Thomas C. Irving, Ph.D.
Director, Biophysics Collaborative Access Team (BioCAT)
Professor of Biology and Physics
Phone:
312.567.3489
Fax:
312.567.3494
Email:
Office:
166A Robert A. Pritzker Science Center
Website:
Education
Ph.D. University of Guelph
M.Sc. University of Guelph
B.Sc. University of Guelph
Research & Accomplishments
Operate a NIH funded Biotechnology Research Center at the Advanced Photon Source, Argonne National Laboratory for non-crystalline diffraction and scattering from biological molecules and tissues.
Expertise
- Biophysics of muscle contraction, non-crystalline x-ray diffraction, synchrotron radiation instrumentation
Projects
- Determine the Structural Basis of the Frank-Starling Law of the Heart, collaboration with Loyolla University Stritch School of Medicine.
- Deduce the structural and functional l roles of My-BP-C in muscle contraction, collaboration with University of Massachusetts Medical School.
- Study the deleterious effect of mutations in the myosin light chains in cardiomyopathies, collaboration with University of Miami Medical School.
- Deduce the structural and functional and structural roles of nebulin in muscle contraction and their role in nemaline myopathy, collaboration with University of Arizona/NIH.
- Deduce the structural mechanism of delayed stretch activation in striated muscle, collaboration with Duke University Medical School.
Awards
- Ontario Scholar (1974)
- I.O.D.E. Capt. Frederick Bond Memorial University Entrance Scholarship
- Ontario Graduate Scholarship (1983-84)(1985-86)
- Canadian Heart Foundation Post-doctoral Fellowship (1989 - 1991)
- IITRI fellow (1998- 2000)
- Sigma Xi / IIT Award for Excellence in University Research (senior division) 2007
Publications
- 2018 Kiss B, Eun-Jeong Lee EJ, Ma W, Li FW, Tonino P, Mijailovich SM, Irving TC, Granzier HL. Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle. Proc Natl Acad Sci USA. 2018. In press.
- 2018 Ma W, Gong H, Kiss B, Lee EJ, Granzier H, Irving TC. Thick filament extensibility in intact skeletal muscle. Biophysical Journal. 2018. In press. 10.1016/j.bpj.2018.08.038
- 2018 Ma W, Gong H, Irving TC. Myosin Head Configurations in Resting and Contracting Murine Skeletal Muscle. Int J Mol Sci. 2018 Sep 6;19(9). pii: E2643. doi: 10.3390/ijms19092643.
- 2018 Anderson RL, Trivedi DV, Sarkar SS, Henze M, Ma W, Gong H, Rogers CS, Gorham JM, Wong FL, Morck MM, Seidman JG, Ruppel KM, Irving TC, Cooke R, Green EM, Spudich JA. Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers. Proc Natl Acad Sci USA. 2018 Aug 28;115(35):E8143-E8152. doi: 10.1073/pnas.1809540115
- 2018 Gonzalez-Martinez D, Johnston JR, Landim-Vieira M, Ma W, Antipova O, Awan O, Irving TC, Bryant Chase P, Pinto JR. Structural and functional impact of troponin C-mediated Ca2+ sensitization on myofilament lattice spacing and cross-bridge mechanics in mouse cardiac muscle. J Mol Cell Cardiol. 2018 Aug 21;123:26-37. doi: 10.1016/j.yjmcc.2018.08.015.
- 2018 Yuan CC, Kazmierczak K, Liang J, Zhou Z, Yadav S, Gomes AV, Irving TC, Szczesna-Cordary D. Sarcomeric perturbations of myosin motors lead to dilated cardiomyopathy in genetically modified MYL2 mice. Proc Natl Acad Sci USA. 2018 Mar 6;115(10):E2338-E2347. doi: 10.1073/pnas.1716925115
- 2018 Malaby AW, Das S, Chakravarthy S, Irving TC, Bilsel O, Lambright DG. Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors. Structure. 2018. 26(1):106-117.e6. DOI: 10.1016/j.str.2017.11.019.
- 2018 Joureau B, de Winter JM, Conijn S, Bogaards SJP, Kovacevic I, Kalganov A, Persson M, Lindqvist J, Stienen GJM, Irving TC, Ma W, Yuen M, Clarke NF, Rassier DE, Malfatti E, Romero NB, Beggs AH, Ottenheijm CAC. Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3). Ann Neurol. 2018. Feb;83(2):269-282. doi: 10.1002/ana.25144
- 2017 Szymusiak M, Kalkowski J, Luo H, Donovan A, Zhang P, Liu C, Shang W, Irving TC, Herrera-Alonso M, Liu Y. Core-shell Structure and Aggregation Number of Micelles Composed of Amphiphilic Block Copolymers and Amphiphilic Heterografted Polymer Brushes Determined by Small-Angle X-ray Scattering. ACS Macro Lett. 2018. 6 (9), pp 1005–1012.
- 2017 Chassé MH, Muthurajan UM, Clark NJ, Kramer MA, Chakravarthy S, Irving T, Luger K. Biochemical and Biophysical Methods for Analysis of Poly(ADP-Ribose) Polymerase 1 and Its Interactions with Chromatin. Methods Mol Biol. 2017. 1608:231-253. doi: 10.1007/978-1-4939-6993-7_16
- 2017 Yuan CC, Kazmierczak K, Liang J, Kanashiro-Takeuchi R, Irving TC, Gomes AV, Wang Y, Burghardt TP, Szczesna-Cordary D. Hypercontractile mutant of ventricular myosin essential light chain leads to disruption of sarcomeric structure and function and results in restrictive cardiomyopathy in mice. Cardiovasc Res. 2017. 113(10):1124-1136. DOI: 10.1093/cvr/cvx060
- 2016 Mijailovich SM, Kayser-Herold O, Stojanovic B, Nedic D, Irving TC, Geeves MA. Three-dimensional stochastic model of actin-myosin binding in the sarcomere lattice. J. Gen Physiol. 148(6):459-488
- 2016 Ait-Mou Y, Hsu K, Farman GP, Kumar M, Greaser ML, Irving TC, de Tombe PP. Titin strain contributes to the Frank-Starling law of the heart by structural rearrangements of both thin- and thick-filament proteins. Proc Natl Acad Sci USA. 113(8):2306-11. PMID: 26858417 DOI: 10.1073/pnas.1516732113.
- 2016 Prodanovic M, Irving TC, Mijailovich SM. X-ray diffraction from nonuniformly stretched helical molecules. J Appl Crystallogr. 49(Pt 3):784-797. PMID: 27275136 PMCID: PMC4886979 DOI: 10.1107/S1600576716003757
- 2016 Muthurajan U, Mattiroli F, Bergeron S, Zhou K, Gu Y, Chakravarthy S, Dyer P, Irving TC, Luger K. In vitro chromatin assembly: strategies and quality control. Methods Enzymol. 573:3-41. PMID: 27372747 DOI: 10.1016/bs.mie.2016.01.002
- 2015 Prodanovic M, Nedic D, Irving TC, Mijailovich SM. Estimation of local forces in myofilaments using X-ray diffraction patterns and muscle mechanics data. Biophysical Journal. 108(2):422a-423a. DOI: http://dx.doi.org/10.1016/j.bpj.2014.11.2312
- 2015 Nedic D, Svicevic M, Stojanovic B, Geeves MA, Irving TC, Gilbert RJ, Mijailovich SM. Effect of mutations in cMyBP-C on sarcomere mechanical function. Biophysical Journal. 108(2):200a. DOI: http://dx.doi.org/10.1016/j.bpj.2014.11.1108
- 2015 Yuan CC, Ma W, Schemmel P, Cheng YS, Liu J, Tsaprailis G, Feldman S, Southgate AA, Irving TC. Elastic proteins in the flight muscle of Manduca sexta. Archives of Biochemistry and Biophysics. 568:16-27. PMID: 25602701
- 2014 Hitchcock-DeGregori SE, Irving TC. Hugh E. Huxley: the compleat biophysicist. Biophys J. 107(7):1493-1501. PMID: 25296301, PMCID: PMC4190654
- 2014 Barrea RA, Antipova O, Gore D, Heurich R, Vukonich M, Kujala NG, Irving TC, Orgel JP. X-ray micro-diffraction studies on biological samples at the BioCAT Beamline 18-ID at the Advanced Photon Source. J Synchrotron Radiat. 21(Pt 5):1200-1205. PMID: 25178013, PMCID: PMC4151685
- 2014 Nobrega RP, Arora K, Kathuria SV, Graceffa R, Barrea RA, Guo L, Chakravarthy S, Bilsel O, Irving TC, Brooks CL 3rd, Matthews CR. Modulation of frustration in folding by sequence permutation. Proc Natl Acad Sci USA. 111(29):10562-10567. PMID: 25002512, PMCID: PMC4115504
- 2014 Kathuria SV, Kayatekin C, Barrea R, Kondrashkina E, Graceffa R, Guo L, Nobrega RP, Chakravarthy S, Matthews CR, Irving TC, Bilsel O. Microsecond barrier-limited chain collapse observed by time-resolved FRET and SAXS. J Mol Biol. 426(9):1980-1994. PMID: 24607691, PMCID: PMC4010103.
- 2014 Witayavanitkul N, Ait Mou Y, Kuster DW, Khairallah RJ, Sarkey J, Govindan S, Chen X, Ge Y, Rajan S, Wieczorek DF, Irving TC, Westfall MV, de Tombe PP, Sadayappan S. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium. J Biol Chem. 289(13):8818-8827. PMID: 24509847, PMCID: PMC3979389
- 2014 Prodanovic M, Irving TC, McOwen R, Mijailovich SM. X-Ray diffraction pattern of non-uniformly stretched actin filament. Biophysical Journal. 106(2):768a.
- 2014 Witayavanitkul N, Sarkey J, Aitmou Y, Kuster DWD, Khairallah RJ, Govindan S, Chen X, Ge Y, Rajan S, Wieczorek DF, Irving TC, de Tombe PP, Sadayappan S. Myocardial infarction-induced N-terminal fragment of cMyBP-C impairs myofilament function in human left ventricular myofibrils. Biophysical Journal. 106(2):347a.
- 2014 Yuan CC, Muthu P, Kanashiro-Takeuchi R, Liang J, Rojas AI, Kazmierczak K, Hare JM, Irving TC, Szczesna-Cordary D. The structure-function analysis of myosin pseudo-phosphorylation in mouse model of FHC. Biophysical Journal. 106(2):771a.
- 2014 Huang W, Liang J, Kazmierczak K, Muthu P, Yuan CC, Rojas AI, Duggal D, Borejdo J, Irving TC, Szczesna-Cordary D. Familial hypertrophic cardiomyopathy-linked mutation (K104E) in the myosin regulatory light chain affects sarcomeric structure and function in Tg-mice. Biophysical Journal. 106(2):33a.
- 2014 Hsu KH, Zhang M, Witayavanitkul N, Irving TC, de Tombe PP. Impact of troponin-I phosphorylation on human cardiac myofilament function. Biophysical Journal. 106(2):770a.
- 2014 Hsu KH, Ait-Mou Y, de Tombe PP, Irving TC. Titin-based modulation of sarcomere structure as revealed by equatorial X-ray diffraction. Biophysical Journal. 106(2):161a.
- 2014 Orgel J, Irving TC. Advances in fiber diffraction of macromolecular assembles. John Wiley & Sons, Ltd., ISBN: 9780470027318
- 2013 Kathuria SV, Chan A, Graceffa R, Paul Nobrega R, Robert Matthews C, Irving TC, Perot B, Bilsel O. Advances in turbulent mixing techniques to study microsecond protein folding reactions. Biopolymers. 99(11):888-896. PMID: 23868289, PMCID: PMC3843316
- 2013 Graceffa R, Nobrega RP, Barrea RA, Kathuria SV, Chakravarthy S, Bilsel O, Irving TC. Sub-millisecond time-resolved SAXS using a continuous-flow mixer and X-ray microbeam. J Synchrotron Radiat. 20(Pt 6):820-825. PMID: 24121320, PMCID: PMC3795536
- 2013 Williams CD, Salcedo MK, Irving TC, Regnier M, Daniel TL. The length-tension curve in muscle depends on lattice spacing. Proc Biol Sci. 280(1766):20130697. PMID: 23843386, PMCID: PMC3730583
- 2013 George NT, Irving TC, Williams CD, Daniel TL. The cross-bridge spring: can cool muscles store elastic energy? Science. 340(6137):1217-1220. PMID: 23618763, PMCID: PMC3865433
- 2013 Singh B, Miller SR, Bhandari HB, Graceffa R, Irving TC, Nagarkar VV. High-speed detector for time-resolved diffraction studies. J Phys Conf Ser. 425(9). pii: 092005. PMID: 24489595, PMCID: PMC3905683
- 2013 Daniel TL, George NT, Williams CD, Irving TC. In vivo time resolved X-ray diffraction reveals radial motions of myofilaments in insect flight muscle. Biophysical Journal. 104(2):485.
- 2013 Mijailovich SM, Stojanovic B, Nedic D, Svicevic M, Gilbert RJ, Geeves MA, Irving TC. Modulation of crossbridge cycling kinetics and length dependent calcium sensitivity by titin and nebulin. Biophysical Journal. 104(2):310.
- 2013 Muthu P, Huang W, Kazmierczak K, Liang J, Rojas AI, Irving TC, Szczesna-Cordary D. Structural defects induced by malignant mutations in the regulatory light chain of myosin. Biophysical Journal. 104(2):157.
- 2013 Perz-Edwards RJ, Irving TC, Reedy MK. Full tropomyosin movement during stretch activation requires strong binding crossbridges. Biophysical Journal. 104(2):37a.
Editorial Boards
- Frontiers in Molecular Biosciences, review editor
Professional Societies
- American Crystallographic Association
- American Physical Society Division of Biological Physics
- Biophysical Society