine, NP Manes, HS Smallwood, HH Wang, J Forbes, P Gros, S Uzzau, KD Rodland, F Heffron, RD Smith, and TC Squier. 2006. "Proteomic Analysis of Salmonella enterica Serovar Typhimurium Isolated from RAW 264.7 Macrophages: identification of a novel protein that contributes to the replication of serovar Typhimurium inside macrophages." Journal of Biological Chemistry 281:29131-29140.  doi:10.1074/jbc.M604640200
• Weber TJ, HS Smallwood, LE Kathmann, LM Markillie, TC Squier, and BD Thrall. 2006. "Functional link between TNF biosynthesis and CaM-dependent activation of inducible nitric oxide synthase in RAW 264.7 macrophages ." American Journal of Physiology. Cell Physiology 290(6):C1512-C1520.  doi:10.1152/ajpcell.00527.2005
• Xiong Y, L Shi, B Chen, MU Mayer, BH Lower, londer, S Bose, MF Hochella, JM Zachara, JK Fredrickson, and TC Squier. 2006. "High-Affinity Binding and Direct Electron Transfer to Solid Metals by the Shewanella oneidensis MR-1 Outer Membrane c-type Cytochrome OmcA." Journal of the American Chemical Society 128(43):13978-13979.  doi:10.1021/ja063526d
• Yan P, Y Xiong, B Chen, S Negash, TC Squier, and MU Mayer. 2006. "Fluorophore-Assisted Light Inactivation of Calmodulin Involves Singlet-Oxygen Mediated Cross-Linking and Methionine Oxidation." Biochemistry 45(15):4736-4748.  doi:10.1021/bi052395a

2005

• Anbanandam A, RJ Urbauer, RK Bartlett, HS Smallwood, TC Squier, and JL Urbauer. 2005. "Mediating molecular recognition by methionine oxidation: Conformational switching by oxidation of methionine in the carboxyl-terminal domain of calmodulin." Biochemistry 44(27):9486-96.  doi:10.1021/bi0504963
• Bigelow DJ, and TC Squier. 2005. "Redox Modulation of Cellular Signaling and Metabolism Through Reversible Oxidation of Methionine Sensors in Calcium Regulatory Proteins." Biochimica et Biophysica Acta--Proteins and Proteomics 1703(2):121-134. 
• Bigelow DJ, and TC Squier. 2005. "Redox modulation of cellular signaling and metabolism through reversible oxidation of methionine sensors in calcium regulatory proteins." Biochimica et Biophysica Acta--Proteins and Proteomics 1703(2):121-134.  doi:10.1016/j.bbapap.2004.09.012
• Chen B, MU Mayer, and TC Squier. 2005. "Structural Uncoupling between Opposing Domains of Oxidized Calmodulin Underlies the Enhanced Binding Affinity and Inhibition of the Plasma Membrane Ca-ATPase." Biochemistry 44(12):4737-4747.  doi:10.1021/bi0474113
• Chen B, MU Mayer, LM Markillie, DL Stenoien, and TC Squier. 2005. "Dynamic Motion of Helix A in the Amino-terminal Domain of Calmodulin is Stabilized Upon Calcium Activation." Biochemistry 44(3):905-914. 
• Chen B, MU Mayer, LM Markillie, DL Stenoien, and TC Squier. 2005. "Dynamic Motion of Helix A in the Amino-terminal Domain of Calmodulin is Stabilized Upon Calcium Activation." Biochemistry 44:905-914. 
• Galeva NA, SW Esch, TD Williams, LM Markillie, and TC Squier. 2005. "Rapid Method for Quantifying the Extent of Methionine Oxidation in Intact Calmodulin." Journal of the American Society for Mass Spectrometry 16(9):1470-80. 
• Li J, CB Boschek, Y Xiong, CA Sacksteder, TC Squier, and DJ Bigelow. 2005. "Essential Role for Pro(21) in Phospholamban for Optimal Inhibition of the Ca-ATPase ." Biochemistry 44(49):16181-16191. 
• Mayer MU, L Shi, and TC Squier. 2005. "One-step, non-denaturing isolation of an RNA polymerase enzyme complex using an improved multi-use affinity probe resin." Molecular Biosystems 1(1):53-56.  doi:10.1039/b500950b
• Nauser T, ME Jacoby, WH Koppenol, TC Squier, and C Schoneich. 2005. "Calmodulin Methionine Residues are Targets For One-Electron Oxidation by Hydroxyl Radicals: Formation of S therefore N three-electron bonded Radical Complexes." Chemical Communications 5:587-589. 
• Nauser T, ME Jacoby, WH Koppenol, TC Squier, and C Schoneich. 2005. "Calmodulin Methionine Residues are Targets For One-Electron Oxidation by Hydroxyl Radicals: Formation of S.:N three-electron bonded Radical Complexes." Chemical Communications 587-89.  doi:10.1039/b414687e
• Shi L, CT Lin, LM Markillie, TC Squier, and BS Hooker. 2005. "Over-expression of Multi-heme C-type Cytochromes." BioTechniques 38(2):297-299. 

2004

• Chen B, TC Squier, and DJ Bigelow. 2004. "Calcium Activation of the Ca-ATPase Enhances Conformational Heterogeneity Between Nucleotide Binding and Phosphorylation Domains ." Biochemistry 43(14):4366-4374. 
• Li J, Y Xiong, DJ Bigelow, and TC Squier. 2004. "Phospholamban Binds in a Compact and Ordered Conformation to the Ca-ATPase." Biochemistry 43(2):455-463. 
• Li J, DJ Bigelow, and TC Squier. 2004. "Conformational Changes Within the Cytosolic Portion of Phospholamban Upon Release of Ca-ATPase Inhibition." Biochemistry 43(13):3870-3879. 
• Tan X, D Hu, TC Squier, and HP Lu. 2004. "Probing Nanosecond Protein Motions of Calmodulin by Single-Molecule Fluorescence Anisotropy." Applied Physics Letters 85(12):2420-2422. 
• Tan X, D Hu, TC Squier, and HP Lu. 2004. "Probing Nanosecond Protein Motions of Calmodulin by Single-Molecule Fluorescence Anisotropy." Applied Physics Letters 85(12):2420-2422. 
• Weber TJ, S Negash, HS Smallwood, KS Ramos, BD Thrall, and TC Squier. 2004. "Calmodulin Involvement in Stress-Activated Nuclear Localization of Albumin in JB6 Epithelial Cells." Biochemistry 43(23):7443-7450. 
• Whittier JE, Y Xiong, MC Rechsteiner, and TC Squier. 2004. "Hsp90 Enhances Degradation of Oxidized Calmodulin by the 20S Proteasome ." Journal of Biological Chemistry 279(44):46135-46142. 

2003

• Smallwood HS, NA Galeva, RK Bartlett, RJ Urbauer, TD Williams, JL Urbauer, and TC Squier. 2003. "Selective Nitration of Tyr(99) in Calmodulin as a Marker of Cellular Conditions of Oxidative Stress." Chemical Research in Toxicology 16(1):95-102. 
• Bartlett RK, RJ Urbauer, A Anbanandam, HS Smallwood, JL Urbauer, and TC Squier. 2003. "Oxidation of Met(144) and Met(145) in Calmodulin Blocks Calmodulin Dependent Activation of the Plasma Membrane Ca-ATPase." Biochemistry 42(11):3231-3238. 
• Li J, DJ Bigelow, and TC Squier. 2003. "Phosphorylation by cAMP-dependent Protein Kinase Modulates the Structural Coupling Between the Transmembrane and Cytosolic Domains of Phospholamban." Biochemistry 42(36):10674-10682. 

2002

• Buchanan MV, F Larimer, HS Wiley, SJ Kennel, TC Squier, JM Ramsey, KD Rodland, GB Hurst, RD Smith, Y Xu, DA Dixon, MJ Doktycz, SD Colson, R Gesteland, CS Giometti, ME Young, and RM Giddings. 2002. "Genomes to Life "Center for Molecular and Cellular Systems": A research program for identification and characterization of protein complexes." OMICS. A Journal of Integrative Biology 6(4):287-303.